Best before yesterday

Open neuroscience talk at the University of Sussex next Wednesday - by me :)

2010-09-27T12:08:00.004+01:00

I've been asked to give a talk to the Artificial Life Reading Group (Alergic) at the University of Sussex next Wednesday (Oct 6). I'm gonna take the opportunity to articulate my understanding of brains as spiking attractor networks that seek operant control through dopamine-mediated reward learning. This is actually a simple mix of old ideas, but my model system - the buccal ganglia - and experimental technique - the multielectrode array - allows me to quantify and visualize the various components of the theory. I'll also have the opportunity to test some new thoughts on brain-computer interfacing.

Network dynamics, dopamine and operant control: lessons from the molluskan buccal ganglia

Time: Oct 6, 16:30-18:00

Abstract

Multielectrode array (MEA) analysis of molluskan nervous systems is an experimental technique recently developed at the University of Sussex (Harris et al., 2010). Here I discuss our current understanding of the molluskan buccal ganglia, with examples from the MEA work, and relate it to more general theories of network dynamics, pattern generation, dopamine-mediated reward and operant control. Variance in the neural pattern for feeding behaviour, which the buccal ganglia continue to generate in vitro, allows the brain to search for optimal feeding strategies in changing environments (Brezina et al., 2006) and can be considered a rudimentary form of free will (Brembs, in press). I argue that this ability to generate variable, reward-sensitive motor output is a central function of brains, and discuss experimental and computational approaches toward a better understanding of it.

References: Brembs (in press) Proc of the Royal Soc; Harris et al (2010) J Neurosci Methods 186(2):171-8; Brezina et al (2006) Neurocomputing 69(10-12):1120-1124.

The talk will be recorded and will hopefully be available on the iPlant channel in a few weeks but please get in touch if you are in the UK and would like to attend the talk (and the enjoyable post-talk discussion in the bar). RSVP on Facebook here.

Sackler Centre for Consciousness Science - Facebook Page

2010-09-21T14:25:00.000+01:00

I recently set up and will now manage the Facebook Page of the Sackler Centre for Consciousness Science and the Neurodynamics and Consciousness Lab at the University of Sussex. These are interdiciplinary groups headed by Dr Anil Seth. There's also a Twitter account.

Part of the mission statement:

How do conscious experience, subjectivity and free will arise from the brain and the body? Even in the late 20th century, consciousness was considered by many to be beyond the reach of science. Now, understanding the neural mechanisms underlying consciousness is recognized as a key objective for 21th century science. Powerful new combinations of functional brain imaging, computational modelling and basic neurobiology bring real hope that human ingenuity can resolve this central mystery of life. Practically, an enhanced understanding of consciousness will transform clinical approaches to a wide range of neurological and psychiatric disorders, from coma to insomnia, from depression and schizophrenia to autism and dementia...

More info at the University website: http://www.sussex.ac.uk/sackler

Spontaneous and dopamine-driven brain activity

2010-09-11T18:08:00.001+01:00

Last weekend I started working on a video aimed at giving viewers a feel for the beauty and complexity of the network activity we record in the lab (see this entry for details). The trigger for this was meeting a friend who was able to create for me the Java code necessary to run the spike rate data through JFugue. My own attempts at this had not been completely successful. Simultaneously, Björn Brembs started posting a series of excellent and quite closely related videos over on his YouTube channel, which kept me motivated (also, being able to point to videos from Bill Kristan's lab certainly helped convince my supervisors of the wisdom of the idea).

There will be more of these, at least I intend for there to be, because it was a lot of fun to make and there are a range of variations and improvements on the audiovisual presentation to explore, as well as a whole bunch of specific topics I'd like to address. But for now, this is it.

Myers vs Kurzweil

2010-08-21T13:32:00.003+01:00

In a recent post, PZ Myers aggressively critizises Ray Kurzweil's prediction that the human brain will be digitally simulated by 2029. Yesterday Kurzweil responded, restating his belief that the complexity of the brain, though considerable, must not be overestimated. One of Ray's arguments is that the genetic blue-print for the brain is about 50 MB. (Update: Myers has now responded to Kurzweil's reply.)

I'm torn here. Intuitively I agree with Myers: the brain consists of biological tissue and therefore has a theoretically infinite complexity. Our understanding even of a single synapse is for example still very limited, as evidenced by entire journals being dedicated to research on synapses. But there is of course a considerable degree of noise in the brain, suggesting a limit to useful complexity (Eliasmith 2000).

How much of the brain's complexity must we include in digital simulations for them to, say, pass the Turing test? This is where Kurzweil makes mistakes. Phrases and assertions like "the cerebellum (which has been modeled, simulated and tested)" and "We have sufficiently high-resolution in-vivo brain scanners now that we can see how our brain creates our thoughts and see our thoughts create our brain" do indeed indicate that, as Myers puts it, Kurzweil does not understand the brain, and only serve to remind us of Henry Markrams scathing (but accurate) dismissal of the IBM cat brain simulation.

The issue seems to be this: Kurzweil's successful predictions - the decoding of the human genome, the growth of the internet - concerned discrete systems, where units (base pairs decoded, computers connected) could be clearly defined and counted. Digital simulations of brains are growing exponentially in size and complexity, but we truly do not know how complex they need to be before they can be said to match their biological counterparts. Kurzweil needs to present a scientifically robust theory of brain function before neuroscientists will take his 2029 prediction seriously.

New academic summary (update 4)

2010-07-03T16:00:00.007+01:00

I just finished writing a new 'academic objectives' blurb for my university, Mendeley and Academia.edu profiles. Constructive criticism warmly welcomed.

I'm a DPhil (PhD) student in my final year at the University of Sussex (UK). I'm looking for a post-doctoral research position in the United States or Canada where I can continue working in electrophysiology and learn optogenetic techniques. I'm interested in how brains generate, select and maintain adaptive neural and behavioural activity. This process, particularly the often central role of dopamine-mediated reward-learning, is fascinating in its own right because it's intrinsic to how our lives develop, but its breakdown is also the hallmark of a wide range of psychiatric conditions in urgent need of effective medical treatment.

For my PhD I have developed a multielectrode technique to interface with a semi-intact invertebrate preparation and study the effects of sensory input, neuromodulators and electrical current on the brain's dynamic repertoire and adaptive output (Harris et al., 2010). Moving forward I want to learn techniques to interface with the mammalian brain and contribute to the development of models and technologies to help patients achieve adaptive neural and behavioural activity; control brain-computer interfaces for example or overcome maladaptive patterns of behaviour. I'm particularly interested in optogenetic photo-stimulation techniques, which have yet to reach clinical trials but already show extraordinary potential to address the theoretical and medical problems I want to work with, including dopamine-mediated reward-learning (e.g. Tsai et al., 2009; Bass et al., 2010).

References: Harris et al (2010) J Neurosci Methods 186:171-8. Tsai et al (2009) Science 324;5930:1080-4. Bass et al (in press) J Neurochem.

A brain and a robot walk into a bar.. (MEA2010, day 3)

2010-07-01T12:17:00.000+01:00

Not surprisingly there are a few posters here on two-way connections between robots and neurons cultured on multielectrode arrays (MEAs). One of them offer an open source software package to do it, called Cult2Robot. The authors use the software to let a culture of neurons on an MEA move a robot in four directions and avoid obstacles, all through a Bluetooth connection. Spike rates in the culture are monitored and whenever they cross a threshold at one of the four edges of the square MEA the robot goes in that direction. If the robot's sensors detect an object in any of the four directions, electrical stimulation is applied to neurons on the opposite site of the array, making them more prone to fire and bring the robot away from the obstacle.

It's a simple principle but it illustrates a point I've been trying to formulate for months:

Activity in brains and neural networks can be understood as a fixed number of neurons with a spike rate 0-200 Hz (120.000 neurons in this particular culture)
Some patterns of activity result in defined actions (here supra-threshold activity along an MEA edge results in ipsilateral movement)
Some actions are adaptive, others maladaptive, depending on the circumstances
Given adaptive sensory- and/or reward-feedback, neurons change their activity to produce more adaptive output (here objects are avoided by stimulation of neurons with contralateral output)
The number of adaptive activity patterns a network can reliably assume in the context of changing sensory- and/or reward-feedback is a measure of its operant control (in brains we call this creativity, intelligence, self-discipline etc; as an infant learns new words, its operant control increases)
By using sensory- and/or reward-feedback protocols and good electrophysiological or brain imaging techniques we can map the dynamic range of activity states a brain or network can assume and explore/model the network properties that determine its degree of operant control

A pressing question is how adaptive various networks can be. Could we for example program the MEA-culture-robot above to move not just in four directions but in the 360 directions of a circle? Could the network learn that certain spatial and/or temporal patterns of network output drive power-moves in the robot (like jumping, climbing or crawling) that scale difficult obstacles, the presence of which might be indicated by specific sensory feedback patterns? The link between specific obstacles and appropriate outputs could be strengthened by application of dopamine... you get the idea. Moreover, to make use of the rich and variable activity of neural networks, they should be given the ability to control the robot's actions along continuums like amplitude, duration, and correlation with other actions. And remember, its not just academic curiosity driving these explorations: a constant theme of this conference has been neural prostheses, and the ability of human brains to generate and respond to many arbitrary patterns of activity along continuums is exactly what gives them the ability to control and respond to brain computer interfaces that restore function and improve lives daily, all over the world, but which are still very immature and problematic.

MEA Meeting 2010, day two

2010-06-30T12:27:00.001+01:00

I'm in Germany this week, in a sleepy little southern town called Reutlingen, attending the MEA2010 conference. I'm here to present our most recent work, talk to other MEA nerds and berate Multi Channel Systems employees until they implement basic spike sorting in MC_Rack. MEA stands for multielectrode array; the focus of the conference is multi-unit electrophysiology, mostly neural networks cultured on titanium arrays in glass dishes, but the whole spectrum of techniques and analysis methods is represented: yesterday we saw analysis of data from an electrode net the size of a small hand that goes right on the top of the brain, more on that in a bit.

German is frustratingly close to my native Swedish and yet impossible to understand. Almost. Spielplatz must mean playground, speil sounding like a variant of spel (game in Swedish) and platz like plats (ground in this context, though it really means location). Spielplatz = gameground. In Swedish we say lekplats, lek meaning play. It doesn't help, I'm still a tourist, and the heat is just as bad here as in England. People at the conference are mostly from Europe and East Asia, many languages spoken in the hallways and a lot of poor English (Globish, according to yesterday's Start The Week). There's maybe 200 people here in the big hall now, though it's still pretty early; leave it to the Germans to serve food and wine until 23:00 and then start talks at 8:30 the next morning. It's ok, my hotel is ten minutes away.

The opening lecture yesterday was by Pascal Fries and entitled 'Unravelling the brain-wide web of attention'. It was very good. Fries looks like he could be 25 years old but is a Prof., a P.I. and an M.D. He was showing us evidence that objects are held in visual attention by selective synchronization of distributed but functionally relevant brain regions in the gamma (feed forward, Granger = 0.02) and beta (feed back) bands (and a mystery band at 30 Hz). The data was recorded using a large net of a few hundred 1 mm diameter electrodes placed at 2 mm distance across almost the entire right hemisphere of two monkeys trained to respond to some visual stimuli and ignore others. The stimuli was known to hit specific regions in visual cortex, and activity in these region was subsequently compared with activity across the brain, using the net. The degree of synchrony in the gamma band predicted fast reaction time, so I'm wondering if synchrony in the molluskan buccal ganglia predict feeding rate. In question time I asked him what his thinking was on the mechanism by which the network associated with one stimulus becomes able to entrain others. The answer: given sufficient dopamine and noradrenaline tone, the network will establish coherence by activating interneurons in target regions. Signal-to-noise.

I actually asked him two questions, and having finished answering the first question he appeared ready to move to another questioner before catching himself and exclaiming "Oh, right, the second stimulus.. eh I mean second question". It's ok man, no need to speak humaneese, we're all neuroscientists here. Anyway, I should pay attention to the talks. Great wireless at a conference is both a blessing and a curse. Mostly blessing though.

Entitled Opinions update

2010-06-20T11:34:00.000+01:00

"Because to recognize oneself as a material being.. a number of human beings find that too disenchanting a view.. and if that's what it means to recognize myself, I'd rather continue to decieve myself" --Robert Harrison

Despite somewhat unfortunate statements such as this, Robert Harrison's Stanford radio program/podcast 'Entitled Opinions' is still going strong. Recent highlights include a program on Karl Marx, and a another, with Harrison's brother Thomas, on Pink Floyd.

Silence must be heard!

Prelude 1 - Breasts

2010-06-19T13:58:00.004+01:00

This is a prelude to the iPlant novel. The original text can be read here http://brainimplant.blogspot.com/2008/12/breasts.html

The first three chapters of the novel are available here http://www.iplant.eu/fiction.html

The most recent addition to the novel is http://brainimplant.blogspot.com/2010/05/first-run.html

CC licenced images in the video:

Attractor Poisson Saturne by Nicolas Desprez (http://commons.wikimedia.org/wiki/File:Atractor_Poisson_Saturne.jpg). Licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

Midbrain (http://commons.wikimedia.org/wiki/File:Midbrain_small.gif). Licensed under the Creative Commons Attribution-Share Alike 2.1 Japan license.

Syringe needle by Andrew Magill (http://commons.wikimedia.org/wiki/File:Syringe_Needle.jpg). Licensed under the Creative Commons Attribution 2.0 Generic license.

First run

2010-05-28T18:39:00.005+01:00

"I am still your body, you're just a brain!! You have no right..!"
"A brain with electronic motivation", Meg whispered.
"Fuck you!", her body shouted, in its own way, and ramped up lactic acid synthesis. Meg pressed on. It hurt, but the pain was part of her running, and she wanted to run. She'd been running non-stop for almost two hours on the big treadmill in the lab. The brain network maintaining her posture, driving her legs, arms and lungs, was lean, mean and optimized. Pressure-sensors in her shoes triggered dopaminergic electrodes in her brain with every step; honing, shaping, supporting and reinforcing the neuronal network and its muscle contractions. Interruption was impossible. Tiredness irrelevant. Even pain was part of the purpose, part of her strength, her will, her artificial motivation.

Lucy stood at the door, watching her. "It's time" she called.
"Noo.." Meg groaned.
"It's time", Lucy said again.
"Fuck!" Meg shouted and punched the stop button on the treadmill. The treadmill started slowing down, and for a moment Meg found herself trying to keep it going, pressing her hands against the railing and pushing her feet against the rubber sheet, harder and harder, the network in her refusing to disassemble, even though the link was lost, the sensors in her shoes inactive.
"Wow" she gasped, between strained gulps of air, and stopped. "Wow."
She released the railing, jumped off the edge of the treadmill and stomped both feet hard against the floor, putting all her weight and strength into it. But the sensors were silent. She groaned again and collapsed on the floor.

Lucy watched her from the door.
"You ok?" she asked?
Meg rolled over on her back, spread-eagle, and lay panting, staring at the ceiling. "Wow."

More iPlant fiction here

Drifting

2010-05-28T18:17:00.000+01:00

You're on a train, staring out the window at power lines, green planes and sky. Your mind wanders. You think of things that happened years ago, people still important in your life. You recall an exchange, you relive the feel of it; embarrassment, adoration, indifference, adventure, but context-dependent and with a specific, complex taste; you're watching rows of hedges, trees and sheep flash by, but in your mind's eye you see streets, places, a room where years ago someone close to you slept. The room most likely remains but you know nothing of the persons living there now; they never enter your mind in any way, why should they? Your friend lives elsewhere now, lives where the train is heading. For three hundred and thirty two seconds your brain attracts around those memories - the room, the bathroom, food and conversations you had there, films you watched - then stops, and you snap out of it, reach for your bottled water, and reconnect with your surroundings; with the people moving or sitting still around you. You don't know why your mind drifted to those particular memories, or what made it stop suddenly - or rather, you DO know, about quasi-stable patterns of brain activity, maintained by dopamine and obvious given your destination - but why that PARTICULAR chain of thoughts and memories, and why the sudden stop? You imagine the dyanmics of your brain, imagine a brain-shaped animation of swirling electrical potential, action potentials, ever-changing, save for brief periods where stable configurations are reached that attract the swirling mass around a recognizable shape, a place, a thought, a memory, before loosing interest and drifting off. You look around again, search the environment for stability, attraction, dopamine. The woman next to you in black, with the clean features, the headphones, the short hair and the eyebrows. The landscape outside, darker now; houses, horses, a town. There's nothing there to keep you, and your mind begins to drift again. It makes you sad, restless, and you put the music back on.

Craig Venter unveils "synthetic life"

2010-05-21T16:32:00.002+01:00

Chapter 3 - New job

2010-05-09T22:15:00.000+01:00

Optogenetics: brain stimulation by light

2010-03-28T16:47:00.002+01:00

Brains as spiking attractor networks

2010-03-21T13:35:00.005Z

Thank you to everyone who commented, online and in person, on my previous post. I hope this updated version will address the issues you raised, but I warmly welcome further comments. If the following is good enough I'll use it in a video entitled 'Basic neuroscience' that I'm making for YouTube, and in my analysis of neuronal multielectrode array data (Harris et al., 2010).

What I'm after is agreement on a simple but formally correct quantitative framework for describing brain activity. What determines the spiking (1) or non-spiking (0) of a neuron at a given time t is, as several people pointed out, an enormously complex interplay of cellular and synaptic processes, and it is the job of neuroscientists to discover the conditions (e.g. synaptic weights) necessary for artificial neural networks to replicate the spike patterns of biological brains. However, the spiking/non-spiking binary is clearly the most salient computational property of neurons, and in multielectrode recordings it is often the only value we can reliably detect.

Several people pointed out that the state of a brain (X) at time t, is a vector (an array of values) rather than a sum, i.e.

X(t) = [V₁(t), V₂(t),... V_N(t)]

where N is the number of neurons in the brain and V is the spiking (1) or non-spiking (0) of a particular neuron. Thus, a brain containing 100 neurons has 2¹⁰⁰ possible states, e.g.

X(t₁) = [ 0 1 1 1 1 0 0 0 1 0 1 1 1 1 1 1 0 0 0 0 0 0 1 1 0 1 1 1 1 1 1 0 0 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 1 0 1 1 1 1 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 ]^T

X(t₂) = [ 0 1 1 1 1 0 1 1 0 0 1 1 1 1 1 1 0 0 1 1 1 1 0 0 0 1 1 1 1 1 1 0 0 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 1 0 1 1 1 1 0 0 0 0 1 1 0 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 ]^T

X(t₃) = [ 0 0 0 0 1 0 1 1 0 0 1 1 1 1 1 1 0 0 1 1 1 1 0 0 0 1 1 1 1 1 1 0 0 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 0 0 1 1 0 0 1 1 0 0 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 ]^T

where red highlights a change in neuronal activity from the previous time point, and T stands for transpose (change from row to column) since the states of a neuron at successive time steps are usually arranged in a row (e.g. a raster plot, spike density function or voltage trace).

So far so good, but now to the heart of the matter: how do we use this simple framework to describe the complex brain activity manifest in cognition, behaviour and key neural processes?

The 2¹⁰⁰ (1.2676506 × 10³⁰) possible states of a brain with 100 neurons are referred to as its state space. Some of these states are not possible under biologically plausible conditions, and only a fraction of all biologically plausible states will be expressed during the lifetime of a brain. The order in which brain states occur is referred to as the trajectory of the brain's activity in state space. If we plot against one another the spike patterns (e.g. spike density functions) of two or more antagonistic neurons or neural networks, such as those that drive walking, breathing or swimming, they form a cyclic trajectory in state space, called an attractor, e.g.

Cyclic attractors in state space. After displacement (blue) one system (a) returns to its main trajectory while a different system (b) switches to a different trajectory, which drives a different behaviour. Figure from Briggman and Kristan (2008) Multi-Functional Pattern Generating Circuits.

Some commenters questioned the usefulness of the attractor concept for understanding complex cognitive processes and behaviours, such as making coffee, that involve large brain networks. In the absence of an alternative though, I still think the attractor model is worth pursuing, because the activity of sensory and motor neurons is tightly constrained by complex behaviours, and can therefore be described as attractors in the state space of the brain. In making coffee for instance, extending the arm and grasping the kettle must precede pouring hot water into the cup, and all three actions map directly onto tuning curves of specific neurons in the hand and arm regions of the left (typically) motor cortex. Therefore, these neurons will generate very similar spike patterns every time the action is performed. I believe the activity of neurons not directly constrained by the sensory and motor demands of the task, and therefore not obviously part of the behaviour, will nevertheless be selected for its ability, through direct and indirect synaptic connections, to create and maintain the required attractor among the sensory and motor neurons.

In terms of the present framework the question is, for each neuron or group of neurons N, how similar their spike patterns V have to be, morning-to-morning, for coffee to be successfully made. Neurons that are constrained in some way can be considered part of the coffee-making attractor. We can approach the question for instance by hypothesizing that the activity V of neurons in the pre-motor cortex will be more constrained than that of neurons in the temporal cortex, and then use EEG to measure variability in these regions on successive mornings. In animal models the recordings could be at the level of individual neurons and perturbations could be introduced. The relationship of the spike pattern of a neuron to an ongoing attractor may be complex and depend on the spike patterns of many other neurons, and some behaviours clearly require more neuronal resources than others, but these are empirical questions that, to me at least, seem fruitful.

Some further questions:

In what ways can some neuronal activity V_N(t) be said to participate in an ongoing attractor?
How do we characterize, mathematically and visually (or perhaps audibly) an attractor in N dimensional space?

Lorenz attractor

How should we think about brains?

2010-03-11T21:28:00.012Z

This is a simplified but, I hope, formally correct framework for thinking about brain activity. Please help me by pointing out errors and obscurities.

The human brain is a network of some 100 billion neurons. The generation, recognition and modulation of neuronal activity patterns by neural networks in the brain are physical manifestations of thoughts, feelings, actions and sensations. Efforts to understand, reproduce and communicate the activity and capacities of brain networks are hampered by the inaccessibility and extraordinary complexity of these networks. However, a general understanding of brains as dynamical systems has emerged.

Consider a brain consisting of N neurons with an activity state V indicating activity (1) or inactivity (0). At time t the state (X) of this brain is equal to the activity state V_i(t) of neuron i, where i = 1,2,...N labels the N neurons of the brain. Formally, we write

which simply means that at a given time (t) the state of the brain (X) is the sum of the activity or inactivity (V) of its N neurons (i). The neurons are said to be the state variables of the system. Thus, a brain consisting of 100 neurons has total of 100^100 possible states, e.g.

Possible brain states. Red indicates a change in V from the previous time point.

The 100^100 possible states of this brain are referred to as its state space. Given biologically plausible rules for neuronal activation however only a fraction of the 100^100 states are practically possible. For example, it is not practically possible for all the neurons in your brain to become simultaneously active, or for all neurons in one hemisphere to be active and all neurons in the other hemisphere inactive. Furthermore, only a fraction of all practically possible brain states will be expressed during the life of a brain. For example, although it is practically possible for your brain to learn and express brain states associated with the articulation of words in Swahili, in actual fact you probably will never express those states. Conversely, some classes of brain states may recur frequently (see below).

The order in which a brain expresses its various states is referred to as its trajectory through state space. In some brain networks the trajectory is rhythmic and continuous. For example, neurons in the Pre-Bötzinger complex drive breathing from the moment of birth to the moment of death, and can only be temporarily displaced from their oscillatory trajectory in state space. Networks driving episodic rhythmic behaviours such as chewing go into a particular oscillatory trajectory when the behaviour is expressed, but may also be quiescent for long periods of time, or express different trajectories that drive other behaviours involving the same muscle groups (e.g. speaking, licking, coughing).

Rhythmic trajectories (also referred to as neuronal oscillations or "limit cycles") through a 3D state space. After displacement (blue) the system (a) returns to its main trajectory or (b) switches to a different trajectory. Figure from Briggman & Kristan (2008) Multi-Functional Pattern Generating Circuits.

A region or path in state space that attracts nearby network trajectories is called an attractor or attractor basin. For example, consider making coffee in the morning: this behaviour is a precise trajectory through the state space of your brain, involving movement to the kitchen, location of appropriate equipment, pouring hot water into a cup etc. If you're like me, your brain will revolve in the basin of this attractor untill coffee is produced regardless of where you wake up, what the time is, what you dreamt etc. In other words, your brain tends to travel through the coffee-making attractor regardless of its starting point in state space in the morning. This is not to say that every behaviour necessarily corresponds to an attractor - by relying on environmental cues a neural network with just one attractor can express several problem solving states (Buckley et al., 2008) - but it is a very useful simplification for thinking about brain activity.

Attractor basins (green) and hills (red) in a 2D state space.
The brain state spaces discussed here have N dimensions.

Attractors are also useful for understanding sensory classification, memories and habits of thought. For example, sensory categories are thought to result from neural networks associated with aspects of a class of objects (e.g. sensory networks responding to the sight, bark or smell of dogs) being repeatedly activated together and thus linked through Hebbian plasticity. In other words, the networks form an attractor "of" the abstract concept 'dog', such that all nearby brain states (e.g. neurons in the auditory cortex responding to a bark, or neurons in the visual cortex responding to a furry tail) will tend to converge on the same attractor basin and classify as instances of 'dog'.

That's it for now. Topics for future blog posts: How are attractors continually formed and dissolved in the state space of brains and networks? How can we study neural network dynamics and attractors? How can we visualize them, quantify them and use them in computing and in our everyday understanding of ourselves and others?

New questions about the iPlant

2010-03-01T21:34:00.003Z

A few days ago I received a set of unusually sharp thoughts and questions about the iPlant from an unknown person. My reply got rather lengthy, and I'm posting it here for future reference:

You're right that strong conditional rewarding brain stimulation, e.g. the kind that's been used to make rats exercise (Burgess et al., 1991; Garner et al., 1991), would probably create a powerful addiction in human patients and might disrupt normal interests and activities. Early on in the development of iPlants this might not be a huge concern, since patients undergoing the required surgery would already a) be in a desperate state and b) suffer from some form of addiction. I'm thinking of, for instance, morbidly obese patients in dire need of heavy physical exercise, or drug addicts who need to program themselves to stay clean.

In the context of widespread use of iPlants however surgeons will probably need to work with rewarding electrical current that is relatively weak. In my opinion, the current should if possible be just strong enough to motivate you through your two or so hours of very challenging behaviour; just enough to enable you to pull through, but no more. Rewarding brain stimulation is not an all-or-none phenomenon. For example, rats will get bored with pressing a button that delivers low intensity rewarding current after a certain number of trials, and will continue to prefer things like food, sex and play. It all depends on the intensity of the rewarding electrical current.

The problem, as far as widely used iPlants are concerned, would be getting the current intensity right, because although a lot may be learned from those first patients and from lab experiments, there would still be individual variability. The issue you raise at the end of your email may be a partial solution. That is, if we could monitor the amount of dopamine that's released in the brain in response to different intensities of electrical current, that might help surgeons find the current that works best for individual patients. However, although Paul Garris' and other labs have done some good work towards monitoring dopamine in the human brain, and an interesting study came out of MIT a few days ago on the subject, I still expect the growing experience of surgeons, combined with the reports and behaviour of the patient, to be the main way this problem is handled, just as is currently the case whenever deep brain stimulation is applied to treat psychiatric conditions. It's a hard and central problem, and my little novel-in-writing starts with an instance of this process going horribly, violently wrong.

Your second concern is equally central: how do we tie rewarding electrical current to specific activities, and ensure that the conditional rewarding brain stimulation remains conditional on the user performing the required behaviours? Again, this may not be a big problem in the early days, when patients can be required to perform work-outs, drug-tests, learning routines etc. at the hospital where they have their surgery. Patients would connect, e.g. to a rowing machine or an exercise bike, via the kind of transdermal communication equipment that's already used to re-program deep brain stimulation implants post-implantation (such a controller is shown next to an implant below). Only at the hospital would the iPlant be activated and pulses delivered, e.g. with each pull on the rowing machine or as long as the patient uses the exercise bike. Use of smoothly running equipment might not even require hospital staff supervision.

But again the question is how to this would work in the context of widespread public use. The risks of misuse and abuse are of course enormous and range from benign attempts to increase current intensity a little; through attempting to subvert the need to complete the required task to receive stimulation; to flat out mind control by external, malicious agents. Perhaps the least appealing solution would be to maintain the requirement that iPlants be activated and used only in certain supervised settings, such as hospitals and certified gyms. This would require hardware, software and policy routines that comprehensively prevent iPlants being used in other situations. Such access control is hard to ensure, even when the electronics are embedded under skin, and with widespread use some individuals bent on self-experimentation would probably sooner or later damage their implants or themselves: this is a very serious concern. It should also be noted that deep brain stimulation implants for certain psychiatric conditions already target the reward system (Greenberg et al., 2008, Schlaepfer et al., 2008, Malone et al., 2009, Bewernick et al., (2010)) and could thus in theory be hacked and used as iPlants, for good or ill.

If access control, encryption and intended use could be comprehensively ensured however, we can imagine a whole range of scenarios in which people might be able to use iPlants in the comfort of their own homes. The implant would deliver rewarding stimulation if activated by a computer command through the transdermal patch, and this command could be generated by all sorts of authorized hardware and software. An example I frequently use is a modified e-learning program designed to help people with learning difficulties by reinforcing correct answers typed into a software dialogue with rewarding current. More elaborate schemes include iPlant-driven research, where completion of some segment of a research protocol would give the user access to rewarding brain stimulation. See chapter two of the novel for more on this.

I hope this sheds at least some light on your questions, feel free to come back with more. Working on these problems in public and defining what iPlants would have to be like to function in our society is the whole point of the iPlant project. If you have a blog I hope you post your thoughts there too so other people can take part in the discussion, and with your permission I'd like to post your questions with my answers on my own blog at http://brainimplant.blogspot.com/2010/03/new-questions-about-iplant.html.

All good,
Chris

Neuroscience is only getting started

2010-02-20T20:05:00.000Z

Studying the formation of patterns in the invertebrate nervous system

2010-02-07T16:47:00.003Z

Now that my first article has been published (Harris et al., 2010) I should finally able to talk and write about my PhD research. Pre-publication attempts to do so earned me a few slaps on the wrist.

My work builds on the electrophysiological analyses of molluscan nervous systems that my university has specialised in for more than three decades (Benjamin & Rose, 1979; Benjamin & Kemenes, 2008). The use of relatively simple invertebrate systems as models for understanding brains in general goes back to the characterization of the action potential (Hodgkin & Huxley, 1939; 1952), through to the molecular mechanisms of synaptic memory formation (Kandel, 2001) and the study of dynamic neural circuits (Selverston & Ayers, 2006; Briggman & Kristan, 2008; Elliot & Suswein, 2002). Whereas the vertebrate brain, for the most part, remains impossibly complex, invertebrate nervous systems are small (20.000 neurons in the molluscan brain - 100 billion neurons in the human brain) and have large, relatively accessible neurons that survive and remain functional in vitro. Moreover, the location, connectivity and function of invertebrate neurons are virtually identical among members of a species, much unlike the individualistic vertebrate brain.

"In the mammalian brain, the precise relationship between the dynamics of individual neurons and functional networks remains extremely complex. The main reason for this is a lack of knowledge of the detailed cell-to-cell connectivity patterns and the biophysical properties of the individual neurons and their synaptic connections. Attempts to understand brain dynamics by large-scale modeling have been attempted frequently but without knowledge of the detailed parameters such as the number and kind of synaptic connections, the results have been disappointing (e.g., Foldiak and Young 1995). Moreover, each physiological synapse may result from numerous anatomical synapses that may have complex spatial geometries in neuronal branches. The numerically less complex microcircuits of invertebrates have neurons and synapses which are identifiable from animal to animal. Therefore, a much more detailed understanding of neural circuit dynamics is possible." - Selverston & Ayers (2006)

Unlike many other sciences, neuroscience lacks what Gerald Edelman calls a "global brain theory", a conceptual and mathematical foundation for understanding brain and behaviour. In this context, the aim of invertebrate neuroscience is the development of principles and computer models that describe the operations of biological neural networks in general. The tacit assumption here is that vertebrate brains work like their spineless cousins, and though this has proved largely accurate on the molecular and cellular level, it has not been conclusively established on the poorly understood level of neuronal networks, although there are tantalizing similarities (Yuste et al., 2005; Grillner 2006).

Of particular interest, at least in our lab, is the generation, by these networks, of the complex patterns of electrical activation that underlie the adaptive behaviour of living organisms. Invertebrates show a striking degree of adaptive variability in the way they behave, which through processes of sensory feedback, neuromodulation and reinforcement learning allows them to behave intelligently in a constantly changing environment (Horn et al., 2004; Selverston & Ayers, 2006), an ability currently unavailable to computer software and robotics. We are also concerned with reinforcement learning on longer time-scales, and with the competitive and cooperative interactions between neural networks that allow organisms to select different behaviours in different situations.

We study these processes primarily through a detailed analysis of a network of neurons that control the feeding musculature in the freshwater gastropod Lymnaea stagnalis. The network comprises some 500 neurons in two almost identical ganglia (shown below, black dots are extracellular electrodes).

The network occasionally generates a complex pattern of activation (below), which in vivo drives sequential muscle contractions that extend a tongue-like structure, scoop food into the mouth cavity and swallow it (a video of this behaviour can be found here). Remarkably, the neural network continues to generate the appropriate sequential activation of motor neurons for hours even when the brain is isolated and monitored with microelectrodes. Each cycle of activity is then called a "fictive" feeding cycle. Below are five such cycles, recorded on 14 of the extracellular electrodes in the figure above (note the cycle-to-cycle variability).

A number of methods have been developed for experimental initiation of feeding cycles, including intracellular activation of cerebral command-neurons, dopamine perfusion, and perfusion of sensory tissues with gustatory stimuli.

I'll return to this work in future posts, because there is an enormous number of questions and avenues for research here, and I know some of my readers work on similar projects. There are also a number of direct links between this research and reinforcement learning, motivation, dopamine, the iPlant, and the overarching goal of developing a qualitative, easily communicable understanding of the living human brain.

27 January 2010

2010-01-27T15:55:00.000Z

Dear readers, I'm acutely aware that my blog has stagnated. I blame FriendFeed and Facebook, where people actually INTERACT with my links and loose thoughts, but the real reason is simply contentment: life is going well at the moment, all things considered, and so I have nothing to say, no tensions to sublimate or at least whine about. Fear not though, I intend to create NEW TENSIONS by having an ABSOLUTELY ALCOHOL-FREE FEBRUARY!

In the meantime, here is the original version of a column I wrote, which, after some peculiar mangling by the editors, was recently published in the local student paper. Readers of this blog will find the text annoyingly simplistic, or at least old hat; I post it here simply to stress that I would never - ever - make such use of question- and exclamation-marks.

The most important thing in life
Christopher Harris

What fascinates me most about the brain is its motivation, the fact that it wants and desires. I'm also acutely aware of the limits of my own free will: eat less, exercise more, study more, be more social, dare to do this, stop doing that; it's like a never-ending struggle with my own will, and I know I'm not the only one frustrated by this experience, especially now, with new year's resolutions failing left and right. So what's going on?

In the middle of your brain you have half a million neurons that release dopamine into your frontal lobes. These neurons form the core of your brain's reward system, which generates your motivation. Rewards, like food, drink, play, sex and addictive drugs, raise dopamine concentrations in your brain, as do learned rewards like money. Unexpected rewards are particularly effective, and dopamine builds up in anticipation of uncertain rewards, making everyone at the bus stop stare at the bend where the bus will appear. Low dopamine concentrations on the other hand make you distracted and disinterested.

Different behaviours are produced by different groups of neurons in the frontal lobes. These neuronal groups run on dopamine, and so the behaviour you feel most motivated to perform at any given moment is that of the group that generates the most dopamine. Eating sweets is easy: with a few simple muscle movements it activates your dopamine neurons through your taste buds. Studying for a distant exam is hard: it requires your full attention and activates your dopamine neurons only indirectly, through your prefrontal cortex, which simultaneously has to inhibit more immediate urges like surfing the web, going out or watching a film. You may have heard of Phineas Gage, who destroyed his prefrontal cortex in an accident and lost his impulse control and his ability to follow plans for the future.

New year's resolutions fail because we make them considering only the wonderful goal, which by itself produces plenty of dopamine, especially when it's new and feels like a fresh start. We don't realize how hard it will be for our prefrontal cortices to provide the new neuronal groups with enough dopamine to make us runregularly, or read in the library, or go to the gym, or in any way compete with the entrenched neuronal groups that have us sit on the couch, or over-eat, or smoke. On a normal day, the further away a goal is, the less attractive it seems, because the further away a reward is, the less dopamine it generates. So the trick to keeping new year's resolutions: be nice to your prefrontal cortex.

There's more to motivation of course, the reward system is enormously complex. This is how I like to think about it though, and it's worked so far. It helped me quit smoking, knowing that the urge was strong because dopamine neurons are covered in nicotine receptors, but that the brain would 'forget' this in a few months and the urge would go away. It helps me understand all kinds of thoughts, habits, excitements and hang-ups. It helps me understand my own brain. Check in next week for another bit of this story, and join the dopamine fan page on Facebook for references and more information.

See you February.

The Known Universe

2009-12-20T14:30:00.002Z

Aubrey de Grey talks regenerative therapy on CNN :)

2009-12-02T18:26:00.000Z

President Obama on the Way Forward in Afghanistan and Pakistan

2009-12-02T09:17:00.000Z

Ken Dychtwald - The Consequences of Human Life Extension

2009-11-28T18:30:00.000Z

A very interesting and well-delivered talk on aging and the inevitable and dramatic changes that will take place in society and in individual lives over the coming decades as people in the West grow increasingly older and older and older. Also available on iTunes.

http://www.longnow.org/seminars/02004/dec/03/the-consequences-of-human-life-extension/

One memorable quote: “Of all the humans who have ever lived over 65, two-thirds are now alive now.”

Brembs (2006) Brains as output/input devices

2009-11-27T13:26:00.003Z

I just finished reading an excellent blog post (paper?) by Björn Brembs entitled Brains as output/input devices. I admit that I too have tended to think of brains as stimulus-response machines, paying little attention to spontaneous behaviour and operant learning. Indeed, the old iPlant programming section on my website used to begin "Like a digital computer, the brain generates output from input". On the contrary, Brembs argues, the brain generates input from output. That is, the main function of brains is to control the environment they're in - and thus the sensory input and rewards/punishments they receive - by figuring out the right motor output for a given situation.

"input/output transformations may only account for a small fraction of what brains are doing. Maybe a much more significant portion of the brain is occupied with the ongoing modelling of the world and how it might react to our actions?"

Furthermore, Brembs argues, the variability we observe in spontaneous behaviour is a feature of operant learning: it is a way for the brain to find and develop patterns of behaviour that give it optimal control over its environment. "Faced with novel situations, humans and most animals spontaneously increase their behavioural variability", presumably in order to figure out how this particular environment responds to behaviour. It's the environment that responds, not the animal. Perhaps even the subtle variability we see in the invertebrate feeding system is an expression of the molluscan brain trying to figure out the best way to eat this particular sea-weed. If so, such variability should be selectively enhanced by reward learning. Is it? Other questions:

How is behavioural/neuronal variability generated in small and large brains?
What % of behavioural/neuronal variability is really subject to learning/operant control in different networks?
What features of neuronal activity are most likely to be subject to learning/operant control? In other words, where do we look? Spike rate of individual neurons? Network patterns? Duration of the different phases of motor programs?
How is reward conditioning/operant control of spontaneous variability instantiated in small and large brains?
How can we incorporate output-input functions in artificial neural networks and robotics? That is, what kind of tasks could such networks realistically perform today or in the future?
What is the cultural effect (within in the neuroscience community and generally) of treating brains as output/input devices rather than input/output devices?

P.S. It was particularly stupid of me to emphasise the input-output side of things on the iPlant website, as the whole point of conditional rewarding brain stimulation is to modify output-input learning by rewarding beneficial but endogenously under-rewarded behavioural variations (rigorous exercise in morbidly obese patients etc.) with electrical pulses to the reward system.

iPlant fiction - Chapter 3

2009-11-22T13:22:00.006Z

This is the third chapter of my novel-in-progress. This and previous chapters are available on the main website.

- "Every time, every time we meet she's late"
Lucy and Ike stood waiting outside D's assistant's office. The glass door was shut and the room inside in semi-darkness. The assistant was almost twenty minutes late.
- "Dopamine deficiency, swear to God", Lucy said.
- "Which one?", Ike said.
- "Midbrain insufficiency. Plain cell numbers, not enough dopamine."
- "Not a receptor problem? D1, D2? Unresponsive adrenal glands?"
- "Adrenal problems don't cause chronic lateness, she relies on her adrenal stress response to get her ass off the couch in the morning, but that doesn't kick in until she's critically late and then there's terrible traffic or some shit and we end up loosing our fucking morning staring at her door.."
- "Never heard you curse before", Ike said.
- "Period", Lucy said, holding her elbow and stepping restlessly on the spot.
- "D1 then? D2? Receptors not growing the way they should?"
- "Midbrain insufficiency"
- "How do you know? How would you know without scanning her? You got her scans??"
- "No. I just know."
- "Bullshit"
- "Fuck you"
They glared at each other for a brief moment.
"It's not D1", Lucy said, "because she's not inattentive and certainly not impulsive. And it's not D2 because she's a vicious learner, not just memoranda but procedure as well, that's why D hired her."
- "When was that?"
- "Same as me, for a while I thought we'd work together - her background is biotech and biomedical patents - but she's all administration now and real close to D."
- "Balanced D1 and D2 deficienciencies then? Hyperactive dopamine transporter?"
- "Knew you'd say that"
- "Well?"
- "You're pretty obvious Ike, as a person"
- "You're stalling"
- "Midbrain insufficiency. Not enough dopamine neurons."
- "How could you possibly know that without looking at her scans?!"
- "Calm down", Lucy said and lowered her voice as a small group of people emerged from the elevator at the end of the corridor and disappeared around a corner. "Look, first of all Meg and I agree on it and that's rare and I trust her judgement when it comes to guessing phenotypes and so should you. Second, Marlena is unstable, not in a way that really impacts her work but she's selectively anhedonic, severely - sometimes she truly doesn't see the point or doesn't care unless she's told and I bet you she's a lot less polished at home. But it's a partial problem and if you don't look for it you might not notice: and that's the point, receptor deficiencies have a smooth psychological profile, transporter deficiencies doubly so. Marlena's problem comes in patches. Third, look at her forehead! I'm not saying she's got a small midbrain, I'm saying her forebrain is oversized and sometimes she doesn't have the dopamine to keep all her units running, especially in the morning, which is why we're standing here wasting time."
Ike watched her speak.
- "Don't you ever tell anyone what I just said", Lucy said and suddenly looked nervous.
- "Course not"
- "I shouldn't have said all that"
- "I'm not telling, why would I tell?"
- "Shouldn't have said that"
- "Look, we're not gonna work well together if you keep distrusting me"
- "'Keep'?"
Ike paused, unsure.
- "Meg", he said finally, "You're trying to protect her from me"
Lucy burst into a high laugh.
- "Don't wanna sound cliché or theatrical but I'm more concerned about what she'll do to you, if you step on her feet. Do whatever you want, just don't fuck up so you can't work together."
- "How about some pointers then? What do you mean 'what she'll do' to me? She 'unstable' too?"
- "Oh no, I've gossiped more than enough"
They were silent for a while.
- "How about you tell me something?", Lucy said after a while, "How about you tell me where you got that scar?" She stroked the left side of her jaw, indicating a thick scar on his.
- "Stepped on someone's feet", Ike mumbled.
Marlena suddenly appeared from the elevator at the end of the hallway and hurried towards them.
- "I'm so sorry I'm late", she said, "Traffic's terrible and it's raining. Please come along."
Lucy and Ike looked with surprise at eachother as they followed Marlena down the corridor towards D's office, which she opened with a metal key.
- "We need Ike fully installed by the end of the day", Marlena said. She sat down behind D's large black desk, roused his computer with a quick mouse shake, typed out a long string of characters and hit enter unnecessarily hard. The computer logged in, showing the company logo against a dark background. She gestured for them to sit down in two easy chairs opposite the desk. "Water?" She fished up a bottle of sparkling mineral water from a drawer.
- "No thanks", they both said, attentive.
Marlena paused and looked at them.
- "You've been hired", she finally said to Ike, "I thought you knew."
Ike beamed.
- "D wants you installed and ready to work by the end of the day, you're going with the others to Brussels tomorrow."
- "That's excellent!", Ike exclaimed.
- "You need to bring your scans, we need you to discuss them with some people from the council"
There was a pause.
- "The brain scans", Marlena continued, looking steadily at him "You and Chris used his new ligands to make scans of your brain. You imaged your serotonin system a week ago in the PET scanner. You found substantial changes."
- "Chris told you?", Ike said, "He told D? He said I'd get him fired if I told anyone. So did you.", he turned to Lucy.
- "I don't know anything about this", Lucy said and held up her hands "don't particularly want to know"
- "You're going to Brussels to determine the council's true limits on experimental and commercial deep brain stimulation", Marlena said, "You want to work here because, one day, you want to undergo such surgery yourself - sooner rather than later I understand"
- "I want an iPlant", Ike said.
- "The iPlant is a theoretical construct as far as human application is concerned", Marlena said. "We need a battery of permissions and suspicions cleared before we can proceed with surgery. You're going to Brussels to test the European medical law authorities on that particular point. You'll pursue the argument that our implants and surgical procedure are worth the risks of surgery to customers who have never been hospitalized but who might nevertheless consider themselves neurologically handicapped. Your scans will provide a vivid example of such a case."
- "Do we really want to use one unauthorized procedure to get permission for another?", Lucy asked.
- "You're not going there to get permisison, just to test the waters..", Marlena began.
- "I know", Lucy said, "And to be frank we'll probably proceed with the iPlant either way. I'm asking whether these scans might do more harm than good."
- "D tells me they are quite convincing", Marlena said and looked at Ike.
The three fell silent for a moment.
- "Jeez Ike", Lucy finally said, "How much ecstasy did you have?"
- "It makes sense", Ike said, "I'm in"
- "Brilliant", Marlena said and began filling out a form she'd pulled up on the screen.
- "How much did you have?", Lucy asked again.
- "Enough", Ike said.
- "If you'll come with me over here..", Marlena said and led Ike over to an eye and finger-scanner beside a small safe in the far corner of the room, next to a large liquor cabinet. "Just place your fingertips here please.. and look at the white dot there.. and again.. excellent."

And here I was thinking us humans couldn't build running robots

2009-11-04T08:21:00.002Z

Notes on electrical rhythms in the brain

2009-11-02T19:24:00.006Z

I'm reading George Buszáki's Rhythms of the Brain at the moment. Here are some notes on what I've read so far. Please correct me if I've got something wrong.

Electrical fluctuations in the cortex are organized into rhytmic oscillations at different spatial and temporal scales. The resting cortex is characterized by oscillations primarily in the alpha band (8-12 Hz, the brain's 'default network'). The active (i.e. behaving, percieving) cortex is characterized by oscillations primarily in the gamma band (25-100 Hz). Buszáki and others argue that cortical neurons that synchronize their membrane oscillations in the gamma band 'bind' their respective functions (e.g. visual feature detection) together into cognitive processes (e.g. object perception). Such formations of neurons are called neuronal groups or assemblies. Particularly striking are neuronal groups in the gamma range emerging in the prefrontal cortex for the duration of time that human patients are asked to hold items in working memory.

(alpha)

(gamma)

Cortical neurons sponaneously synchronize their membrane oscillations in the gamma range and form transient neuronal groups even in the absence of stimuli. This is, at least in part, due to the time constants of GABA curents, synaptic delays and synaptic potentiation. Buszáki writes:

"If neurons are already engaged in internal synchronization, the external stimulus will compete with the central oscillator, and the coutcome depends on the relative timing and strenght of the external input and the propensity of the internal oscillator. The stimulus may be ignored, or it may enhance or quench the internal oscillation." p.255

In other words, the effect of a stimulus on cortical activity depends strongly on the prior state of the brain. This explains the significant variability in brain activity (e.g. on EEG/MEG/fMRI) seen within and between subjects in response to invariant stimuli. Buszáki laments the fact that this variability is usually averaged out and treated as 'noise'. Björn Brembs often makes a similar argument.

Stimuli interact with ongoing cortical activity in various ways. Whereas a weak stimulus may reset the phase of ongoing oscillations, a strong or salient stimulus may completely change the type and distribution of oscillations in the cortex. Several studies have found that strong ongoing oscillations in the gamma, theta or alpha ranges prior to stimulus presentation promote efficient memory encoding. A stimulus that resets a strong rhythm presumably has a larger impact on brain activity than one that resets a weak rhythm. The presence or absence of strong rhythms in the brain is directly related to states of attention and catecholamine concentrations.

A complete cell-by-cell recording from a human brain

2009-10-25T11:00:00.009Z

Two thought experiments have been bugging me lately. I've not made much progress on either one so I thought I'd write them down here and consider why they're interesting and maybe get some input.

The first thought is, what would be the value of a complete cell-by-cell recording of electrical activity from a human brain? Not sub-threshold resolution, but rather 100 billion channels recording the location and time (in milliseconds) of every action potential fired in the brain, as if an extracellular electrode had been wrapped around each and every axon. 30 billion channels (firing patterns) for the cortex, 10 billion channels for the subcortical forebrain (hippocampal region, basal ganglia and thalamus), 1 billion channels for the brainstem and spinal cord, and the rest for the grainy cerebellum. I asked this question on Mahalo Answers several months ago but nothing came of it.

What I'm really after I guess is the long-term purpose and potential of brain imaging (everything from fMRIs to neural networks cultured on multielectrode arrays). How would neuroscience change if brain imaging data was not limited to diffuse blobs, squiggly lines or a handful of individually recorded neurons? It seems clear that we would learn a tremendous amount, but what exactly?

One impulse is to model the data, but how would we do this without knowing the connectivity of the neurons? Seth (2005) and others would argue that we could work out causal, if not synaptic, connectivity through statistical analysis of the information-content of the firing pattern of each neuron relative to the others. If we had the computational resources to do that, what might we learn? People interested in evolutionary algorithms on the other hand might argue that we could use simple spiking model neurons (Izchikevich, 2003) and let synaptic weights and properties evolve until the model behaved and responded to input like the recorded brain did. (I just made that up, I have no idea if it makes sense. A caveat at this point is that I'm NOT a mathematician or anywhere near as familiar with neural network modelling as I'd like to be. I'm sure there are abstract functional rules and graph-theoretical relationships or whatever that one could retrieve from a complete cell-by-cell recording of the dynamics of a human brain. But I want them named. Control theory? OK, what might happen in control theory? Neural network software? OK, how would artificial neural networks change? Etc.)

A second impulse is to compare the complete cell-by-cell data with existing knowledge and models of the brain. We know a fair bit about gross anatomical and functional structure. We have a lot of rapid EEG and MEG activity which we don't understand but which seems relevant to various cognitive activities. We'd be able to learn an awful lot about what various states of heightened electrical (e.g. gamma buzz, hippocampal theta rhythm) or metabolic (e.g. BOLD-response) activity look like 'from the inside', on a cell-by-cell basis. But then what? What sort of understanding would we gain from turning a BOLD blob into the electrical chatter of millions of neurons?

A third impulse is to look for neural correlates of sensory, cognitive and behavioural events. The English language is composed of 40 or so phonemes (smallest units of sound), each of which presumably corresponds to a specific posture of the mouth and larynx. Each such posture should correspond to a more or less fixed pattern of activity in spinal C1 motorneurons and perhaps even in the motor cortex. It should therefore be possible to ask the brain/person to name an object and PREDICT the activity of some of its/his/her neurons from the word you expect it/him/her to utter. A similarly fixed pattern of activation would be induced by photons impinging on the retina, which might allow one to predict the activity of individual neurons in visual thalamus and the visual cortex. Similar predictions should be possible in the auditory system. We also know of a few deep brain regions where activity of individual neurons is predictable, such as the bursts of midbrain dopamine neurons in response to unexpected rewards. Would these fixed points of neural activity in combination with simple or complex tasks allow us to understand/predict a bit better the activity of the rest of the brain? Not sure where I'm going with this one but I think it's important.

Yet another impulse would be simply to ask the brain/person to describe its/his/her subjective experience/internal processes as cell-by-cell recordings in regions of interest are taking place. Many theories in cognitive and affective neuroscience could be directly applied ('Let's see, you're feeling hungry, a little bit anxious and quite indecisive, right? Not hungry? That's weird, your NPY neurons are quite active..'), and many new ones could be developed. Moreover, I strongly believe the cultural impact of people being able to see and play with visual reconstructions of subjective states and cognitive events would be enormous. Right? What kind of visual reconstructions? Of which states or events? How would people come in contact with them? Statistical analysis of 100s of neurons in the leech nerve cord allowed Briggman et al. (2005) to identify 'decision-making' neurons whose activity predicted which of two possible activity states the nervous system would adopt in response to a stimulus. Benjamin Libet continues to annoy the world with his decision-predicting EEG events which supposedly occur a few hundred milliseconds before awareness, and recent versions of the experiment claim successful decision-making forecasts as early as 10 seconds before consciousness. These experiments use crude scalp electrodes. What awesomely weird conclusions about human beings would a complete cell-by-cell recording generate?

And so on. I'll return later with the other thought experiment, which is a (somewhat) more realistic and practical version of the same question.

Interview about the 2009 Nobel Peace Prize

2009-10-09T22:50:00.000+01:00

Jealousy

2009-10-08T23:46:00.005+01:00

Warning, a fair bit of profanity in this one.

They'd been in a pub, Lucy told me. Him, her and Meg, celebrating. Some guy at the table next to theirs had been loudly regurgitating the usual agonies of jealousy.
- "I don't know what to do, I don't know what to fucking do with this, I can't sleep, I can't think straight.. It's not even her fucking fault I hadn't called her for weeks. Fuck. But she didn't have to fucking fuck the guy twice! TWICE!! What's in her fucking mind??!.. If I see him I'm gonna fucking floor him, fucking dickless piece of shit, I'm gonna fucking floor him.. I don't know, I don't know, I don't wanna see her now, what the fuck am I supposed to say to her. 'It's OK, I understand.' Eat shit, bitch! Burn! She didn't even say sorry.. Hurts so fucking bad. That dick fucking her. His hands on her.. and she fucking likes it, she liked it, she went back to him."
- "Eat some beta blockers!" Ike shouted when it became clear the guy wasn't intending to stop.
- "What?" the guy had said, shaken, redirecting his anger. He was big but Ike was on his fifth beer.
- "We get it - you're jealous, it's a physiological process, your adrenal glands are hyperactive. Get some beta blockers online or at the gym and take the edge off that shit. Don't sit around shouting blame."
- "Who the fuck are you? She's cheating on me! Motherfucker, she's sucking cock right fucking now!"
- "So what, you don't even like the girl much. You don't appreciate her - she starts seeing other people: happens every day, happens to thousands of people every day man. But that anger, that bullshit is all on you."
The guy was up, poking Ike in the chest.
- "Say what?"
- "Ike!" Lucy tried to pull him back.
- "Your body tells you your woman might get impregnated. It's pouring cortisol and adrenaline into your blood to get you mad enough to do something about it. But it's just chemicals in your system man, don't let it get to you. Cortisol and adrenaline, it's a stress response, like being in danger. Beta blockers will take the edge off that shit."
- "Who are you?" the guy had said said, temporarily stopped in his tracks.
- "Why are you trying to blame? You're trying to blame her. You hate the fact that she liked it. Means you're not in control. Means you can't be sure. Means she might do it again."
The guy had pulled Ike off the high chair and broken his jaw with three right-hand punches before he dropped him on the floor and kicked him in the stomach.

He didn't understand

2009-09-28T20:05:00.000+01:00

Chronic electrical stimulation of cultured hippocampal networks increases spike and burst rate, and changes burst structure

2009-09-27T12:58:00.008+01:00

Brewer GJ, Boehler MD, Ide AN, Wheeler BC (2009) Chronic electrical stimulation of cultured hippocampal networks increases spontaneous spike rates. Journal of Neuroscience Methods.

Neural cultures developing in vitro lack the incoming stimulation/information of their natural (in vivo) environment. In this paper Brewer and collegues applied chronic electrical stimulation to cultures of E18 rat hippocampal neurons developing on 60 channel multi electrode arrays.

30 uA paired pulses (50 ms ISI; biphasic, 100 us/phase duration, positive first) with a 5s wait between pulse pairs were delivered to 30 of the 60 electrodes, one-by-one, in a semi-random sequence for 0 (control), 1 or 3 hrs per day, at 7 11 12 14 18 19 and 21 days in vitro. There were five cultures in each condition. Three minutes of activity were recorded and analysed on day 21. My only problem with these methods is that the cultures recieved stimulation just before recordings were made. This confounds the 'chronic' impact of stimulation during network development - the observed effect could be acute. Recordings further from the time of the last stimulation sequence are required to rule out acute effects.

Interestingly, 1 h of stimulation had a greater impact on almost all spike and burst measures compared to 3 h stimulation, which often was not significantly different from control. Spikes per burst, burst duration, burst rate (bursts/minute) and total spike rate were all up to 2-fold higher in the 1 h stimulation group. However, intra-burst spike frequency was significantly higher in the 3 h group, although bursts in this group were shorter than in the 1 h group. In other words, bursts in the 3 h stimulation group were sharper, more distinct. This was perhaps the most interesting finding in the paper as far as I am concerned. In all groups, 90% of spikes occurred in bursts, with no difference between conditions. Other reserachers have reported similarly high levels of bursting in neuron cultures. "can we reasonably conclude that information coding occurs in bursts and less so in individual or smaller groups of action potentials?" ask the authors. If so, chronic electrical stimulation during development certainly has considerable impact on information coding.

The authors also make some interesting observations on the impact of distance-from-stimulating-electrode on spike rate. Weirdly, they find that spike-rate decreases with increasing proximity to stimulating electrodes in the 1 h stimulation group, but increases (albeit modestly) with increasing proximity to stimulating electrodes in the 3 h stimulation group. Another piece of the puzzle.

In conclusion, the presence of incoming stimulation/information clearly changes the behaviour of developing neural networks. Izhikevich and Edelman similarly found that input was required for activity to emerge and maintain itself in their vast thalamocortical network models.

It's hard to know what to make of these cultured or modeled, essentially random neural networks. They need input and can discriminate complex output in ways your average CPU cannot. They also produce complex, often chaotic output that changes over time with some regularity (Wagenaar's report on superbursts is relevant here). But the question of how to link input to output, output to input, in ways that produce self-organizing, useful, meaningful or even intelligent results has not yet been addressed (as far as I'm aware).

talk nerdy to me 1: science communication

2009-09-21T08:37:00.007+01:00

Episode 1, in which Laura tells Chris about

Maeseele (2007) Science and technology in a mediatized and democratized society
The Royal Society (2006) Survey of factors affecting science communication by scientists and engineers
Bucchi M & Neresini F (2004) Why are People Hostile to Biotechnologies?

This is our first try so bare with us, we know audio is messed up (content too).

40 min download

At the International Neuromodulation Society conference in Seoul 4

2009-09-14T09:30:00.008+01:00

15:46. Departing Hongje subway station for the last time. Tomorrow is the last day of the conference and there are no brain-related talks so I'm gonna go hunt big shiny buildigs. Got three more days in Seoul. I'm very happy I had the opportunity to go to this conference. Learned a lot, particularly about the current state of deep brain stimulation (DBS) for psychiatric conditions, which I'll come back to, but I also met at least one guy I hope to stay in touch with, and got to talk to some surgeons who literally stimulate the reward system on a monthly if not weekly basis. And more than that, just the feel of it: all these doctors, their attitude, their training, their responsibilities - it's helped me understand why Laura says if it wasn't for science she'd probably want to become a medical doctor. There's a certain weight to what they do and how they think: they're the only humans allowed to cut into other humans. They will decide whether conditional rewarding brain stimulation methods (iPlants) are put to human use, and the question will be exceedingly straightforward: can it help patients? That's the question that matters. People who think surgery for psychiatric conditions is existentially wrong need to go away, I've seen and heard some horrible stories these last few days (and I didn't even attend the pain talks). One patient with OCD could not stop scrubbing her baby, she knew it was senseless but couldn't stop, social services almost had to take the baby away. Another was utterly unable to leave the house. Etc etc.

My main observation from this conference is that DBS to the reward system, specifically to the ventral striatum and typically the nucleus accumbens, is attracting a lot of attention, and is being performed more and more frequently for a growing number of psychiatric conditions. OCD, depression, anorexia, substance abuse: they all form a cluster, with conspiciously high co-morbidity, that benefits from strong current being applied to the reward system. What I'm gonna do now is read this one mammoth review on DBS to the accumbens (Greenberg et al 2008) that people kept referring to and then make a video on this.

Will we see DBS to the reward system in people who are not extremely ill? The procedure is FDA approved in the states for up to 5000 patients this year whereas, I was glad to hear, its EU approval (called a CE mark) has no such upper limit. But there are reasons the procedure is last resort. Surgical complications (primarily bleeding) still occur from time to time and there are recurring side-effects, possibly due to tissue damage. More importantly, there are long-term problems regarding displacement of the electrode, buildup of scar tissue around the electrode and depletion of the battery within months, all of which require constant follow-ups and interventions. Head trauma, or even a rough shake of the head can dislodge equipment and cause problems. All this equals risk, but also cost. One speaker working on anorexia in China told me the preferred treatment was DBS to the accumbens rather than capsulotomy (a relatively simple lesion), but that often the family simply could not afford the expensive implant.

That said, these problems are common to all forms of DBS and are enthusiastically worked on, not least by the corporate sponsors of this conference who want to sell more implants and have exceedingly deep pockets. Moreover, as I wrote yesterday, the possibilities of conditional rewarding brain stimulation are beginning to receive serious attention, and if you've read through the iPlant site or watched the videos you know iPlants could benefit many more than just the extremely ill and thus create a wider market that would drive down cost. So we'll see, things are definitely moving.

At the International Neuromodulation Society conference in Seoul 3

2009-09-13T13:32:00.017+01:00

15:06. Just sat through today's keynote by Michael Okun on the current state of DBS for dystonia and OCD. To treat OCD (and depression, and anorexia, and..) you stimulate Broadman area 25 or the nucleus accumbens. Okun reported that, when electrodes in the accumbens (but not BA25) are activated during surgery (DBS patients are awake during implantation), you often see a unilateral smile on the same side as the implant, followed by laughter, euphoria (in BA25 subjects may report a 'dark cloud' lifting, but do not experience euphoria). He showed us a video of a patient having her accumbens electrode turned on for the first time. She kept bursting into an incredulous, wonderful, relieved laugh. Said she felt great. Said, when asked, that she felt like someone had just told her she'd won something (it was something specific but unfortunately I didn't hear it). Okun uses low frequency (60 Hz) long pulse width (120-130 us) stimulation parameters, a massively dense current compared to traditional DBS for PD.

I said something as soon as I could during Q&A. Clearly this was rewarding brain stimulation, strong hedonic pleasure. But didn't Schlaepfer and others report that DBS to the accumbens does not produce liking or any potential for addiction? Okun lit up, the whole issue was fascinating he said. Said they'd had no idea they'd see these behavioural responses when they began operating, but it was definitely eurphoria they were seeing. In fact, mania was occasionally a problem, one patient had stayed up all night once painting her house, ceilings and all. In those cases doctors faced the tricky choice of medicating the mania or reducing current strenght and risking the return of OCD.

I asked him again when the session was over: Had he heard my talk or seen my poster? Did he know that the euphoric deep brain stimulation response had been used as a reinforcer to motivate exercise and problem solving in rats? What did he think about applying the same method to human patients, say obese patients who need exercise? And he tells me they're working on it, they've talked about it, they've even tried electrical reward during learning trials. Said he didn't think anything had been published yet and that it wasn't his project, but gave me his card and said he'd put me in touch with the right people.

Those of you who voted '2010', you may be right.

27 Sep 2009 edit
A misunderstanding - the people in question turned out to be working on using reward signals FROM the brain to improve implant software performance, not reward signals TO the brain to improve HUMAN performance, which is what the iPlant is about.

15:59. I was so tired this morning I put both contacts in one eye.. Spent the whole morning thinking I had weird goo in my eyes blurring my vision. Arriving at the conference centre I figured 'ah! I must have forgot to put a contact in one eye'. Indeed, the left eye was naked in the mirror and I put a reserve in. Spent the day, vision still blurry, wondering if I'd caught swine flu and would go blind. Only realized my mistake as I was leaving and went to take them out and whaddayaknow, two little contacts making love on my right lens.

At the International Neuromodulation Society conference in Seoul 2

2009-09-12T15:34:00.009+01:00

05.40. Lesson 1: if you're flying east and have to be up at 5 local time the second morning, do give yourself more than two days to re-set your bodyclock. got maybe 4 hrs sleep. should be interesting. shit. on a train now, practising the talk and wondering whether there really will be 'continental breakfast' at the conference centre.

10.02. The conference is small compared to SfN of course. Maybe 200-250 people here, not enough to fill either of the two 400 seat conference halls where all talks take place. However! There's free coffee and excellent food! And comfy tables in front of the chairs in the conference halls. There's another big hall packed with mammoth booths by Medtroic, St Jude Neuromodulation, Boston Scientific etc. St Jude serves good coffee.

At the International Neuromodulation Society conference in Seoul

2009-09-11T10:11:00.014+01:00

10.42. Arrived in South Korea yesterday and bussed in to Seoul. They have pine trees here! I guess Russia is just around the corner. Temperature's perfect but the sky's cloudy. Went for a walk around downtown Seoul last night. Lots of neon. Big streets and buildings but not crazy big like Singapore, tho maybe closer to the city centre. I'm a sucker for huge modern buildings.

I'm here to present a poster and give a talk about the iPlant project at the 9th world conference of the International Neuromodulation Society. They're footing the bill. Truth be told I'm not sure what I'm doing here.

16:57. Woke up early and spent the day roaming around north-western Seoul. Still not huge or very rich, just very big and active, lots of cars, lots of people. Took forever to find the conference centre. Spent half an hour hiking up a hill at one point and was greeted by a dead end and a very helpful man who spoke no english. Didn't have a proper map and Google maps sucks here (probably wants korean characters, luckily the trains write and speak english). Got to see a lot though, and take pictures. People differences include sleeping (sitting up) on the train, and quite a few wearing face masks. My hotel (Imperial Palace Hotel) is great, with one caveat: they charge for internet. No internet at the conference centre (Grand Hilton Hotel) either. Sucks. Should paradoxically leave more time for me to blog and make videos though.

I've gone through my talk a few times and will try to record it tonight. Poster presentation and talk tomorrow. Poster needs to be up at 7 and the trip to the conference centre takes 1.5 hrs. Uff. Main concern is I need to not get stage-fright, there will be enough confusion re this project without me adding to it. Seriously, they've squeezed me in between 'Motor Cortex Stimulation for Central Pain and Peripheral Neuropathic Pain' and 'Long term Follow-up in Vagal Nerve Stimulation for Drug-Resistant Epileptic Patients' and put an MD next to my name. Should be interesting.

Have a good day.

Intel CTO Justin Rattner on the singularity and the future of computers

2009-08-20T15:22:00.001+01:00

Social Gadgets for iGoogle

2009-08-12T20:07:00.000+01:00

Stewart Brand on where the world is going

2009-07-26T14:16:00.001+01:00

Jerome Isma-Ae - Smile When You Kill Me

2009-07-12T21:01:00.001+01:00

Obama's speech in Ghana

2009-07-12T08:12:00.002+01:00

The basal ganglia

2009-07-07T15:52:00.005+01:00

Here's my current undestanding of the connectivity of the basal ganglia. Let me know if I've got something wrong or left out something important. Images from the wikipedia entry.

The basal ganglia include striatum, globus pallidus (GPe, GPi), subthalamic nucleus (STN) and substantia nigra (SNc, SNr).

The striatum can be subdivided into a ventral part: nucleus accumbens (NAcc), and a dorsal part: putamen and caudate nucleus (caudate only in primates). NAcc is not included in this diagram, probably because it recieves dopamine separately (from the ventral tegmental area) and is therefore not impaired in Parkinson's disease. NAcc recieves primarily prefrontal cortical input and does reward learning. Caudate-putamen recieves primarily motor cortical input and does sequential movement, from fine motor control to habits.

90% of neurons in the striatum are GABAergic medium spiny neurons. When dopamine input from substantia nigra to caudate-putamen is reduced in Parkinson's disease, inhibition of global pallidus and subthalamic nucleus is disrupted. Lesion or deep brain stimulation to either of these regions is common when L-dopa treatment fails.

Obama's speech in Moscow

2009-07-07T13:15:00.000+01:00

Does secularism fuck you up? part 3

2009-06-30T09:46:00.010+01:00

Dad,

You write: "You seem to be saying that inner states (subjective experiences) are dependent on brain states for their “existence”. Let’s call brain states A (as seen from the third person perspective) and inner states B (as seen from the first person perspective). It can be easily shown that changes in A bring about changes in B. Is the opposite true? Do changes in B bring about changes in A?"

I don't think the two should be thought of as separate or as having effects on one another. Inner states ARE brain states, and vice versa. They are the same ongoing process. Accepting this is hard because we have so much knowledge (subjective experience) about the inner states of our own brain, and so little knowledge about the inner states of brains in general scientific terms. But brains feel; they can be in states of compassion or angst or anger or trust and so on. It seems absurd to us that a physical object could have deep thoughts and feelings only because of our ignorance about the hyper-astronomical complexity of the brain.

Changes in our inner states are changes in our brain states. Meditation, for instance, seems to involve a profound reorganization of the frontal lobes, which you experience in enormous detail if you engage in meditation. This is what is meant by neuroplasticity - even in adult life the brain re-organizes; that's how we learn and change. Even the memory of what happened a moment ago requires plasticity; the brain re-organizing its synaptic connections to incorporate the new memory.

I think the deep inner brain states you emphasize in your work (contemplation, meditation, compassion, silence, unity, gratitude, trust) are challenging because they involve much more profound re-organization of the brain in which they occur. How can such re-organization be facilitated? Under what conditions is a brain most capable of deep change? I think answering these questions has always required and will continue to require deep human understanding of our brains as persons with bodies and social environments and rich lived experiences.

Part 1, part 2

Does secularism fuck you up? part 2

2009-06-28T16:37:00.014+01:00

Dad,

You write: "Do you mean that “feelings of meaninglessness” and “feelings of compassion” are nothing other than electrochemical activity? Can we fully understand “feelings of meaninglessness” and “feelings of compassion” by just grasping what is going on in the brain, “a network of neurons”?".. Human history reveals that techniques for changing inner (subjective) states [contemplation, meditaion, compassion] have played a major role in the evolution of culture. Are these techniques now something of the past? What is the next step in the evolution of culture? Where are we going?"

The key, I think, is in the phrase "nothing other than". It implies a destructive reductionism. But brain states are hyper-astronomical in their complexity and profoundly sublime and beautiful in their dynamics. Neuroscience does not reduce rich inner states to simple things - it shows that rich inner states are astonishingly complex processes in the brain. That's what I meant when I said "inner states are brain states, no more no less". The phrase "by just grasping what's going on in the brain" similarly suggests that such understanding is readily available. It's not: we are nowhere near a good understanding of the brain. We don't even, as you point out, understand how snails learn to chew, much less the feelings they experience as they learn.

An understanding of feelings of meaninglessness or compassion would be utterly incomplete without understanding brains as persons with deep relationships to other persons, to their history, to culture and language, and to his or her subjective experience. We know very little about how to relate brains to other brains, to their upbringing, or to their inner life. We do nevertheless know that inner states are brain states; that they can be transformed or turned off by altering the state of the brain. As far as I'm concerned this doesn't degrade subjective experience, or reduce its significance or complexity, quite the opposite. However, I do very much think that our cultural transition from souls to brains will be a profound challenge, a real adventure. Neuroscience only really got going in the 1990s, and we will learn much much more in the years ahead. Inner states will no longer be completely subjective or private.

The challenge in all this is to avoid a nihilism that exists at the core. Descartes failed to do so when he concluded that animals, lacking souls, were "just machines" that could not have feelings, and proceeded to carry out vivisections and experiments of the most hellish kind on dogs and other species. This nihilism says that if all our rich inner states are "nothing but" brain states, then they are meaningless, worthless, and can be abused. This nihilist temptation is amplified by the shortcuts of consumerism and new technology, and by the sheer complexity of the neuroscientific world-view that is emerging. Therefore, as we travel through this cultural transition, it will be more important than ever to emphasise the reality and importance of deep inner states, and the role of contemplation, meditation, compassion, silence, unity, gratitude and trust.

Part 1, part 3

Does secularism fuck you up?

2009-06-27T14:12:00.008+01:00

Dad,

I'm not sure a secular neuroscience necessarily leads to a spiritually impoverished reductionism with no interest in the deeper side of life. Some people worry that the scientific method reduces a rich inner life to "just another brain state" but among neuroscientists there's usually considerable awe at the enormous complexity of those brain states, and how very little we know about them. There is also an interest in deep inner states such as meditation - see this video for the interesting history of that side of neuroscience http://www.bu.edu/phpbin/buniverse/videos/view/?id=247

I think a secular world-view will however change our understanding of ourselves and our inner lives profoundly; much much MUCH more than secularists realize or are willing to admit. Thoughts, feelings, decision-making, values, personality traits, morality, existential judgements, love and fear will no longer seem to inhabit a distinctly mental realm, but will be described neuroscientifically in immense detail. I don't think the terms will go away: we all have a 'theory of mind'; we can all take the 'intentional stance'. But as neuroscience progresses people will come to accept that they are brains; that their inner states are brain states, no more no less. My opinion is that this will lead to (1) widespread moral relativism, not in the sense of anarchy or cruelty but if moral values are well-defined, vividly visualized brain states explained in high-school biology textbooks then nothing IS right or wrong, it just SEEMS right or wrong; (2) widespread adoption of techniques to change the brain, driven by and driving neuroscientific advances and moral relativism; and (3) a situation where a scientific understanding of people in general and yourself in particular will be extremely valuable, not displacing subjective forms of knowledge but rather enhancing and being enhanced by them.

Where does this leave spiritual experience and the search for deeper meaning beyond the material? I don't know. Maybe, as traditional organized religion gradually acquires the status of myth and make-belief not suitable for a scientifically aware 21st century person, civilization will see an even greater hunger for transcendence and religious conviction. Maybe not. Maybe you can fill that hunger with ever larger TV screens and new technology, maybe not. Maybe we will turn our eyes toward a medical and technological defeat of the aging process and explore the stars together.

Part 2, part 3

Obama's speech in Cairo

2009-06-11T08:47:00.002+01:00

In the news this morning

2009-06-08T09:24:00.004+01:00

The ruling coalition defeats Hezbollah in Lebanese election. Phew.

The two US journalists arrested in North Korea are sentenced to 12 years of hard labour..

St Jude Medical, who have incorporated Advanced Neuromodulation Systems and is Medtronic's only real comptetitor in the deep brain stimulation arena, just completed clinical trials showing that their Libra implant works just as well as Medtronic's Activa. Hey bigshots, want to make an obscene ammount of money selling those things? I have a suggestion.

And finally, you know the Pirate Bay, the guys getting beat up in court? They just got 7.1 % of the Swedish vote in the Europpean election. Ah, I love my country.

Mitt bidrag till Nationaldagen

2009-06-06T13:07:00.011+01:00

Det är sorgligt hur dålig ens svenska blir efter sex år utomlands. Men nationaldagen till ära tog jag mig till slut i kragen och översatte förstasidan på min hemsida till svenska. Texten följer nedan.

Jag skulle också vilja passa på att åter igen understryka att iPlant-projektet har en starkt svensk vinkel. Villkorlig belönande hjärnstimulering är inte en teknik som kommer att skapa en överklass med överlägsen intellektuell kapacitet. Tvärt om, tekniken har mycket litet att erbjuda manniskor som redan har stark självdisciplin. Däremot kan den komma att vara till stor hjälp for människor som lever med ett litet sjalvdisciplinskapital, och som därfor inte kunnat tillgodogöra sig en lång utbildning eller en vältranad kropp. Jag har hållt på med det här projektet i ett och ett halvt år nu, och jag har hela tiden märkt att de som är emot projektet är individer som finner det lätt att utöva självdisciplin, medan de som lider av begränsad självdisciplin har varit betydligt mer positiva. Det är mycket svårt att med djup hjärnstimulering förbättra en redan optimalt fungerande hjärna, en hjärna som har ett 'rikt' förråd av monoaminer. Det är mycket lättare att förbättra en hjärna som inte fungerar optimalt, en 'fattig' hjarna. Låt inte de rika hjärnorna övertyga dig att det är 'rätt' att alla måste dras med sin naturliga hjärna hela livet. Allvarligt. Neuroteknologisk socialism!

Välkommen

Ett iPlant är ett hjärnimplantat som i princip inte skiljer sig från dagens djuphjärnstimuleringselektroder, men som ännu inte utvecklats för människor. iPlantet skulle på elektronisk väg regulera flödet av monoaminer i hjärnan och därmed ge användaren ökad kontroll över hans eller hennes motivation, humör, inlärning och kreativitet. Liknande hjärnimplantat har funnits tillgängliga för djur i årtionden: genom att associera belönande hjärnstimulering med specifika beteenden har de bland annat använts för att motivera råttor att utföra hård fysisk träning (Burgess et al 1991, Garner et al 1991) och lösa problem (Hermez-Vasquez et al 2005). iPlants skulle på samma sätt kunna hjälpa människor att utföra svåra handlingar, t.ex. fysisk träning, inlärning och forskning (se programmering). iPlants skulle möjligen också kunna erbjuda ett mer dynamiskt alternativ till traditionell regulering av monoaminer, såsom stimulerande och antidepressiva psykofarmaka.

Denna hemsida förespråkar etisk utveckling av iPlants och allmän medvtenhet och debatt om monoaminrelaterad hjärnforskning, djup hjärnstimulering och villkorlig belönande hjärnstimulering. Mer generellt utforskar hemsidan 'personligt anpassad hjärnmodulering' (personalized neuromodulation): vad händer när vi människor med tiden förbättrar vår förmåga att på teknisk väg kontrollera våra egna hjärnors kemi?

Senaste nytt Mars 2009

Reclaim, ett djuphjärnstimuleringsimplantat som forbättrar beteende och humor genom att modulera hjärnaktivitet i människans belöningsssystem (ventrala striatum) fick i februari 2009 tillstånd av FDA att marknadsforas i USA. Forskare och doktorer som använder djup hjärnstimulering för att påverka det mänskliga belöningssystemet ar fullt medvetna om att proceduren skulle kunna generera njutningsfull, belönande hjärnstimulering, men undviker detta genom att använda stimuleringsparametrar som skiljer sig från de som används när belönande hjärnstimulering testas på djur. I en studie skrev forskarna: "Morfin-benzedrin grupp skalan.. användes för att fastställa subjektiva effekter.. samtliga patienter fick 0 poäng.. ingen njutning genererades.. till skillnad från Heath som raporterade att.. elektroder i djupa regioner av hjärnan kunde orsaka extremt belönande effekter" (Schlaepfer et al 2008) Men genom att inte diskutera och undersöka hur belönande hjärnstimulering skulle kunna hjälpa människor missar vi en enorm möjlighet. Belönande hjärnstimulering skulle kunna användas för att belöna och därmed motivera svåra beteenden hos patienter som saknar självdisciplin.

Belönande hjärnstimulering skulle till exempel kunna användas för att motivera hård fysisk träning, vilket tidigare demonstrerats i experiment med råttor (Burgess et al 1991, Garner et al 1991). Djup hjärnstimulering hade då detta skrevs använts vid två tillfällen för att bota extrem fetma genom att dämpa hunger i hypofysen, ett inte sarskilt framgångsrikt projekt (e.g. Hamani et al 2008). Belönande hjarnstimulering som ges på villkor att patienten utför fysisk träning skulle kunna ha en mer pålitlig effekt eftersom fysisk träning har en sa god effekt pa vår hälsa. Villkorlig belönande hjärnstimulering skulle ocksa kunna användas för att motivera inlärning och andra beteenden som vissa individer har mycket svårt att utfora, vilket tidigare demonstrerats i experiment med råttor (Hermez-Vasquez et al 2005).

Villkorlig belönande hjärnstimulering skulle kräva ett avtal mellan doktor och patient som säkerstaller att belönande hjärnstimulering ges endas om patienten utfor vissa specifika, välgorande beteenden, t.ex. använder en roddmaskin eller en traningscykel. Ett sådant arrangemang, i vilket patienten frivilligt accepterar restriktioner på hennes eller hans mojlighet att aktivera Reclaim implantatet, väcker en hel del etiska frågor som behöver artikuleras och diskuteras.

Sedan tillkommer även en praktisk fråga gällande vilka stimuleringsparametrar som skulle vara bäst för att generera belönande hjärnstimulering i en mänsklig hjärna med ett Reclaim implantat. Denna fråga skulle kunna besvaras omedelbart om några av de patienter som har Reclaim implantat skulle vara villiga att gå med i en studie med målet att testa effekten av att tillfalligt ändra deras stimuleringsparametrar till de som andvänds då belönande hjärnstimulering genereras i nucleus accumbens hos djur (e.g. Prado-Alcalá & Wise 1984).

iPlant 101

2009-06-01T14:19:00.000+01:00

Dopamine, attention, working memory, neuronal groups and the prefrontal cortex

2009-05-27T14:05:00.001+01:00

YouTube video messed up, use this one http://www.facebook.com/video/video.php?v=591916852334

Funky quotes

2009-05-16T09:54:00.002+01:00

"We're not playing"
-- Craig Venter on accusations of playing God, 2008

"We slaughter our finest impulses every day"
-- Henry Miller, 1949

"You should try the cheap substitute, it's pretty good"
-- Daniel Dennett on free will, 2008

"To be honest I hope we never get too good at this."
-- Neurosurgeon Patrik Blomstedt talking about deep brain stimulation, 2008

"the moral issues surrounding biotechnology are so primitive compared to the complexity of the phenomena"
-- Robert Harrison, 2005

"externally controlled shaping of appropriate behaviors might be accomplished through using pleasure-yielding stimulation as a positive reinforcement for wanted responses"
-- Robert Heath, 1972

"I would not live forever, because we should not live forever, because if we were supposed to live forever, then we would live forever, but we cannot live forever, which is why I would not live forever."
-- Heather Whitestone (Miss Alabama 1994)

"The slippery slope I think is a very unhelpful metaphor. When you're thinking about slippery slopes you need to know how slippery they are, what the coefficient of friction is and indeed what way they're pointing."
-- Raymond Tallis on assisted dying

"See that thing in this image that looks like a Martian vehicle descending by parachute to the surface of Mars? That's the Phoenix lander, captured in mid-drop, still glowing from entry into the atmosphere, by the Mars Reconnaissance Orbiter. How badass awesome is it to be a human? Super badass awesome."
-- Cory Doctorow, 26 May 2008

"This is really a profound challenge to the way most of us think about ourselves. I mean we we we think there is some core to who I am, to who you are, there is something essential that is continuous that kinda defines who we are. You're saying, from this scientific perspective you're mapping out, that that's an illusion."
-- Steve Paulson in conversation with James Hughes about transhumanism

"However odd or uncomfortable the idea of engineering the human brain might seem, if yours is broken enough, the philosophical arguments cease to hold any water: you just want it fixed." .. "What bit of themselves would each of us wish to control? Where would we direct our own transcranial magnetic stimulator, if we could? It's a terrible responsibility to shoulder. What is the mind that's choosing the shape of its own brain?"
-- Quinn Norton, 2009

Wolfram Alpha

2009-05-16T09:18:00.006+01:00

I just woke up and realized Wolfram Alpha went live during the night. I don't know what to make of this search engine that isn't a search engine yet. But I asked it for the chemical structure of dopamine and I got it. And how could you not love its error message:

Big words

2009-05-14T12:55:00.009+01:00

existential density
natural selection
a conscious chaos that won't let go

new desire
a new desire, worth living and dying for
a war of words
bare bones
brain bled dry
icy sun rising

it won't stop till you wise up you know
accept it
it's the purest rage of frustration you've ever felt, nothing more

pointless behaviour and moral ignorance
dopaminergic logic
the instinct trickling down your spine
and in the woods, animals eat eachoter

but
emphasise the creation of positive feedback loops
stop stressing
it is warmer on the other side
nothing can be red and green all over, yet this is irreducible to logic

what's your configuration?
why this obsession with relative inferiorities; with desires turned into systems?
you're a healthrisk
you're social sugar

resuscitation
sexual attention
expression of affection and psychadelic drugs
anatomy of the medial forebrain bundle

listen, it's simple
stay optimistic
try new things
and exercise self-control
the world, my friend, is an extension of the breast: it was Socrates who erected the idea of a different world; an anti-monism; an appearance-reality split

but i digress

scientific expressionism
flattening our subjectivity; our private religion
man as a meaning making machine
an intellectual smuggler
profoundly disrupted by technology
seeking physical and spiritual release

and that is the intellectual and moral spirit of the age
a neurobiology of meaning
skipping from urge to urge
impulse to consume information; calories; dopamine - it's all the same
a crowded skull
a brain distrustful of its own frontal lobes

frontal lobes... I look forward to a day when amygdala, frontal lobe and midbrain will be as familiar to people as heart, lung and liver; when people know their DNA, brain structure and chemical profile as they now know shoe size, blood group and favourite food

emancipation from folk psychology
embracing disenchantment
true self-governance
and never again accepting a normative value as a fact

indeed

imagine how the world will change as we gain more controll over the chemistry of our own minds

What we need to accelerate biomedical research and fight aging

2009-05-12T13:21:00.011+01:00

A few hundred years ago I could not have been born. I was massive - 4.9 kg - and the birth eventually turned caesarean and took many long hours. I owe my life to medical science. One day, 11 years later, I was out biking and realized for the first time that the annihilation following my death would be infinite. Now, 25 years after my complicated birth, I think a lot about whether medical science, rejuvenation research of the SENS variety in particular, will save me a second time.

Sciences from genetics to pharmacology to artificial intelligence have run into the quagmire of complexity. How can we model and manipulate complex systems when the numbers of variables are enormous and the combinatorial possibilities seem endless? How can we search and find genuine cures for cancer and HIV when the little buggers are the playground of evolution itself? How can we interfere with the aging process when the ways in which aging is expressed in the body could fill an encyclopaedia?

The solution will probably involve a concerted move to vast, quasi-open repositories of research data that can be crawled by statistical algorithms (Anderson 2008, Halevy et al 2009). But good research data is expensive and progress is slow. High-throughput research centres are rare. If you agree with me that drastic methods are called for, here is my suggestion:

What we need to accelerate biomedical research and fight aging

1. Safe and inexpensive brain surgery

To do better biomedical research we need better control over the chemistry of our own brains. Specifically, we need safe and inexpensive application of deep brain stimulation (DBS) implants to the reward circuit of anyone who wants it. This sounds daunting but fortunately it's happening already. DBS to the reward circuit turns out to be an extremely effective treatment for various psychiatric conditions: in February of 2009 Medtronic received FDA approval to use the procedure to treat obsessive compulsive disorder, and clinical trials for depression, potentially a much larger patient group, are well under way (read the press release here). More generally, DBS is becoming standard treatment in late-stage Parkinson's disease, dystonia and tremor. The most popular implant - Medtronic's Activa system - has been applied to more than 40.000 patients since 1997, and DBS is currently being explored as a treatment option for everything from epilepsy and chronic pain to anorexia and obesity. The risk of serious complications such as hemorrhage is currently at 1-3% and the cost of the procedure is at €30.000 (not counting the cost of regular follow-ups). By comparison, plastic surgery generally cost ca $3.000-6.000. Give it a few years.

2. Widespread use of enhanced motivation through deep brain stimulation

Electrodes in the reward circuit can generate highly rewarding brain stimulation (RBS) in rats and humans alike (Wise 1996 , Heath 1972). In human patients, this is carefully avoided - DBS implants in the reward circuit are used merely to normalize brain activity (Schlaepfer et al, 2008). In rats however, RBS has been used as a powerful operant reinforcer to motivate animals to perform various behaviours, such as run on treadmills, lift weights and learn new skills (Burgess et al 1991, Garner et al 1991, Hermez-Vasquez et al 2005). There is every reason to assume that the same kind of training could be utilized by human beings with DBS implants in their reward circuits.

If brain surgery could be made as safe and inexpensive as plastic or dental surgery, I believe millions would opt for an implant that gave them the artificial incentive necessary to enjoy challenging behaviours for several hours every day: RBS for every stroke on a rowing machine; RBS for every correct answer on a maths-tutorial; RBS for learning a new language or skill; RBS for drug-free urine samples; RBS for anything you normally wouldn't know how to get done. Given the enormous health-benefits of regular physical exercise, it is quite possible that RBS-driven exercise would pay for itself on a societal level and eventually be recommended by doctors. How would you spend two daily hours of artificial motivation?

3. RBS-driven research centres and biomedical outsourcing

Obviously, a project as ethically charged as this one would require legislation and policy to prevent abuse. Hospitals and private clinics would carefully regulate which behaviours were allowed artificial reinforcement: physical exercise, sure, as long as there's a time limit; academic learning, maybe, as long as there's no way to cheat. I believe a third form of behaviour - RBS-driven research - would also be permitted. That is, it would be possible to set up research centres, similar to blood banks, where volunteers with DBS implants could come to participate in basic biological or medical research, using pedagogical instruction (e.g. JoVe, bioscreencast), with RBS being delivered at key points in the protocols to drive enthusiasm for mundane and repetitive tasks: RBS for getting the PCR going; RBS for having pipetted all the antibodies onto microarrays; RBS for getting the samples from the freezer; RBS for each classified blot; RBS for each autoclaved tray of equipment. You get the idea.

Such research centres, involving hundreds of thousands of volunteers world-wide, working a few hours every week, would allow something we could call biomedical outsourcing - industry, hospitals and academic institutions could request large quantities of data without having to organize and finance the necessary research. 100 volunteers working four hours per week could save an institution more than a quarter million euro every year and would free scientists up to pursue more challenging tasks. With a sufficient number of volunteers, research would accelerate dramatically, particularly in fields such as biology where much of the practical work is monotonous and requires little or no understanding of the broader purpose of the techniques involved.

English Man describes his treatment using Deep TMS (2 min Brainsway video)

2009-04-28T13:48:00.000+01:00

Seesmic Desktop Gets Full Facebook Open Stream API Support (2 min loic.tv cideo)

2009-04-27T22:38:00.000+01:00

Alex Tabarrok on how ideas trump crises (14 min TED video)

2009-04-27T22:33:00.000+01:00

What is rewarding brain stimulation?

2009-04-26T14:11:00.000+01:00

I can has freedom and dignity?

2009-04-26T09:46:00.006+01:00

A while ago a good soul sent me a copy of B.F. Skinner's 1971 book 'Beyond Freedom and Dignity'. Would, he asked me, the book, in particular the chapter entitled 'The Design of a Culture', be relevant to someone developing a device like the iPlant? In case you're interested, and because I'm unlikely to write a review of the book, here's what I replied:

It's very relevant. The tricky thing with the iPlant is that it's hard to imagine what society would end up looking like if a powerful behavioural technology was in widespread use. I've tried to imagine how people might use it to overcome health problems and contribute to scientific research, but the applications are truly endless (and some are disturbingly bleak). This makes people resist the development of iPlants and makes it difficult to formulate policy and legal safety-nets. This book may be the first I've read that's truly ambitious in thinking about making behaviour more effective and better controlled. It articulates an overarching goal: making people more and more influenced by the long-term consequences of their behaviour and the evolution of their society. It articulates and responds to objections regarding de-humanization and abuse. All this is very relevant to thinking about future behavioural technologies like the iPlant. I guess I wish Skinner would have included a chapter describing in detail which behaviourist practises he personally thought society should adopt, how we should go about adopting them (including how to deal with the backlash when traditions are challenged) and what society would or could look like once we had adopted them. Does he spell this out in detail somewhere else? Walden Two maybe? I'm also curious what the critics said about this book in particular (not, as you say, the partisan bickering around behaviourist science as such).

Thanks again
Chris

How bad do you want it? (update 1)

2009-04-21T13:14:00.015+01:00

Deep brain stimulation (DBS) electrodes offer a window into regions of the human brain that would otherwise, for obvious ethical reasons, not be available for scientific analysis. Interesting activity related to sensation, cognition and behavior can, for example, be recorded from DBS electrodes placed in the subthalamic nucleus for the purpose of treating Parkinson's disease (e.g. Balaz et al 2008, Bronte-Stewart et al 2009).

More and more, DBS is being applied to the human reward circuit to treat obsessive-compulsive disorder and depression (see previous blog post). Specifically, the nucleus accumbens (ventral striatum) is being targeted. Dopamine release into the nucleus accumbens is the strongest reward-signal we know of; it is core to the generation of motivation and learning.

So, what will we see when we start recording from DBS electrodes placed in the human nucleus accumbens? I'll bet my boots that we'll be able to detect changes in dopamine release and reward-processing with MUCH higher precision than when we use brain scanners. Averaged over many trials and patients, recordings like that could allow us to quantify the reward value of things in the world, and relate the activity of the human reward circuit not just to sensation but also to cognition and behavior.

← Monkey reward circuit neurons respond to a liquid reward. How exactly would the human reward circuit respond to a liquid reward? Or an invitation to a BBQ? Or two political candidates? Or heroin? Or boredom? Or praise? Or coffee? Or any of the various reinforcers that shape our behaviour, thoughts and feelings? I think we're about to find out.

Edit: publications exploring this line of research are already available: Münte et al 2008, Cohen et al 2009, Zaghloul et al 2009, Cohen et al 2008.

I can has operant conditioning?

2009-04-21T08:40:00.003+01:00

"The struggle for freedom and dignity has been formulated as a defense of autonomous man rather than as a revision of the contingencies of reinforcement under which people live. A technology of behavior is available which would more successfully reduce the aversive consequences of behavior, proximate or deferred, and maximize the achievements of which the human organism is capable, but the defenders of freedom oppose its use."

- B.F. Skinner (1971) Beyond Freedom and Dignity, p125

April

2009-04-19T13:47:00.003+01:00

Spending a few weeks in Sweden. It's sunny here, but cold. Glad to be here. Went to a seminar about intelligent, critical Christianity yesterday, which was really good. Reading Skinner's 'Beyond Freedom and Dignity', which is also good.

Had too much coffee while reading this morning (4 cups) and just went through a manic phase of cleaning the kitchen and installing some new software but now I'm rapidly running out of energy. Best get some good podcasts on the iPod and get out in the sun before I crash.

Why it's hard to stop smoking

2009-04-18T17:02:00.000+01:00

Some new logos and a wonderful TED video

2009-04-15T19:44:00.003+01:00

Dopamine and the frontal lobes

2009-03-27T23:41:00.001Z

Idiot (update 3)

2009-03-26T22:49:00.011Z

I just deleted my most frequently viewed youtube video by accident.

Very unhappy now.

It was called 'What is dopamine?' and is still available here on facebook but I seem to be too stupid to capture the sound without muffling it.

I put up $1 on Mahalo for anyone who can help me get it back but I had a look around myself and I'm not hopeful. Started a YouTube forum discussion too.

Maybe this is an opportunity to do a new one, speak slower and so on. Great.

Update: Mahalo linked me to a YouTube forum that already covered this. No undelete. Fuck.

Update 2: Laura linked me to a greasemonkey script that let me download the facebook video. It's now back on YouTube :)

Update 3: The video got picked up by Bora Zivkovic over at Scienceblogs.com :)

Philoctetes Center, I love you

2009-03-25T11:51:00.001Z

Techno-Buddhism

2009-03-24T18:25:00.005Z

Strongly recommend a recent NPR interview with J Hughes on technological change. The interview starts 45 min into the mp3 and is 8 min long. Interviewer Steve Paulson's knee-jerk reactions are textbook. Quote:

"This is really a profound challenge to the way most of us think about ourselves. I mean we we we think there is some core to who I am, to who you are, there is something essential that is continuous that kinda defines who we are. You're saying, from this scientific perspective you're mapping out, that that's an illusion."

Personally, I don't think like that, but I'm happy to listen to people who do.

Slippery slopes

2009-03-23T18:52:00.003Z

Heard on the latest episode of Philosophy Bites:

"The slippery slope I think is a very unhelpful metaphor. When you're thinking about slippery slopes you need to know how slippery they are, what the coefficient of friction is and indeed what way they're pointing."

Enormously true. Made me lol heartily.

Me reading iPlant fiction

2009-03-22T17:52:00.003Z

Having finally aquired a decent microphone I decided to do a reading of the first two chapters of my novel-in-writing, creatively named iPlant. Wish I didn't sound so morose but if you go back and change things every time it doesn't sound right you never get anything uploaded. My hope is that I'll be able to record chapter three without actually doing any writing; have it be a bit more like storytelling and then simply cut away everything I don't want before finally converting it back to text. We'll see. Anyway, here's chapter one and two.

Using Medtronic's Reclaim implant to generate artificial motivation

2009-03-14T09:57:00.015Z

(This post was re-printed on the Institute for Ethics and Emerging Technologies website and on Future Blogger)

I recently blogged and vlogged about Medtronic starting a clinical trial where deep brain stimulation (DBS) would be applied to the ventral striatum (part of the human reward circuit) to treat depression in up to 200 patients. Then the article on CNNmoney that I was basing this on disappeared and I worried that the whole thing might have been a mistake or a hoax. But the article has resurfaced on the Wall Street Journal and elsewhere, and I finally got around to digging up Medtronic's original press release from 19 Feb 2009, which confirms that they are conducting a clinical trial of DBS as a treatment for depression.

But more than that. It turns out that the entire implant procedure that they're using isn't new at all - it's the same procedure they use to treat OCD (recently FDA approved for up to 4000 patients). The implant is called Reclaim and (quoting the press release) "the anatomical target in the brain is the.. ventral striatum.. which is a central node in the neural circuits believed to regulate mood and anxiety". So it seems DBS implants have been placed in the human reward circuit since the OCD trials started, many years ago. This is good news because it means we're even better at putting DBS implants in the human reward circuit than I thought we were. Basically, DBS applied to the ventral striatum (VS) didn't just alleviate the behavioural tics of OCD patients but also improved their mood. Studies like Schlaepfer et al 2008 (3 patients) and Malone et al 2009 (15 patients), which I thought were ground-breaking, merely confirmed that DBS applied to the VS improves the mood of severely depressed patients as well.

My interest in all this, as always, is that electrical stimulation of the reward circuit is how rewarding brain stimulation (RBS) is generated in experimental animals (see Wise 1996 for a review). By changing the stimulation parameters of the Reclaim implant to match those used in RBS-experiments we should thus be able to use the Reclaim implant to generate RBS in humans. Such RBS could subsequently be used as an operant reinforcer (a pleasurable reward) to motivate difficult behaviors in people lacking self-discipline, as described in the programming section on the iPlant website, and as demonstrated in animal experiments such as Burgess et al 1991, Garner et al 1991 and Hermez-Vasquez et al 2005. It would be an important step toward artificial motivation.

Now, the researchers who apply DBS to the human reward circuit are fully aware that the procedure could generate RBS but try to avoid it. Quoting Schlaepfer et al 2008: "Subjective effects were assessed using the morphine-benzedrine group subscale of the Addiction research center inventory.. scores were 0 for all patients.. there was no 'liking'.. in contrast to findings reported by Heath, who observed that.. electrodes in subcortical structures induced extreme rewarding effects (Heath 1972)." Basically, clinicians today use DBS electrodes to disrupt or normalize electrical activity in dysfunctional brain regions, not to stimulate. They use stimulation parameters different from those applied in RBS-experiments. But by not engaging in discussion and research into beneficial applications of RBS in human beings we are missing an important opportunity.

For example, human RBS could be used to motivate heavy physical exercise, as previously demonstrated in rats (Burgess et al 1991, Garner et al 1991). At the time of writing DBS has been applied twice to treat obesity by suppressing hunger, with varying degrees of success (eg Hamani et al 2008). Human RBS made conditional on the patient engaging in physical exercise might have a more reliable effect, especially considering the health benefits of rigorous exercise. Conditional RBS could also be used to motivate learning and other behaviors that some individuals find exceedingly difficult, as previously demonstrated in rats (Hermez-Vasquez et al 2005).

Conditional RBS in humans would require a patient-doctor agreement and supporting technology to ensure that RBS is delivered if and only if the patient engages in desirable, pre-specified behaviours, such as the use of a rowing machine or an exercise cycle. Such an arrangement, where the patient voluntarily accepts restrictions on his/her ability to activate the Reclaim implant, raises a number of ethical issues that need to be articulated and discussed.

There is also a more practical question as to what stimulation parameters would best support RBS in the human VS. I think the reason DBS to the human VS does not have rewarding effects in current studies is that researchers are using too high a frequency, too narrow a pulse-width and/or a biphasic as opposed to a monophasic pulse. This question could be addresed immediately if some of the patients who have already recieved a Reclaim implant would be willing to participate in a study to assess the effects of temporarily changing the stimulation parameters of their implants to match those used in animal experiments involving RBS.

Wired-article-induced neuroscience rant

2009-03-07T12:24:00.012Z

Part of the reason I enjoy researching, writing and talking about neuroscience is sheer awe. Gradually realiazing how one's conscious will can be understood as a physical process is threatening to some but I find it enormously fascinating and liberating. Neuroscientific understanding is often counterintuitive, because our cultural understanding of ourselves has been - and still is - uninformed by neuroscientific fact. But that growing body of fact is true, and potentially enormously empowering.

That brings me to another reason I do what I do: I want to help people redesign their brains, should they want to. Quoting a recent article in Wired about transcranial magnetic stimulation (TMS) and neuroengineering:

"However odd or uncomfortable the idea of engineering the human brain might seem, if yours is broken enough, the philosophical arguments cease to hold any water: You just want it fixed."

and

"What bit of themselves would each of us wish to control? Where would we direct our own TMS, if we could? It's a terrible responsibility to consciously shoulder. What is the mind that's choosing the shape of its own brain?"

So, what are the options?

Pharmaceutical drugs and other psychoactive substances is the obvious one. Keep an eye out for over-the-counter stimulants in the next few years (see this recent article in Nature on cognitive-enhancing drugs).

Transcranial magnetic stimulation (TMS) is another important technology. Look for TMS equipment that can be used in the privacy of your own home (open-source initiative here, dedicated blogs here and here).

And finally there is deep brain stimulation: currently rare and somewhat dangerous but poised to go mainstream given its extraordinary potential as well as the willingness of people and surgeons alike to operate on healthy individuals (plastic surgery). Look for success in Medtronic's rumoured depression trial and pilot studies applying conditional rewarding brain stimulation to treat obesity and related problems.

Anyway, enough of this, spring is here - time to go buy the year's first football.

Freeman Dyson: Let's look for life in the outer solar system

2009-02-28T22:46:00.000Z

13 PowerPoint slides on Jonathan D Moreno's 2007 book 'Mind Wars'

2009-02-28T15:45:00.001Z

Hell yea :)

2009-02-28T15:18:00.000Z

@ev speaks about Twitter at TED

2009-02-28T00:43:00.001Z

Deep brain stimulation for depression

2009-02-24T22:20:00.003Z

Sorry about the sound quality.

Schlaepfer et al (2008) Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression. Neuropsychopharmacology 33, 368-377.

Kamp (2009) After Long Wait, Medtronic Starts Big Depression Study. CNNmoney.com.

Visit www.iplant.eu for more information

Transcript:
"So I wanted to make a comment on a paper from 2008 by Schlapfer and collegues called deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. The reason I want to comment on this paper now is that Medtronic - the largest US vendor of deep brain stimulation implants - have just decided to proceed with phase II clinical trials, involving up to 200 patients, testing this method, testing deep brain stimulation to the human reward circuitry as a method for treating depression. This is major stuff, because

"So DBS is a well established technique for treating brain dysfunction, it's been applied in tens of thousands of cases. You basically take one or two implants the size and shape of spagetthi sticks and insert them into the brain. The tips of the implants contain electrode arrays that are used to deliver current into the brain regions that have become dysfunctional.

"Now what they've done here is they've inserted these implants into the human reward circuit, specifically into the nucleus accumbens, which is a central point for generating feelings of pleasure, reward and motivation. Because one of the central features of depression is that you can't experience these things, they figured DBS in this region might be able to normalize human reward function in severely depressed patients. And IT WORKS! It works and they're now proceeding to show that it works properly in phase II clinical trials.

"Now the thing about this is that if deep brain stimulation applied to the human reward circuit becomes fairly standard treatment so that tons of papers are written on it; so that doctors, surgeons, people all over the world become comfortable and knowledgeable about how to apply DBS to the human reward circuit then eventually it will become blindingly clear that this could be used as an iplant; that this could be used as a brain implant that delivers rewarding brain stimulation if you perform some pre-defined behavior, such as exercise in morbidly obese patients. The very same surgical procedure they use here could be used as a treatment for, say, morbid obesity in patients that can't get themselves to exercise as much as they should. They could be given rewarding brain stimulation as a motivator. But of course it doesn't stop there - it could be used to motivate ANY behavior that's sufficiently simple, that can be defined operationally so that you can attach a specific electrical reward to it. Any behavior - learning, different elements of research - could be motivated in this way. So it's an opportunity for billions of people who feel that they cannot live life the way they would like to: people who severely lack self-discipline, for them this would be a way out. To me at least this seems very very crucial."

Kurzweil can has movie?

2009-02-24T09:55:00.001Z

Via Sentient Developments

After long wait, Medtronic starts big depression study

2009-02-23T04:59:00.008Z

Via the Therapeutic Neuromodulation Weblog
'After long wait, Medtronic Starts Big Depression Study'
(CNNmoney, 19 February 2009)

From the CNN post: 'Medtronic's study will start with enrollment of 30 people at five sites, but there are plans to enroll up to 200 patients from 20 sites. Patients in the study will have a device implanted, but for some patients, the device won't be turned on for the first 16 weeks - this way the trial can be randomized between patients who are receiving treatment and not receiving treatment.'

This is the first large (phase II) clinical trial in which deep brain stimulation (DBS) is applied to the human reward system. Previous trials (Schlaepfer et al, 2008) successfully alleviated anhedonia by applying DBS to the nucleus accumbens (NAcc), but involved only a handful of patients. The next step in the development of decent iPlants is for Medtronic and others to begin to consider how enormously valuable artificial motivation would be to individuals suffering from exceedingly poor self-control. Importantly, a study involving conventional DBS to hunger centres in the hypothalamus recently had to be interrupted because of a mnemonic side-effect (Hamani et al, 2008). At some point, clinical trials will appear where DBS is applied to motivate exercise in morbidly obese patients, as first demonstrated in rats by Burgess et al and Garner et al back in 1991.

A cure for addiction?

2009-02-21T14:21:00.015Z

At present, there is no reliable treatment for addiction. However, inhibitory closed-loop deep brain stimulation of the reward circuit might increase cognitive control in patients suffering from addiction.

Electrical inhibition of deep brain structures has been performed since neurosurgeons began doing stereotactic surgery aimed at the thalamus and basal ganglia (Kiss et al, in press). The procedure involves placing one or several implants with their electrode-covered tips in pathologically hyperactive brain regions. Current at inhibitory frequencies is to disrupt or normalize neural activity in the region. The operation takes 8-12 hours and costs ~£25.000. 1-3% of operations result in serious complications. Since 1997, 40.000 patients have recieved a Medtronic's Activa System - the most widely used deep brain stimulation (DBS) implant (Schwalb & Hamani, 2008). Many disorders, including Parkinson's, essential tremor, dystonia and obsessive compulsive disorder are characterized by hyperactive brain regions. Deep brain stimulation is replacing lesioning as standard treatment for these disorders, is EMA and FDA approved and is 'very benificial' in 80% of cases (Gritsun et al, 2006).

I suspect a DBS electrode placed in the human reward circuit could be trained to detect, extracellularly, the unique pattern of spikes, or even the readiness potential, of an unwanted behavior, such as a cue-induced or spontaneous drug-seeking behavior, or consumption of a drug (indicated by a sharp increase in firing frequency) (see Lee et al, 2008, for the latest in closed-loop DBS).

I also think such an implant could be programmed to disrupt activity in the reward circuit upon detection of an unwanted pattern of activity, through application of current at inhibitory frequencies. This should reduce the probability of the behavior being fully expressed or repeated.

This is not suggested as a method for law enforcement or rehabilitation of criminals, although such use is a possibility that should be discussed and probably prevented. Rather, it is suggested as a voluntary cure for addiction. Many addicts experience a profound desire to abstain from their drug of choice but find themselves compelled to increasingly frequent drug-seeking behavior and use. They should have the choice of simply turning their addiction off available to them. Moreover, deep brain stimulation is already being applied to the human reward system (nucleus accumbens) in successful attempts to use current at stimulating frequencies to treat depression (see image below). Furthermore, such implants should make decent iPlants, and patients suffering from addiction may be particularly well-suited for behavioral programming.

Image from Schlapfer (2008) Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression

Related material: Deep brain stimulation and exercise

Squishy

2009-02-18T15:49:00.012Z

I saw my first human brain today. I'd seen them in jars in museums and I've attended brain surgery, but this time it was right in front of me, I could have touched it. And next to it another one, in four coronal sections, the medial midbrain dark with melanin and all.

I made some drawings, but the level of detail was incredible and I couldn't draw the three dimensions of an egg properly if I tried. More than that though, there were few clear boundaries, only whitish and darkish convoluted brain tissue in various fractal constellations.

Back to work.

Another really good TED talk

2009-02-17T16:59:00.000Z

Interlude

2009-02-17T09:25:00.007Z

I dodged a bullet last night. The week ahead will not be pretty, I'll be depressed, but at least I didn't make it worse. Now I have a chance of climbing out of the hole.

I'm 25. I'm a neuroscience DPhil student (they call it a 'PhD' across the pond). I study the electrical properties of isolated cells and ganglia. I've been a DPhil student for 7 months, but I've worked on this project for two years - I know what I'm doing, sort of.

On the side I work on a web-based science outreach project. I find the ease with which human consciousness, will, thought and feeling can be 'reduced' to the science of monoamines and neural networks awesome, in the true sense of the word, and I try to communicate that growing understanding.

I run, though my waistline seems to be growing faster than my self-discipline. I'm in a weekly creative writing group; I still find it difficult to write about stuff other than brains or sex or death. I see a psychoanalyst twice weeekly, which is great, but at the moment it's killing my budget. I don't know how or if I'm ever gonna make any serious money.

HAHAHAHAHAHA

2009-02-06T20:45:00.000Z

Amore Infelice

2009-02-04T18:02:00.001Z

HT Laura

Dissociation of sensibility

2009-01-30T12:18:00.006Z

Beh. Just got a blue screen of death on my ailing lab-PC. Now it won't start. Gotta get it replaced.

Sitting in the lab, working lazily and listening to an old Philoctetes Center classic: Origin of Norms, with Gerald Edelman among others.

Friend talked yesterday about the dangerous spiral of depression->unemployment->worsening economy->more unemployment->more depression that goes largely untreated in many developing countries. Makes sense. As I've said before, I'm finding it difficult to see how the Anglo-Saxon world, with its small population, maintains such a lead in living standards.

Computer still won't start. Dammit.

I read the transcript for the dopamine video at a creative writing session a few days ago and someone said "You think that's really how it works?". She didn't mean was I correct about the details but did I think desire and motivation was all about chemistry. I said there was no question about it. She talked about a "part of us that doesn't want it to be like that". I wonder. What is lost when we think of the mind as a machine? Magic? The ghost or soul? For some, a sense of wonder and mystery. Control. Because, remember, most people are not neuroscientists.

I talked to a guy on a bus once, he was an English student and on hearing that I studied neuroscience he said "I don't know anything about the brain". I told him 'Yes you do, you have one!'. If only that were true. If only people were as knowledgeable about their brains as they are about their computers, cars, kitchens, feelings, children. If we could track the rise and fall of transmitter concentrations as we can track the rise and fall of sleepiness, hunger, lust, and see how they're related. A brain scan for every man, woman and child in Europe!

Computer still won't start. I understand we'll be getting a new one next week if all goes right.

You know, I realized the other day there's actually a pretty advanced MRI here at the university. Maybe I'll go sign up for an experiment and see if I can a few images of my brain.

Hehe

2009-01-30T11:00:00.000Z

What is dopamine?

2009-01-23T09:32:00.001Z

This is a first draft, I need a better microphone and I'm not sure about the text. Any constructive criticism?

Transcript: Dopamine is a very important chemical that regulates thought, movement, attention, motivation and learning. It's synthesized by neurons in the middle of the brain but is released all over, in small and large doses.

In small doses, it activates D2 receptors, which reinforces ongoing thoughts and movements. If you're eating pizza, the pleasant taste will activate dopamine neurons, raise dopamine concentrations in your brain, and you'll feel motivated and keep on eating. If you're experiencing something new or expecting something good, dopamine levels can rise up to 100% and you feel excited and completely focused. Being unfocused and easily distracted means your brain is low on dopamine - that's why Ritalin, amphetamine and coffee helps people with attention deficit disorder concentrate.

When something important, unexpected or rewarding happens, large amounts of dopamine are released, which activate D1 receptors and stimulate learning and the formation of new connections between neurons. Memories and habits are formed this way. All addictive drugs release large amounts of dopamine in the brain, but so does good food and drink, and sex, social pleasure, and money.. everything you want releases dopamine, and you want it because it releases dopamine. Things are important and valuable only if they activate your dopamine neurons; if you're still watching this video it's because it's releasing dopamine; and whatever you do when this movie stops will be what releases most dopamine.

More on dopamine: http://www.iplant.eu/monoamine.html

January

2009-01-10T17:49:00.001Z

Rami Khouri on Gaza (from The Economist)

2009-01-07T17:30:00.001Z

The Sundays - Here's Where The Story Ends

2009-01-05T21:05:00.001Z

2009

2009-01-01T17:34:00.002Z

Time to stop messing around and get back to work.

Breasts

2008-12-14T21:20:00.010Z

It was the fucking tits. The primeval, all-encompassing, undeniable fullness of them. Smooth and warm and alien like lava. He'd squeezed them, squeezed them and felt them push back against his hands. Again, and again, and again; squeezed and played with the nipples; one, then the other, and with each short breath her chest moved and the breasts hung between his fingers; molten rock merging his hands with her human frame.

She held him, hugged him, whispered to him, pressed her rough patch against his and enveloped him in her intelligence, her ribs, her bones, her firm stripes of muscle. But it was the tits, the breasts, the exotic. He'd squeezed them, moved them like they were part of him now, and they squeezed him; fed him, fed straight into his midbrain and held it as he held them; squeezed it as he squeezed them and he groaned as electrical discharge crashed into his frontal lobes.

She stroked and kissed his forehead, one with the chemical storm in there, but he kept his lips pressed firm against her breasts, rolled his head against them; one, then the other, again and again and again, living every second far beyond himself, living only to express the indescribable lust they were in him.

Two days later he injected 125 milligrams of cocaine into his left cephalic vein. Over a pair of fucking tits. It'd been three years since he last injected, three years since he was thrown out of medical school and had fallen through his own safety net: never ever inject. Never ever ever inject.

He'd been too rough with a first year intern and she'd told the higher-ups about the stolen morphine he kept in his dorm. They had stripped him of his identity with feigned incredulity. That night her brothers had all but smashed his jaw off his head. The black arc of his self-destruction had caught up with him then. Unable to continue his passion for biology and medicine, unable to resist the smoke, the drink, the powder and the acids, and the underworld from whence he got it all, he found himself too strung out to maintain a job. He'd lost it for a time, waking up soaked in wine and sweat and cum and vomit, unable to remember where he was or how he got there. Eventually he travelled to China for a year, hoping to resume his medical studies with a clean record, but never broke the language barrier and soon found himself back in Europe; in Paris this time, living in an attic with a small group of speedball junkies who kept afloat by producing and selling high-quality porn.

And yet somehow he'd kept himself from injecting. Somehow the hope lived on in him that if he kept up with research, stayed in touch with benevolent teachers, kept asking and kept contributing, maybe one day they would let him back into the flock. Not as a doctor perhaps but maybe as research officer or department administrator, anything really, if only he could come back and be where he belonged.

Until now. His body shook but his hand was steady as he penetrated the skin. God damn it! He could avoid the drugs, could avoid drink and bars, even cut himself off from the other users still undiscovered at the school. But women; women, bras, thongs, transparent white linen, tank tops, bright voices, long hair, the thrill of seduction and the primeval dance of sex; the tits were everywhere, calling for his starved midbrain with never-ending streams of pure monoamines, plans and fantasies. Until now. Now that the moment had come and gone even the siren song of tits had silenced and he was alone with his thirst. He had been defeated by the comedown off a pair of fucking tits.

Riding a bike

2008-12-14T11:38:00.011Z

I was 5 when I learned to ride a bike. I remember the place - a thin strip of asphalt surrounded by very green grass, just beside a small patch of forest - where I first managed to ride it for a stretch without dad holding it steady and without falling over. Imagine my brain at the time. Imagine two pulsating groups of active neurons in each prefrontal cortex, slowly circling each other. One, oscillating slowly, projecting to the motor cortex right at the top of my head and down between the lobes, driving the oscillating contractions of leg and foot on the pedal. The other, pulsating a seemingly patternless pattern to the motor cortex below the upper sides of the skull, constantly adjusting the handle bar with a cramped grip, keeping the whole circus upright. Both groups, closely connected to eachother and to their mirror images in the opposite lobe, receiving a constant barrage of input: sight from the back of the brain and the colliculus, balance from the inner ear, kinetics from the spinal cord. Both groups constantly adjusting their output to maximize the flow of reinforcing dopamine from their respective midbrains. And that's why I remember it so well, that moment when the groups finally got the output right, for a time, and were showered with dopamine as all regions of the brain reported success. The dopamine reinforced them, and with them every other process that was active in my frontal lobes at the time - the location, the weather, the color of the grass.

After that of course, I've kept on biking, for years and years and years, milking those two groups for all the dopamine they were worth, until they were neat and trimmed and refined to a point where almost all the oscillation and rotation and complex feedback loops have been moved over to small, dedicated central pattern generators in my motor cortex and spinal cord.

The Monty Python Channel on YouTube

2008-12-13T17:59:00.000Z

Morphine - A good woman is hard to find

2008-12-12T21:04:00.003Z

She painted a bull's eye on my mind.
No matter how I moved her aim was never high.
I guess that was what I needed at the time.

A good woman is hard to find. A good woman is hard to find.
A good woman is hard to find. A good woman is hard to find.

She was heavy, on the back beat. See played me just like a tambourine.
Well, she took me to church, prayed till it hurt.

A good woman is hard to find. A good woman is hard to find.
I'll live to love another one more time. A good woman is hard to find.

She was a helluva woman, from a helluva town.
She took me all the way, it was a long way down.
She makes me wonder, wonder, all day long.
Can a good woman, ever be found? Can a good woman, never be found?

She was beauty and adventure. She seemed so glad to be alive.
I want to be happy, but not all the time.

A good woman is hard to find. A good woman is hard to find.
I'll live to love another one more time. A good woman is hard to find.

She wrapped me up. Saved me for later.
Left me no way to penetrate her. Guess that was what I needed at the time.

A good woman is hard to find. A good woman is hard to find.
I'll live to love another one more time. A good woman is hard to find.

(Happy birthday Chris)

I've got too much time on my hands

2008-12-10T23:39:00.003Z