28 February 2009
27 February 2009
24 February 2009
Deep brain stimulation for depression
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."
22 February 2009
After long wait, Medtronic starts big depression study
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.
'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.
21 February 2009
A cure for addiction?
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.
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.
18 February 2009
Squishy
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.
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.
17 February 2009
Interlude
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.
06 February 2009
04 February 2009
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