Best before yesterday: deep brain stimulation

Showing posts with label deep brain stimulation. Show all posts

14 September 2009

At the International Neuromodulation Society conference in Seoul 4

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.

13 September 2009

At the International Neuromodulation Society conference in Seoul 3

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.

08 June 2009

In the news this morning

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.

21 April 2009

How bad do you want it? (update 1)

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.

18 March 2008

Deep brain stimulation papers 3

The hypothalamus, apparently a common deep brain stimulation (DBS) target in the treatment of cluster headaches (CH), has also been tried for facial pain, obesity, and aggression. The lateral portion of the hypothalamus contains a segment of the medial forebrain bundle (MFB) and is exceptionally supportive of brain stimulation reward (BSR).

Obesity

Sani et al (2007) DBS for treatment of obesity in rats. Rush University Medical Center. DBS of the lateral hypothalamus decreased food intake in rats. Interestingly, the authors use 0.25mm diameter bipolar electrodes.

Lacan et al (2008) Modulation of food intake following DBS of the ventromedial hypothalamus in the vervet monkey. Laboratory investigation. David Geffen School of Medicine at UCLA. Bilateral DBS of the ventromedial hypothalamus increased food intake in two vervet monkeys.

Hamani et al (2008) Memory enhancement induced by hypothalamuc/fornix DBS. University of Toronto. Hypothalamic DBS inadvertently triggered strong recall.

Aggression

Franzini et al (2007) Chronic high frequency stimulation of the posteromedial hypothalamus in fascial pain syndromes and behaviour disorders. Instituto Nazionale Neurologico Carlo Besta. Posteromedial hypothalamus DBS as a treatment for aggression.

Franzini et al (2005) Stimulation of the posterior hypothalamus for medically intractable impulsive and violent behavior. Instituto Nazionale Neurologico Carlo Besta. Posterior hypothalamus DBS effective treatment for aggression in two patients.

Cluster headache

Vetrugno et al (2007) Effect on sleep of posterior hypothalamus stimulation in CH. University of Bologna. Posterior hypothalamus DBS improved sleep in three CH patients and had no effect on body temperature.

Starr (2007) Chronic stimulation of the posterior hypothalamuc region for CH: technique and 1-year results in four patients. University of California at San Francisco. Posterior hypothalamus DBS produced a 50% reduction in CH intensity/frequency in two of four patients.

Bussone et al (2007) DBS in craniofascial pain: seven years' experience. Fondazione IRCCS Instituto Neurologico Carlo Besta. Posterior inferior hypothalamus DBS resulted in a persistent pain-free or almost pain-free state in 13 of 16 treatment-resistent CH patients. (a similar paper from the same group here.)

May et al (2006) Hypothalamic DBS in positron emission tomography. University of Hamburg. The authors argue against a simple inhibition based model of hypothalamic DBS in CH treatment.

Schoenen et al (2005) Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. CHR Citadelle. Out of six patients ventroposterior hypothalamus DBS is highly effective in three cases, fatal in one.

Miscellaneous

Cortelli et al (2007) Effect of DBS of the posterior hypothalamic area on the cardiovascular system in chronic CH patients. University of Bologna. Posterior hypothalamic DBS is associated with certain cardiovascular changes.

Cordella et al (2007) Spontaneous neuronal activity of the posterior hypothalamus in trigeminal autonomic cephalalgias. Fondazione IRCCS, Istituto Nazionale Neurologico C. The authors seems to have used the DBS electrodes of three patients to record the activity (24 spikes/s, random, tonic) of a handful of neurons in the posterior hypothalamus. Did not know you could just do that.

07 March 2008

Deep brain stimulation papers 2

(13 page pdf) Anderson et al (2004) Mechanisms of deep brain stimulation: an intracellular study in rat thalamus. J Physiol 559(pt1), p301-313. Intracellular recordings from thalamic rat slices during 125hz electrical stimulation. The authors find two distinct membrane responses that may underlie 'functional inactivation'.

(11 page pdf) McIntyre et al (2004) How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophysiol 21(1), p40-50. Review paper that looks at four hypotheses for the mechanism of DBS in movement disorders: depolarization blockade, synaptic inhibition, synaptic depression and stimulation-induced modulation of pathologic network activity.

(20 page pdf) Feng et al (2007) Toward closed-loop optimization of deep brain stimulation for Parkinson's disease: Concepts and lessons from a computational model. J Neural Engineering 4(2), l14-21. The authors describe an algorithm for closed-loop selection of novel, more efficient DBS waveforms.

(3 page pdf) Kiss et al (in press) Frequency dependent effects of deep brain stimulation: Clinical manifestations and neural network modelling. When low DBS frequencies (2,5hz-20hz) are applied to traditional targets there is a worsening of motor symptoms, suggesting an activating as opposed to inhibiting effect and possibly indicating appropriate frequencies for DA(t) and 5HT(t).

Bekar et al (2007) Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. Nature Medicine 14, p75-80. The authors suggest that DBS induced inhibition of thalamic tissue is mediated by stimulation of local adenosine receptors.

In other news, Entitled Opinions is a Stanford University radio show hosted by Italian lit prof Robert Harrison. The 1hr long discussions are on iTunes (why does everything academic on iTunes seem to come out of Stanford or Berkeley? Mostly litterature, including some gems like Heidegger, Freud, Nabokov and the Historical Jesus. I've only heard one full interview (a stimulating interview with a gloomy Richard Rorty) but they all seem very authentic, if you're in that kind of mood.