Human 2.0: New Minds, New Bodies, New Identites

The MIT Media Lab is holding a conference on May 9th, “Human 2.0: New Minds, New Bodies, New Identites” which will launch a number of new initiatives centered around the goal of inventing a better future via direct engineering of the human. Amongst these things will be the initiation of the MIT Center for Human Augmentation, and the launch of a number of novel applied Neurotechnology Projects.

Guest speakers on May 9th will include MIT professors (Roz Picard, Hugh Herr, myself, etc.) and many acclaimed speakers such as Oliver Sacks and John Donoghue. Registration may be close to being full, but it will be webcast.

More information at:
http://h20.media.mit.edu

— posted by Ed

Brain stimulation and depression?

Brain stimulation and depression has been one of the hot topics of the last decade. Now, a Washington Post story suggests that at least some of this may be overrated, at least for the NeuroStar Transcranial Magnetic Stimulation (TMS) device from Neuronetics:
A novel machine designed to treat depression by zapping the brain with magnetic pulses shows no clear evidence of working, federal health advisers concluded Friday.

The device is called the Neurostar TMS, or transcranial magnetic stimulation, system. It uses magnetic energy to induce electrical currents in the region of the brain associated with mood…

A clinical trial of the device provided results that, in one analysis, suggested it’s no better than sham treatment, according to FDA documents.”

Going to be a long slog. TMS *has* been approved for treating depression in Canada and Israel, for the company NeoPulse.

OpenStim: The Open Noninvasive Brain Stimulator

Transcranial magnetic stimulation (TMS) is a popular technology for stimulating human cortical neurons, due to its safety, noninvasiveness, and efficacy. A TMS device is just a little coil of wire, through which 10,000 Amps of current is cranked during a period of only a few hundred microseconds; the resultant rapidly-changing magnetic field induces eddy currents in the brain. Depending on the protocol used, TMS can drive/inhibit a region of cortex corresponding to roughly a cubic centimeter or two, and is being explored for the treatment of depression, the reduction of auditory hallucinations during schizophrenia, and the alleviation of tinnitus and migraines. Thousands of papers on medicine and psychology have been written using this tool.

Yet the device itself is expensive and rare — they can run from $20,000 to $50,000 or even more, despite the fact that they are, in essence, a coil, a switch, a bank of capacitors, and a power supply. Much of the art lies in making the devices safe and fail-proof. Is it possible to hack/engineer a system that is safe, fault-tolerant, efficacious, and inexpensive? And furthermore, can we facilitate a community that will devise such devices, and share information about protocols and approaches to brain hacking?

This past August at Foo Camp, a hackers’ conference in Northern California, a group of people got together and set out to do just that. We are designing a safe, noninvasive, modular, and “open source” brain stimulator that will open up the field of circuit modulation to a wider audience. Members of the group include therapists and mental health professionals, engineers, programmers, and others interested in either the development of such devices, or the sharing of information on this front. Key to the design is safety — we want to make sure that the devices we create are as safe as devices on the market. Also, all the information is released under the Creative Commons “Attribution and Sharealike” license. This is a new model for “open source” medical device development — which may move it beyond the domain of simply creating “cool toys,” and to creating real devices.

You can find out more information, or contribute to the project, or learn from the project, at
http://transcenmentalism.org/OpenStim/

Ed

Overexpression of Rab1 prevents Parkinson-like cell death

{alpha}-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson’s Models — Cooper et al., Science

Fascinating evidence pointing toward a treatment for parkinson’s. Basically, Lindquist’s group finds that overexpression of a trafficking protein Rab1 that moves folded proteins from the ER to the Golgi can prevent alpha-synuclein accumulation-triggered death of rat neurons.

Of course, in vitro is not in vivo. And, for all we know, Parkinson’s could be a complex, multi-mechanism disease. But this looks promising!

Abstract:

Alpha-synuclein misfolding is associated with several devastating neurodegenerative disorders including Parkinson’s Disease (PD). In yeast cells and in neurons {alpha}Syn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following {alpha}Syn expression in yeast was a block in endoplasmic reticulum (ER) to Golgi vesicular trafficking. In a genome-wide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab GTPase Ypt1p, which associated with cytoplasmic {alpha}Syn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against {alpha}Syn-induced dopaminergic neuron loss in animal models of PD. Thus synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.

NYT on pharmacological advances in addiction treatment

An Anti-Addiction Pill? – New York Times

Lots of interesting stuff here on new treatments for addiction, including: A methadone (heroin-substitute) replacement called buprenorphine with less dependency and less of a high; an injectible version of alcoholism treatment naltrexone called Vivitrol, which is injectable and lasts one month; some medications that increase GABA production; and, perhaps most innovative is a vaccine against nicotine that allows antibodies to bind nicotine and prevent crossing through the blood-brain barrier.

Excerpts with some of the neat experiments involving dopamine receptors and environmental factors in addiction are after the jump.
Continue reading

Complex regional pain syndrome

Doctors Struggle to Treat Mysterious and Unbearable Pain – New York Times

Hadn’t heard about this before:

[…] she felt a sudden pop in her hamstring. “It felt like a guitar string had been plucked and it had broken,” said Ms. Toussaint, who is now 45.

An intense burning sensation followed; it felt as if her leg had been doused in gasoline and set on fire, she said. The next day, the college athletics trainer determined that she had pulled her hamstring. But even years later, the pain would not subside. It migrated to her other leg, leaving her bedridden for nearly a decade, and overtook her vocal cords, leaving her temporarily mute.

All the while, doctors puzzled over and even doubted her mysterious condition.

Ms. Toussaint now knows that she is among an estimated one million Americans living with complex regional pain syndrome, a nerve disorder formerly known as reflex sympathetic dystrophy syndrome. For patients with the disorder, a trauma as mild as a fractured wrist or a twisted ankle can cause the nerves to misfire, so much so that intense pain messages are constantly sent to the brain.

Interestingly, neural stimulation only provides a short-term benefit with eventual adaptation. In some cases, ketamine administration (enough to put the patients in a temporary coma) has completely stopped the pain. Ketamine is an anesthetic (although it has been known to actually stimulate circulation at certain doses) with well-known psychedelic properties. It is also a non-competitive NMDA antagonist that is often used in conjunction with traditional opiods for an analgesic effect.

I wonder if this effect is simply due to the interaction with the NMDA receptor or is something more complex. (For example, the analgesic effects of ketamine when combined with a opiods seem unrelated.)

Here’s a link to the original paper in the journal Pain, which suggests that CRPS patients have suffered damage to small-diameter PNS nociceptive fibers.

TR: Future of Neurotechnology

Technology Review: Emerging Technologies and their Impact

I don’t know too much about Zach Lynch, other than that he has a blog and refers to his company as the “neurotechnology market authority”, but there are some interesting tidbits from the TR interview:

TR: Research suggests that antidepressants are effective partly because they stimulate neurogenesis. So companies such as BrainCells, based in San Diego, CA, are screening compounds that promote growth of neural stem cells in the brain. They say these drugs could bring new therapies for depression and, eventually, neurodegenerative diseases.

ZL: It’s an exciting area, and the investment community is certainly interested. But the jury is still out.

TR: We’re also starting to see a new kind of therapy for brain-related illnesses — electrical stimulation. Various types of stimulation devices are now on the market to treat epilepsy, depression, and Parkinson’s disease. What are some of the near- and far-term technologies we’ll see with this kind of device?

ZL: We’re seeing explosive growth in this area because scientists are overcoming many of the hurdles in this area. One example is longer battery life, so devices don’t have to be surgically implanted every five years. Researchers are also developing much smaller devices. Advanced Bionics, for example, has a next-generation stimulator in trials for migraines.

In the neurodevice space, the obesity market is coming on strong. Several companies are working on this, including Medtronics and Leptos Biomedical. In obesity, even a small benefit is a breakthrough, because gastric bypass surgery [one of the most common treatments for morbid obesity] is so invasive.

In the next 10 years, I think we’ll start to see a combination of technologies, like maybe a brain stimulator that releases L-dopa [a treatment for Parkinson’s disease]. Whether that’s viable is a whole other question, but that possibility is there because of the microelectronics revolution.

The real breakthrough will come from work on new electrodes. This will transform neurostimulator applications. With these technologies, you can create noninvasive devices and target very specific parts of the brain. It’s like going from a Model T to a Ferrari. Those technologies will present the real competition for drugs.

GABA in cosmetics to "freeze" skin

Take 10 Years Off My Face, in 60 Seconds – New York Times

Relevant details:

The company says the freezing effect comes from two ingredients: gamma aminobutyric acid, a substance found in the human nervous system that can block signals between nerves and muscles, and gynostemma pentaphyllum extract, derived from an herb used in traditional Chinese medicine. The company contends that gamma aminobutyric acid, a molecule that stays on the skin’s surface, activates smaller gynostemma molecules and sends them through the skin, where they signal muscles to relax, according to Gene Beilis, a pharmacist who is the vice president for product development at Freeze 24/7.

But the company has no scientific evidence to back up its claim that its products actually affect facial muscles.

And further down:

Mr. Beilis agreed that gamma aminobutyric acid is a powdery substance that coagulates when it dries, gripping the skin in place. Another ingredient in the product, eugenol, a clove derivative used in dentistry as an analgesic, “gives you a cool, numbing, tingling sensation,” he said.

SSRIs: Could anti-depressant action be mediated by the liver?

Platelet-Derived Serotonin Mediates Liver Regeneration — Lesurtel et al. 312 (5770): 104 — Science

Although it is not suggested by this paper (which was brought to my attention by F1000 biology), I’d like to suggest this as a very, very naive hypothesis: That some part of the anti-depressant effect of SSRIs could be mediated by their ability to promote liver regeneration, as the above Science article suggests. The paper itself details how 5HT-2A and 2B receptors are upregulated during regeneration and how 2A & 2B antagonists slow regeneration.

There is some evidence for a connection between liver disease and depression. (Also, traditional chinese medicine views depression as a disease of the liver.) Without a doubt, the liver plays a well-established role in general detoxification.

Although I have no evidence to suspect it, I think it would be interesting to see if the SSRIs were leading to increased liver serotonin, resulting in liver regeneration and hence less depression.

Is the Twinkie Defense for Real?

Does Eating Salmon Lower the Murder Rate? – New York Times

Neat stuff on the role nutrition can play in brain function… it surprises me that the effect can be so large.

Most prisons are notorious for the quality of their cuisine (pretty poor) and the behavior of their residents (pretty violent). They are therefore ideal locations to test a novel hypothesis: that violent aggression is largely a product of poor nutrition. Toward that end, researchers are studying whether inmates become less violent when put on a diet rich in vitamins and in the fatty acids found in seafood.