neurodudes

This article in the latest issue of the Journal of Neuroscience is interesting in the sense that they are do human brain stimulation of the hypothalamus, for the treatment of cluster headaches – but they then do positron emission tomography (PET) to examine the downstream neural circuits responsible for the abolition of the perception of headache.

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

This moves the field of brain stimulation from simple stimulate-and-see-what-happens, towards more of a study of human neural circuitry and how stimulation drives activity in connected locations. It’s possible this will lead, in the future, to better and more focal stimulation protocols, as people figure out what the “circuit-level” phenomena are that correct particular aspects of neural dysfunction. Perhaps someday we will have a map of the “hot spots” where stimulation of a small chunk of matter can modulate a wide degree of neural circuitry for the better.

(Last year, Helen Mayberg and colleagues’ deep-brain-stimulation-and-depression paper got at this issue as well, in which they stimulate the cingulate and (perhaps surprisingly) sent depressed patients into remission, and furthermore changed the activity of frontal structures from the abnormal state, back to a more normal pattern of activity.)

These studies are perhaps setting a good precedent for brain-stimulating neuroclinicians to follow.

— Ed

Artificial limbs that walk naturally

Not too much info about the device, but basically, without any active electronics, the foot has a natural enough gait that people do not notice it is a prosthesis. Pretty cool.

Nerve Stimulation and Revenue Growth – New York Times

Some interesting tidbits about the backroom financial manueverings of some vagus nerve stimulator startups. Hadn’t heard of Advanced Neuromodulation Systems before.

The Pablo Picasso Alzheimer’s Therapy – New York Times

Interesting connection: Art appreciation seems to ease Alzheimer’s symptoms. Less memory loss. Less repetition.

Super interesting… there’s a lot to say here. There are of course many documented cases of particular brain lesions causing marked changes in personality or hobbies. But this appears to be something different. There is both an interest change (ie. people are more interested in art) but the neurological disease itself is somehow lessened (temporarily) by the interest itself.

The article mentions that there is very little research in the area. Does anyone know of any studies? It’s fascinating to think that such a simple, non-invasive therapy could be so powerful.

Either that, or it just means that art critics (“It’s like he’s trying to tell a story using words that don’t exist” — critic or patient?) have something in common with those with neurodegenerative disease.

Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice — PNAS

This article has some very promising results. I haven’t read the paper in detail, but here’s the executive summary. Human neural stem cells (hNSCs) were injected into mice that received a precision contusion (laminectomy) injury at spinal level T9. Control groups had vehicle and human fibroblast cell injections after receiving the same injury.

The group receiving hNSCs showed a significant functional recovery from the vehicle group. The fibroblast group did not. Then, to prove that the functional recovery was due to the new neurons and glia from the hNSC, the investigators injected the recovered mice with diptheria toxin, which affects human neurons while essentially leaving mouse neurons alone. After the toxin injection, the recovered mice with hNSC regressed back to the same behavioral performance as the vehicle group. That is, the functional recovery reversed after selective de-activation of the hNSC-derived neurons.

Additionally, the hNSCs produced both neurons and oligodendrocytes (myelin producers) in the mice. Through EM, it was verified the hNSC-derived neurons formed synapses with endogenous mouse neurons.

Amazing. Work like this shows how genetically similar mouse and human neurons (well, at least spinal cord neurons) must be. And, with regard to the race to understand and control stem cell development, this provides further evidence of how strongly the local environment can influence differentiation.

Study Finds Little Advantage in New Schizophrenia Drugs – New York Times

Looks like the current crop of schizophrenia drugs come up short.

The study, which looked at four new-generation drugs, called atypical antipsychotics, and one older drug, found that all five blunted the symptoms of schizophrenia, a disabling disorder that affects three million Americans. But almost three-quarters of the patients who participated stopped taking the drugs they were on because of discomfort or specific side effects.

NEUROSCIENCE: Preventing Alzheimer’s: A Lifelong Commitment? — Marx 309 (5736): 864 — Science

Some quotes of interest:

For example, a 1997 study of 642 elderly people, conducted by Denis Evans of Rush Presbyterian-St. Luke’s Medical Center in Chicago and his colleagues, found that each year of education reduces a person’s risk of Alzheimer’s disease by 17%.

[...]

As in other studies, Snowdon and his colleagues found that high education levels seem to protect against Alzheimer’s disease. The researchers originally thought that this supported the idea that more education leads to a higher cognitive reserve. But analysis of biographical essays the sisters had written when they entered the convent, usually in their early 20s, pointed in a different direction. The early writings, Snowdon says, were an even better predictor of who would get Alzheimer’s disease than education level. “Those who had the lowest linguistic skills at age 22 had a very high risk of Alzheimer’s,” Snowdon says. Indeed, most of the cases occurred in the nuns whose essays put them in the bottom third on the linguistic ability scale.

[...]

A few years ago, Arthur Kramer of the University of Illinois, Urbana-Champaign (UIUC), and his colleagues performed a meta-analysis of 18 trials involving adults between the ages of 55 and 80 that explored the effects of physical exercise on performance of various cognitive tasks. They concluded that the answer to the question, “Does aerobic exercise enhance cognition?” was an “unequivocal yes.”

[...]

As reported in the April issue of the American Journal of Epidemiology, study members who engaged in four or more physical activities, which could be anything from gardening to jogging or biking, had about half the risk of dementia as that of participants who engaged in one or none. The effect was primarily seen, however, in persons who did not carry a gene variant called ApoE4 that’s known to increase Alzheimer’s risk. In the ApoE4-endowed population at least, genetics seems to trump activity.

[...]

Another possibility is that exercise turns up production of proteins that stimulate neuronal growth. About 10 years ago, Carl Cotman’s team at UC Irvine, found that the brains of rats who ran voluntarily on a wheel show increases in one such factor, BDNF (for brain-derived neurotrophic factor). The increase was particularly strong in the hippocampus, an area involved in learning and memory that’s hard-hit by Alzheimer’s disease.

Looks like spinal cord regeneration might be the first target for embryonic stem cell therapy trials in humans. More info in the Science article.

It looks like Geron has developed a protocol to reliably induce ES cells to become oligodendrocytes, the glial cells that produce the myelin sheath. Here’s the details from the article:

For newly injured rats, the results are promising. In animals that received oligodendrocyte precursors 7 days after their injury, the cells survived and apparently helped repair the spinal cord’s myelin. Within 2 weeks, treated rats scored significantly better on standardized movement tests than control animals, which had received human fibroblasts or a cell-free injection.

The March issue of Nature Rev. Neuroscience includes an interesting article about an herbal remedy, ibogaine, which appears to upregulate glial-derived neurotrophic factor (GDNF) in the VTA (ventral tegmental area, which seems to play a key role in reward learning). Apparently, an increase in GDNF activity makes alcohol (and presumably other VTA-involved compounds, like opiates) less addictive.

A round up of a bunch of potential analgesics. Not computational or anything, but interesting if you’re into the neurobiology or treatment of pain.

http://nytimes.com/2005/02/15/health/15pain.html