neurodudes

Salon has an interesting piece condemning a recent PBS show purportedly on Alzheimer’s treatment but really more of a sketchy informercial. The program concerns a neurologist with tenuous ties to UC Irvine who advocates SPECT (single photon emission computed tomograpy, a technique which, similar to PET, uses a radiotracer) and some unfounded preventative treatments for Alzheimer’s. The neurologist Bill Amen has appeared on many big-name media outlets including CNN, the Today Show, and Fox News (and the real sign of media success — Oprah) although his approach to Alzheimer’s detection and treatment is lacking in scientific credibility:

“SPECT scans are not sufficiently sensitive or specific to be useful in the diagnosis of A.D.,” neurologist Michael Greicius , who runs the Stanford University memory clinic, and has a special interest in the use of functional brain imaging in the diagnosis of A.D., tells me. “The PBS airing of Amen’s program provides a stamp of scientific validity to work which has no scientific validity.”

Continued pontification on neuroethics issues after the jump. (more…)

If the Fish Liver Can’t Kill, Is It Really a Delicacy? [NYT, login]

Amazing. It looks like TTX (tetrodotoxin, a potent voltage-gated sodium channel blocker well-known to electrophysiologists) is not made by the pufferfish (which I had always assumed), rather it is from the bacteria/food consumed by the fish.

Decades earlier, another Japanese scientist had identified fugu’s poison as tetrodotoxin, a neurotoxin that leaves victims mentally aware while they suffer paralysis and, in the worst cases, die of heart failure or suffocation. There is no known antidote.

Researchers surmised that fugu probably got the toxin by eating other animals that carried tetrodotoxin-laden bacteria, developing immunity over time — though scientists then did not rule out the possibility that fugu produced the toxin on its own.

By this year, Mr. Noguchi had tested more than 7,000 fugu in seven prefectures in Japan that had been given only feed free of the tetrodotoxin-laden bacteria. Not one was poisonous.

“When it wasn’t known where fugu’s poison came from, the mystery made for better conversation,” Mr. Noguchi said. “So, in effect, we took the romance out of fugu.”

Aside from the interesting science, it appears there is also a small Japanese “industry” (de-ttx? detox?) seriously affected by TTX-free fugu. More after the jump (more…)

The relatively recently discovered cannabinoid receptors has me wondering how many other neuroreceptors may be left to discover. One way to estimate the number of these is to screen the genome and look for sequences that look like receptors. This paper says that people have done that for the special case of G protein-coupled receptors (GPCRs), and that the result is that, excluding receptors involved in “chemosensory responses such as taste and olfaction”, there are “367 receptors (1), of which some 200 have been shown to bind known transmitters (3). This leaves about 160 orphan GPCRs that are not activated by any known transmitters and thus are genes with unknown function.”

I didn’t notice this before, but in a study of about 4000 subjects, people who took Rimonabant (marketed as Acomplia), a selective antagonist of the cannabinoid type 1 receptor (CB1), apparently had a 3.2% incidence of depressive disorders where placebo-takers apparently had a 1.6% incidence. Also, irritability went from .6% to 1.9%, parasomnia from .2% to 1.5%, nervousness from .2% to 1.2%, sleep disorders from .4% to 1.0%, memory loss from .9% to 1.6%, hypoesthesia from .6% to 1.6%, and sciatica from .4% to 1.0%. Psychiatric adverse events were dose-dependent.

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Happy Labor Day (US)! Topping the NYT most popular articles list right now is an interesting article about a new schizophrenia treatment that targets certain glutamate receptors unlike previous dopaminergic drugs. The drug, which is being developed by Eli Lilly, is partially due to this interesting observation:

For decades, psychiatrists have known that users of PCP, a street drug sometimes called angel dust, have symptoms nearly identical to those of people with schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain receptors that are triggered by an amino acid called glutamate. This led some companies and scientists to study ways to stimulate glutamate receptors as a treatment for schizophrenia.

But the brain has many different kinds of glutamate receptors, and figuring out how to stimulate or block them in medically beneficial ways has proved complicated. Instead of focusing on the receptors blocked by PCP, Dr. Schoepp concentrated on modulating the action of glutamate receptors in the brain’s prefrontal cortex, an area responsible for personality and learning.

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Recently, I was pointed to this article in the WSJ (”A Pentagon Agency Is Looking at Brains — And Raising Eyebrows“) by Sharon Begley. It touches on some noninvasive recording techniques for assessing affective state and cognitive enhancers like ampakine CX717 (previously mentioned on Neurodudes here and here).

It was the very last paragraph that caught my eye:

Ever since the atomic bomb, physicists have known that their work has potential military uses, and have spoken up about it. But on the morality of sending orders directly to the brain (of a soldier, employee, child, prisoner …), or of devices that read thoughts and intentions from afar, neuroscientists have been strangely silent. The time to speak up is before the genie is out of the bottle.

Whoa! To me, the physicists who spoke out early on against nuclear proliferation seemed (and still seem) both very courageous and prescient in their ideas. Are we neuroscientists dropping the ball? I would love to start a discussion on this subject and to hear your responses (both from neuro people and others) in the comments below.

I’ll start: I personally don’t think the arena of neural enhancement/intrusion (mind reading, mind control, cognitive enhancement, etc.) is comparable to the sheer destructive power of nuclear weapons. I do see in the near future the unfortunate potential for abuse of neurotechnology and violation of personal freedoms, but the threat does not seem as horrifying or deadly. Still, if neurotechnology allows governments greater control over their citizens, it seems reasonable that scientists who enable such technologies should intervene. Perhaps it is time for a neural bill of rights, which, similar to the freedoms granted by the US Bill of Rights, will clearly state what aspects of a person’s mental state or capacity cannot be infringed upon without permission from that person. Thoughts?

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.
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Fluoxetine targets early progenitor cells in the adult brain — Encinas et al. 103 (21): 8233 — Proceedings of the National Academy of Sciences

One of the first mechanistic attempt at explaining the effects of SSRIs. But how do new progenitors affect depression? Maybe this is an epiphenomenon. Maybe not.

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.

Neuron : Uncertainty, Neuromodulation, and Attention

Haven’t read this article from Peter Dayan’s lab yet but some interesting Bayesian modeling implicating acetylcholine as a signal of expected uncertainty and norepinephrine as a signal of unexpected uncertainty.

Abstract:

Uncertainty in various forms plagues our interactions with the environment. In a Bayesian statistical framework, optimal inference and prediction, based on unreliable observations in changing contexts, require the representation and manipulation of different forms of uncertainty. We propose that the neuromodulators acetylcholine and norepinephrine play a major role in the brain’s implementation of these uncertainty computations. Acetylcholine signals expected uncertainty, coming from known unreliability of predictive cues within a context. Norepinephrine signals unexpected uncertainty, as when unsignaled context switches produce strongly unexpected observations. These uncertainty signals interact to enable optimal inference and learning in noisy and changeable environments. This formulation is consistent with a wealth of physiological, pharmacological, and behavioral data implicating acetylcholine and norepinephrine in specific aspects of a range of cognitive processes. Moreover, the model suggests a class of attentional cueing tasks that involve both neuromodulators and shows how their interactions may be part-antagonistic, part-synergistic.