Sunday, July 17, 2011

Brain Overclocking: Living a More Intense Life

Neurons recruited for local computations exhibit rhythmic activity at gamma frequencies. The amplitude and frequency of these oscillations are continuously modulated depending on stimulus and behavioral state. This modulation is believed to crucially control information flow across cortical areas....by rapidly balancing excitation with inhibition, the hippocampal network is able to swiftly modulate gamma oscillations over a wide band of frequencies. _ScienceDirect
SPIE

Besides finding ways to prolong one's life, it would be worthwhile to find ways to live one's life more intensely. We have discussed ways in which we might reduce the amount of time spent in sleep, without suffering from diminished mental or physical health. There are also everyday ways in which a person can intensify his experience of his waking time. Some examples are listed at the end of this piece.

From the neurocognitive standpoint, the concept of the controlled "overclocking" of the brain -- speeding up the functioning of brain processes so that more can be experienced and accomplished in less time -- is just coming into the realm of possiblity. The concept, once developed, will rest upon a sound understanding of brain processing and inter-brain communications.
Brain activity changes between different brain states, whether awake, asleep, drugged, etc. Besides the activation of different centers in the brain according to brain state, the actual speed (frequency) of brain activity varies with different brain states.

It is thought that synchronous oscillations involving gamma carrier waves (30 to 100 Hz) modulated by theta frequencies (4 to 8 Hz) allow multiple brain processes to occur, including the transfer of working memory to long-term memory, and the binding of different sensory or other inputs into a coherent mental image of an object or idea. In other words, the way the oscillations of the brain are organised on a moment to moment basis, is what allows us to "think" and remember. (see Working Memory: The Importance of Theta and Gamma Oscillations, Lisman, Current Biology Vol 20 No 11)
Gamma oscillations are thought to transiently link distributed cell assemblies that are processing related information1, 2, a function that is probably important for network processes such as perception1, 2, 3, attentional selection4 and memory5, 6. This 'binding' mechanism requires that spatially distributed cells fire together with millisecond range precision7, 8; _Nature
The idea of a synchronous oscillator, or "clock", involved in thinking and memory suggests the possibility of "speeding up the clock" or "overclocking," analogous to the overclocking of a computer processor to achieve higher computing speeds. In reality, of course, things work much differently in the brain, and no central processing unit is available for safe and controlled overclocking.

But we do know that the top end of the gamma "carrier wave" frequency can vary between types of animals. Some kinds of insects, for example, exhibit brain synchrony at frequencies up to 200 Hz in certain circuits. (Kirschfeld PNAS USA Vol. 89, pp. 4764-4768, May 1992 Neurobiology)

Different frequencies of gamma oscillation serve to connect different brain centers, in practise. This allows for simultaneous parallel activity between multiple circuits. Therefore, when "overclocking," one must be sure not to "step on" the frequencies used by different brain circuits.

There are a number of other cautions, assuming that one had a good idea how to begin to go about ramping up gamma oscillation carrier wave frequencies in the first place. The intricacy of neuronal signaling of brain circuits should discourage any attempts to permanently alter neuronal oscillatory activity. For example, gamma frequencies are closely controlled and modulated by inhibitory interneurons. You cannot change the timing of one type of cell and expect to maintain a system of smooth communication between brain nuclei. Rather, multiple keys that control the timing of networks across the brain will have to be discovered and mastered.

Why should we bother to attempt something which will require so much work? It is possible, after all, to intensify the experience of everyday life without resorting to the extremes of genetic modification of the brain.

Below are some of the everyday means by which some persons provide themselves with temporary experiences of high intensity consciousness:

Pharmacological brain stimulants have been used for this purpose for centuries, but in general they extract a steep price from the user who does not exercise prudence. Veterans of combat can attest to the consciousness-intensifying effect of the life-or-death experience. But we are looking for something more sustainable and less risky. Sky-diving, hang gliding, scuba diving, whitewater kayaking, etc. are less risky than combat, but provide a temporary aura of intensity which lingers after the experience. In occupational settings, life or death emergencies attended to by firefighters, police officers, EMS personnel, medical personnel in hospitals, etc. provide temporary "fixes" of intensity. And under the category of "not to be recommended," the commission of a crime and the attendant risk of being caught supplies the outlaw with a feeling of intensity which can become addictive to some. Similarly, committing acts which may be legal but which are socially or occupationally frowned upon, can sometimes provide a touch of that "outlaw intensity," that accompanies risk.

Perhaps the most dangerous method of intensifying experience is to fall in love. The fallout from such a turn is apt to be fatal to any number of persons involved and in the immediate vicinity. ;-)

As for using brain science to overclock the brain, I will be exploring some of the ideas that might be tried eventually in short works of fiction on another Al Fin blog.

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Monday, June 04, 2007

Ampakines Back in the News

Brain boosting drugs in the new Ampakine class are back in the news--this time in connection with the problem of respiratory depression from sedative/hypnotic drugs.
Researchers at the University of Alberta (Edmonton, AB) and Cortex Pharmaceuticals (Irvine, CA) believe that AMPAKINE drugs may provide protection from drug-induced respiratory depression, while simultaneously allowing the sedative or analgesic to continue working as it was intended.

The drug tested in this study belongs to a novel class of molecules known as AMPAKINE compounds being developed by Cortex Pharmaceuticals, Inc. located in Irvine, California. AMPAKINE compounds act on the most common excitatory receptor in the brain, the AMPA "Glutamate type receptor," which has been shown in rodent models to boost the brain's own protein for improving age-related deficits in memory mechanisms. In primate models AMPAKINE compounds have replicated the studies in rodents and in adults patients suffering from Attention Deficit Hyperactivity Disorder, significant clinical and statistical improvement in increase attention and decrease hyperactivity have been observed. The U. Alberta research provide evidence that another important AMPAKINE indication is to stimulate primitive areas of the brain called the pre-Botzinger Complex responsible for breathing, without causing side effects. The pre-Botzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties that have been identified in this brain region.

In a study published in 2006, Dr. John J. Greer of U. Alberta demonstrated that certain AMPAKINE compounds enhance the respiratory drive and breathing rhythm at the brain-stem level containing the pre-Botzinger Complex in laboratory rats whose respiration rates were purposely suppressed by administration of central nervous system depressants.

Dr. Greer found that respiratory depression induced by these agents can be reversed or prevented in test animals with an experimental AMPAKINE drug, without a reduction of pain relief or sedation.

Greer and coworkers treated rats with the opioids analgesic fentanyl or the barbiturate sedative Phenobarbital, both commonly prescribed in the United States. Greer used a technique known as plethysmography, which measures blood flow throughout the body, to determine the level of respiratory distressed caused by the drugs. When drugged rats were treated with the AMPAKINE , the respiratory distress quickly resolved. The drug worked in both newborn and adult rats. Interestingly, the drug on its own did not affect blood flow in animals not treated with the sedative drugs, nor did administration of the drug cause noticeable arousal in the animals.

Greer concluded, in a study published in the September 20, 2006 issue of the American Journal of Respiratory Critical Care Medicine, that CX546, "effectively reverses opioid- and barbiturate-induced respiratory depression without reversing the analgesic response."

"These results open up the real possibility of combining an ampakine compound with commonly prescribed barbiturates or opiates to reduce the likelihood that life-threatening respiratory depression will occur," noted explained Roger G. Stoll, Ph.D., Chairman, President, and CEO of Cortex.
Source

Ampakines hold out a promise for effective palliative treatments for Alzheimer's and other neurodegenerative disease. Currently, the Cortex drug CX717 is being held up by the FDA over toxicity concerns. Consequently the stock price of Cortex is currently quite low--trading below US $3 a share for over a year.

It is easy to see that should Cortex navigate through the labyrinthine bureaucracy of the FDA and reach approval for any of its Ampakines in development, that the stock price could rise rapidly.

Frankly, it is the potential for cognitive enhancement in normal people that fascinates me the most about the Ampakines. But the potential to make a substantial profit on a fairly small investment is also attractive. But do your own research before investing.

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