Sunday, June 24, 2012

Damsio On the Complexity of the Mind and the Limitations of Pharmacology

After a long lull, powerful new technologies are putting the charting of brain circuitry back on neuroscientists' agenda. Michael Eisenstein explores the challenge of mapping the mammalian mind.

I finished Antonio Damasio's brilliant book Descartes' Error: Emotion Reason, and the Human Brain early this morning, and almost immediately lauunched into his 2003 book, Looking for Spinoza: Joy, Sorrow, and the Human Brain.

Damasio's writing is wonderfully evocative, compassionate, ecclectic, and poetic, as well as informative. As I delve deeper into neuroscience and neuropsychology, it becomes more and more apparent that the "chemical imbalance" theory of mental disorders is at best oversimplified, and at worst, a marketing meme exploited by Big Pharma.

Here he addresses the mind-boggling complexity of the brain: "It is obvious what we want to understand depends largely on the operation of neurons, and we do have a substantial knowlege about the structure and function of these neurons, all the way down to the molecules constituting them and making them do what they do best: fire or engage in patterns of excitement. We even know something about the genes that make those neurons be and operate in a certain fashion. But clearly, human minds depend on the overall firing of those neurons, as they constitute complicated assemblies ranging from local, microscopic scale circuits to macroscopic systems spanning several centimeters.There are several billion neurons in the circuits of one brain. The number of synapses formed among those neurons is at least 10 trillion, and the length of the axon cables forming neuron circuits totals something on the order of several hundred thousand miles. The product of activity in these circuits is a pattern of firing that is transmitted to another circuit. This circuit may or may not fire, depending on a host of influences, some local, provided by other neurons terminating in the vicinity, and some global, brought by chemical compounds such as hormones, arriving in the blood. The time scale for the firing is extrememly small, on the order of tens of milliseconds -- which means that within one second in the life of our minds, the brain produces millions of firing patterns over a large variety of circuits distributed over various brain regions.

It should be clear, then, that the secrets of the neural basis of mind cannot be discovered by unraveling all the mysteries of one single neuron, regardless of how typical that neuron might be; or by unraveling all the intricate patterns of local activity in a typical neuron circuit. To a first approximation, the elementary secrets of mind reside with the interaction of firing patterns generated by many neuron circuits, locally and globally, moment by moment, within the brain of a living organism.

There is not one simple answer to the brain/mind puzzle, but rather many answers, keyed to the myriad components of the nervous system at its many levels of structure. The approach to understanding those levels calls for various techniques and proceeds at various paces. some of the work can be based on experiments in animals and tends to develop relatively fast. But other work can be carried out only in humans, with the appropiate ethical cautions and limitations, and the pace must be slower.

Much of each brain's circuitry, at any given moment of adult life, is individual and unique, truly reflective of that particular organism's history and circumstances. Naturally, that does not make the unraveling of neural mysteries any easier. Second, each human organism operates in collectives of like beings; the mind and the behavior of individuals belonging to such collectives and operating in specific and cultural and physical environments are not shaped merely by the activity-driven circuitries mentioned above, and even less are they shaped by genes alone.To understand in a satisfactory manner the brain that fabricates human mind and human behavior, it is neccessary to take into account its social and cultural context. And that mkes the endeavor truly daunting."

You said it, brother.

And here's Damasio on the thorny snags of relying on pharmacology alone, "If an increase in serotonin levels, for instance, can not only treat depression but also reduce aggression, make you less shy, and turn you into a more confident person, why not take advantage of the opportunity? Would any but the most spoilsport, puritanical creature deny a fellow human being the benefits of these wonder drugs? The problem, of course, is that the choice is not clear cut, for a large number of reasons. First, the long range biological effects of the drugs are unknown. Second, the consequences of socially massive drug intake are equally mysterious. Third, and perhaps most important of all: if the proposed solution to individual and social suffering bypasses the causes of individual and social conflict, it is not likely to work for very long. It may treat a symptom, but it does nothing to the roots of the disease."

Of. course, like all such writings, I hasten to add as a disclaimer -- do not discontinue any medications without first consulting your physician.

5-HT neurons coexpress genes directing 5-HT synthesis (Tph2, Aadc, Gch1, Gfrp, Ptps, Qdpr), reuptake (Sert), vesicular transport (Vmat2), autoreceptor signaling (Htr1a, Htr1b) and metabolism (Maoa, Maob). Tetrahydrobiopterin (BH4), an essential cofac. Basically it means, just take your pill, dude.

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