Neuroscience For Dummies
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Researchers are at the brink of a revolution in treatment of brain diseases. Following are the current strategies (like deep brain stimulation) that show a lot of promise and cutting-edge technology (like neuroprostheses) that show a lot of potential.

Correcting developmental disorders through gene therapy

Genetic mutations, copying errors, unfortunate gene combinations, and environmental toxins can produce profound disorders that severely compromise human potential, even before birth. Among the most well-known developmental genetic disorders are Down, Rett, and Fragile X syndromes.

One route to altering genes or gene expression is with the use of retroviruses. Retroviruses are RNA viruses that produce DNA in the host cell after they enter. This DNA is incorporated into the host's genome, after which it replicates with the rest of the host cell's DNA. Retroviruses can be engineered with sequences that knock out host genes or insert new genes into the host.

Any genetic anomaly that was detected early in pregnancy could, in theory, be treated by a specifically engineered retrovirus that functionally substitutes a "normal" gene for the mutated or defective one. Early phase clinical trials have already shown some success with gene therapies for some forms of hereditary retinal degeneration in adolescents.

Augmenting the brain with genetic manipulation

Most medical interventions into the body or brain are attempts to fix something that is broken, rather than to improve upon what is considered "normal." This is changing, however. The genes that are the most interesting in this regard aren't the ones that make proteins for cell structures or metabolism, but the genes that regulate other genes.

There are, of course, Frankensteinian implications associated with these kinds of augmentations. Genetic modification for intelligence augmentation will probably be outlawed altogether in most developed countries. However, even so, it's hard to imagine that someone, somewhere will not try to do it. And, once done, a gene injected into a fertilized ovum that produces a transgenic modification that will be in the germ line — that is, in all future generations.

Using deep brain stimulation to treat neurological disorders

One of the most exciting recent developments in the treatment of several neurological disorders is the use of deep brain stimulation (DBS) to substantially alleviate the symptoms of the disorder. So far, most targets for DBS have been in the basal ganglia to treat movement disorders. In DBS, one or more electrodes is permanently inserted into the basal ganglia target nucleus, and an implanted electronic device akin to a cardiac pacemaker passes current pulses through the electrode(s) to stimulate neurons in the ganglia. At this point, researchers aren't totally clear whether the main effect of the stimulation is general excitation, general inhibition, or the production of some beneficial pacemaking activity by causing many cells to fire synchronously.

The results of DBS in many patients have been dramatic. These electronic devices can be turned on and off at will. Some Parkinson's patients, for example, can be seen to exhibit the typical stooped posture and shuffling gate with the device off, but, as soon as the current is turned on, they are able to walk and engage in sports like basketball.

FDA approval has also been given for DBS to treat pain and major depression. Some experimental DBS treatments have been done for obsessive-compulsive disorder and Tourette's syndrome. The field is so new that the long-term effects and possible side effects are currently unclear, but in many patients, the symptom relief has been far better than any drug treatment with considerably fewer side effects.

Stimulating the brain externally through TMS and tDCS

There are two very new types of noninvasive brain stimulation: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS).
  • TMS involves creating a very short high magnetic field pulse via a coil outside the head over the brain area to be stimulated. TMS appears to produce relatively localized, transient electrical currents that disrupt neural activity. TMS has some resemblance to electroconvulsive therapy (ECT) except that ECT clinicians normally try to induce a seizure, whereas in TMS seizures are usually avoided. Although TMS was initially used as a research tool to indicate what brain area is involved in execution of a task by temporarily silencing activity in that area, it has recently been used to treat mental disorders, like depression, by repetitively stimulating brain areas. In this case, like ECT, the effects seem to last much longer than the treatment.
  • tDCS is a newer technology to gain popularity. It involves injecting a small direct current between two electrodes on the scalp. Areas of the brain near the anode appear to be generally stimulated and areas near the cathode depressed. Reports have been made of results as wide ranging as improving math scores on standard tests to alleviating schizophrenic symptoms. If these results hold up, tDCS may be a powerful, yet simple tool for minimally invasive modulation of brain activity. There is a large "amateur" industry in self-delivered tDCS because the 2 ma stimulator can be made from a 9-volt battery and a 3.5 k-ohm current-limiting resistor.

Addressing paralysis with neuroprostheses

Spinal cord injuries and strokes have caused paralysis in millions of Americans, and many more millions worldwide. Although considerable research continues to try to discover how to neurally repair a spinal transaction, there continues to be no way to regrow damaged axons and cells necessary to allow movement for most spinal cord injury victims.

Many neuroscientists believe electronically bypassing spinal cord injuries should be possible. The strategy would be to record the activity of command neurons in the primary motor cortex that are sending signals to move the muscles but which don't reach them because of the injury. Microelectrode arrays would record these signals, and electronic circuits would analyze and transfer these signals past the transaction to either the motor neurons controlling the muscles or to the muscles directly.

An alternative therapy to restoring movement of one's own limbs is to record and analyze brain signals to control a prosthetic device such as an artificial arm, or move a cursor and click mouse buttons for computer control. Because opening the brain and installing recording arrays is highly invasive, this approach hasn't been tried extensively. Recent optogenetic techniques for optically stimulating and recording genetically modified neurons may make such implants less invasive and more selective. Neural activity can be read out optically, and used to control a prosthetic device.

Building a better brain through neuroprostheses

Gene modification carries the ability to create something beyond what is normal for a human, as well as for repairing defects. The same is true for neuroengineering, which involves interfacing the nervous system to electronic devices such as computers and the Internet.

Cochlear implants for deafness and deep brain stimulation are only the beginnings of new technology that will link the brain directly to computers. Microelectrode arrays with hundreds and soon thousands of electrodes can both record and stimulate assemblages of neurons at the single cell level.

Experiments have demonstrated that humans (and monkeys) can use electrode arrays implanted in their motor cortices to move computer cursors and artificial arms just by thinking about doing so. Imagine sending requests for information to the Internet by a wireless relay from a recording array in your brain and receiving the answer wirelessly back through a stimulating array. You could soon conceivably communicate with any person on earth just by thinking about doing so. You could also request and receive the results for any data search or calculation.

Given that the basic principles of nervous system stimulation used routinely for cochlear implants and experimentally for visual prostheses can deliver information into the brain, it's not at all beyond imagining a near future (a decade) in which these capabilities are available.

And once we connect the brain to electronics, it's not too far-fetched to imagine modifying the brain, genetically or with stem cells, to facilitate such connections. Sound like a B-movie science fiction plot, with modified people versus "natural" ones? Keep in mind that, unlike much science fiction that is based on made-up science, the techniques for brain-computer interfacing are already here, already being used, and rapidly improving.

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Frank Amthor is a professor of psychology at the University of Alabama at Birmingham, where he also holds secondary appointments in the UAB Medical School Department of Neurobiology, the School of Optometry, and the Department of Biomedical Engineering. His research is focused on retinal and central visual processing and neural prostheses.

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