By Frank Amthor

Revolutions in neuroscience that will have significant ramifications on humanity will occur within 20 years in these two areas: treatments and cures for dysfunctions and augmentation of the brain beyond its heretofore “normal” capabilities.

Treating dysfunction

Until the last quarter of the 20th century, attempts to treat brain problems were a lot like trying to fix a computer with a hammer and a hacksaw. Scientists simply lacked the appropriate tools and the knowledge about how to use them. Research on the brain has started to change this, and the change is now happening very rapidly.

Pharmacological therapies

Most major mental disorders, including depression, schizophrenia, anxiety, and obsessive-compulsive disorder, are currently treated primarily with drugs. Most of these drugs target neurotransmitter systems.

Pharmacological therapies vary in their effectiveness and side effects. Lessons learned from first- and second-generation drugs are being used to design and screen third- and higher-generation agents. Although the cost of bringing a major new drug to market is currently on the order of one billion dollars, there are extensive international, private, and publicly funded efforts to develop new drugs. Drugs that are effective in eliminating most mental illness, substance abuse, or sociopathy would transform humankind.

Transplants

Neural transplants offer great hope for treating neurological disorders such as Parkinson’s disease, which are caused by the death of relatively small numbers of cells in specific brain areas (the substantia nigra, in the case of Parkinson’s). Transplants may consist of either donor tissue or stem cells that can differentiate into the needed cell types when transplanted into the affected region.

Many laboratories are working on transplanting tissue containing foreign secretory cells shielded from the recipient’s immune system by membranes that allow the secretory products out but not the host’s immune cells in. If the encapsulated cells respond to circulating levels of neurotransmitters in the host in an appropriate way, they may be able to regulate the levels of what they secrete more accurately and effectively than can be done by taking pills.

Electrical stimulation

Deep brain stimulation (DBS) is a technique in which the balance of activity in a neural circuit involving several brain areas is altered by continuous stimulation of neurons in one part of the circuit. This technique evolved partly from attempts to achieve the same ends by surgically removing brain areas that were thought to be over-activated in the basal ganglia circuit in Parkinson’s disease.

DBS has seen extensive success in treating Parkinson’s disease and certain kinds of tremors. DBS has also shown promise in treating certain kinds of depression.

Another kind of electrical stimulation is transcranial magnetic stimulation (TMS). TMS uses a strong, pulsed magnetic field generated just outside the skull to produce localized currents within the brain areas underneath the coil. These currents initially excite and then shut off brain activity for some period of time. Despite the short duration of the direct effects, long-term benefits have been observed in situations such as intractable depression. In this, TMS appears to act somewhat like the old “shock therapy” (electroconvulsive therapy, or ECT), but without producing seizures and some other unintended side effects.

An electrical stimulation technique called transcranial direct current stimulation (tDCS) has also shown promise in enhancing learning, reducing depression, and possibly increasing self-control. tDCS involves injecting about 2 milliamps of current between anode (positive) and cathode (negative) electrodes placed on different brain areas, depending on what brain area is to be modulated. Most studies suggest that brain activity under the anode is enhanced, while brain activity under the cathode is depressed. As with TMS, effects seem to last much longer than the treatment time, which is usually about 20 minutes for tDCS.

Neural prostheses

Paralysis from spinal cord and brain injuries has been almost impossible to treat because the motor neurons that would activate the muscles were either all killed in the original injury or degenerate from lack of use afterward. A long-time rehabilitation dream has been to intercept brain signals commanding movements, relay them past the interruption, and drive muscles directly with electrical stimulation.

Another type of neural prosthesis is for sensory replacement. By far the most successful of these is the cochlear implant for deafness. Over 80,000 of these have been implanted worldwide at the time of this writing. In most cases these prostheses allow the recipient to carry on normal conversations, even on the telephone.

Prostheses for vision have been less successful. This is partly due to the fact that the information channel is so much larger (1 million ganglion cell axons versus 30,000 auditory nerve fibers), and partly because the cochlea presents a unique environment suitable for the introduction of a stimulating prosthesis. Demonstration projects for visual prostheses have implanted them in both retina and visual cortex, but neither approach has achieved clinically relevant effectiveness. Work continues, however.

Genetic therapies

Much psychological and neurological dysfunction occurs because some neurotransmitter systems are overactive, underactive, or out of balance with other systems. Given that neurotransmission is regulated by gene expression, modification of that expression is an obvious therapeutic target. Recently, the insertion of new genes in adult animals and humans has been accomplished with viral transfection therapies, such as modifying adenoviruses (the viruses that produce the common cold) to insert a desired gene in a patient’s genome that will then be expressed like the patient’s own native DNA but will correct the neurotransmitter imbalance. Genetic therapies are likely to revolutionize medicine and neuroscience research and therapy in the next decades.

Augmenting function: Changing who people are

Humans are now beginning to augment themselves. This augmentation will go far beyond the vaccines, surgical procedures, and prosthetics that alter bodies, because it will involve brains being directly connected to electronic circuits and, through those circuits, to the universe.

Using likely extensions of current technology, imagine using an implanted neural prosthesis to access the Internet just by thinking about it. Similar prostheses could translate languages in your head or allow you to do complex mathematical calculations. They could allow you to communicate with anyone on earth simply by thinking about that person.

Sound far-fetched? Consider that neuro-prostheses consisting of hundreds of electrodes have already been experimentally implanted in a few people who were either paralyzed or blind. The principles involved in recording from or stimulating individual neurons in the brain are well within current technology. What remains to be done is achieve better resolution and signal processing and longer lasting implants, which no doubt will happen in 20 years.