Neuromodulation: advances in the next decade.

Many nervous system disorders (e.g., Parkinson's disease, mood disorders) involve neurotransmitters as well as electrical activity. Pharmacologic treatment does not target the precise location(s) where neurotransmitter imbalances occur. Additionally, non-neuronal cells in the brain--notably astrocytes--influence neuronal activity through both electrical and neurochemical modulation of nearby neurons. Precise monitoring/recording and modulating/stimulating (both electrical and neurochemical) can optimize therapy in specific disorders and specific patients. Carbon-fiber microelectrodes (5 microm diameter) in freely moving rodents have shown that dopamine release is heterogeneous within various regions in the nucleus accumbens, a region involved in many mood disorders. Because neurons are only several microns in diameter (axons, dendrites, and synaptic clefts smaller still), ultramicroelectrodes will be essential to selectively monitor/modulate the cell body, the axon, or at the intracellular level. Nanoelectrode arrays can monitor both electrical activity and dopamine in real time with submicron resolution, and stimulate neurons with equal precision. Computational models indicate that precise monitoring/modulating (electrically and neurochemically) at the subnucleus or neuron level will be necessary to restore normal firing patterns and neurotransmitter levels in many brain disorders. Endovascular techniques can introduce ultramicroelectrodes (0.5 micron or smaller) into the brain via capillaries; such electrodes can stimulate/record neuronal tissue with a response virtually identical to extra-vascular microelectrodes. Within the next decade, hundreds if not thousands of submicron-sized monitoring/modulating electrodes can be placed wherever needed to restore brain function to normal. The term "neuromodulation" will likely replace deep brain stimulation (DBS) as both neurochemistry and electrical activity are included in the therapeutic modalities.