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Neurostimulation modalities modulate activity in prespecified regions of the neuraxis or, through trans-synaptic propagation, in prespecified circuits. The exact mechanism by which electrical stimulation results in therapeutic gains is unknown. Possibilities include changes in neurotransmission, changes in synaptic plasticity (e.g., long-term potentiation [LTP] and long-term depression [LTD]), hippocampal neurogenesis or other regional structural changes, changes in gene expression (e.g., brain-derived neurotrophic factor [BDNF]), changes in second messenger systems, neuroendocrine changes, or most likely, some combination of these. Neurostimulation modalities can be broadly divided into invasive approaches (which involve neurosurgical hardware implantation) or noninvasive approaches. Noninvasive brain stimulation (NIBS) involves cortical stimulation through the skull, scalp, and meninges. NIBS modalities include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and newer technologies such as focused ultrasound and optically based strategies. Invasive approaches include deep brain stimulation (DBS) and vagal nerve stimulation (VNS). In this chapter we provide an overview of a select number of neurostimulation modalities, for example, TMS, tDCS, ECT, VNS, and DBS and briefly discuss focused ultrasound and optically based strategies. We recognize that some emerging modalities are not included (e.g., transcranial alternating current stimulation [tACS], low-field magnetic stimulation [LFMS]); our aim is to emphasize those modalities that, at the time of this writing, show the most promise for eventual clinical deployment. We review clinical applications of the main modalities, with special focus on their use in major depressive disorder, particularly in treatment-resistant depression (TRD).


Table 9-1 provides a quick reference about the various neurostimulation techniques.

TABLE 9-1Summary of Neurostimulation Modalities.

Transcranial Magnetic Stimulation (TMS)

TMS operates on the principle of electromagnetic induction, discovered by Michael Faraday, wherein a rapidly changing magnetic field creates a current in a conductive medium. Developed in 1985 by Barker, the TMS apparatus consists of a stimulator which delivers a large current into an attached TMS coil—consisting of loops ...

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