Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

Abstract

Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies.

Figure 1

Clinical vagus nerve stimulation (VNS). The VNS generator (a) contains a small battery that generates electrical impulses. A surgeon implants the generator subcutaneously over the chest (b) and attaches the electrodes to the left vagus nerve (c). Intermittent signals from the VNS device travel up the vagus nerve (d) and enter the medulla. (Reprinted with permission from APPI, from Higgins and George (2008)).

Figure 2

Transcranial magnetic stimulation (TMS). Current from the wall (a) is used to charge a bank of large capacitors (b). These capacitors send a pulsing electrical current to the coils (c) resting on the scalp (d). The powerful but brief electrical current in the coil creates a transient magnetic field, which passes unimpeded through the skin and skull and results in electrical impulses in neurons in superficial cortex under the coil (e). Depending on the type of cell that is engaged, this then results in secondary transynaptic effects. (Reprinted with permission from APPI, from Higgins and George (2008)).

Figure 3

Brain stimulation and imaging. The combination of brain imaging with brain stimulation allows for more direct examination of the role of circuit activity in brain behavior relationships. Historically most brain imaging has been relatively passive, and changes in a circuit occur along with a behavior, but causality is not known. By combining actual stimulation with imaging one can move a step closer to causal statements, as well as prepare the stage for potential clinical translation and therapeutic uses of brain stimulation approaches. In general, one can image simultaneously with stimulation (a), or one can use the brain imaging result (structural or functional or some combination) to guide the placement of the brain stimulation (in this case TMS) (b). Finally, one can stimulate a region with TMS or tDCS, produce brain changes, and then use brain imaging to examine changes in circuit behavior (c). (Reprinted with permission from Elsevier and adapted from Siebner et al (2009)).

Figure 4

State-dependent interregional interactions evoked by transcranial magnetic stimulation (TMS) interleaved with fMRI. Some groups can actually use TMS within an MRI scanner (Bohning et al, 1998). These images show the (a) main effect of left hand grip, irrespective of TMS stimulation intensity. This illustrates how one can obtain blood-oxygenation-level-dependent (BOLD) activation maps during concurrent application of TMS pulses (five pulses, 11 Hz) inside a magnetic resonance image (MRI) scanner. (b) Task-state-dependent effects of TMS on causal interactions in the human motor system. At rest, TMS applied to the left dorsal premotor cortex (PMd) increased activity in contralateral PMd and primary motor cortex (M1) at high stimulation intensity (110% of resting motor threshold), compared with stimulation at a lower control intensity (70% active motor threshold). In contrast, this effect was reversed during a simple motor task that activated right PMd and M1. Now high-intensity stimulation increased task-related activity, compared with lower intensity stimulation. The results show how TMS can causally affect activity in contralateral regions, and that these influences are dependent on the activation state of these regions (adapted from Bestmann et al (2003) and reprinted with permission from Elsevier and Siebner et al (2009)).

Figure 5

Transcranial direct current stimulation (tDCS). A tDCS device uses an anode and cathode connected to a direct current source much like a 9 V battery (a). The direct current passes through the intervening tissue, with some shunting through the skull but much of it passes through the brain and changes resting electrical charge, particularly under the cathode (b). Reprinted with permission from APPI, from Higgins and George (2008).