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EVALUATION OF NEUROMODULATION USING MRI 43

straightforwardly predictable in terms of the effects inexpensive, easy to use, safe, and well tolerated.
that are conventionally associated with increases or Electrodes can be placed anywhere on the scalp to
decreases in excitability. influence a brain region(s) or network(s) thought to
Unlike TMS, which directly elicits action potentials, subserve a particular function that could be altered
tDCS appears to affect cortical excitability through by changing brain excitation or inhibition. Large elec-
multiple mechanisms during stimulation and for a trodes can be held in place with an elastic headband,
short period of time after stimulation. Inhibitory while multiple small electrodes can be held in place
neurotransmitters such as gamma-aminobutyric acid with caps much like EEG. In general, one session lasts
(GABA) may be reduced by anodal tDCS while excit- 10–30 minutes. To minimize reactions at the elec-
atory neurotransmitters such as glutamate may not trode-skin interface, tDCS should be performed with
be affected (76). This increases the propensity for non-metallic, conductive rubber electrodes, covered
affected neurons to fire in response to additional by saline soaked sponges or with electrodes made
inputs (5). tDCS also affects ionic shifts that enhance of metal or rubber that are separated from the skin
sodium and calcium conductance in affected neurons and electrical contact established with conductive
as well as alter the resting membrane potential such gel. Extensive data support the safety of tDCS with
that neurons are more likely to fire in response to only mild and transient adverse effects (13,56). In
their natural inputs (53). Increased regional cerebral a systematic review, Brunoni et al. (20) concluded
blood flow and oxyhemoglobin are also noted in that 56% of the investigations reported adverse
cortical and subcortical areas near the anode (36). effects, but these were generally limited to itching
The mechanisms of cathodal inhibition are less well or tingling under the electrodes, headache, and dis-
studied though cathodal stimulation results in both comfort. Moreover, the adverse effects reported were
glutamate and GABA decreases (76). The sustained also present in participants receiving sham tDCS,
effects of tDCS on cortical excitability after stimula- suggesting that side effects may not be attributable
tion ends are dependent on the N-methyl-D-aspartate wholly to the current itself. Recent studies utilizing
glutamate receptor subtype (54). Animal and human imaging (EEG and fMRI) showed that tDCS does
studies indicate that tDCS may also induce long-term not induce elevations of a neuronal damage marker
potentiation and depression-like processes (LTP and (neuron-specific enolase) and is not associated with
LTD) that strengthen or weaken synaptic communi- evidence of edema or other maladaptive functional
cation in affected neuronal pathways depending on or structural changes (30,55,56). However, plasticity
how they are applied (77). Following LTP induction, in neurophysiology and in white matter integrity has
a pre-synaptic stimulation induces a “potentiated” been demonstrated (62).
post-synaptic response whereby a lower stimulus tDCS may play an important role in neuroscience
intensity may activate the set of synapses or the same research to provide causal evidence for the involve-
stimulus intensity may activate a larger set of synapses. ment of a specific brain region in a particular task.
Increased excitability may promote improvements in Importantly, tDCS has been observed to enhance
task performance by facilitating LTP-like processes performance in cognitive tasks in healthy individuals
between the neurons involved in the task. Therefore, (15,17,28,44,81) and to delay, suspend, or reverse the
increasing neuronal excitability with brain stimula- effects of aging in cognition and motor skill (80). It
tion may provide a means of inducing a physiological has also been examined as a treatment for neurolog-
state supporting improved task performance or the ical and psychiatric disorders, including addiction,
acquisition of novel skills (21,64). In contrast, cath- Alzheimer’s disease (9), chronic pain (1), depression
odal stimulation may induce LTD-related reduction (7), developmental disorders (10), eating disorders
in neuronal synapse efficacy and be important in (70), epilepsy (37), migraine headaches (2), mild
suppressing responses (20). cognitive impairment (47), multiple sclerosis (51),
The application of tDCS has attracted some Parkinson’s disease (6), schizophrenia (12,14,49,60),
attention for multiple reasons. tDCS is relatively substance use disorders (8), and stroke (31).