Neurostimulation: any intervention intended to alter nervous system function by using energy fields such as electricity, magnetism, or both.
- Electroconvulsive therapy (ECT)
- Vagus nerve stimulation (VNS)
- Repetitive transcranial magnetic stimulation (rTMS)
- Deep brain stimulation (DBS)
a recent surge of interest
- targeting specific brain regions or circuits – a level of focality
- increased use of medical technology
- superior tolerability for use alone or in combination with pharmacotherapy or psychotherapy
- potential to improve cognition or nonspecific symptoms
SECTION 1: Electrical Engineering and Neurophysiology
tCS
- tDCS (direct current stimulation): a constant, or “direct”, waveform
- CES (cranial electrial stimulation): proprietary waveforms that may fluctuate over time
- tACS (alternating current stimulation): sine waves
- tRNS (random noise stimulation) : broadband noise
- eTNS (external trigeminal nerve stimulation)
- tVNS (transcutaneous vagus nerve stimulation)
Ohm’s law (V = I x R)
Spatial Targeting: Electrode Montages
- Spatial targeting using computer simulations of the electrical field distribution, as a function of electrode number, size, and location, has been proposed (8) but lacks validation as an approach to guide clinical tCS.
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given the distrib- uted and complex deficits in neuronal networks associated with psychiatric disorders, identifying the correct target area(s) for therapeutic stimulation in a specific disorder or symptom remains an important challenge for the field.
Neurophysiological Effects of tCS

Subthreshold membrane fluctuations are not sufficient to generate an action potential (left). However, if intrinsic fluctuations in a neuron’s membrane voltage move it closer to its threshold, application of an inherently subthreshold input, such as low-intensity transcranial current stimulation (tCS), can trigger an action potential (right). Dashed line indicates threshold.
Communication between individual neurons and neuronal networks is nonlinear and complex, with a large number of inputs influencing the activity of any individual neuron. Therefore, even a small change in the membrane voltage may impact neuronal firing.
SECTION 2: REVIEW OF PUBLISHED RANDOMIZED CONTROLLED TRIALS
Randomized Controlled Trials of tCS for Schizophrenia
Montages
- anode: left DLPFC
- cathode: temporoparietal junction, supraorbital area
- Brunelin et al (40) (N=30) conducted the first randomized controlled trial and observed that active tDCS reduced auditory hallucinations acutely (p,0.001) and over 3 months (p,0.001) and reduced negative symptoms (p=0.01).
- This was followed by a study by Smith et al. (45) (N=33) that found active stimulation improved cognition (p=0.008) but had no effect on positive or negative symptoms (all p.0.1),
- whereas Palm et al. (44) found that tDCS reduced negative symptoms (p=0.016) and Mondino et al. (43) found that tDCS reduced hallucinations (p,0.001).
- Several studies using tDCS (Fitzgerald et al. [41], N=24, and Frohlich et al. [42], N=26) and tVNS (Hasan et al. [46], (N=20) found no difference between active and sham stimulation.
- The currently available data do not support use of tCS for schizophrenia. The evidence base comprises a small number of randomized controlled trials with conflicting results.
- More work is clearly needed to develop tCS for treatment of patients with schizophrenia.
SECTION 3: POTENTIAL RISKS OF tCS
Device-Related Risks
Risk of Adverse Cognitive Effects
Risk of Interference With Psychiatric Treatment
SUMMARY: EFFICACY AND SAFETY OF tCS IN PSYCHIATRIC DISORDERS