Abstract
Transcranial direct current stimulation (tDCS) is a non-invasive stimulation technique that can be applied to modulate cortical activity through induction of cortical plasticity. Since various neuropsychiatric disorders are characterized by fluctuations in cortical activity levels (e.g., schizophrenia), tDCS is increasingly investigated as a treatment tool. Several studies have shown that the induction of cortical plasticity following classical, unilateral tDCS is reduced or impaired in the stimulated and non-stimulated primary motor cortices (M1) of patients with schizophrenia. Moreover, an alternative, bilateral tDCS setup has recently been shown to modulate cortical plasticity in both hemispheres in healthy subjects, highlighting another potential treatment approach. Here we present the first study comparing the efficacy of unilateral tDCS (cathode left M1, anode right supraorbital) with simultaneous bilateral tDCS (cathode left M1, anode right M1) in patients with schizophrenia. tDCS-induced cortical plasticity was monitored by investigating motor-evoked potentials induced by single-pulse transcranial magnetic stimulation applied to both hemispheres. Healthy subjects showed a reduction of left M1 excitability following unilateral tDCS on the stimulated left hemisphere and an increase in right M1 excitability following bilateral tDCS. In schizophrenia, no plasticity was induced following both stimulation paradigms. The pattern of these results indicates a complex interplay between plasticity and connectivity that is impaired in patients with schizophrenia. Further studies are needed to clarify the biological underpinnings and clinical impact of these findings.
Highlights
Despite more than 50 years of research, the availability of a diverse range of antipsychotics from different chemical classes, and the development of evidence-based treatment guidelines, a significant proportion of patients with schizophrenia suffer from treatment resistance [1]
BASELINE EXCITABILITY FOR BOTH HEMISPHERES Independent t -tests between both groups comparing the left and right hemispheres revealed no significant differences for S1 mV, RMT, motor-evoked potential (MEP) amplitudes, short-latency intracortical inhibition (SICI), or CSP
Our findings offer a new view on N -methyl-daspartate-receptors (NMDAR)-dependent cortical plasticity and highlight the difficulty associated with inducing plasticity in the schizophrenic brain with a single session of non-invasive brain stimulation
Summary
Despite more than 50 years of research, the availability of a diverse range of antipsychotics from different chemical classes, and the development of evidence-based treatment guidelines, a significant proportion of patients with schizophrenia suffer from treatment resistance [1]. Transcranial direct current stimulation (tDCS) has been introduced to treatment studies in patients with schizophrenia [4,5,6,7,8,9,10]. TDCS modulates spontaneous neuronal activity via a subthreshold tonic depolarization (anodal tDCS) or hyperpolarization (cathodal tDCS) of neuronal membranes [11,12,13,14] Both animal and human studies have indicated that these polarity changes are related to the molecular processes underlying longterm potentiation (LTP) and long-term depression (LTD) [15,16,17,18,19,20]. Recent publications have shown that bilateral application of tDCS on the primary motor cortices can be effective in modulating cortical excitability on both hemispheres in healthy humans [21]. As with other transcranial brain stimulation techniques, tDCS only modulates cortical excitability at the stimulated site, and impacts www.frontiersin.org
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