Transcranial Bipolar Direct Current Stimulation of the Frontoparietal Cortex Reduces Ketamine-Induced Oscillopathies: A Pilot Study in the Sedated Rat

Abstract

During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies). Neural oscillations are electro-biomarkers of the connectivity state within systems. A single systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological model may help the research and development of innovative treatments against the psychotic transition. Transcranial electrical stimulation is recognized as an appropriate non-invasive therapeutic modality since it can increase cognitive performance and modulate neural oscillations with little or no side effects. Therefore, our objective was to set up, in the sedated adult rat, a stimulation method able to normalize the ketamine-induced oscillopathies. Unilateral transcranial frontoparietal anodal stimulation by direct current (<+1 mA) was applied in ketamine-treated rats. A concomitant electroencephalographic recording of the parietal cortex measured the stimulation effects on its spontaneously-occurring oscillations. A 5-min bipolar anodal tDCS immediately and quickly reduced, significantly with an intensity-effect relationship, the ketamine-induced oscillopathies at least in the bilateral parietal cortex. A duration effect was also recorded. These preliminary neurophysiological findings are promising for developing a therapeutic proof-of-concept against neuropsychiatric disorders.