A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway

Abstract

Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30–80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N-methyl-d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders.

Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies

“…However, the cell-to-network mechanisms underlying the immediate and downstream effects of regional tDCS remain to be elucidated. They may include immediate and in-cascade, short- and medium-term network, synaptic, cellular, and molecular processes, including multiple plasticity processes [ 30 , 48 , 55 , 56 , 57 ]. A computational study predicts that focal stimulation can trigger new functional large-scale neural connections [ 58 ].…”

MultimodalMRIassessment for first episode psychosis: A major change in the thalamus and an efficient stratification of a subgroup

“…In contrast to the widespread DTI features, within the functional modality we found more localized effects, and the thalamus was among the areas providing the greatest contribution to classification. The particular pattern of connectivity between the thalamus and the somato‐sensorial cortex we observed in S‐FEP aligns with observations in patients with psychotic disorders, individuals at high risk, and those in early and chronic stages of schizophrenia, as well as with reports by our group and others of structural and metabolic abnormalities centered in the thalamus (Agcaoglu et al, 2017; Altamura et al, 2017; Anticevic, 2017; Cho et al, 2016; Cho et al, 2019; Dandash, Pantelis, & Fornito, 2017; Dietsche, Kircher, & Falkenberg, 2017; Gheiratmand et al, 2017; Guo et al, 2015; Li et al, 2017; Merritt, Egerton, Kempton, Taylor, & McGuire, 2016; Murray & Anticevic, 2017; Pinault, 2017; Stephan, Friston, & Frith, 2009; Tu et al, 2019; van Erp et al, 2016; Wang et al, 2019; Woodward & Heckers, 2016; Woodward, Karbasforoushan, & Heckers, 2012; Yaesoubi et al, 2017). Note that thalamus was identified as an important structure for classification “cross‐modalities,” adding evidences to its core involvement in psychosis.…”

Reduced sleep spindle density in adolescent patients with early-onset schizophrenia compared to major depressive disorder and healthy controls

“…In schizophrenia structural alterations of the brain affect the thalamic reticular nucleus (Ferrarelli and Tononi, 2017;Pinault, 2011Pinault, , 2017Pratt and Morris, 2015) and the mediodorsal thalamus (Buchmann et al, 2014;Shimizu et al, 2008;Volk and Lewis, 2003) and functional alterations include GABA and glutamate signaling in neural circuitry relevant for spindle generation and maintenance (Catts et al, 2013;Pratt et al, 2017;Thankachan et al, 2019;Théberge et al, 2002).…”