title: 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 glutamateN-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.
authors.affiliation: INSERM U1114, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Strasbourg F-67085, France. pinault@unistra.fr.|Unistra, Université de Strasbourg, Strasbourg F-67000, France. pinault@unistra.fr.|Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de Médecine, Strasbourg F-67085, France. pinault@unistra.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Pinault
keywords: ">d-aspartate; N-methyl-; animal model; gamma frequency oscillations; glutamate; ketamine; network synchrony; psychosis; sleep spindles; thalamic reticular nucleus; thalamus