Cortical Inhibition, Excitation, and Connectivity in Schizophrenia: A Review of Insights From Transcranial Magnetic Stimulation

Abstract

Schizophrenia (SCZ) is a debilitating mental illness with an elusive pathophysiology. Over the last decade, theories emphasizing cortical dysfunction have received increasing attention to explain the heterogeneous symptoms experienced in SCZ. Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation that is particularly suited to probing the fidelity of specific excitatory and inhibitory neuronal populations in conscious humans. In this study, we review the contribution of TMS in assessing inhibitory and excitatory neuronal populations and their long-range connections in SCZ. In addition, we discuss insights from combined TMS and electroencephalography into the functional consequences of impaired excitation/ inhibition on cortical oscillations in SCZ.

RETRACTED: Identification of gene ontologies linked to prefrontal–hippocampal functional coupling in the human brain

“…A study of cortical thickness in patients with schizophrenia found decreases in the structural connectivity of the left and right DLPFC to be correlated with poor WM performance (36). Additionally, real-time transcranial magnetic stimulation techniques, which allow researchers to indirectly study synaptic plasticity in vivo (37,38), have shown that inducing synaptic plasticity in the right DLPFC leads to altered prefrontal-hippocampal functional interactions during WM (3). These findings are in keeping with the "two hit" hypothesis of schizophrenia, whereby early environmental and genetic factors confer vulnerability of neural circuitry to adverse events during adolescence, such as excessive synaptic pruning or impaired plasticity (14,39).…”

A Neural “Tuning Curve” for Multisensory Experience and Cognitive-Perceptual Schizotypy

“…[34][35][36] This variability is even greater along the whole spectrum from healthy to clinical conditions, such as schizophrenia and autism, 37,38 which are associated with abnormally increased E/I ratio. [39][40][41] Importantly, genetic association studies of schizophrenia and autism 42,43 suggest that some of the variability in the E/I balance may be genetically driven. Specifically, both early candidate gene studies [44][45][46][47] and the most recent genome-wide associated study (GWAS) of schizophrenia 48 have associated the disorder with single nucleotide polymorphisms (SNPs) within or near genes known to regulate GABA or glutamatergic signaling.…”

Use of Repetitive Transcranial Magnetic Stimulation in Treatment of Negative Symptoms of Schizophrenia

“…Study results suggest that schizophrenia is associated with reduced cortical inhibition that is reversed in part by antipsychotic drugs [8]. Abnormally short-interval intracortical inhibition has also been reported in patients with schizophrenia [9]. Short-interval intracortical inhibition abnormalities may link to core symptoms of schizophrenia with several studies reporting correlations between positive symptoms and short-interval intracortical inhibition strength.…”