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The search for biological targets in psychiatric disorders is essential to better understand illness mechanisms and also to monitor and predict response to currently available therapeutic interventions. To this end, the combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) has emerged as a powerful clinical research tool. TMS-EEG allows cortical properties, such as excitability, inhibition, oscillatory activity, and connectivity, to be directly probed within a specific region of the cortex. This review will summarize the state of the current literature on TMS-EEG and its potential to uncover biological targets in psychiatric illnesses, with a focus on major depressive disorder, bipolar disorder, and schizophrenia. Collectively, the reviewed studies suggest that alterations in gamma-aminobutyric acid-mediated inhibition and gamma oscillations in the dorsolateral prefrontal cortex and neighboring frontal regions are potential shared biomarkers in psychiatry, highlighting the potential of TMS-EEG to help identify translational biomarkers., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Several lines of evidence suggest that deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission are implicated in the pathophysiology of schizophrenia, bipolar disorder, major depressive disorder and obsessive-compulsive disorder. Cortical inhibition refers to a neurophysiological process, whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to measure cortical inhibition, excitability and plasticity in the cortex. These measures were traditionally specific to the motor cortex, which is an important limitation when nonmotor neurophysiological processes are of primary interest. Recently, TMS has been combined with electro encephalography (EEG) to derive such measurements directly from the cortex. This review focuses on neurophysiological studies related to inhibitory and excitatory TMS paradigms, linking dysfunctional GABAergic neurotransmission to disease states. We review evidence that suggests cortical inhibition deficits among psychiatric populations and demonstrate how each disorder has a specific neurophysiological response to treatment. We conclude by discussing the future directions of TMS combined with EEG, demonstrating the potential to identify biological markers of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Previous studies have shown that patients with schizophrenia and bipolar disorder have deficits in cortical inhibition. Through the combination of interleaved transcranial magnetic stimulation and electroencephalography, we have recently reported on methods in which cortical inhibition can be measured from the dorsolateral prefrontal cortex, a cortical region that is more closely associated with the pathophysiology of schizophrenia. Furthermore, it is possible to index cortical inhibition of specific oscillatory frequencies including the gamma band (30–50 Hz) whose modulation has been related to higher order cortical processing. In this study, we show that patients with schizophrenia have significant deficits of cortical inhibition of gamma oscillations in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder, while no deficits are demonstrated in the motor cortex. These results suggest that the lack of inhibition of gamma oscillations in the dorsolateral prefrontal cortex may represent an important frontal neurophysiological deficit, which may be responsible for the spectrum of deficits commonly found in schizophrenia. [ABSTRACT FROM PUBLISHER]