Natasha Radhu, BSc, MSc; Lakshmi N. Ravindran, MD; Andrea J. Levinson, MD, MSc; Zafiris J. Daskalakis, MD, PhD
From the Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont.
Several lines of evidence suggest that deficits in Î³-aminobutyric acid (GABA) inhibitory neurotransmission are implicated in the pathophysiology of schizophrenia, bipolar disorder, major depressive disorder and obsessiveâ€“compulsive disorder. Cortical inhibition refers to a neurophysiological process, whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons. Transcranial magnetic stimu lation (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.
Submitted Jan. 2, 2012; Revised Mar. 20, 25, 2012; Accepted Mar. 28, 2012.
Acknowledgements: This work was supported, in part, by the Canadian Institutes of Health Research Clinician Scientist Award (Z.J. Daskalakis), by an operating award from the Ontario Mental Health Foundation (Z.J. Daskalakis), by Constance and Stephen Lieber through a National Alliance for Research on Schizophrenia and Depression Lieber Young Investigator award (A.J. Levinson, Z.J. Daskalakis) and Independent Investigator Award (Z.J. Daskalakis). We thank Anosha Zanjani for creating figures S2 and S3 for Appendix 1 of this review article.
Competing interests: Z.J. Daskalakis declares external funding through Neuronetics and Brainsway Inc., Aspect Medical and a travel allowance through Pfizer and Merck; speaker funding through Sepracor Inc.; and advisory board membership with Hoffmann- La Roche Limited. This work was supported by the Ontario Mental Health Foundation, the Canadian Institutes of Health Research, the Brain and Behaviour Research Foundation and the Grant Family through the Centre for Addiction and Mental Health Foundation.
Contributors: All authors designed the study, analyzed the data and wrote the article. N. Radhu and L Ravindran acquired the data. All authors reviewed the article and approved the final version for publication.
Correspondence to: Z.J. Daskalakis, Schizophrenia Program, Centre for Addiction and Mental Health, 7th Floor â€” Clarke Division,
250 College St., Toronto ON M5T 1R8; Jeff_Daskalakis@camh.net