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Abstract
Objectives. Preclinical studies suggest that cortical alterations within the prefrontal cortex (PFC) are critical to the pathophysiology of alcohol dependence. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows direct assessment of cortical excitability and inhibition within the PFC of human subjects. We report the first application of TMS-EEG to measure these indices within the PFC of alcohol-dependent (ALD) patients post-detoxification. Methods. Cortical inhibition was assessed in 12 ALD patients and 14 healthy controls through single and paired-pulse TMS paradigms. Long-interval cortical inhibition indexed cortical inhibition in the PFC. In the motor cortex (MC), short- interval intracortical inhibition and cortical silent period determined inhibition, while intracortical facilitation measured facilitation, resting and active motor threshold indexed cortical excitability. Results. ALD patients demonstrated altered cortical inhibition across the bilateral frontal cortices relative to controls. There was evidence of altered cortical excitability in ALD patients; however, no significant differences in MC inhibition. Conclusions. Our study provides first direct evidence of reduced cortical inhibition in the PFC of ALD patients post-detoxification. Altered cortical excitability in the MC may reflect hyper-excitability within the cortex associated with chronic alcohol consumption. These findings provide initial neurophysiological evidence of disrupted cortical excitability within the PFC of ALD patients.
Acknowledgements
Sincere appreciation is also expressed to Jerome Maller, Neil Bailey and Karyn Richardson for their support and contribution throughout the study.
Statement of Interest
Dr. Jodie Naim-Feil is a recipient of both the Graduate Women Victoria scholarship and the Australian Post–Graduate Award from Monash University which supported the development of this study. Prof. Paul B. Fitzgerald has received equipment for research from Medtronic Ltd, MagVenture A/S and Brainsway Ltd. He has undertaken research with funding and equipment from Cervel Neurotech. He is supported by a NHMRC Practitioner Fellowship. In the last 3 years, Prof. Zafiris J. Daskalakis received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. Prof. Zafiris J. Daskalakis has also served on the advisory board for Hoffmann-La Roche Limited and Merck and received speaker support from Eli Lilly. This work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the Brain and Behaviour Research Foundation and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. No conflict of interest to declare. All of the sponsors who donated generously to the authors involved in the study had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.