Abstract
Background Preclinical studies suggest that alterations within the frontal cortex play a critical role in the neurophysiology of alcohol dependence. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) allows a direct assessment of cortical excitability and inhibition within the frontal cortex in human subjects. We report the first application of TMS-EEG to measure these indices within the frontal cortices of patients with alcohol dependence. Methods Cortical inhibition was assessed in 12 patients with alcohol dependence and 14 healthy controls through single and paired-pulse transcranial magnetic stimulations (TMS) paradigms delivered to both the frontal and motor cortices. Long interval cortical inhibition (LICI) was used to index inhibition in the frontal cortex. Short intracortical inhibition (SICI) and cortical silent period (CSP) was used to index inhibition, while intracortical facilitation (ICF) measured facilitation, in the motor cortex. Cortical excitability was indexed by the resting motor threshold (RMT) and active motor threshold (AMT). Results The alcohol dependent group demonstrated deficits in LICI across both the left and right dorsolateral prefrontal cortex relative to healthy controls. The alcohol dependent group also exhibited reduced RMT and AMT. In terms of motor cortex inhibition, there were no significant differences in SICI, ICF or CSP, although increased intra-trial-variability in SICI was observed in the alcohol dependent group. Conclusions The current study provides the first direct evidence of reduced cortical inhibition that is specific to the frontal cortex of patients with alcohol dependence. Our study also revealed evidence of altered cortical excitability in the motor cortex of patients with alcohol dependence; however, the utility of using the motor cortex to index cortical alterations related to alcohol dependence remains unclear. Although these findings are preliminary, they provide critical neurophysiological evidence of disrupted cortical excitability within the frontal cortex of alcohol dependent patients.
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