Dysbalance of cortical inhibition and excitation in abstinent cocaine-dependent patients

The effects of chronic cocaine dependence on cortical inhibitory/excitatory processes are not well characterized. Employing transcranial magnetic stimulation measures of motor cortical excitability, we have previously reported an elevation of motor threshold (MT) suggesting reduced excitability and an increased long-interval intracortical facilitation (LICF) suggesting increased excitability. In the current study, we used an expanded battery of TMS cortical excitability measures to further examine motor cortex excitability in a larger sample of well-characterized and closely monitored for drug use, abstinent cocaine-dependent subjects (N = 52) and healthy controls (N = 42). Furthermore, coil-to-cortex distance was assessed in a subsample of both groups. We verified that long-interval intracortical facilitation (LICF), possibly representing glutamatergic cortical neurotransmission, was significantly increased in cocaine-dependent patients. Significantly longer cortical silent periods (CSP) and elevated MT were also observed while there was no significant abnormality in long-interval intracortical inhibition (LICI). Increased LICF and CSP duration suggest increased cortical excitability and increased inhibition, respectively, of different neurotransmitter systems in cocaine-dependent patients. Increased MT might reflect an adaptation to those effects of cocaine abuse that enhance cortical excitability. Overall, the data point to the complex nature of chronic cocaine dependence on the balance of cortical inhibitory/excitatory mechanisms.