Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8 ± 30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1±26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.

The dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of several psychiatric illnesses including major depressive disorder and schizophrenia. In this regard, the DLPFC has been targeted in repetitive transcranial magnetic stimulation (rTMS) studies as a form of treatment to those patients who are resistant to medications. The '5-cm method' and the '10-20 method' for positioning the transcranial magnetic stimulation (TMS) coil over DLPFC have been scrutinised due to poor targeting accuracies attributed to inter-subject variability. We evaluated the accuracy of such methods to localise the DLPFC on the scalp in 15 healthy subjects and compared them with our novel neuronavigational method, which first estimates the DLPFC position in the cortex based on a standard template and then determines the most appropriate position on the scalp in which to place the TMS coil. Our neuronavigational method yielded a scalp position for the left DLPFC between electrodes F3 and F5 in standard space and was closest to electrode F5 in individual space. Further, we found that there was significantly less inter-subject variability using our neuronavigational method for localising the DLPFC on the scalp compared with the '5-cm method' and the '10-20 method'. Our findings also suggest that the '10-20 method' is superior to the '5-cm method' in reducing inter-subject variability and that electrode F5 should be the stimulation location of choice when MRI co-registration is not available.

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.