Long-Interval Cortical Inhibition from the Dorsolateral Prefrontal Cortex: a TMS–EEG Study

Abstract

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.

Investigating TMS–EEG Indices of Long-Interval Intracortical Inhibition at Different Interstimulus Intervals

“…Using TMS-EEG, several studies have shown that LICI is associated with reduced excitability in both motor and nonmotor areas of cortex [23,[39][40][41]. For the primary motor cortex, the magnitude of this inhibition correlates with inhibition of the MEP, demonstrating the involvement of mechanisms comparable to those reflected by conventional LICI measurements.…”

“…For all analyses, the TEP generated by test alone stimulation was compared to that generated following LICI 100 and LICI 150 . However, prior to quantification of paired-pulse TEPs, a correction procedure was carried out to remove the TEP generated by the conditioning stimulus from the TEP generated by the test stimulus [23,25,31]. This was achieved by time-shifting the TEP generated by test alone stimulation to coincide with the application of each conditioning stimulus, and subtracting it from the paired-pulse data (Fig 1; this was performed separately for LICI 100 and LICI 150 data).…”

“…In addition, combining these two methods provides significantly more information about the local and global response to ppTMS than can be derived from the MEP [21,22]. For LICI, previous studies utilising TMS-EEG in M1 have identified cortical indices of inhibition within TMS-evoked EEG potentials (TEPs), with specific TEP peaks produced by the test stimulus being reduced in amplitude when a conditioning stimulus is applied 100 ms earlier [23]. Furthermore, by varying stimulus intensities [24] and applying pharmacological interventions [25], recent studies have also found that the modulation of individual TEP peaks following LICI applied with a 100 ms ISI likely reflects the inhibition of more than one mechanism.…”

Potentiation of Gamma Oscillatory Activity through Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex

“…Taken together with the finding that 20 Hz rTMS potentiates GABAergic inhibitory neurotransmission indexed through CSP (Daskalakis et al, 2006), we contend that high-frequency rTMS exerts its effects on g-oscillatory activity through GABA receptor-mediated inhibitory neurotransmission to ultimately affect WM performance. Future studies combining paired-pulse TMS with EEG recording to index GABA receptor-mediated neurotransmission in the DLPFC (Daskalakis et al, 2008) will be needed, however, to determine whether g-oscillatory activity is indeed potentiated directly through enhanced GABA.…”

Neurobiology of Comorbid Substance Use Disorders in Mental Illness: A Closer Look at the Underlying Commonalities between Cannabis and Schizophrenia

“…Among patients with schizophrenia, several studies have demonstrated pervasive cortical inhibition deficits. For example, Daskalakis et al [41] reported pervasive GABA B deficits in the motor and DLPFC using TMS-EEG. In healthy cannabis users, Fitzgerald et al examined light versus heavy cannabis use in healthy controls, and reported reduced cortical inhibition regardless of cannabis use status [42].…”