Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS–EEG

Abstract

Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABA A receptor-mediated inhibition and glutamatergic excitatory transmission, respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from the dorsolateral prefrontal cortex (DLPFC) using combined TMS and electroencephalography (TMS-EEG). We first characterized the neural signature of SICI and ICF in M1 in terms of TMS-evoked potentials (TEPs) and spectral power modulation. Subsequently, these paradigms were applied in the DLPFC to determine whether similar neural signatures were evident. With TMS at M1, SICI and ICF led to bidirectional modulation (inhibition and facilitation, respectively) of P30 and P60 TEP amplitude, which correlated with MEP amplitude changes. With DLPFC stimulation, P60 was bidirectionally modulated by SICI and ICF in the same manner as for M1 stimulation, whereas P30 was absent. The sole modulation of early TEP components is in contradistinction to other measures such as long-interval intracortical inhibition and may reflect modulation of short latency excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Overall, the data suggest that SICI and ICF can be recorded using TMS-EEG in DLPFC providing noninvasive measures of glutamatergic and GABA A receptor-mediated neurotransmission. This may facilitate future research attempting to ascertain the role of these neurotransmitters in the pathophysiology and treatment of neurological and psychiatric disorders.

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS‐EEG and working memory performance

“…The present data did not show a significant increase in P60 amplitude following iTBS. Recent studies suggest that P60 provides a marker of neural excitability (Cash et al, ; Hill et al, ). It should be noted that the SNR for P60 is substantially lower than for N100, and the current protocol with ∼47 single TMS pulses may have been insufficient to capture significant changes.…”

Characterization of the influence of age on GABAA and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG

“…Further, it is thought that SICI consists of at least two phases of inhibition: the conditioning pulse elicits short-lasting inhibitory postsynaptic potentials in corticospinal neurons through activation of a low-threshold cortical inhibitory circuit mediated by the GABA A receptors, which inhibits action potential generation in these neurons by a suprathreshold second pulse [3, 9, 11-14]. In addition, SICI is maximal when the suprathreshold second TMS pulse is administered at the intensity to induce 1mV peak-to-peak MEP amplitudes [9, 10, 15, 16].…”

“…Further, based on our prior analytic method, we did not subtract the CS TEP from paired pulse TEP [11]. In the TEP analyses, we calculated the modulation of TEPs by the ratio of CS&TS / TS.…”

Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

“…Repetitive TMS (rTMS) provides another option to modulate brain regions that are critical for inhibition of motor responses. 43,45,46 Moreover, another potential future application is combining this protocol with simultaneous EEG to quantify TMS-evoked cortical potentials in non-M1 regions 47 to characterize cortical physiology associated with motor response inhibition.…”