Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) enables non-invasive neurophysiological investigation of the human cortex. A TMS paradigm of short-latency afferent inhibition (SAI) is characterised by attenuation of the motor evoked potential (MEP) and modulation of N100 of the TMS-evoked potential (TEP) when TMS is delivered to motor cortex (M1) following median nerve stimulation. SAI is a marker of cholinergic activity in the motor cortex, however, the SAI has not been tested from the prefrontal cortex. We aimed to explore the effect of SAI in dorsolateral prefrontal cortex (DLPFC). SAI was examined in 12 healthy subjects with median nerve stimulation and TMS delivered to M1 and DLPFC at inter-stimulus intervals (ISI) relative to the individual N20 latency. SAI in M1 was tested at the optimal ISI of N20+2ms. SAI in DLPFC was investigated at a range of ISI from N20+2 to N20+20ms to explore its temporal profile. For SAI in M1, the attenuation of MEP amplitude was correlated with increase of TEP N100 from the left central area. A similar spatiotemporal neural signature of SAI in DLPFC was observed with marked increase of N100 amplitude. SAI in DLPFC was maximal at ISI N20+4ms at the left frontal area. These findings establish the neural signature of SAI in DLPFC. Future studies could explore whether DLPFC-SAI is neurophysiological marker of cholinergic dysfunction in cognitive disorders.
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