SA78. Cholinergic Activity as Measured by Short-Latency Afferent Inhibition From the Dorsolateral Prefrontal Cortex in Nonsmokers With Schizophrenia: A Combined TMS–EEG Technique

Abstract

Background: Short-latency afferent inhibition (SAI) is the neurophysiologi-cal transcranial magnetic stimulation (TMS) paradigm that indexes central cholinergic activity from the motor cortex (M1). Recently, we established a method to index SAI from the dorsolateral prefrontal cortex (DLPFC), an area implicated in the pathophysiology of schizophrenia (SCZ). Here, we investigated SAI in both M1 and the DLPFC in SCZ patients compared to healthy controls (HC). We hypothesized that modulation of N100 on TMS-evoked potential (TEP) by SAI paradigm from the DLPFC would be attenuated in SCZ compared to HC. Further, the modulation of N100 would be correlated with cognitive performance. Methods: Age-matched 12 SCZ and 12 HC were examined with a combined TMS-electroencephalography (EEG). SAI from the left M1 (M1-SAI) and DLPFC (DLPFC-SAI) were indexed by conditioning a single suprathresh-old TMS with right median nerve stimulation at interstimulus intervals of N20+2ms (M1-SAI) and N20+4ms (DLPFC-SAI), respectively. TEPs by M1-and DLPFC-SAI were analyzed using independent component analysis individually. Results: With M1-SAI paradigm, there was no signifcant change in TEP N100 (t11 =-2.30, P =.822) in the SCZ group or no signifcant difference in N100 modulation between the HC and SCZ groups (t22 = 1.917, P = 0.068). However, with DLPFC-SAI paradigm, we observed a signif-cant N100 attenuation at the DLPFC (t11 =-4.926, P < HC). Furthermore, the N100 modulation by DLPFC-SAI was signifcantly correlated with executive function as measured with the Trail Making Test (r =-0.740, P =.006, N = 12). Conclusion: The modulation of N100 by the DLPFC-SAI may refect the prefrontal pathophysiology of SCZ and thus could be a potential bio-marker for cholinergic and executive dysfunction in SCZ. Funding: This research was supported by the Temerty Centre for Therapeutic Brain Intervention through the CAMH Foundation, and Canada Foundation for Innovation.