Reduced Prefrontal Short-Latency Afferent Inhibition in Older Adults and Its Relation to Executive Function: A TMS-EEG Study.

Yoshihiro Noda,Robin F. H. Cash,Tarek K. Rajji,Mera S. Barr,Daniel M. Blumberger,Reza Zomorrodi,Felicity Backhouse,Robert Chen,Zafiris J. Daskalakis

doi:10.3389/fnagi.2017.00119

Abstract

Combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for the assessment of various neurophysiological processes in the human cortex. One of these paradigms, short-latency afferent inhibition (SAI), is thought to be a sensitive measure of cholinergic activity. In a previous study, we demonstrated the temporal pattern of this paradigm from both the motor (M1) and dorsolateral prefrontal cortex (DLPFC) using simultaneous TMS–EEG recording. The SAI paradigm led to marked modulations at N100. In this study, we aimed to investigate the age-related effects on TMS-evoked potentials (TEPs) with the SAI from M1 and the DLPFC in younger (18–59 years old) and older (≥60 years old) participants. Older participants showed significantly lower N100 modulation in M1–SAI as well as DLPFC–SAI compared to the younger participants. Furthermore, the modulation of N100 by DLPFC–SAI in the older participants correlated with executive function as measured with the Trail making test. This paradigm has the potential to non-invasively identify cholinergic changes in cortical regions related to cognition in older participants.

Highlights

Transcranial magnetic stimulation (TMS) allows for the non-invasive measurement of various inhibitory and excitatory processes in the human brain (Hallett, 2011)
Cross-sectional comparisons between young and older participants in the M1–short-latency afferent inhibition” (SAI) paradigm revealed that N45 and N100 TMS-evoked potentials (TEPs) were significantly less modulated in older participants compared with younger participants
The findings of M1–SAI showing lower modulations of N45 and N100 in older participants may demonstrate an agemediated decline of modulation in both early and late phase of TEPs at M1 it is possible that GABAA receptormediated inhibition of N45 (Ferreri et al, 2011; Premoli et al, 2014) and cholinergic mediated modulation of N100 (Ferreri et al, 2012; Noda et al, 2016) may be declined in an age-dependent manner

Summary

Introduction

Transcranial magnetic stimulation (TMS) allows for the non-invasive measurement of various inhibitory and excitatory processes in the human brain (Hallett, 2011). Different TMS paradigms produce distinct inhibitory responses in cortical activity, and TMS paradigms administered sequentially produce unique neurophysiological interactions (Chen, 2004; Ni et al, 2011). One such paradigm involves median nerve stimulation (MNS) followed by a single TMS pulse to the motor cortex (M1) approximately 20 ms later. The MNS followed by the inter-stimulus interval (ISI) of 20 ms produces a marked reduction of motor-evoked potentials (MEP) from a single TMS pulse (Classen et al, 2000; Tokimura et al, 2000), and has been termed “short-latency afferent inhibition” (SAI) (Sailer et al, 2003). Lorazepam reduces (Di Lazzaro et al, 2005a) and diazepam slightly increases (Di Lazzaro et al, 2005b) SAI, suggesting that gamma-aminobutyric acid (GABA)A receptor-mediated inhibitory circuits are involved in this neurophysiological response

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