Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults

Abstract

IntroductionExcitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex.MethodsNinety-seven healthy middle-aged adults (53 male) completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold (RMT) and Long-Interval Intracortical Inhibition (LICI) were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning.ResultsIn the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions.ConclusionGreater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association.

Deficient GABABergic and glutamatergic excitability in the motor cortex of patients with long-COVID and cognitive impairment

“…In fact, alterations of ppTMS parameters in neurodegenerative and psychiatric diseases reflect alterations of cognitive rather than motor functions (Benussi et al, 2020, 2018, 2017, 2016; Fatih et al, 2021 ). Given the correlation between LICI and executive functions ( Redondo-Camós et al, 2022 ), whose heavy reliance on frontal processing has been extensively demonstrated ( Peters, 2006 ; Sanger et al, 2001), one could suspect that the Long COVID dysexecutive deficits that have been reported in our sample of patients could be partially explained by pathogenetic processes involving the frontal areas of the brain. Unfortunately, to obtain a measurable TMS output from regions different than the motor cortex is technically demanding.…”

“…SICI is also reduced in central nervous system disorders inducing chronic fatigue ( Liepert et al, 2005 , McDonald et al, 2010 , Vucic et al, 2011 ). In particular, reductions in LICI have been described in patients affected by frontotemporal dementia (FTD, Benussi et al, 2020), and could be related to working memory in healthy middle-aged adults ( Redondo-Camós et al, 2022 ). In addition, a trend for decreased LICI, although not significant, has also been observed in Mild Cognitive Impairment (MCI) due to FTD ( Benussi et al, 2021 ) and in pre-symptomatic genetic FTD ( Benussi et al, 2016 ).…”

“…GABAa and GABAb receptor-mediated inhibition would have distinct roles in respectively balancing and terminating “Up” and “Down” states of activity ( Mann et al, 2009 ). Disruption of GABAb signaling in the prefrontal cortex has been linked to the impairment of many executive functions such as working memory ( Redondo-Camós et al, 2022 , Bañuelos et al, 2014 , Luo et al, 2016 , Major and Tank, 2004 , Mederos et al, 2021 ) and goal-directed behavior ( Mederos et al, 2021 ). In our study, the pp-TMS findings could highlight possible alterations of GABAb-mediated inhibition in Long COVID patients.…”