Gender impact on transcranial magnetic stimulation-based cortical excitability and cognition relationship in healthy individuals

Abstract

Objective We sought to determine whether cortical excitability, measured via transcranial magnetic stimulation (TMS), is associated with cognition in healthy individuals and whether gender and education have an impact on this relationship. Methods Fifty-four healthy individuals (31 males, mean age = 41.94, SD = 21.98; 23 females, mean age 48.57; SD = 22.84) underwent TMS to assess their resting motor threshold (RMT) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognition. Multiple regression analyses were conducted to assess the association between RMT, education, gender and cognition. Results The multiple regression model revealed a significant association between RBANS Total Index Score and RMT in the female group (B = 0.624, β = 0.602, P = 0.001) and not the male group (B = 0.048, β = 0.034, P = 0.858). Conclusion This study demonstrated that lower cortical excitability is associated with better global cognition in healthy female and not male individuals. RMT could be further studied as a tool to better personalize brain stimulation protocols that aim at enhancing cognition.

Normal parameters for diagnostic transcranial magnetic stimulation using a parabolic coil with biphasic pulse stimulation

“…The reason for such a difference remains unclear and may be explained by the different methods used between the studies. Also, Akilan [ 43 ] attempted to explain the disparity between the RMT as measured by TMS and cognitive function, i.e., MMSE and RBANS scores. However, we found no difference in the mean RMT as 46.06 ± 7.81 in males and 49.96 ± 11.16 SD in females, which are in the normal range as mentioned in our study, 44.31 ± 8.06.…”

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

“…Our results are in line with previous research investigating physiological mechanisms of neurological disorders, showing that motor hyperexcitability is related to global cognitive dysfunction ( Takahashi et al, 2013 ; Higashihara et al, 2021 ; Zadey et al, 2021 ) due to increased excitatory activity or/and an inhibitory deficit ( Joseph et al, 2021 ; Meder et al, 2021 ; Mimura et al, 2021 ). Similarly, in healthy subjects, it has been found that hyperexcitability of the motor cortex is associated with impaired attention ( Bolden et al, 2017 ; Akilan et al, 2020 ), suggesting that cortical excitatory and inhibitory balance is necessary for optimal brain and cognitive functioning ( Páscoa dos Santos and Verschure, 2022 ).…”

“…Very little is present in the literature on this issue, and the few existing pieces of evidence appear somehow contradictory. Schicktanz et al (2014) observed that lower motor cortical excitability was related to better working memory in men ( Schicktanz et al, 2014 ), while Akilan et al (2020) observed that an increase in cortical excitability was related to global cognition in women ( Akilan et al, 2020 ). However, beyond these inconsistencies, which need and deserve deeper study, previous and our results confirm the existence of biological sex differences ( Schicktanz et al, 2014 ; Akilan et al, 2020 ) in the relation between cortical excitability/inhibition and cognition.…”

“…This variability may be due to differences depending on the cortical area or specific cognitive functions assessed. For example, while higher excitability after stimulation of the left prefrontal cortex has been related to better executive functions and working memory ( Redondo-Camós et al, 2022 ), other studies have observed that excessive excitability of the primary motor cortex was associated with impaired attention and global cognition ( Bolden et al, 2017 ; Akilan et al, 2020 ). Other aspects that may modulate the association between cortical E/I balance and cognitive functioning may relate to age, given the different degrees of preservation of gamma-aminobutyric acid (GABA) circuits linked to physiological aging ( McGinley et al, 2010 ; Opie and Semmler, 2014 ; Hermans et al, 2018 ).…”

“…Long-Interval Intracortical Inhibition (LICI), where two suprathreshold stimuli separated by an interstimulus interval (ISI) between 50 and 200 ms are applied, has been used to study cortical inhibition ( Valls-Solé et al, 1992 ; Nakamura et al, 1997 ) and reflects the activity of GABA-B receptors ( McDonnell et al, 2006 ; Opie et al, 2017 ). While many studies have shown that RMT and LICI offer valuable biological markers in different neurological disorders ( Fatih et al, 2021 ; Guerra et al, 2021 ; Mimura et al, 2021 ; Versace et al, 2021 ), only a few have explored their association with brain health and cognitive performance in healthy, cognitive-unimpaired, middle-aged adults, and how biological sex affects the results ( Schicktanz et al, 2014 ; Akilan et al, 2020 ).…”