Investigation of the relationship between sex, stress, and internalizing symptoms with resting motor threshold assessed via transcranial magnetic stimulation (TMS)

Background

Cortical excitability, commonly assessed by resting motor threshold (RMT) in transcranial magnetic stimulation studies, has been increasingly linked to psychiatric symptom dimensions such as depression, anxiety, and stress-related constructs. However, the relationship between RMT and clinical symptom severity remains unclear, particularly in small exploratory samples.

Objectives

This preliminary study aimed to investigate the associations between RMT and psychiatric symptom measures, including depression (PHQ-9), anxiety (GAD-7), and perceived stress (PSS), as well as demographic variables such as age and sex.

Methods

A total of 32 participants were included in the study, comprising 16 females and 16 males. Participants were selected from individuals with no current psychiatric diagnosis and no current use of psychiatric medication. Participants completed self-administered questionnaires related with psychiatric symptom measures including PHQ-9, GAD-7 and PSS one day prior to TMS application. Transcranial magnetic stimulation (TMS) was applied, and motor evoked potentials (MEPs) were recorded using electromyography (EMG). EMG recordings were obtained from the first dorsal interosseous muscle, and TMS was applied over the corresponding region of the primary motor cortex. Resting motor threshold (RMT) was defined as the minimum stimulation intensity required to elicit at least 5 MEPs with amplitudes ≥ 50 µV out of 10 consecutive stimuli. Descriptive statistics were calculated for age, RMT, and psychometric measures. Due to non-normal distribution of several variables (as indicated by Shapiro–Wilk tests), group differences were examined by Mann–Whitney U tests. Spearman’s rank correlation coefficients were computed to assess relationships in RMT and clinical variables.

Results

The sample had a mean age of 22.9 years (SD = 5.02). Mean RMT was 48.37 (SD = 9.60). Average scores for PHQ-9, GAD-7, and PSS were 9.03 (SD = 5.93), 7.22 (SD = 5.36), and 25.31 (SD = 8.42), respectively. No significant sex differences were observed for RMT or any clinical variables (all p > .05). No significant differences were observed for RMT also when participants were categorized as depressive (n=13) and non-depressive (n=19) based on PHQ-9 cutoff of 10 and over (p = 0.495). Correlation analyses revealed no significant associations between RMT and age, depression, anxiety, or stress scores. In contrast, strong positive correlations were found in symptom measures themselves, such that PHQ-9 with GAD-7 (r = 0.858, p < .001) and PSS (r = 0.838, p < .001), and GAD-7 with PSS (r=0.791, p<0.01).

Conclusions

In this preliminary sample, RMT was not associated with psychiatric symptom severity or demographic variables. However, strong intercorrelations among depression, anxiety, and stress measures were observed. These findings suggest that while symptom domains cluster together, their relationship with cortical excitability may be more complex and requires investigation in larger, well-powered samples. Future studies with larger and more diverse samples, including clinical populations, should also incorporate paired-pulse TMS measures such as short-interval cortical inhibition (SICI) and long-interval cortical inhibition (LICI), as well as the cortical silent period (CSP), to more comprehensively characterize cortical excitability and inhibitory mechanisms and their potential links to psychiatric symptom dimensions.

References

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