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Circadian characterization of motor cortical excitability in humans

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Author(s):
Pedro Sudbrack Oliveira
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Andre Russowsky Brunoni; Ary Gadelha de Alencar Araripe Neto; Elizabeth Shephard; Marcel Simis
Advisor: Andre Russowsky Brunoni
Abstract

INTRODUCTION: In humans, differences in motor cortex excitability levels related to time of day have already been described. This phenomenon is potentially mediated by the interaction between the circadian timing system and inhibitory cortical circuits. However, evidence in this regard is still scarce and the possibility of influence of the homeostatic component of sleep pressure has been little explored. Behavioral circadian preference (chronotype) is another factor that can influence excitability measurements. OBJECTIVE: To characterize the circadian profile of cortical excitability in healthy individuals from serial measurements with the technique of transcranial magnetic stimulation of the motor cortex coupled with electromyography (TMS-EMG), taking into account the participants\' chronotype and sleep pressure. METHODS: Twenty healthy individuals had their chronotype assessed using the Morningness-Evenings Questionnaire. Additionally, the amplitudes of motor evoked potentials triggered by single and paired pulses, in addition to the cortical silent period, were measured in serial assessments over a 24-hour period. In order to ensure the presence of an adequate period of sleep and promote the participants\' habituation to external conditions, the study began after a night\'s sleep in a laboratory/hospital environment. Throughout the TMS-EMG evaluations, the acute levels of subjective sleepiness were assessed. The association between predictor and response variables was verified using linear mixed effects models. RESULTS: Individuals with morning chronotype showed lower cortical inhibition in the morning in evaluation by short-interval paired pulses (2 and 5 ms), with a progressive increase over time and same-day peak inhibition in the afternoon period (ratio 5pm/9am: 1.54 ; 95% CI: 1.06 - 2.22; p = 0.02). No significant associations were observed between the other excitability measures in relation to the time of day for this chronotype, nor significant changes in any of the measures related to evening or intermediary chronotypes and in the entire sample over time. Additionally, the morning and evening subgroups showed distinct profiles of inhibition at long intervals, dependent on the employed interval and independent of the time of day. CONCLUSIONS: Measures of cortical inhibition show distinct profiles and trajectories over time, depending on the chronotype. The findings of this work expand the understanding of the physiology of the primary motor cortex, with implications for the implementation of excitability-based biomarkers of neuropsychiatric diseases, as well as the development of non-invasive neuromodulation protocols that target this region, either in basic research or in future clinical trials (AU)

FAPESP's process: 19/10760-9 - Circadian variability of motor cortex excitability in patients with Mesial Temporal Lobe Epilepsy: a Transcranial Magnetic Stimulation (TMS) study
Grantee:Pedro Sudbrack Oliveira
Support Opportunities: Scholarships in Brazil - Doctorate