Longitudinal changes in intracortical excitability during Ramadan diurnal intermittent fasting: A paired-pulse...

Ramadan diurnal intermittent fasting (RDIF) represents a natural model of prolonged daily intermittent fasting associated with metabolic and circadian alterations. This study investigated longitudinal changes in intracortical excitability across pre-, mid-, and post-Ramadan timepoints in healthy adults observing RDIF. Thirty fasting participants in this prospective observational cohort study underwent paired-pulse transcranial magnetic stimulation at three timepoints (pre-, mid-, and post-Ramadan). A non-fasting control group (n = 11) was assessed at pre- and mid-Ramadan. Conditioned motor-evoked potentials were recorded at interstimulus intervals of 2-10 ms and normalized to unconditioned responses. A linear mixed-effects model assessed effects of Timepoint and interstimulus interval (ISI). Secondary outcomes included blood glucose, cognitive performance, sleep duration, and reaction time. A significant main effect of Timepoint (p < 0.001) indicated longitudinal modulation of intracortical excitability, with increased MEP ratios at mid-Ramadan and partial persistence post-Ramadan. The ISI effect confirmed the inhibition-facilitation gradient (p < 0.001). The Timepoint × ISI interaction was not significant (p = 0.566), indicating a global shift in excitability without ISI-specific modulation. Blood glucose and sleep duration decreased significantly at mid-Ramadan. RDIF is associated with a time-dependent increase in intracortical excitability, most appropriately interpreted as a generalized shift rather than selective modulation of inhibitory or facilitatory circuits. These changes occur in the context of concurrent metabolic, sleep, and circadian alterations and may reflect combined physiological influences of these factors; however, their individual contributions cannot be disentangled within the present naturalistic observational design. Because the non-fasting comparison group was not evaluated after Ramadan, the persistence of elevated intracortical excitability beyond Ramadan requires confirmation in adequately controlled longitudinal studies.