Longitudinal changes in intracortical excitability during Ramadan diurnal intermittent fasting: A paired-pulse transcranial magnetic stimulation study.
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, occurring in the context of concurrent metabolic, sleep, and circadian alterations.
Key Findings
Results
Ramadan diurnal intermittent fasting was associated with a significant longitudinal modulation of intracortical excitability across pre-, mid-, and post-Ramadan timepoints.
Thirty fasting participants underwent paired-pulse transcranial magnetic stimulation (ppTMS) at three timepoints: pre-, mid-, and post-Ramadan.
A linear mixed-effects model revealed a significant main effect of Timepoint (p < 0.001).
MEP (motor-evoked potential) ratios increased at mid-Ramadan and showed partial persistence post-Ramadan.
The change was characterized as a global shift in excitability rather than selective modulation of specific circuits.
Results
The Timepoint × ISI interaction was not significant, indicating a generalized rather than circuit-specific shift in intracortical excitability.
Conditioned motor-evoked potentials were recorded at interstimulus intervals (ISIs) of 2–10 ms and normalized to unconditioned responses.
The Timepoint × ISI interaction was not significant (p = 0.566).
This non-significant interaction indicates no ISI-specific modulation, meaning neither short-interval intracortical inhibition nor intracortical facilitation circuits were selectively altered.
The ISI main effect confirmed the expected inhibition-facilitation gradient (p < 0.001), validating the measurement approach.
Results
Blood glucose levels decreased significantly at mid-Ramadan during fasting.
Blood glucose was measured as a secondary outcome across timepoints.
Blood glucose decreased significantly at mid-Ramadan.
This metabolic change occurred concurrently with the observed increases in intracortical excitability.
The authors noted that individual contributions of metabolic, sleep, and circadian factors to excitability changes could not be disentangled within the naturalistic observational design.
Results
Sleep duration decreased significantly at mid-Ramadan in fasting participants.
Sleep duration was a secondary outcome alongside blood glucose, cognitive performance, and reaction time.
Sleep duration decreased significantly at mid-Ramadan.
The authors identified sleep changes as one of several concurrent physiological alterations (alongside metabolic and circadian changes) that may collectively contribute to the observed excitability shifts.
The naturalistic observational design precluded isolation of sleep's individual contribution to intracortical excitability changes.
Results
Elevated intracortical excitability showed partial persistence beyond the Ramadan fasting period in the fasting group.
Post-Ramadan TMS assessments were conducted only in the fasting group (n = 30), not in the non-fasting control group (n = 11).
The non-fasting comparison group was assessed only at pre- and mid-Ramadan timepoints.
The authors stated that 'persistence of elevated intracortical excitability beyond Ramadan requires confirmation in adequately controlled longitudinal studies.'
The partial persistence post-Ramadan was identified as a limitation of the current design due to the absence of a post-Ramadan control comparison.
Methods
A non-fasting control group of 11 participants was included but was only assessed at pre- and mid-Ramadan timepoints, limiting post-Ramadan comparisons.
The study used a prospective observational cohort design with 30 fasting participants and 11 non-fasting controls.
The control group was not evaluated after Ramadan, precluding controlled assessment of post-Ramadan excitability persistence.
The authors identified this as a key limitation requiring confirmation in future adequately controlled longitudinal studies.
The naturalistic design also prevented disentangling individual contributions of metabolic, sleep, and circadian factors.
What This Means
This research suggests that observing Ramadan fasting — which involves abstaining from food and drink during daylight hours for approximately one month — leads to measurable changes in brain excitability. Using a technique called paired-pulse transcranial magnetic stimulation (TMS), which applies brief magnetic pulses to the scalp to measure how responsive the brain's motor cortex is, the researchers found that the brains of fasting adults became more excitable during the middle of Ramadan compared to before fasting began, and that this heightened excitability partially persisted even after Ramadan ended. Importantly, the change appeared to be a broad, generalized increase in brain excitability rather than a specific change in either the brain's inhibitory or facilitatory circuits.
The study also found that fasting participants experienced lower blood sugar levels and shorter sleep duration during mid-Ramadan, both of which coincided with the peak in brain excitability. Because all of these changes — metabolic shifts, sleep reduction, and alterations in daily rhythms — happened simultaneously during Ramadan, the researchers were unable to determine which factor (or combination of factors) was most responsible for the changes in brain excitability. The non-fasting control group of 11 people helped confirm that the context of Ramadan itself was relevant, but because the controls were not assessed after Ramadan ended, it remains unclear how much of the post-Ramadan brain excitability change was specifically due to the fasting.
This research matters because it provides one of the first longitudinal looks at how a naturalistic, culturally widespread form of intermittent fasting affects the brain's excitability over time. Understanding how fasting changes brain physiology could have implications for research on brain health, neurological conditions, and the effects of diet and lifestyle on neural function. However, because the study was purely observational and could not control for all the variables involved in Ramadan (including changed sleep schedules, dietary patterns, and social behaviors), future controlled studies would be needed to pinpoint which aspects of fasting drive these brain changes.
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Kim M, Mostafa I, Al-Sharman A, Saad N, Khalil H, Hadoush H. (2026). Longitudinal changes in intracortical excitability during Ramadan diurnal intermittent fasting: A paired-pulse transcranial magnetic stimulation study.. PloS one. https://doi.org/10.1371/journal.pone.0349740