Menstrual cycle phase alters corticospinal excitability and spike-timing-dependent plasticity in healthy females

The known fluctuations in ovarian hormone concentrations across the eumenorrheic menstrual cycle contribute to modulations in cortical excitability and inhibition. However, how such changes affect spike-timing-dependent plasticity (STDP) has not been systematically studied. This research aimed to determine the effect of the menstrual cycle on corticospinal excitability and STDP. Twelve eumenorrheic female participants (age: 25 ± 5 yr) visited the lab in three menstrual cycle phases: early follicular (EF), late follicular (LF), and mid-luteal (ML). Visits comprised of corticospinal excitability [motor evoked potential (MEP)/<i>M</i>_max], short-intracortical inhibition (SICI), and intracortical facilitation (ICF) measures, recorded in the resting first dorsal interosseous. Followed by a paired associative stimulation (PAS) protocol, utilizing ulnar nerve and transcranial magnetic stimulation (25-ms interstimulus interval) to elicit neuroplasticity. To assess the time course of STDP, measurements were repeated at 15 and 30-min post PAS. Corticospinal excitability (MEP/<i>M</i>_max) was greater in the LF phase (<i>P</i> ≤ 0.001) compared with EF and ML, with no phase effects observed for SICI or ICF (<i>P</i> ≥ 0.170). PAS elicited an increase in MEP/<i>M</i>_max across all phases at 15-min (112 ± 5, 116 ± 5, and 114 ± 7% baseline, <i>P</i> ≤ 0.037), whereas at 30 min only ML was facilitated (126 ± 5% baseline, <i>P</i> = 0.044). The present data demonstrate facilitatory STDP can be induced with PAS across the tested menstrual cycle phases, but responses are prolonged and potentiated in the ML phase. In addition, increased corticospinal excitability in the LF phase is likely due to intrinsic changes within the descending tract, as no changes in intracortical neurotransmission were observed.<b>NEW & NOTEWORTHY</b> Does the menstrual cycle modulate spike-timing-dependent plasticity? In the present study, a facilitatory paired associative stimulation protocol was used to probe Hebbian plasticity in three hormonally distinct menstrual cycle phases. Facilitation was induced in all menstrual cycle phases, but this effect lasted longer and was of greater magnitude in the luteal phase when estrogens and progesterone were both elevated. This provides insights into the potential mechanisms by which these hormones influence neuroplasticity in females.