Enhancing plasticity through repeated rTMS sessions: the benefits of a night of sleep.

OBJECTIVE: Previous work has demonstrated that corticospinal facilitation from 20Hz repetitive transcranial magnetic stimulation (rTMS) was greater during a second rTMS session 24h after the first. We sought to determine whether such metaplasticity is dependent on a particular phase of the normal sleep-wake/circadian cycle. METHODS: Twenty healthy participants received two sessions of 20Hz rTMS over the hand motor cortex (M1) spaced 12h apart, either over-day or overnight. RESULTS: Baseline corticospinal excitability did not differ by group or session. The time-of-day of Session 1 did not influence the relative increase in excitability following rTMS. However, the increase in excitability from the second rTMS session was 2-fold greater in the overnight group. CONCLUSIONS: When a night with sleep follows rTMS to M1, the capacity to induce subsequent plasticity in M1 is enhanced, suggesting sleep-wake and/or circadian-dependent modulation of processes of metaplasticity. SIGNIFICANCE: TMS treatment of neuropsychiatric disorders entails repeated sessions of rTMS. Our findings suggest that the timing of sessions relative to the sleep-wake/circadian cycle may be a critical factor in the cumulative effect of treatment. Future studies using this paradigm may provide mechanistic insights into human metaplasticity, leading to refined strategies to enhance non-invasive stimulation therapies.