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Objective: We assessed the individual level reliability of neural plasticity changes induced by paired associative stimulation (PAS), which combines peripheral nerve stimulation with transcranial magnetic stimulation to induce short-term plastic changes in the brain. Methods: For 5 consecutive weeks, motor evoked potentials (MEPs) of 8 healthy subjects were acquired every 10 minutes post-PAS intervention for a period of 60 minutes. The post-PAS MEPs were evaluated against base- . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/130856 doi: bioRxiv preprint first posted online Apr. 26, 2017; line MEPs using permutation and Kolmogorov-Smirnov tests to determine whether the MEP magnitudes changed after PAS. Moreover, various sample sizes of the MEP data were used to deduce the minimum number of MEPs needed to reliably detect individual propensity to neural plasticity. Results: Group analysis exhibited significant increase in post-PAS MEPs, confirming previous results. While high between-sessions variability was observed at individual level, data show that between 40 to 50 MEPs can reliably assess each subject's responsiveness to PAS. Subjects exhibited three different plasticity patterns: in the modulated hemisphere only, both hemispheres, or neither hemisphere. Conclusions: PAS can reliably assess individual differences in neural plasticity. Significance: A marker of individual plasticity may be useful to predict the effects of a motor rehabilitation, drug or other intervention to increase recovery of function after brain injury.

Paired associative stimulation (PAS) is a widely used noninvasive brain stimulation protocol to assess neural plasticity. Its reproducibility, however, has been rarely tested and with mixed results. With two consecutive studies, we aimed to provide further tests and a more systematic assessment of PAS reproducibility. We measured intraclass correlation coefficients (ICCs)—a widely used tool to assess whether groups of measurements resemble each other—in two PAS studies on healthy volunteers. The first study included five PAS sessions recording 10 MEPS every 10 min for an hour post-PAS. The second study included two PAS sessions recording 50 MEPS at 20 and 50 min post-PAS, based on analyses from the first study. In both studies PAS sessions were spaced one week apart. Within sessions ICC was fair to excellent for both studies, yet between sessions ICC was poor for both studies. We suggest that long term meta-plasticity effects (longer than one week) may interfere with between sessions reproducibility.

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