Roberts DR, Ramsey D, Johnson K, Kola J, Ricci R, Hicks C, Borckardt JJ, Bloomberg JJ, Epstein C, George MS. Cerebral cortex plasticity after 90 days of bed rest: data from TMS and fMRI. Aviat Space Environ Med 2010; 81:30–40. Introduction: Microgravity animal models have demonstrated corticospinal plasticity; however, little is understood of its functional significance. In this pilot study, we explored corticospinal plasticity in a bed rest model. We hypothesized that the lack of weight bearing would induce cortical reorganization correlating with performance. Methods: Four subjects underwent functional MRI (fMRI), transcranial magnetic stimulation (TMS), and functional mobility testing (FMT) before and after 90 d of bed rest. Recruitment curves (RC) were created by measuring motor evoked potentials over a range of TMS intensities with changes in the slope of the RC reflecting changes in corticospinal excitability. Results: Significant leg RC slope decreases were observed on post-bed rest day 1 (P1) (t(2805) = −4.14, P < 0.0001), P2 (t(2805) = −6.59, P < 0.0001), P3 (t(2805) = −6.15, P < 0.0001), P5 (t(2805) = −7.93, P < 0.0001), P8 (t(2805) = −3.30, P > 0.001), and P12 (t(2805)= −3.33, P = 0.0009), suggesting a group decrease in corticospinal excitability in the immediate post-bed rest period with recovery approaching baseline over the following 2 wk. Significant effects were observed for hand RC slopes only for P2 (t(2916) = 1.97, P = 0.049), P3 (t(2916) = −2.12, P = 0.034), and P12 (t(2916) = −2.19, P = 0.029); no significant effects were observed for days P0 (t(2916) = −1.32, ns), P1 (t(2916) = 1.00, ns), P5 (t(2916) = −0.21, ns), or P8 (t(2916) = −0.27, ns). fMRI showed no change in activation for the hand but an increase in activation post-bed rest for the leg. On an individual basis, a more heterogeneous response was found which showed a potential association with performance on FMT. Discussion: Results of this research include a better understanding of the cortical plasticity associated with leg disuse and may lead to applications in patient and astronaut rehabilitation.