RT Journal Article SR Electronic T1 Keep your hands apart: independent representations of ipsilateral and contralateral forelimbs in primary motor cortex JF bioRxiv FD Cold Spring Harbor Laboratory SP 587378 DO 10.1101/587378 A1 Heming, Ethan A A1 Cross, Kevin P A1 Takei, Tomohiko A1 Cook, Douglas J A1 Scott, Stephen H YR 2019 UL http://biorxiv.org/content/early/2019/03/24/587378.abstract AB It is generally accepted that each cortical hemisphere primarily drives the opposite side of the body. Yet, primary motor cortical (M1) activity has been robustly correlated with both contralateral and ipsilateral arm movements. It has remained unanswered as to why ipsilaterally-related activity does not cause contralateral motor activity. Here we apply multi-joint elbow and shoulder loads to the left or right arms of monkeys during a postural perturbation task. We show that many M1 neurons respond to mechanical disturbances applied to either the contra- or ipsilateral arms. More neurons respond to loads applied to the contralateral arm with response magnitudes that were ~2x as large and had onset times that were ~10ms earlier. However, in some cases, neurons exhibited large and earlier responses to loads applied to the ipsilateral arm than loads applied to the contralateral arm. Similar effects were observed when the monkeys were maintaining postural control well after the load had been applied. Importantly, we show that the load preference to one arm has little predictive power on a neuron’s preference in the opposite arm. Furthermore, we found contralateral and ipsilateral neural activity resided in orthogonal subspaces allowing for a weighted sum of neural responses to extract the contralateral activity without interference from the ipsilateral activity, and vice versa. These data show how activity in M1 unrelated to downstream motor targets can be segregated from downstream motor output.