Research ReportMultimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion

- Spared brainstem circuits offer an alternate route for motor control after injury.
- Co-activating cortical and brainstem circuits may strengthen corticobulbar synapses.
- This hypothesis was tested in mice with unilateral corticospinal injury.
- Multimodal cortical and brainstem exercises tended to improve behavioral recovery.

In the context of injury to the corticospinal tract (CST), brainstem-origin circuits may provide an alternative system of descending motor influence. However, subcortical circuits are largely under subconscious control. To improve volitional control over spared fibers after CST injury, we hypothesized that a combination of physical exercises simultaneously stimulating cortical and brainstem pathways above the injury would strengthen corticobulbar connections through Hebbian-like mechanisms. We sought to test this hypothesis in mice with unilateral CST lesions. Ten days after pyramidotomy, mice were randomized to four training groups: (1) postural exercises designed to stimulate brainstem pathways (BS); (2) distal limb-grip exercises preferentially stimulating CST pathways (CST); (3) simultaneous multimodal exercises (BS+CST); or (4) no training (NT). Behavioral and anatomical outcomes were assessed after 20 training sessions over 4 weeks. Mice in the BS+CST training group showed a trend toward greater improvements in skilled limb performance than mice in the other groups. There were no consistent differences between training groups in gait kinematics. Anatomically, multimodal BS+CST training neither increased corticobulbar fiber density of the lesioned CST rostral to the lesion nor collateral sprouting of the unlesioned CST caudal to the lesion. Further studies should incorporate electrophysiological assessment to gauge changes in synaptic strength of direct and indirect pathways between the cortex and spinal cord in response to multimodal exercises.