Global disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury

Abstract

The induction of large-scale plasticity in the adult brain should be key for recovery from severe damage of the central nervous system. Here, drastic motor recovery was observed after subhemisection spinal cord injury in macaques that received intensive training and cortical electrical stimulation. During recovery, movement-related activity increased in ipsilesional sensorimotor areas and functional connectivity from ipsilesional to contralesional areas was strengthened. Electrical stimulation applied widely across bilateral sensorimotor areas induced muscle twitches in affected and intact forelimbs. The interhemispheric inhibition observed before injury was switched to facilitation. Furthermore, massive re-routing occurred in corticospinal axons from the contralesional motor cortex. Such global disinhibition and massive plasticity would open the workspace for the reorganization of motor networks to recruit novel areas for recovery.

Younger adult brain utilizes interhemispheric strategy of recruiting ipsilateral dorsal premotor cortex for complex finger movement, but not aging brain

“…For example, when the brain or the spinal cord is injured, the brain often recruits normally-underused cortical sensorimotor areas (dorsal premotor cortex [PMd], primary motor cortex [M1], primary somatosensory cortex [S1], and superior parietal cortex of Area 2) during ipsilateral hand/finger movements (Grefkes & Fink, 2020; Hoy et al, 2004; Jang et al, 2004; Lotze et al, 2006; Ward et al, 2008). Recently, animal studies have suggested that such recruitment of ipsilateral sensorimotor cortices is mediated by disinhibition of interhemispheric inhibition between the left and right motor cortices (Yamaguchi et al, 2023) by acetylcholine modulating GABAergic interneurons (Handa et al, 2024). In stroke patients, jamming transcranial magnetic stimulation (TMS) to the ipsilateral sensorimotor cortices disrupts finger movement, especially the TMS to the PMd disrupts the movement more than when it is applied to the M1 and the superior parietal lobule (Lotze et al, 2006).…”

Theoretical proposal for restoration of hand motor function utilizing plasticity of motor-cortical interhemispheric interaction

“…In other words, this bilateral mode is the first step toward restoring motor function (Grefkes and Fink, 2020). Recent animal studies have suggested that this bilaterally active mode is caused by disinhibition of interhemispheric inhibition between the left and right motor cortices (Yamaguchi et al, 2023) by acetylcholine modulating GABAergic interneurons (Handa et al, 2024).…”