Peripheral Nervous System Reconstruction Reroutes Cortical Motor Output—Brain Reorganization Uncovered by Effective Connectivity

Abstract

Cortical reorganization in response to peripheral nervous system damage is only poorly understood. In patients with complete brachial plexus avulsion and subsequent reconnection of the end of the musculocutaneous nerve to the side of a phrenic nerve, reorganization leads to a doubled arm representation in the primary motor cortex. Despite, homuncular organization being one of the most fundamental principles of the human brain, movements of the affected arm now activate 2 loci: the completely denervated arm representation and the diaphragm representation. Here, we investigate the details behind this peripherally triggered reorganization, which happens in healthy brains. fMRI effective connectivity changes within the motor network were compared between a group of patients and age matched healthy controls at 7 Tesla (6 patients and 12 healthy controls). Results show the establishment of a driving input of the denervated arm area to the diaphragm area which is now responsible for arm movements. The findings extend current knowledge about neuroplasticity in primary motor cortex: a denervated motor area may drive an auxilliary area to reroute its motor output.

Plasticity of the Central Nervous System Involving Peripheral Nerve Transfer

“…Connection of the preexisting cortical network of interneurons in arm representation with intercostal corticospinal neurons is thought to be responsible for this cortical shifting phenomenon [ 65 , 66 ]. Similarly, patients with complete brachial plexus avulsion, who receive phrenic-to-musculocutaneous nerve transfer for the restoration of elbow flexion, have the same course of clinical recovery and cortical shifting phenomenon of the motor cortex in the third stage as those with intercostal-to-musculocutaneous nerve transfer [ 67 ]. The bold fMRI data analyzed using the dynamic causal modeling method indicate that the new neuroplastic connection between the arm and the diaphragm area indeed occurs [ 66 ].…”

“…The bold fMRI data analyzed using the dynamic causal modeling method indicate that the new neuroplastic connection between the arm and the diaphragm area indeed occurs [ 66 ]. A portion of the cortical regions representing phrenic nerves could be gradually separated for the charge of the new elbow flexion function [ 66 , 67 ]. The connection between the separated and original cortical regions weakens, and the separated cortical regions make new connections with the deprived arm area [ 66 , 67 ].…”

“…A portion of the cortical regions representing phrenic nerves could be gradually separated for the charge of the new elbow flexion function [ 66 , 67 ]. The connection between the separated and original cortical regions weakens, and the separated cortical regions make new connections with the deprived arm area [ 66 , 67 ]. Finally, the cortical region representing the arm area delivers the motor control command of elbow flexion to the cervical spinal cord via the new relay diaphragm area [ 66 , 67 ].…”

Kinematic Changes in the Uninjured Limb After a Traumatic Brachial Plexus Injury

“…In another line of evidence, several studies have demonstrated that TBPI is capable of promoting structural and functional modifications in the sensory (S1) and motor (M1) primary cortices contralateral and ipsilateral to the affected side ( Mano et al, 1995 ; Malessy et al, 1998 ; Beaulieu et al, 2006 ; Anastakis et al, 2008 ; Taylor et al, 2009 ; Davis et al, 2011 ; Jaggi and Singh, 2011 ; Yoshikawa et al, 2012 ; Liu et al, 2013 ; Fraiman et al, 2016 ; Lu et al, 2016 ; Amini et al, 2018 ; Torres et al, 2018 ; Fischmeister et al, 2020 ). Liu et al (2013) observed changes in interhemispheric connectivity between motor areas, while Fraiman et al (2016) observed reduced functional connectivity in the representation of the trunk and upper limbs bilaterally in M1, suggesting that TBPI might result in alterations of motor control beyond the affected limb.…”

A New Rehabilitative Mechanism in Primary Motor Cortex After Peripheral Trauma

“…Currently, it is not exactly known how this functional reorganization is realized, however, a recent study by our group indicates the establishment of a driving input of the denervated arm area to the diaphragm area which is now responsible for arm movements (16).…”