Theoretical proposal for restoration of hand motor function based on plasticity of motor-cortical interhemispheric interaction and its developmental rule

Abstract

After stroke, the poorer recovery of motor function of upper extremities compared to other body parts is a longstanding problem. Based on our recent functional MRI evidence on healthy volunteers, this perspective paper proposes systematic hand motor rehabilitation utilizing the plasticity of interhemispheric interaction between motor cortices and following its developmental rule. We first discuss the effectiveness of proprioceptive intervention on the paralyzed (immobile) hand synchronized with voluntary movement of the intact hand to induce muscle activity in the paretic hand. In healthy participants, we show that this bilateral proprioceptive-motor coupling intervention activates the bilateral motor cortices (= bilaterally active mode), facilitates interhemispheric motor-cortical functional connectivity, and augments muscle activity of the passively-moved hand. Next, we propose training both hands to perform different movements, which would be effective for stroke patients who becomes able to manage to move the paretic hand. This bilaterally different movement training may guide the motor cortices into left-right independent mode to improve interhemispheric inhibition and hand dexterity, because we have shown in healthy older adults that this training reactivates motor-cortical interhemispheric inhibition (= left-right independent mode) declined with age, and can improve hand dexterity. Transition of both motor cortices from the bilaterally active mode to the left-right independent mode is a developmental rule of hand motor function and a common feature of motor function recovery after stroke. Hence, incorporating the brain's inherent capacity for spontaneous recovery and adhering to developmental principles may be crucial considerations in designing effective rehabilitation strategies.

Keywords: EMG; development; fMRI; hand motor function; interhemispheric interaction; motor cortex; neurorehabilitation; proprioception.

Figure 1

Possible neural mechanisms underlying passive extension of the right index finger synchronized with the voluntary extension of the left finger (A) and EMG results (B). (A) We hypothesize that passive movement of the right hand synchronized with voluntary movement of the left hand will lead the left and right motor cortices to a bilaterally active mode, and interhemispheric functional connectivity must be enhanced between the two motor cortices. This enhanced functional coupling may allow the bilateral motor cortices to share the voluntary motor signal input to the right motor cortex and the proprioceptive input to the left motor cortex, promoting sensory-motor associations between them. If the sensory-motor association occurs in the left motor cortex, the voluntary motor signal may effectively activate the intrinsic transcortical circuit between the left motor cortex and the right hand muscles, leading to muscle activity increase in the right passively-moved finger. If this association also occurs in the right motor cortex, the cortex might also become part of the network increasing the muscle activity, in concert with the left one. (B) EMG results from the left active (LA; blue), right passive (RP; green), and in-phase (IN; red) tasks. Small bars on the graph indicate standard errors of the mean across participants. ^*p < 0.005, ^**p < 0.001.

Figure 2

fMRI results. (A) Bilateral motor-cortical activations (red) when comparing the IN task with the LA and RP tasks. The left and right motor cortices (orange) in which activity enhanced functional coupling with the right or left motor-cortical cluster (red), respectively. (B) Brain activity in the peaks of the left and right motor-cortical clusters in each task. (C) The left and right motor cortices (pink) in which activity significantly correlated with the EMG activity during the IN task. (D) Interparticipant correlation between the left or right M1 activity and log value of EMG activity. LA, left active; RP, right passive; IN, in-phase; M1, primary motor cortex; R, right; a.u., arbitrary unit.

Figure 3

Transition of the left and right motor cortices from the bilaterally active mode to the left–right independent mode. This is a rule of typical development of hand motor function and also a common feature of motor function recovery after stroke. Proposed interventions during recovery are shown at right bottom. IHI, interhemispheric inhibition.