Motor compensation and its effects on neural reorganization after stroke

Abstract

Stroke instigates a dynamic process of repair and remodelling of remaining neural circuits, and this process is shaped by behavioural experiences. The onset of motor disability simultaneously creates a powerful incentive to develop new, compensatory ways of performing daily activities. Compensatory movement strategies that are developed in response to motor impairments can be a dominant force in shaping post-stroke neural remodelling responses and can have mixed effects on functional outcome. The possibility of selectively harnessing the effects of compensatory behaviour on neural reorganization is still an insufficiently explored route for optimizing functional outcome after stroke.

Figure 1 |. The motor cortex and its descending projection pathways are often affected by strokes that result in upper-extremity impairments.

a | Simplified illustrations of motor cortical regions of a human (left), and of motor cortical regions of a naive rat, derived using intracortical microstimulation (right), are shown. The colours show the cortical territories that are responsible for the movement of different body parts. The motor cortical control of the upper limbs is mostly crossed, such that the left hemisphere controls movement of the right side and vice versa. b | Occlusions or ruptures in the cerebral vasculature (red) that supplies motor cortical regions (the distal middle cerebral artery) and its projection pathways (for example, the anterior choroidal and striate arteries) position strokes (the dark grey regions on the rat coronal sections on the right) that either kill the cortical neurons that control upper-limb movement or disconnect their projections to the spinal cord and other subcortical structures, such as the red nucleus and reticular formation. The degree of disruption of the descending motor cortical pathway due to either cortical or subcortical strokes predicts the severity of motor impairment^–. The colours of the corticospinal neurons correspond to the body parts that they control as in the motor cortical regions in part a. The rat coronal sections show the locations of ischaemic infarcts that have been used to model post-stroke upper-extremity impairments; these infarcts are located in the forelimb region of the primary motor cortex^, (M1; which is supplied by the distal middle cerebral artery) and in the posterior limb of internal capsule^, (which is supplied by the anterior choroidal artery). The dashed lines indicate the disconnection of descending cortical projections.

Figure 2 |. Illustrations of compensatory movement strategies for upper-limb hemiparesis.

a | The illustration shows typical reach and grasp movements in healthy humans. b | When reaching with the paretic upper limb after stroke, forward trunk and shoulder displacement and rotation compensate for the diminished control of more-distal movements^,. If not instructed otherwise, the non-paretic side often assists movements of the paretic side. c | More commonly, the non-paretic side is used for unimanual tasks^,. d | The illustration shows typical movements used by healthy rats to reach for and consume a palatable food pellet (green sphere) in an apparatus that forces the use of one forelimb (that is, an inner chamber wall placed close to the reaching window on the side of the trained limb blocks the body position needed to reach the pellet with the other forelimb. An alternative method is to place bracelets on the wrist of the other forelimb that prevent its extension through the reaching window (not shown)). e | After unilateral motor system injury, rats perform reaching tasks with the paretic forelimb using compensatory movements of the trunk, head and non-paretic forelimb^,,. This includes the use of trunk rotation to control paretic paw position (left) and greater head movement (right) to bring the mouth to the paretic paw (rather than the paw to the mouth). The paw orientation is suboptimal for grasping the pellet. f | The non-paretic forelimb is often used to assist in paretic limb movements.

Figure 3 |. Different trajectories of cortical reorganization depending on forelimb behavioural experiences after motor cortical infarcts in rodent models.

Rodents in a standard laboratory cage have limited opportunity to practice fine motor skills with the forelimbs, affording a strong degree of experimental control over these experiences. a | In the absence of interventions, increased reliance on the non-paretic forelimb for movements in the home cage (known as unskilled compensation) promotes synapse addition and selective synapse maturation in the contralesional primary motor cortex (M1). These changes in the contralesional cortex have no known functional relevance for the paretic limb. b | The changes in the contralesional cortex are amplified if animals are trained with the non-paretic forelimb on a skilled reaching task that is novel for this limb. The same training worsens impairment severity in the paretic forelimb. c | Rehabilitative training of the paretic forelimb in a skilled reaching task promotes the maintenance and re-emergence of the remaining forelimb motor maps in the peri-infarct M1 and improves paretic limb reaching performance^,. The performance improvements can reflect the recovery of more-normal movements, the refinement of compensatory movements or both. d | The performance improvements and forelimb motor map maintenance that result from rehabilitative training are diminished as a result of prior skill learning with the non-paretic forelimb. This is associated with the addition of multisynaptic boutons (MSBs) in the peri-infarct M1, which may reflect competitive influences of the two limbs on synapse addition and maturation in the peri-infarct cortex. The motor cortical map illustrations on the top and bottom-right brains are adapted with permission from REF. 116, Society for Neuroscience.