Progressive recruitment of contralesional cortico-reticulospinal pathways drives motor impairment post stroke

J Physiol. 2018 Apr 1;596(7):1211-1225. doi: 10.1113/JP274968. Epub 2018 Feb 19.


Key points: Activation of the shoulder abductor muscles in the arm opposite a unilateral brain injury causes involuntary increases in elbow, wrist and finger flexion in the same arm, a phenomenon referred to as the flexion synergy. It has been proposed that flexion synergy expression is related to reduced output from ipsilesional motor cortex and corticospinal pathways. In this human subjects study, we provide evidence that the magnitude of flexion synergy expression is instead related to a progressive, task-dependent recruitment of contralesional cortex. We also provide evidence that recruitment of contralesional cortex may induce excessive activation of ipsilateral reticulospinal descending motor pathways that cannot produce discrete movements, leading to flexion synergy expression. We interpret these findings as an adaptive strategy that preserves low-level motor control at the cost of fine motor control.

Abstract: A hallmark of hemiparetic stroke is the loss of fine motor control in the contralesional arm and hand and the constraint to a grouped movement pattern known as the flexion synergy. In the flexion synergy, increasing shoulder abductor activation drives progressive, involuntary increases in elbow, wrist and finger flexion. The neural mechanisms underlying this phenomenon remain unclear. Here, across 25 adults with moderate to severe hemiparesis following chronic stroke and 18 adults without neurological injury, we test the overall hypothesis that two inter-related mechanisms are necessary for flexion synergy expression: increased task-dependent activation of the intact, contralesional cortex and recruitment of contralesional motor pathways via ipsilateral reticulospinal projections. First, we imaged brain activation in real time during reaching motions progressively constrained by flexion synergy expression. Using this approach, we found that cortical activity indeed shifts towards the contralesional hemisphere in direct proportion to the degree of shoulder abduction loading in the contralesional arm. We then leveraged the post-stroke reemergence of a developmental brainstem reflex to show that anatomically diffuse reticulospinal motor pathways are active during synergy expression. We interpret this progressive recruitment of contralesional cortico-reticulospinal pathways as an adaptive strategy that preserves low-level motor control at the cost of fine motor control.

Keywords: motor control; neural plasticity; stroke.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / pathology*
  • Muscle Weakness
  • Paresis / etiology*
  • Paresis / pathology
  • Pyramidal Tracts / pathology*
  • Reflex*
  • Reticular Formation / pathology*
  • Spinal Cord / pathology*
  • Stroke / complications*