The Emergence of Stereotyped Kinematic Synergies when Mice Reach to Grasp Following Stroke

 Why wasn't this done with humans? There are 10 million yearly stroke survivors

to choose from.

The Emergence of Stereotyped Kinematic Synergies when Mice Reach to Grasp Following Stroke

Gustavo Balbinot, PhD, Sebastien Denize, MSc, Diane C. Lagace, PhD

First Published November 19, 2021 Research Article Find in PubMed 

https://doi.org/10.1177/15459683211058174

Article information

Abstract

Reaching tasks are commonly used in preclinical and clinical studies to assess the acquisition of fine motor skills and recovery of function following stroke. These tasks are often used to assess functional deficits in the absence of quantifying the quality of movement which requires kinematic analysis. To meet this need, this study uses a kinematic analysis in mice performing the Montoya staircase task at 5 and 14 days following a cortical photothrombosis-induced stroke. Following stroke, the mice had reaching impairments associated with sustained deficits including longer, unsmooth, and less individuated paw trajectories. Two weeks after stroke we also detected the emergence of abnormal elbow and shoulder angles, flexion/extensions, and stereotyped kinematic synergies. These data suggest that proximal and distal segments acting in concert is paramount during post-stroke reaching and encourage further analysis of synergies within the translational pipeline of preclinical to clinical studies.

Keywords

stroke, mice, kinematics, synergy, compensation, reach

Introduction

Advances in acute stroke treatment have resulted in a significant increase in the number of individuals surviving stroke, yet the trajectory for recovery after stroke has not significantly changed.¹ Stroke remains one of the leading causes of chronic disability, with 80% of patients having motor impairments that often affect the control of the movement of the face, arm, and leg of one side of the body.^2,3 These deficits are characterized by the loss of upper motor neuron control over voluntary movements, as well as the emergence of abnormal movement patterns or synergies.^4-6

There are multiple definitions for synergy; however, in general, they all refer to the spatiotemporal pattern of coordinated activation of the limbs, muscles, or joints involved in the performance of a movement.⁶ These synergy patterns are determined early in life⁷ and are able to generate complex motor commands, but are sensitive to modification by training, and cortical injury such as stroke.^8-10 The two main synergies of the upper limbs following stroke include flexion synergy, which is characterized by simultaneous shoulder abduction and elbow flexion, as well as extension synergy, which is characterized by simultaneous shoulder adduction and elbow extension.⁶ These proximal upper limb synergies reduce the precision and smoothness of the movements and limit the ability to coordinate movement in flexible and adaptable patterns.

In the clinic, the quantification of stereotyped movements and abnormal synergies are often measured using functional ordinal scale measures such as the Fugl-Meyer.^11,12 In addition to the use of these functional measurements, the quantification of the quality of movement through fine-grained kinematic analysis has been recommended by the second International Stroke Recovery and Rehabilitation Roundtable taskforce.¹³ This recommendation is based on the need to distinguish movements that are responsible for restitution versus compensation, to aid in the development of rehabilitation approaches that target processes underlying motor control and recovery post-injury.^13-15

Similar to clinical research, preclinical research has mainly relied on functional outcome measures and there is a growing interest in measuring kinematic movements to enhance translation from the bench to bedside.^16,17 Due to the striking similarities between human and rodent reaching movements in grasping tasks, unilateral skilled reaching tasks such as the staircase test and single pellet reaching task are often utilized in both mice and rats.^18-23 Both of these tasks are sensitive to detect functional deficits post-stroke as assessed by a reduction in the number of pellets retrieved or reaches performed.^18,22,24-31 Kinematic analysis of reaching on these tasks has also illustrated abnormal quantitative distal paw and qualitative proximal movement patterns post-stroke.^30,32-36 Additionally, we have previously shown that rats performing the staircase task have abnormal kinematic synergies with inefficient reaching trajectories at 7 days after stroke including elbow flexion, shoulder adduction, and shoulder rotation.²⁵ How these synergies modify with time after a stroke and whether similar deficits in synergies occur post-stroke in mice remains to be determined. This study, therefore, tested if kinematic distal and proximal movement deficits and/or abnormal kinematic synergies occurred in mice performing the staircase test at 5 and 14 days after a focal stroke.