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

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: compensation; kinematics; mice; reach; stroke; synergy.

Figure 1.

Kinematic model and analysis. (A) Montoya staircase apparatus and kinematic model: a four-point 2D kinematic model is used to reconstruct upper shoulder (trunk), lower shoulder (shoulder joint), elbow, and wrist segments. (B) Time-domain features were extracted from linear and angular waveforms; for example, maximum, minimum, negative and positive increments, root mean square (RMS), first and last value. (C) Synergy analysis was conducted considering the frame-by-frame interaction between waveforms. Briefly, we used the first derivative to detect the instantaneous variation of the multi-articular movement, thus, if the limb is advancing and the elbow is flexing the algorithm output was a percent calculated by limb advance—elbow flexion.

Figure 2.

PT stroke induces sustained deficits in staircase performance. (A) The number of pellets retrieved over the 14 days of training on the staircase prior to stroke significantly increased over time. (B) Representative microphotographs of an average lesion size stained using cresyl-violet staining and representative image of the minimum (black), average (gray), and maximum (light gray) stroke volumes at 45 days post-stroke. There was a significant reduction in the (C) number of total pellets retrieved, as well as (D) relative percentage of pellets retrieved post-stroke. This was accompanied by a significant reduction in the (E) number of reach attempts, as well as (F) relative percentage of reaching attempts. Mean ± SEM (n = 9). *P < .05 (pre vs 5 days post-stroke), #P < .05 (pre vs 14 days post-stroke), †P < .05 (5 days vs 14 days post-stroke), **P < .05 (pre vs 42 days post-stroke), and ††P < .05 (5 days vs 42 days post-stroke).

Figure 3.

Reduced smoothness following stroke is defined by increased vertical velocity, trajectory adjustments and peak velocity during reaching. (A) Paw trajectory smoothness is quantified by the number of changes in direction (trajectory adjustment) or velocity (velocity adjustments) of the wrist. Acceleration data during the reach from a representative animal at pre-stroke (B; n = 29 trials), 5 days (C; n = 30 trials) and 14 days post-stroke (D; n = 29 trials). At 5 (C) and 14 (D) days the acceleration pattern is more variable with several velocity adjustments when compared to pre-stroke. Post-stroke there is a significant increase in the average number of vertical (E) velocity adjustments, (F) trajectory adjustments, and (G) peak velocity. Mean ± SEM (n = 9); *P < .05 (pre vs 5 days post-stroke), #P < .05 (pre vs 14 days post-stroke), †P < .05 (5 days vs 14 days post-stroke).

Figure 4.

Increased wrist and shoulder path lengths are accompanied by decreased segmentation and increased shoulder protraction during the reach post-stroke. (A) Path length (Euclidian distances) of both the shoulder and wrist were determined during the reach. Both the (B) wrist and (C) shoulder path length is significantly increased following stroke. (D) At 14 days post-stroke there was a significant decrease in the movement segmentation (indicated by an increase in the movement segmentation index), which is the ratio of the wrist to shoulder path lengths. (E) Analysis of shoulder marker displacement through the reach identified an increase in (F) shoulder posterior to anterior movements (shoulder protractions) following stroke (thick lines represent the mean for all animals and thin grey lines represent the standard error). (G) There was a significant increase in average shoulder protraction accompanied by (H) a significant reduction in intra-subject variability post-stroke. Mean ± SEM (n = 9); *P < .05 when compared to Pre, #P < .05 when compared to Pre.

Figure 5.

Emergence of abnormal elbow and shoulder angles, flexion and extensions, and synergies 14 days post-stroke. (A) Voluntary reaching is preceded by a brief aiming positioning (left panel; 0%) followed by limb lift, advance, and drop (not shown) and ending in pellet grasp positioning (right panel; 100%). B) Elbow joint angle during the reach, lower angles are more flexed, greater angles are more extended. At aiming and grasping the (C) elbow and (D) shoulder are more flexed at 14 days post-stroke. (E) Mean normalized elbow angle from aim to grasp, the negative increments indicate flexion (-Δ) and positive increments extension (+Δ) Similar findings are evident for (F and G) elbow and (H and I) shoulder angular excursions.. (J-O) During limb advance, consistent abnormal flexor synergies as measured by the shoulder and elbow joints are used at 14 days after stroke. (J) Analysis of both the elbow and shoulder during limb advance revealed an increase in (K) shoulder flexion synergies accompanied by (L) a significant reduction in intra-subject variability by 14 days post-stroke. (M) Similarly there was an increase in (N) elbow flexion synergies accompanied by (O) a significant reduction in intra-subject variability by 14 days post-stroke. (P) Analysis of the shoulder ventro-dorsal movement during limb advance revealed an increase in (Q) shoulder lift accompanied by (R) a significant reduction in intra-subject variability by 14 days post-stroke. Mean ± SEM (n = 9); *P < .05 (pre vs 5 days post-stroke), #P < .05 (pre vs 14 days post-stroke), †P < .05 (5 days vs 14 days post-stroke).

Figure 6.

Principal components analysis (PCA) reduced the dataset dimension and identified 1 group at pre-stroke and day 14 post-stroke. (A) Data of each subject for pre-stroke (black circles), 5 days (gray squares), and 14 days (blue triangles) post-stroke are represented in a new space defined by PC1 and PC2 (%, percent of explained variance). PCA cluster identified a group of mice pre-stroke (visually grouped in gray ellipse) and another cluster at 14 days post-stroke (triangles visually grouped in blue ellipse). Mice at pre-stroke and 14 days post-stroke displayed (B) a significant difference in PC1 and PC2 scores, with (C) many individual parameters being significant within the PC loads of PC1 and PC2. # in the black parameter box in C identifies a significant difference for both PC1 and PC2. *P < .05.