Neural correlates of outcome after stroke: a cross-sectional fMRI study

Abstract

Recovery of motor function after stroke may occur over weeks or months and is often attributed to neuronal reorganization. Functional imaging studies investigating patients who have made a good recovery after stroke have suggested that recruitment of other motor-related networks underlies this recovery. However, patients with less complete recovery have rarely been studied, or else the degree of recovery has not been taken into account. We set out to investigate the relationship between the degree of recovery after stroke and the pattern of recruitment of brain regions during a motor task as measured using functional MRI. We recruited 20 patients who were at least 3 months after their first ever stroke, and 26 right-handed age-matched control subjects. None of our patients had infarcts involving the hand region of the primary motor cortex. All subjects were scanned whilst performing an isometric, dynamic visually paced handgrip task. The degree of functional recovery of each patient was assessed using a battery of outcome measures. Single-patient versus control group analysis revealed that patients with poor recovery were more likely to recruit a number of motor-related brain regions over and above those seen in the control group during the motor task, whereas patients with more complete recovery were more likely to have 'normal' task-related brain activation. Across the whole patient group and across stroke subtypes, we were able to demonstrate a negative correlation between outcome and the degree of task-related activation in regions such as the supplementary motor area, cingulate motor areas, premotor cortex, posterior parietal cortex, and cerebellum. This negative correlation was also seen in parts of both contralateral and ipsilateral primary motor cortex. These results further our understanding of the recovery process by demonstrating for the first time a clear relationship between task-related activation of the motor system and outcome after stroke.

Fig. 1

Axial structural T₁-weighted MRI scans at the level of maximum infarct volume for each patient performed at the time of the fMRI.

Fig. 2

Results for a single stroke patient (Patient 4) with only moderate recovery. (A) The main effects of left (affected) handgrip compared with rest and displayed on the patient’s own structural T₁-weighted anatomical image in axial section. The front of the brain is upwards and the right side of the brain displayed on the right. (B) The comparison of the main effects of left handgrip for a single subject (Patient 4) versus the control group. The display is as in (A). Plots of the task-related parameter estimates for main effects of left handgrip are shown for each subject in the control group and Patient 4 for (C) the right supplementary motor area (x = 18, y = −12, z = 54), and (D) the ipsilateral (contralesional) deep central sulcus (x = −16, y = −26, z = 54).

Fig. 3

SPM{Z}s representing voxels for in which there was a negative (linear) correlation between recovery and task-related BOLD signal within different stroke subtypes. Results are surface-rendered onto a canonical brain. The brain is shown (from left to right) from the left side, from above (left hemisphere on the left) and from the right. All voxels are significant at P < 0.05, corrected for multiple comparisons across the whole brain.

Fig. 4

SPM{Z} representing regions in which there was a linear inverse correlation between recovery and task-related BOLD signal across all stroke subtypes (internal capsule infarcts, MCA infarcts, pons infarcts). Results are surface-rendered onto a canonical brain. The brain is shown (from left to right) from the left side, from above (left hemisphere on the left) and from the right. All clusters are significant at P < 0.05, corrected for multiple comparisons across the whole brain.

Fig. 5

Plots of parameter estimates (size of effect) against relative recovery score (normalized) for all stroke patients in different areas of the brain. Correlation coefficient and associated P value for peak voxel in each region (see Table 5) shown. (A) Contralateral M1 (x = 38, y = −26, z = 52) (r² = 0.60, P = 0.0001). (B) Ipsilateral inferior M1 (r² = 0.67, P < 0.0001). (C) Contralateral lateral dorsal premotor cortex (r² = 0.64, P < 0.0001). (D) Ipsilateral lateral dorsal premotor cortex (r² = 0.67, P < 0.0001). (E) Ipsilateral posterior central sulcus (primary sensory cortex) (r² = 0.69, P < 0.0001). (F) Contralateral insula cortex (r² = 0.65, P < 0.0001). (G) ipsilateral cerebellum (VI) (r² = 0.77, P < 0.0001). (H) Contralateral cerebellum (VI) (r² = 0.71, P < 0.0001). (I) Contralateral supplementary motor area (r² = 0.64, P < 0.0001). (J) Ipsilateral supplementary motor area (r² = 0.63, P < 0.0001). (K) Contralateral caudal cingulate sulcus (r² = 0.76, P < 0.0001). (L) Ipsilateral caudal cingulate sulcus (r² = 0.72, P < 0.0001).