Motor system activation after subcortical stroke depends on corticospinal system integrity

Abstract

Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.

Fig. 1

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

Fig. 2

MEP recruitment curves from the affected hemisphere of each patient. The values shown are the mean MEP amplitudes (mV) elicited at each stimulus intensity (relative to the rMT) prior to correction for M-wave amplitude.

Fig. 3

GRIP and NHPT plotted against RC_AH.

Fig. 4

SPM {Z}s representing regions in which there is a negative correlation between RC_AH and task-related signal change. Results are displayed on a ‘glass brain’ shown from the right side (top left image), from behind (top right image), and from above (bottom left image). Voxels are significant at P < 0.001 (uncorrected), and clusters are significant at P < 0.05 (corrected), for the purposes of display.

Fig. 5

Plots of task-related signal change (parameter estimate for the main effect of handgrip) versus RC_AH for (A) ipsilesional primary motor cortex (BA 4p, x = 42, y = −14, z = 44), (B) contralesional primary motor cortex (BA 4a, x = 32, y = −26, z = 68), (C) contralesional primary sensory cortex (BA 1, x = 52, y = 14, z = 52). Corresponding correlation coefficients are given in Table 3.

Fig. 6

Plots of task-related signal change (parameter estimate for the main effect of handgrip) versus RC_AH for (A) contralesional premotor cortex (x = −28, y = −8, z = 56), (B) contralesional premotor cortex (x = 52, y = −4, z = 44), (C) contralesional premotor cortex (x = −36, y = −10, z = 64). (D) ipsilesional premotor cortex (x = 32, y = −10, z = 54), (E) ipsilesional premotor cortex (x = 50, y = −6, z = 50), (F) contralesional cingulate sulcus (x = −2, y = −2, z = 50), (G) contralesional SMA (x = −6, y = −8, z = 64), (H) ipsilesional SMA (x = 2, y = −2, z = 66). Corresponding correlation coefficients are given in Table 3.

Fig. 7

Plots of task-related signal change (parameter estimate for the main effect of handgrip) versus RC_AH for (A) contralesional intraparietal sulcus (x = −38, y = −54, z = 58), (B) ipsilesional intraparietal sulcus (x = 26, y = −62, z = 56), (C) contralesional dorsolateral prefrontal cortex (x = −36, y = 36, z = 36), (D) ipsilesional dorsolateral prefrontal cortex (x = 24, y = 32, z = 38). Corresponding correlation coefficients are given in Table 3.