White matter integrity is a stronger predictor of motor function than BOLD response in patients with stroke

Abstract

Objective: Neuroimaging techniques, such as diffusion tensor imaging (DTI) and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), provide insights into the functional reorganization of the cortical motor system after stroke. This study explores the relationship between upper extremity motor function, white matter integrity, and BOLD response of cortical motor areas.

Methods: Seventeen patients met study inclusion criteria; of these 12 completed DTI assessment of white matter integrity and 9 completed fMRI assessment of motor-related activation. Primary clinical outcome measures were the Wolf Motor Function Test (WMFT) and the upper limb portion of the Fugl-Meyer (FM) motor assessment. Structural integrity of the posterior limb of the internal capsule was assessed by examining the fractional anisotropy (FA) asymmetry in the PLIC. Laterality index of motor cortical areas was measured as the BOLD response in each patient during a finger pinch task. Linear regression analyses were performed to determine whether clinical outcome was associated with structural or functional MRI measures.

Results: There were strong relationships between clinical outcome measures and FA asymmetry (eg, FM score [R(2) = .655, P = .001] and WMFT asymmetry score [R(2) = .651, P < .002]) but relationships with fMRI measures were weaker.

Conclusion: Clinical motor function is more closely related to the white matter integrity of the internal capsule than to BOLD response of motor areas in patients 3 to 9 months after stroke. Thus, use of DTI to assess white matter integrity in the internal capsule may provide more useful information than fMRI to interpret motor deficits following supratentorial brain injury.

Figure 1

Activated voxel counts (in numbers of voxels) in the principal ROIs for affected finger pinching varied among subjects. Abbreviations: M1, primary motor cortex; PMC, premotor cortex; SMA, supplementary motor area

Figure 2

(A.1) Subject12 (left middle cerebral artery [MCA]) diffusion tensor imaging (DTI) showed slightly decreased fractional anisotropy (FA) in L-PLIC (posterior limb of the internal capsule; indicated by white circle) compared with R-PLIC. FA asymmetry was low (0.09), indicating integrity of damaged L-PLIC was only slightly worse than that of the R-PLIC because R-PLIC FA was in the normal range. R, right; L, left. Combined FA and directional map. Color hue indicates direction as follows: red, medial–lateral; green, anterior–posterior; blue, superior–inferior. This convention applies to all the directional maps. Brightness is proportional to FA. (A.2) Subject12 functional magnetic resonance imaging (fMRI) showed bilateral activation of M1, supplementary motor area (SMA), premotor cortex (PMC), and BA7 during affected hand (right) pinch. Clinical motor functions tests showed moderate impairment of the right hand in this subject (Fugl-Meyer motor assessment [FM] = 34, Wolf Motor Function Test [WMFT] asymmetry = 0.52, log affected WMFT = 0.86). The statistical threshold was set at a threshold of P < .05 corrected. The color map shows the t scores. Pinching-specific activity is shown as higher t scores, or reddish-orange. (B.1) Subject5 (left MCA) DTI showed low FA in L-PLIC (indicated by white circle) due to obvious disruption of white matter in this region. The high FA asymmetry (0.32) indicates less integrity of L-PLIC compared with the R-PLIC, which was associated with low motor scores for the right hand (FM = 28, WMFT asymmetry = 0.82, log WMFT = 1.99). R, right; L, left. (B.2) Subject5 fMRI showed ipsilesional activation of M1 and PMC during affected hand (right) pinch. The statistical threshold was set at a threshold of P < .05 corrected. The color map shows the t scores. Pinching-specific activity is shown as higher t scores, or reddish-orange

Figure 3

Average cortex activation map of cortical motor areas for all subjects, showing more activation in contralesional hemisphere (unaffected side, ipsilateral to the affected hand) during affected hand pinch. Group analysis results, with threshold set at P < .05 (n = 9, corrected for multiple comparisons) are shown. The color map shows the t scores. Pinching-specific activity is shown as higher t score, or reddish-orange. The central sulcus is depicted as a green line. Abbreviations: SMA, supplementary motor area; PMC, premotor cortex; PPC, posterior parietal cortex; M1, primary motor cortex; A, anterior; P, posterior

Figure 4

(A) A significant negative linear relationship between FA asymmetry and FM score (R² = 0.655, P < .002). Higher FA asymmetry is associated with lower FM scores, whereas lower FA asymmetry is associated with greater FM scores. (B) A significant positive linear relationship between FA asymmetry with WMFT asymmetry (R² = 0.651, P = .002), log affected WMFT (R² = 0.636, P = .002), and grip asymmetry (R² = 0.414, P = .02). Lower FA asymmetry is associated with lower WMFT time asymmetry, superior log WMFT performance times, and greater grip force of affected hand. Abbreviations: FA, fractional anisotropy; FM, Fugl-Meyer motor assessment; WMFT, Wolf Motor Function Test