Contribution of Corticospinal Tract and Functional Connectivity in Hand Motor Impairment after Stroke

<div><p>Background</p><p>Motor outcome after stroke is associated with reorganisation of cortical networks and corticospinal tract (CST) integrity. However, the relationships between motor severity, CST damage, and functional brain connectivity are not well understood. Here, the main objective was to study the effect of CST damage on the relationship between functional motor network connectivity and hand motor function in two groups of stroke patients: the severely (n=8) and the mildly impaired (n=14).</p> <p>Methods</p><p>Twenty-two carotid stroke patients with motor deficits were studied with magnetic resonance imaging (MRI) at 3 weeks, at 3 and 6 months. Healthy subjects (n=28) were scanned once. The CST injury was assessed by fractional anisotropy values. Functional connectivity was studied from a whole-hand grip task fMRI in a cortical and cerebellar motor network. Functional connectivity indexes were computed between these regions at each time point. The relationship between hand motor strength, ipsilesional CST damage and functional connectivity from the primary motor cortex (M1) was investigated using global and partial correlations.</p> <p>Findings</p><p>In mildly impaired patients, cortico-cortical connectivity was disturbed at three weeks but returned to a normal pattern after 3 months. Cortico-cerebellar connectivity was still decreased at 6 months. In severely impaired patients, the cortico-cortical connectivity tended to return to a normal pattern, but the cortico-cerebellar connectivity was totally abolished during the follow-up. In the entire group of patients, the hand motor strength was correlated to the ipsilesional functional connectivity from M1. Partial correlations revealed that these associations were not anymore significant when the impact of CST damage was removed, except for the ipsilesional M1-contralateral cerebellum connectivity.</p> <p>Conclusion</p><p>Functional brain connectivity changes can be observed, even in severely impaired patients with no recovery. Upper limb function is mainly explained by the CST damage and by the ipsilesional cortico-cerebellar connectivity.</p> </div

Tracking analysis from the strategic area.

<p>Color code is directional (blue for z-axis, green for y-axis and red for x-axis). A. Superposition of the strategic area (in yellow) on a normalized ADC map. B Association and Projection tracts passing through the strategic area on a coronal view (left image) and on a sagittal view of a normalized ADC map. The color code is directional (pink for the x-axis, blue for z-axis and pink for y-axis). C. Association and Projection tracts travelling though the strategic area (in yellow). Left: The projections tract projections at the top in the following areas: primary motor, premotor, and parietal cortices (blue); Middle: The association tract passing through the yellow region contains part of the superior longitudinal fasciculus (green); Right: The fibers of the corpus callosum passing through the strategic area (pink).</p

Regions-of-Interest for extraction of diffusion parameters.

<p>A preview of the Regions-of-Interest (in red) used in the analysis overlaid on the FMRIB58 fractional anisotropy standard space image. (A) White matter underlying the pre-central gyrus. (B) Corona Radiata. (C) Posterior Limb of Internal Capsule (D) Cerebral Peduncles (E) Genu of the Corpus Callosum.</p

Positive and Negative Predictive Values for good outcome as a function of CoRad-rAD values.

<p>The positive predictive values (PPV in green) correspond to the CoRad-rAD values above the threshold (x-axis). The negative predictive values (NPV in red) correspond to the CoRad-rAD values below the threshold. (A) Good outcome is assessed by NIHSS item 5 for upper limb (UL) scores 0–1 at day 7 post-stroke. (B) Very good outcome is assessed by mRS ≤ 1 at 3 months post-stroke. (C) Good outcome is assessed by mRS ≤ 2.</p

Flow chart of the study.

<p>CGT means Capillary glucose test. As pre-specified in the main protocol, patients for whom ore than 3 CGTs were missing during the treatment had to be excluded. VBA means voxel-based analysis and the VBA study refers to the study presented in this paper.</p

Functional connectivity during hand movements.

<div><p>(A) Movements of the left hand in healthy subjects, and of the paretic hand in (B) mildly impaired and (C) severely impaired patients.</p> <p>In patients, grey lines indicate that correlations were normal and identical to the healthy subjects, red lines indicate that correlations were increased, and green lines indicate that correlations were reduced compared with healthy subjects. Dotted lines indicate that the correlation is not significant in the group of patients. The level of the significant correlations is indicated near the corresponding line. Abbreviations: L: left, R: right, V1, V2 and V3: visit 1, 2 and 3.</p></div

Characteristics of the included patients.

<p>UL = Upper Limb, LL = Lower Limb, MOT = UL+LL. SD = standard deviation. IQR = interquartile range.</p><p>Characteristics of the included patients.</p

Region with lower ADC values at day one in non-recanalized patients and in poor outcome patients.

<p>A. Superposition of the area of day-one ADC decrease associated with 90-day poor outcome (in red) on ADC images (MNI space, z-coordinates). B. Superposition of the area of day-one ADC decrease associated with non-recanalized (vs. recanalized) patients (in blue) on ADC images (MNI space, z-coordinates). Images are shown using neuroradiological conventions (right hemisphere on the left side).</p

Localisation of infarction.

<p>Overlap of infarct lesions on a T1 anatomical template in (A) mildly impaired patients (n=14) and (B) severely impaired patients (n=8). Colour bar indicates the proportion of patients with infarction for each voxel.</p

Determination of the motor network of interest in healthy subjects (n=14).

<p>SPM (T) contrast for the dominant (A) and the non-dominant (B) hand movement. The 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). Clusters are significant at p < 0.05, corrected for multiple comparisons. (C) Overlap of the regions of interest (ROIs) on the MNI T1 template. Cerebellar ROIs are represented in blue (x = -14, y = -58, z= -18 mm for the left, and x = 14, y = 54, z=-18 for the right hemisphere); prefrontal cortex ROIs are represented in green (x = -38, y = 42, z= 22 mm for the left and x= 38, y = 30, z=24 for the right hemisphere); primary motor cortex ROIs are represented in yellow (x = -36, y = -22, z= 52 mm for the left, and x = 34, y=-20, z= 54 for the right hemisphere); supplementary motor area ROIs are represented in pink (x = -6, y = -6, z= 58 mm for the left, and x = 4, y = -6, z= 58 for the right hemisphere); and the lateral premotor cortex ROIs are represented in red (x = -40, y = -4, z= 58 mm for the left and x= 34, y=-4, z=60 for the right hemisphere). Right hemisphere is on the right side.</p