Effect of sensory and motor connectivity on hand function in pediatric hemiplegia

Abstract

Objective: We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development; whereas the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this does not occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions.

Methods: Twenty-four children with unilateral cerebral palsy had physiological and anatomical measures of the motor and somatosensory systems and lesion classification. Motor physiology was performed with transcranial magnetic stimulation and somatosensory physiology with vibration-evoked electroencephalographic potentials. Tractography of the corticospinal tract and the medial lemniscus was performed with diffusion tensor imaging, and lesions were classified by magnetic resonance imaging. Anatomical and physiological results were correlated with measures of hand function using 2 independent statistical methods.

Results: Children with disruptions in the somatosensory connectivity and cortical lesions had the most severe upper extremity impairments, particularly somatosensory function. Motor system connectivity was significantly correlated with bimanual function, but not unimanual function or somatosensory function.

Interpretation: Both sensory and motor connectivity impact hand function in children with USCP. Somatosensory connectivity could be an important target for recovery of hand function in children with USCP. Ann Neurol 2017;82:766-780.

Figure 1

An illustration of the motor and somatosensory connections in normal development and early brain injury. These are models based on previous studies of the effects of injury timing on connectivity. (A) Typical development. After initial bilateral projections, the motor tract (corticospinal tract (CST), is largely pruned to the contralateral one. The somatosensory tract mediating touch, vibration, and proprioception (dorsal column-medial lemniscus (DC-ML)). (B) In case of preterm injury, the contralateral CST is often disrupted, and the ipsilateral CST persists from the uninjured hemisphere. Thalamocortical projections (interrupted line) that are part of the DC-ML develop later and may skirt periventricular lesions to reach primary somatosensory cortex in the contralateral cortex. (C) In case of a larger injury (such as MCA) that can often occur at full term, the thalamocortical projections and primary somatosensory cortex may be disrupted as well. (Colored version of Figure is available online)

Figure 2

Experimental methods. The left panel shows the methods for data acquisition for assessment of physiology and anatomy. The right panel shows the results for one example participant with right hemisphere PV injury with preserved somatosensory connections and ipsilateral motor connections. (A) Sensory physiology. Left: EEG SEPs were evoked with vibrotactile stimulation applied to the tip of each index finger. Right panel shows the spatial topographies and SEPs for left and right hand stimulation. Comparable contralateral evoked response is observed for stimulation of both the left (more affected) and right (less affected) hand. (B) Motor Physiology. Left: Single pulse TMS stimulation applied using neuronavigation evoked MEPs in the first dorsal interosseus muscle. Right: black spheres indicate the sites of stimulation projected onto a 3D rendering of the patient's cortex. The locations that evoked an MEP are shown in dark blue for the contralateral (right) hand and light blue for the ipsilateral (left) hand (same scheme as Fig 1). (C) Anatomy: Left: DTI of the motor and somatosensory tracts displayed on a color-coded DTI FA map. In FA maps the red indicates fibers running along left-right direction, green inferior-superior and blue anterior-posterior. The CST (anterior pair of blue) and medial lemniscus (posterior pair of blue) were seeded on an axial slice at pons level. Right: CST (shown in blue) is found in the left (uninjured) hemisphere, but not in the right hemisphere with the PV lesion. In contrast, the somatosensory tracts (shown in red) are present in both the left and the right hemisphere.

Figure 3

Structural MRI's for all participants, indicating (shown by arrow) the location and type of the lesion. PV: Periventricular, and MCA: Middle Cerebral Artery.

Figure 4

Correlation of somatosensory and motor anatomy and physiology with hand function. Movement tests (Jebsen Taylor, Box & Blocks and AHA) are shown in the left panel and sensation tests (Stereognosis and 2-point Discrimination) in the right. (A) Somatosensory Connectivity: The presence or absence of physiological connectivity in injured cortex, as measured with SEPs, was significantly correlated with all movement and sensation tests. The absence of a SEP was associated with poor hand function. The presence or absence of anatomical connections in injured cortex, as seen with DTI was significantly correlated with hand function for all test except AHA. Absence of tracts was associated with poor hand function. (B) Motor Connectivity: The presence of predominant contralateral or ipsilateral physiological connections, as measured by TMS, was not significantly correlated with most movement and sensation test scores, except AHA. The presence or absence of anatomical connections in injured cortex, as seen in DTI, were not significantly correlated with hand function tests, except Stereognosis. The absence of the crossed CST was associated only with poor stereognosis. Significance was estimated by a non-parametric permutation test: *** = p < 0.001, ** = p < 0.01, * = p < 0.05. (Colored version of Figure is available online)

Figure 5

Correlation of lesion type and sensory and motor function. PV and MCA lesion types are significantly different in their impact on the motor (Jebsen Taylor and AHA) and sensory (Stereognosis and 2-Points) function. PV is generally associated with better hand movement and sensation scores than MCA, except for Box & Blocks. Significance was estimated by a non-parametric permutation test: *** = p < 0.001, ** = p < 0.01, * = p < 0.05.

Figure 6

Clustering of behavioral data. (A) t-SNE allows projections of the 5 hand function tests into 2 dimensions (t-SNE 1 and t-SNE 2) which shows 2 distinct participant groups. (B) Clustering outcome from applying k-means clustering on 5 dimensional hand function data. The two clusters are marked for all pairs of hand movement and somatosensory test scores. Each circle represents a single participant, and circles are filled or open based on the 2 clusters. The clusters fall into the top right quadrant (good hand function: filled circles) and the lower left quadrant (poor hand function: open circles) for all pairs of hand function tests. All tests pairs were also significantly correlated, tested with non-parametric Spearman's rho (p < 0.001), rho is shown in each subplot in parentheses. (C) Cohen's kappa was used to estimate cluster agreement with anatomy, physiology and lesion type. Somatosensory physiology was the most sensitive indicator of good or poor hand function.