Neural Correlates of Proprioception After Stroke

Proprioception, one’s sense of limb and body position (position sense) and movement (kinesthesia), is impaired in up to 64% of individuals after stroke. Proprioceptive deficits in the arm result in poor coordination of multiple joints, leading to decreased reaching accuracy and poor fine motor coordination. After stroke, these impairments have been associated with longer hospital stays and poorer functional recovery. Despite consensus that proprioception contributes to efficient arm movement, relatively little is known about it in comparison to the motor system. The goal of this thesis was to investigate the structural anatomy underlying proprioceptive awareness after stroke and provide a foundation upon which targeted interventions for proprioceptive deficits may be built. In chapter two, a literature review was conducted that examined subcomponents, assessments, and interventions of proprioception. This review identified that few proprioceptive assessments or interventions exist and highlighted considerations that might guide intervention development. In chapter three, a lesion analysis was conducted in a large cohort. Lesions in the parietal lobe, somatosensory association areas, and white matter pathways that connect the parietal, temporal and frontal lobes were associated with poor performance on a robotic proprioceptive matching task at approximately six months post-stroke. In chapter four, a diffusion tractography study was conducted to examine whether altered microstructure of the dorsal column-medial lemniscus (DCML) tract, the postcentral gyrus to supramarginal gyrus (POCG-SMG) association tract, or the postcentral gyrus to Heschl’s gyrus (POCG-HG) association tract was related to poor proprioception after stroke. A moderate correlation was observed between the POCG-SMG and POCG-HG and proprioceptive impairment at one month post-stroke. These findings provided support to those from chapter 3 that identified the supramarginal and Heschl’s gyri as important regions for perceiving proprioceptive information. In chapter five, the association between corticospinal tract damage and motor or proprioceptive impairments was examined. Corticospinal tract damage was significantly associated with both motor and proprioceptive deficits after stroke. Together these results further our understanding of the structural correlates underlying proprioceptive impairments after stroke

Lesion locations associated with persistent proprioceptive impairment in the upper limbs after stroke

Proprioceptive deficits are common after stroke and have been associated with poorer recovery. Relatively little is known about the brain regions beyond primary somatosensory cortex that contribute to the percept of proprioception in humans. We examined a large sample (n = 153) of stroke survivors longitudinally to determine which brain regions were associated with persistent post-stroke proprioceptive deficits. A robotic exoskeleton quantified two components of proprioception, position sense and kinesthesia (movement sense), at 2 weeks and again at 6 months post-stroke. A statistical region of interest (sROI) analysis compared the lesion-behaviour relationships of those subjects with cortical and subcortical stroke (n = 136). The impact of damage to brainstem and cerebellum (n = 17) was examined separately. Results indicate that damage to the supramarginal gyrus, the arcuate fasciculus, and Heschl's gyrus are associated with deficits in position sense and kinesthesia at 6 months post-stroke. These results suggest that regions beyond the primary somatosensory cortex contribute to our sense of limb position and movement. This information extends our understanding of proprioceptive processing and may inform personalized interventions such as non-invasive brain stimulation where specific brain regions can be targeted to potentially improve stroke recovery. Keywords: Proprioception, Lesion analysis, Stroke, Upper extremity, Robotic assessmen

Observational Study of Neuroimaging Biomarkers of Severe Upper Limb Impairment After Stroke

Background and objectivesIt is difficult to predict post-stroke outcome for people with severe motor impairment, as both clinical tests and corticospinal tract (CST) microstructure may not reliably indicate severe motor impairment. Here, we test whether imaging biomarkers beyond the CST relate to severe upper limb impairment post-stroke by evaluating white matter microstructure in the corpus callosum (CC). In an international, multisite hypothesis-generating observational study we determined if: a) CST asymmetry index can differentiate between individuals with mild-moderate and severe upper limb impairment; and b) CC biomarkers relate to upper limb impairment within individuals with severe impairment post-stroke. We hypothesised that CST asymmetry index would differentiate between mild-moderate and severe impairment, but CC microstructure would relate to motor outcome for individuals with severe upper limb impairment.MethodsSeven cohorts with individual diffusion imaging and motor impairment (Fugl Meyer-Upper Limb) data were pooled. Hand-drawn regions-of-interest were used to seed probabilistic tractography for CST (ipsilesional/contralesional) and CC (prefrontal/premotor/motor/sensory/posterior) tracts. Our main imaging measure was mean fractional anisotropy. Linear mixed-effect regression explored relationships between candidate biomarkers and motor impairment, controlling for observations nested within cohorts, as well as age, sex, time post-stroke and lesion volume.ResultsData from 110 individuals (30 mild-moderate, 80 with severe motor impairment) were included. In the full sample, greater CST asymmetry index (i.e., lower fractional anisotropy in the ipsilesional hemisphere, p<.001) and larger lesion volume (p=.139) were negatively related to impairment. In the severe subgroup, CST asymmetry index was not reliably associated with impairment across models. Instead, lesion volume and CC microstructure explained impairment in the severe group beyond CST asymmetry index (p's<.010).ConclusionsWithin a large cohort of individuals with severe upper limb impairment, CC microstructure related to motor outcome post-stroke. Our findings demonstrate that CST microstructure does relate to upper limb outcome across the full range of motor impairment but was not reliably associated within the severe subgroup. Therefore, CC microstructure may provide a promising biomarker for severe upper limb outcome post-stroke, which may advance our ability to predict recovery in people with severe motor impairment after stroke