Resting state functional connectivity associated with impaired proprioception post-stroke.

Deficits in proprioception, the knowledge of limb position and movement in the absence of vision, occur in ~50% of all strokes; however, our lack of knowledge of the neurological mechanisms of these deficits diminishes the effectiveness of rehabilitation and prolongs recovery. We performed resting-state functional magnetic resonance imaging (fMRI) on stroke patients to determine functional brain networks that exhibited changes in connectivity in association with proprioception deficits determined by a Kinarm robotic exoskeleton assessment. Thirty stroke participants were assessed for proprioceptive impairments using a Kinarm robot and underwent resting-state fMRI at 1 month post-stroke. Age-matched healthy control (n = 30) fMRI data were also examined and compared to stroke data in terms of the functional connectivity of brain regions associated with proprioception. Stroke patients exhibited reduced connectivity of the supplementary motor area and the supramarginal gyrus, relative to controls. Functional connectivity of these regions plus primary somatosensory cortex and parietal opercular area was significantly associated with proprioceptive function. The parietal lobe of the lesioned hemisphere is a significant node for proprioception after stroke. Assessment of functional connectivity of this region after stroke may assist with prognostication of recovery. This study also provides potential targets for therapeutic neurostimulation to aid in stroke recovery.

Errors in proprioceptive matching post-stroke are associated with impaired recruitment of parietal, supplementary motor, and temporal cortices.

Deficits in proprioception, the ability to discriminate the relative position and movement of our limbs, affect ~50% of stroke patients and reduce functional outcomes. Our lack of knowledge of the anatomical correlates of proprioceptive processing limits our understanding of the impact that such deficits have on recovery. This research investigated the relationship between functional impairment in brain activity and proprioception post-stroke. We developed a novel device and task for arm position matching during functional MRI (fMRI), and investigated 16 subjects with recent stroke and nine healthy age-matched controls. The stroke-affected arm was moved by an experimenter (passive arm), and subjects were required to match the position of this limb with the opposite arm (active arm). Brain activity during passive and active arm movements was determined, as well as activity in association with performance error. Passive arm movement in healthy controls was associated with activity in contralateral primary somatosensory (SI) and motor cortices (MI), bilateral parietal cortex, supplementary (SMA) and premotor cortices, secondary somatosensory cortices (SII), and putamen. Active arm matching was associated with activity in contralateral SI, MI, bilateral SMA, premotor cortex, putamen, and ipsilateral cerebellum. In subjects with stroke, similar patterns of activity were observed. However, in stroke subjects, greater proprioceptive error was associated with less activity in ipsilesional supramarginal and superior temporal gyri, and lateral thalamus. During active arm movement, greater proprioceptive error was associated with less activity in bilateral SMA and ipsilesional premotor cortex. Our results enhance our understanding of the correlates of proprioception within the temporal parietal cortex and supplementary/premotor cortices. These findings also offer potential targets for therapeutic intervention to improve proprioception in recovering stroke patients and thus improve functional outcome.

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.

Differential Impact of Acute Lesions Versus White Matter Hyperintensities on Stroke Recovery.

Background Understanding how the size of acute lesions and white matter hyperintensities ( WMH ) impact stroke recovery can improve our ability to predict outcomes and tailor treatments. The aim of this exploratory study was to investigate the role of acute lesion volume and WMH volume on longitudinal recovery of specific sensory, motor, and cognitive impairments after stroke using robotic and clinical measures. Methods and Results Eighty-two individuals were assessed at 1, 6, 12, and 26 weeks poststroke with robotic tasks and commonly used clinical measures. The volumes of acute lesions and WMH were measured on fluid-attenuated inversion recovery images. Linear mixed models were used to investigate the role of acute lesions and WMH on parameters derived from the robotic tasks and clinical measures. Regression analysis determined the added value of acute lesion and WMH volumes along with measures of initial performance to predict outcomes at 6 months. Acute lesion volume has widespread effects on sensory, motor, and overall functional recovery poststroke. The impact of WMH was specific to cognitive impairments. Apart from the robotic position sense task, neither lesion volume nor WMH measure had significant ability to predict outcomes at 6 months over using initial impairment as measured by robotic assessments alone. Conclusions While acute lesion volume and WMH may impact different impairments poststroke, their clinical utility in predicting outcomes at 6 months poststroke is limited.

Illusory limb movements activate different brain networks than imposed limb movements: an ALE meta-analysis.

Proprioceptive information allows us to perform smooth coordinated movements by constantly updating us with knowledge of the position of our limbs in space. How this information is combined and processed to form conscious perceptions of limb position is still relatively unknown. Several functional neuroimaging studies have attempted to tease out the brain areas responsible for proprioceptive processing in the human brain. Yet there still exists some disagreement in the specific brain regions involved. In order to consolidate the current knowledge in the field, we performed a systematic review of the literature and an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies of proprioception. We identified 12 studies that used a proprioceptive stimulus of the upper extremity for ALE analysis (n = 141 participants). Two types of stimuli (illusion of movement induced through muscle tendon vibration and passive/imposed movements) were found to be most commonly used to probe proprioceptive networks in the brain. ALE analysis of these two stimulus types revealed that both were associated with activation in the left precentral, postcentral, and anterior cingulate gyri. Interestingly, different patterns of activation were also observed between illusions of movement and imposed movement. In the left hemisphere, imposed movements resulted in activations that were more inferior in the post-central gyrus. In the right hemisphere, imposed movements resulted in two clusters of activation in the inferior aspect of the precentral gyrus and the hand area of the post-central gyrus, while illusions of movement resulted in a single cluster of activation in the inferior parietal lobule. These results suggest that illusions of movement without limb displacement may activate different brain areas compared with actual limb displacement. Careful consideration should be made in future studies when selecting a proprioceptive stimulus to probe these brain networks.

Using Robotics to Quantify Impairments in Sensorimotor Ability, Visuospatial Attention, Working Memory, and Executive Function After Traumatic Brain Injury.

OBJECTIVE: To investigate the use of a robotic assessment tool to quantify sensorimotor, visuospatial attention, and executive function impairments in individuals with traumatic brain injury (TBI). SETTING: Foothills Hospital (Calgary, Canada). PARTICIPANTS: Twenty-three subjects with first-time TBI in the subacute to chronic phase participated in this study. Normative data were collected from 275 to 494 neurologically intact control subjects for each robotic task. DESIGN: A prospective observational case series. Subjects with TBI completed brief clinical cognitive and motor assessments followed by robotic assessments of upper limb reaching, position sense, bimanual motor ability, attention, and visuospatial skills. Scores of subjects with TBI were compared with normative data. MAIN MEASURES: Robotic task performance was computed for each subject on each task, as well as performance on specific task parameters. Clinical assessments included the Montreal Cognitive Assessment, Fugl-Meyer upper extremity assessment, and Purdue Peg Board. RESULTS: Subjects with TBI demonstrated a variety of deficits on robotic tasks. The proportion of TBI subjects who were significantly different from controls ranged from 36% (dominant arm reaching) to 60% (bimanual object hitting task). CONCLUSION: Robotic measures allowed us to quantify a range of impairments specific to each subject, and offer an objective tool with which to examine these abilities after TBI.

A composite robotic-based measure of upper limb proprioception.

BACKGROUND: Proprioception is the sense of the position and movement of our limbs, and is vital for executing coordinated movements. Proprioceptive disorders are common following stroke, but clinical tests for measuring impairments in proprioception are simple ordinal scales that are unreliable and relatively crude. We developed and validated specific kinematic parameters to quantify proprioception and compared two common metrics, Euclidean and Mahalanobis distances, to combine these parameters into an overall summary score of proprioception. METHODS: We used the KINARM robotic exoskeleton to assess proprioception of the upper limb in subjects with stroke (N = 285. Mean days post-stroke = 12 ± 15). Two aspects of proprioception (position sense and kinesthetic sense) were tested using two mirror-matching tasks without vision. The tasks produced 12 parameters to quantify position sense and eight to quantify kinesthesia. The Euclidean and Mahalanobis distances of the z-scores for these parameters were computed each for position sense, kinesthetic sense, and overall proprioceptive function (average score of position and kinesthetic sense). RESULTS: A high proportion of stroke subjects were impaired on position matching (57%), kinesthetic matching (65%), and overall proprioception (62%). Robotic tasks were significantly correlated with clinical measures of upper extremity proprioception, motor impairment, and overall functional independence. Composite scores derived from the Euclidean distance and Mahalanobis distance showed strong content validity as they were highly correlated (r = 0.97-0.99). CONCLUSIONS: We have outlined a composite measure of upper extremity proprioception to provide a single continuous outcome measure of proprioceptive function for use in clinical trials of rehabilitation. Multiple aspects of proprioception including sense of position, direction, speed, and amplitude of movement were incorporated into this measure. Despite similarities in the scores obtained with these two distance metrics, the Mahalanobis distance was preferred.

Robotic Characterization of Ipsilesional Motor Function in Subacute Stroke.

BACKGROUND: Poststroke impairments of the ipsilesional arm are often discussed, but rarely receive focused rehabilitation. Ipsilesional deficits may affect daily function and although many studies have investigated them in chronic stroke, few characterizations have been made in the subacute phase. Furthermore, most studies have quantified ipsilesional deficits using clinical measures that can fail to detect subtle, but important deficits in motor function. OBJECTIVE: We aimed to quantify reaching deficits of the contra- and ipsilesional limbs in the subacute phase poststroke. METHODS: A total of 227 subjects with first-time, unilateral stroke completed a unilateral assessment of motor function (visually guided reaching) using a KINARM robot. Subjects completed the task with both the ipsi- and contralesional arms. Subjects were assessed on a variety of traditional clinical measures (Functional Independence Measure, Chedoke-McMaster Stroke Assessment, Purdue Pegboard, Behavioral Inattention Test) to compare with robotic measures of motor function. RESULTS: Ipsilesional deficits were common and occurred in 37% (n = 84) of subjects. Impairments of the ipsilesional and contralesional arm were weakly to moderately correlated on robotic measures. Magnitude of impairment of the contralesional arm was similar for subjects with and without ipsilesional deficits. Furthermore, we found that a higher percentage of subjects with right-hemisphere stroke had ipsilesional deficits and more subjects with left-hemisphere subcortical strokes did not have ipsilesional deficits. CONCLUSIONS: Magnitude of contralesional impairment and lesion location may be poor predictors of individuals with ipsilesional impairments after stroke. Careful characterization of ipsilesional deficits could identify individuals who may benefit from rehabilitation of the less affected arm.

Localization of Impaired Kinesthetic Processing Post-stroke.

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects (N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network.

Central perception of position sense involves a distributed neural network - Evidence from lesion-behavior analyses.

It is well established that proprioceptive inputs from the periphery are important for the constant update of arm position for perception and guiding motor action. The degree to which we are consciously aware of the position of our limb depends on the task. Our understanding of the central processing of position sense is rather limited, largely based on findings in animals and individual human case studies. The present study used statistical lesion-behavior analysis and an arm position matching task to investigate position sense in a large sample of subjects after acute stroke. We excluded subjects who performed abnormally on clinical testing or a robotic visually guided reaching task with their matching arm in order to minimize the potential confound of ipsilesional impairment. Our findings revealed that a number of regions are important for processing position sense and include the posterior parietal cortex, the transverse temporal gyrus, and the arcuate fasciculus. Further, our results revealed that position sense has dissociable components - spatial variability, perceived workspace area, and perceived workspace location. Each component is associated with unique neuroanatomical correlates. These findings extend the current understanding of the neural processing of position sense and identify some brain areas that are not classically associated with proprioception.

Lesion Sites Associated with Allocentric and Egocentric Visuospatial Neglect in Acute Stroke.

Visuospatial neglect is a disorder that can often result from stroke and is characterized by an inability to attend to contralesional stimuli. Two common subtypes include allocentric (object-centered) neglect and egocentric (viewer-centered) neglect. In allocentric neglect, spatial inattention is localized to the contralesional side of an object regardless of its relative position to the observer. In egocentric neglect, spatial inattention is localized to the contralesional side of the individual's midline. The neuroanatomical correlates of each subtype are unknown. However, recent work has suggested that damage to temporal, inferior parietal, and occipital areas may result in allocentric neglect and that damage to frontoparietal areas may result in egocentric neglect. We used voxel-based lesion-symptom mapping (VLSM) to compare lesion location to behavioral performance on the conventional six subtests of the Behavioral Inattention Test (BIT) in 62 subjects with acute right hemisphere ischemic stroke. Results identified an anatomical dissociation in lesion location between subjects with neglect based on poor performance on allocentric tests (line bisection, copying, and drawing tasks) and on egocentric tests (star, letter, and line cancellation). VLSM analyses revealed that poor performance on the allocentric tests was associated with lesions to the superior and inferior parietal cortices, and the superior and middle temporal gyri. In contrast, poor performance on the egocentric tests was associated with lesions in the precentral gyrus, middle frontal gyrus, insula, and putamen. Interestingly, the letter cancellation test and average performance on egocentric tests were associated with frontal and parietal lesions. Some of these parietal lesion locations overlapped with lesion locations associated with allocentric neglect. These findings are consistent with suggestions that damage to temporal and parietal areas is more associated with allocentric neglect and damage to frontal lobe areas is more associated with egocentric neglect.

Anatomical correlates of proprioceptive impairments following acute stroke: a case series.

BACKGROUND: Proprioception is the sensation of position and movement of our limbs and body in space. This sense is important for performing smooth coordinated movements and is impaired in approximately 50% of stroke survivors. In the present case series we wanted to determine how discrete stroke lesions to areas of the brain thought to be critical for somatosensation (thalamus, posterior limb of internal capsule, primary somatosensory cortex and posterior parietal cortex) would affect position sense and kinesthesia in the acute stages post-stroke. Given the known issues with standard clinical measures of proprioception (i.e. poor sensitivity and reliability) we used more modern quantitative robotic assessments to measure proprioception. METHODS: Neuroimaging (MRI, n=10 or CT, n=2) was performed on 12 subjects 2-10 days post-stroke. Proprioception was assessed using a KINARM robot within the same time frame. Visually guided reaching was also assessed to allow us to compare and contrast proprioception with visuomotor performance. RESULTS AND CONCLUSIONS: Proprioceptive impairments were observed in 7 of 12 subjects. Thalamic lesions (n=4) were associated with position sense (n=1) or position sense and kinesthesia (n=1) impairments. Posterior limb of the internal capsule lesions (n=4) were associated with primarily position sense (n=1) or kinesthesia (n=2) impairments. Lesions affecting primary somatosensory cortex and posterior parietal cortex (n=2) were associated with significant position sense and kinesthesia impairments. All subjects with damage to hypothesized structures displayed impairments with performance on the visually guided reaching task. Across the proprioceptive tasks, we saw that position sense and kinesthesia were impaired to differing degrees, suggesting a potential dissociation between these two components of proprioception.