Robot-Aided Assessment of Ankle Motion Sense and Associated Lesion-Symptom Mapping Analysis in Chronic Stroke

Abstract

Background: Compromised ankle proprioception is a strong predictor of balance dysfunction in chronic stroke. However, objective, accurate methods for testing ankle proprioceptive function in clinical settings are not established. Only sparse data on ankle position sense and no systematic data on ankle motion sense dysfunction in stroke are available. Moreover, the lesion sites underlying impaired ankle proprioception have not been comprehensively delineated.Objectives: To address these knowledge gaps, this study aimed: 1) To examine the feasibility and test-retest reliability of a newly developed robotic technology that uses an adaptive psychophysical forced-choice method to obtain quantitative data on ankle position and motion sense acuity in healthy young adults. 2) To determine the extent and magnitude of ankle motion sense impairment observed in adults with chronic stroke and how such impairment coincides with position sense dysfunction using the robotic system. 3) To identify the brain lesions associated with ankle position and motion sense dysfunction. Methods: To verify aim 1, experiments 1 and 2 were conducted successively. Forty healthy adults (20 in each experiment, mean ± SD age 24 ± 3.9 years, F: 17) were recruited. The feasibility and test-retest reliability of the system were determined in Experiment 1. Experiment 2 was conducted to improve the motion sense test paradigm that controlled for confounding factors (time and position) that a person might use as motion cues to make a perceptual judgment of ankle joint motion. To verify aim 2 and 3, twelve stroke survivors (mean ± SD age, 54 ± 10.9 years, on average 6 years post-stroke, 10 ischemic, 2 hemorrhagic lesions), and 13 neurotypical adults participated. During the testing, the robot passively plantarflexed a participant’s ankle to two distinct positions or at two distinct velocities. Participants subsequently indicated which of the two movements was further/faster. Based on the stimulus-response data, a psychometric function was obtained, and just-noticeable-difference (JND) thresholds, as a measure of bias, and intervals of uncertainty (IU), as a measure of precision were derived. For adults with stroke (n = 11), lesion-symptom analyses identified the brain lesions associated with observed proprioceptive deficits in adults with stroke. Results: For aim 1, objective data on position sense acuity (JND threshold: 0.80° ± 0.10°, IU: 0.84° ± 0.41°) and motion sense acuity (JND threshold: 0.73°/s ± 0.11°/s, IU: 0.60°/s ± 0.29°/s) were obtained in experiment 1. Additionally, moderate-to-excellent test-retest reliability of the system has been established based on the JND threshold for position sense (average intraclass correlation coefficient (ICC) = 0.86 [0.50 - 0.98], standard error of measurement (SEM) = 0.0173°) and motion sense (average ICC = 0.88, SEM = 0.0197°/s). In experiment 2, the results showed that the mean JND motion sense threshold increased almost linearly from 0.53°/s at the 10°/s reference to 1.6°/s at 20°/s (p < 0.0001). Perceptual uncertainty increased similarly (median IU = 0.33°/s at 10°/s and 0.97°/s at 20°/s; p < 0.0001). Both measures were strongly correlated (rs = 0.70). For aim 2, 83% of adults with stroke exhibited abnormalities in either position or motion sense, or both. JND and IU measures were significantly elevated compared to the control group (JNDPosition: +77%, p = 0.03; JNDMotion: +153%, IUPosition: +148%, and IUMotion: +78%, all p < 0.01). The JND and IU values of both senses were strongly positively correlated (rs = 0.56-0.62). For aim 3, lesions in the primary somatosensory, posterior parietal, motor cortices, insula, and temporoparietal regions (supramarginal, superior temporal, Heschl's gyri) were associated with deficits in both senses. Meanwhile, lesions in the medial/lateral occipital cortex were linked to impaired position sense, and temporal pole lesions were associated with impaired motion sense. Moreover, temporal pole lesions were significantly related to motion sense deficit (z-score = 3.26). Conclusion: This research demonstrated that the proposed robot-aided test produces quantitative data on human ankle position and motion sense acuity. It yields two distinct measures of proprioceptive acuity (i.e., bias and precision) as part of a comprehensive analysis of proprioceptive function. Using the robot-aided assessment, this study documented the initial data on the magnitude and prevalence of ankle position and motion sense impairment in adults with chronic stroke. Proprioceptive dysfunction was characterized by elevated JND thresholds and increased uncertainty in perceiving ankle position/motion. Associated cortical lesions for both proprioceptive senses were largely overlapping, but temporal pole lesions were independently linked to motion sense dysfunction.