Faculty Bibliography

(1) Background: The King-Devick (KD) rapid number naming test is sensitive for concussion diagnosis, with increased test time from baseline as the outcome measure. Eye tracking during KD performance in concussed individuals shows an association between inter-saccadic interval (ISI) (the time between saccades) prolongation and prolonged testing time. This pilot study retrospectively assesses the relation between ISI prolongation during KD testing and cognitive performance in persistently-symptomatic individuals post-concussion. (2) Results: Fourteen participants (median age 34 years; 6 women) with prior neuropsychological assessment and KD testing with eye tracking were included. KD test times (72.6 ± 20.7 s) and median ISI (379.1 ± 199.1 msec) were prolonged compared to published normative values. Greater ISI prolongation was associated with lower scores for processing speed (WAIS-IV Coding, r = 0.72, p = 0.0017), attention/working memory (Trails Making A, r = -0.65, p = 0.006) (Digit Span Forward, r = 0.57, p = -0.017) (Digit Span Backward, r= -0.55, p = 0.021) (Digit Span Total, r = -0.74, p = 0.001), and executive function (Stroop Color Word Interference, r = -0.8, p = 0.0003). (3) Conclusions: This pilot study provides preliminary evidence suggesting that cognitive dysfunction may be associated with prolonged ISI and KD test times in concussion.

Voluntary rapid eye movements (saccades) redirect the fovea toward objects of visual interest. The saccadic system can be considered as a dual-mode system: in one mode the eye is fixating, in the other it is making a saccade. In this review, we consider two examples of dysfunctional saccades, interrupted saccades in late-onset Tay-Sachs disease and gaze-position dependent opsoclonus after concussion, which fail to properly shift between fixation and saccade modes. Insights and benefits gained from bi-directional collaborative exchange between clinical and basic scientists are emphasized. In the case of interrupted saccades, existing mathematical models were sufficiently detailed to provide support for the cause of interrupted saccades. In the case of gaze-position dependent opsoclonus, existing models could not explain the behavior, but further development provided a reasonable hypothesis for the mechanism underlying the behavior. Collaboration between clinical and basic science is a rich source of progress for developing biologically plausible models and understanding neurological disease. Approaching a clinical problem with a specific hypothesis (model) in mind often prompts new experimental tests and provides insights into basic mechanisms.

The quantitative analysis of saccades in eye movement data unveils information associated with intention, cognition, and health status. Abnormally slow saccades are indicative of neurological disorders and often imply a specific pathological disturbance. However, conventional saccade detection algorithms are not designed to detect slow saccades, and are correspondingly unreliable when saccades are unusually slow. In this article, we propose an algorithm that is effective for the detection of both normal and slow saccades. The proposed algorithm is partly based on modeling saccadic waveforms as piecewise-quadratic signals. The algorithm first decreases noise in acquired eye-tracking data using optimization to minimize a prescribed objective function, then uses velocity thresholding to detect saccades. Using both simulated saccades and real saccades generated by healthy subjects and patients, we evaluate the performance of the proposed algorithm and 10 other detection algorithms. We show the proposed algorithm is more accurate in detecting both normal and slow saccades than other algorithms.

The transformation of patient-clinician relationships with AI-based medical advice is discussed. many new tools are based on entirely new "˜black-box"™ AI-based technologies, whose inner workings are likely not fully understood by patients or clinicians. Most patients with Type 1 diabetes now use continuous glucose monitors and insulin pumps to tightly manage their disease. Their clinicians carefully review the data streams from both devices to recommend dosage adjustments. Recently new automated recommender systems to monitor and analyze food intake, insulin doses, physical activity, and other factors influencing glucose levels, and provide data-intensive, AI-based recommendations on how to titrate the regimen, are in different stages of FDA approval using "˜black box"™ technology, which is an alluring proposition for a clinical scenario that requires identification of meaningful patterns in complex and voluminous data.

OBJECTIVE:To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). METHODS:Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. RESULTS:At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. INTERPRETATION/CONCLUSIONS:Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.

Background: Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task. Methods: Participants performed KD testing during oculography following instructions to sandbag or give best effort. Results: Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, p < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, p < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, p < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, p < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics. Conclusions: KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.

Sialidosis type 1 is a rare lysosomal storage disorder caused by mutations of the neuraminidase gene. Specific features suggesting this condition include myoclonus, ataxia and macular cherry-red spots. However, phenotypic variability exists. Here, we present detailed clinical and video description of three patients with this rare condition. We also provide an in-depth characterization of eye movement abnormalities, as an additional tool to investigate pathophysiological mechanisms and to facilitate diagnosis. In our patients, despite phenotypic differences, eye movement deficits largely localized to the cerebellum.