Faculty Bibliography

Background: Symptoms related to impaired visuospatial function are relatively common in patients with Parkinson's disease (PD). Restricted visual processing can directly hamper patients' motor function. For example, systematic biases in visual perception may influence navigational veering, thus directly affecting locomotion. In patients with PD, an impaired visual function is linked to negative feelings including depression, fearfulness and reduced self-efficacy. Art Therapy (AT) has the potential of recruiting different neural networks, including those concerned with high visual conscious perception. As such, AT may serve as a neurobehavioral intervention to improve multiple functional domains, including visuospatial functions and emotional wellness.
Method(s): This is a dual-phase exploratory study. 1: cross-sectional, controlled, biomarker study on 30 non-demented PD patients (H&Y 2-3) and 30 age-matched controls; 2: prospective, open label study involving 20 sessions of AT (2sessions/week). Motor and gait functions were assessed by MDS-UPDRS, Timed Up and Go test (TUG), and wearable accelerometers. Cognitive and Visuospatial functions were assessed by neuropsychological inventories (MoCA, Rey-Osterrieth FigureTest, Benton Visual Test), computerized testing (Navon VisualTest, Visual Research Test, and visual reaction time), and binocular eyetracking (Eyelink 2). Psychological wellness was assessed by Beck Depression Index (BDI), Modified Fatigue Impact Scale, and PROMIS-Self-Efficacy scales. Brain imaging included T1-weighted 3D high resolution, DWI, and RSfMRI sequences. Preliminary analyses were conducted on clinical data from 18 PD-patients and 14 controls completing the study. Eye tracking from 4 subjects was analyzed for exploratory purposes.
Result(s): PD-patients and controls were significantly different with respect to BDI score, Navon Visual Test, Rey Figure Test, UPDRSIII, and TUG-3 (maximum gait speed). Following AT, PD patients showed significant improvements in UPDRS-III, UPDRS-total, PROMIS (symptoms management), and Navon Visual Test (number of errors). A strong trend towards improved ReyeFigureTest was observed. On eye tracking analysis, significant increases in exploratory eye movements and fixation patterns were observed spatiotopically during examined stimulus regions.
Discussion(s): According to our preliminary findings, AT may improve visual-constructional abilities, visual recognition, and motor function. These improvements are accompanied by increased self-efficacy and changes in oculomotor behavior characterized by a more efficient visual exploration strategy. The duration of these potential benefits as well as their underlying mechanisms remain to be determined

Accurate detection and interpretation of eye movement abnormalities often guides differential diagnosis, discussions on prognosis and disease mechanisms, and directed treatment of disabling visual symptoms and signs. A comprehensive clinical eye movement examination is high yield from a diagnostic standpoint; however, skillful recording and quantification of eye movements can increase detection of subclinical deficits, confirm clinical suspicions, guide therapeutics, and generate expansive research opportunities. This review encompasses an overview of the clinical eye movement examination, provides examples of practical diagnostic contributions from quantitative recordings of eye movements, and comments on recording equipment and related challenges.

Opsoclonus/flutter (O/F) is a rare disorder of the saccadic system. Previously, we modeled O/F that developed in a patient following abuse of anabolic steroids. That model, as in all models of the saccadic system, generates commands to make a change in eye position. Recently, we saw a patient who developed a unique form of opsoclonus following a concussion. The patient had postsaccadic ocular flutter in both directions of gaze, and opsoclonus during fixation and pursuit in the left hemifield. A new model of the saccadic system is needed to account for this gaze-position dependent O/F. We started with our prior model, which contains two key elements, mutual inhibition between inhibitory burst neurons on both sides and a prolonged reactivation time of the omnipause neurons (OPNs). We included new inputs to the OPNs from the nucleus prepositus hypoglossi and the frontal eye fields, which contain position-dependent neurons. This provides a mechanism for delaying OPN reactivation, and creating a gaze-position dependence. A simplified pursuit system was also added, the output of which inhibits the OPNs, providing a mechanism for gaze-dependence during pursuit. The rest of the model continues to generate a command to change eye position.

Within the domain of motor performance, eye-hand coordination centers on close relationships between visuo-perceptual, ocular and appendicular motor systems. This coordination is critically dependent on a cycle of feedforward predictions and feedback-based corrective mechanisms. While intrinsic feedback harnesses naturally available movement-dependent sensory channels to modify movement errors, extrinsic feedback may be provided synthetically by a third party for further supplementation. Extrinsic feedback has been robustly explored in hand-focused, motor control studies, such as through computer-based visual displays, highlighting the spatial errors of reaches. Similar attempts have never been tested for spatial errors related to eye movements, despite the potential to alter ocular motor performance. Stroke creates motor planning deficits, resulting in the inability to generate predictions of motor performance. In this study involving visually guided pointing, we use an interactive computer display to provide extrinsic feedback of hand endpoint errors in an initial baseline experiment (pre-) and then feedback of both eye and hand errors in a second experiment (post-) to chronic stroke participants following each reach trial. We tested the hypothesis that extrinsic feedback of eye and hand would improve predictions and therefore feedforward control. We noted this improvement through gains in the spatial and temporal aspects of eye-hand coordination or an improvement in the decoupling noted as incoordination post-stroke in previous studies, returning performance toward healthy, control behavior. More specifically, results show that stroke participants, following the interventional feedback for eye and hand, improved both their accuracy and timing. This was evident through a temporal re-synchronization between eyes and hands, improving correlations between movement timing, as well as reducing the overall time interval (delay) between effectors. These experiments provide a strong indication that an extrinsic feedback intervention at appropriate therapeutic doses may improve eye-hand coordination during stroke rehabilitation.

Opsoclonus consists of bursts of involuntary, multidirectional, back-to-back saccades without an intersaccadic interval. We report a 60-year-old man with post-concussive headaches and disequilibrium who had small amplitude opsoclonus in left gaze, along with larger amplitude flutter during convergence. Examination was otherwise normal and brain MRI was unremarkable. Video-oculography demonstrated opsoclonus predominantly in left gaze and during pursuit in the left hemifield, which improved as post-concussive symptoms improved. Existing theories of opsoclonus mechanisms do not account for this eye position-dependence. We discuss theoretical mechanisms of this behavior, including possible dysfunction of frontal eye field and/or cerebellar vermis neurons; review ocular oscillations in traumatic brain injury; and consider the potential relationship between the larger amplitude flutter upon convergence and post-traumatic ocular oscillations.

OBJECTIVE:The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation. Measures of rapid automatic naming (RAN) have been used for over 50 years to capture aspects of vision and cognition. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. We examined MULES performance in youth, collegiate and professional athletes at pre-season baseline and at the sidelines following concussion. METHODS:Our study teams administered the MULES to youth, collegiate and professional athletes during pre-season baseline testing. Sideline post-concussion time scores were compared to pre-season baseline scores among athletes with concussion to determine degrees and directions of change. RESULTS:Among 681 athletes (age 17 ± 4 years, range 6-37, 38% female), average test times at baseline were 41.2 ± 11.2 s. The group included 280 youth, 357 collegiate and 44 professional athletes; the most common sports were ice hockey (23%), soccer (17%) and football (11%). Age was a predictor of MULES test times, with longer times noted for younger participants (P < .001, linear regression). Consistent with other timed performance measures, significant learning effects were noted for the MULES during baseline testing with trial 1 test times (mean 49.2 ± 13.1 s) exceeding those for trial 2 (mean 41.3 ± 11.2 s, P < .0001, paired t-test). Among 17 athletes with concussion during the sports seasons captured to date (age 18 ± 3 years), all showed increases (worsening) of MULES time scores from pre-season baseline (median increase 11.2 s, range 0.6-164.2, P = .0003, Wilcoxon signed-rank test). The Symptom Severity Score from the SCAT5 Symptom Evaluation likewise worsened from pre-season baseline following injury among participants with concussion (P = .002). CONCLUSIONS:Concussed athletes demonstrate worsening performance on the MULES test compared to their baseline time scores. This test samples a wide network of brain pathways and complements other vision-based measures for sideline concussion assessment. The MULES test demonstrates capacity to identify athletes with sports-related concussion.