Faculty Bibliography

Objective: To assess relationships between classic saccade sequences and rapid number naming on the King Devick (K-D) test in concussion. Background: The K-D test is sensitive for concussion detection on athletic sidelines, with longer test times in concussion largely due to inter-saccadic interval (ISI) prolongation. The ISI is a measure of time between saccades that represents a combination of fixation duration and saccade latency. K-D saccade latency cannot be directly measured, as numbers are simultaneously displayed. We assessed saccade latency independent of K-D test. Design/Methods: Twenty-seven chronically concussed participants (mean age 32+/-13 years, range 17-61) and 19 healthy controls (mean age 29+/-8 years, range 19-48) performed K-D and saccade sequences: reflexive, gap, overlap, and antisaccades. Eye movements were recorded with EyeLink 1000+ video-oculography. Results: K-D test times were longer in concussion (54.6s vs 41.5s, p=0.001), as were ISIs (301.9ms vs 241.4ms, p=0.01). Longer reflexive and overlap latencies (reflexive: 198.1ms vs 176.7ms, p=0.04; overlap: 222.3ms vs 182.8ms, p=0.003) and worse accuracy were seen in concussion. Gap latencies showed no difference (160.6ms vs 148.8ms, p=0.13). Antisaccade latencies were longer in concussion (204.9ms vs 182.3ms, p=0.04) for saccades initially made in the incorrect direction, though there was no difference in error rates. Peak velocity and duration versus amplitude relationships showed no differences between groups. Conclusions: ISI prolongation during K-D performance could be due to increased saccade latencies and/or attention and cognitive impairment. In this study, saccade latency prolongation is seen in several saccade types in concussion, suggesting that it may, indeed, contribute to K-D ISI prolongation in concussion. Further, overlap saccade latency prolongation suggests that pre-saccade visual fixation disengagement is altered in concussion. These results suggest that saccade motor planning is impaired in concussion, possibly from damage to frontal lobe saccade control centers prone to traumatic injury

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a new test of rapid picture naming that is under investigation in youth, collegiate and professional athlete cohorts as a concussion screening tool. The purpose of this study is to determine the ocular motor underpinnings, including saccade characteristics, required to perform this vision-based performance measure. Background: The MULES includes 54 color photographs of fruits, objects and animals. It has demonstrated excellent feasibility for administration among adult volunteers and in cohorts of athletes of all ages at pre-season baseline. MULES likely captures a more extensive vision network in the brain compared to rapid number naming, integrating saccades, color perception and object identification. Video-oculographic studies of the King-Devick (K-D) test of rapid number naming demonstrate prolonged inter-saccadic intervals (ISI) among individuals with longer testing times. Design/Methods: Participants underwent testing with the paper-based MULES as well as the computer screen-based version (eMULES) designed for simultaneous testing with infrared-based video-oculography (Eye Link 1000+). Saccade velocity, duration and the inter-saccadic interval were measured. Results: Among adult volunteers (n=23, aged 19-45) and patients with recent concussion (n=6, aged 17-43), those with the greatest number of saccades had the longest eMULES completion times ( f0 . 48 , p=0.008). In this cohort, prolonged ISI was not associated with greater eMULES testing times (AS=0.06, p=0.76). Conclusions: Longer testing times for the MULES likely reflect greater numbers of saccades rather than prolongation of the ISI. This pattern may reflect greater degrees of cognitive activity and visual pathway complexity for picture compared to number naming. Underlying dynamics for eye movements are likely to differ between the MULES and K-D, supporting complementary roles for each in concussion assessment

Objective: To compare video-oculography performed by EyeTribe versus EyeLink during a rapid number naming task. Background: With increasing accessibility of portable, economical, video-based, infrared eye trackers, such as EyeTribe, there is growing interest in eye movement recordings, including in the setting of sports-related concussion. However, prior to implementation, there is a primary need to establish the validity of these low-resolution (30-60 Hz) eye trackers via comparison with high-resolution (500-1000 Hz) devices such as EyeLink. Design/Methods: A convenience sample of 30 controls performed a digitized version of the King-Devick (K-D) test with EyeTribe and EyeLink eye movement recordings. Results: Signal loss and tracings inconsistent with eye movement physiology were common with EyeTribe. Saccade main sequence parameters (fit to decaying exponentials) were significantly different for the two devices (reported as best-fit parameter and 95% confidence interval). Peak velocity versus amplitude relationships revealed a main sequence asymptote of 1674degree/s (CI: 1527, 1852degree/s) for EyeTribe vs. 506degree/s (CI: 499, 513degree/s) for EyeLink and a time constant of 102.9degree (CI: 93.5,115.7degree) for EyeTribe vs. 6.1degree (CI: 5.3, 6.3degree) for EyeLink. Duration versus amplitude relationships also demonstrated significant differences, with an asymptote of 62.7ms (CI: 61.0, 64.3ms) for EyeTribe vs. 83.2ms (CI: 82.2, 84.4ms) for EyeLink and time constant of 4.9degree (CI: 4.6, 5.3degree) for EyeTribe vs. 13.8degree (CI: 13.6, 14.1degree) for EyeLink. Total number of saccades to complete the K-D was significantly lower with EyeTribe, with an average of 110.2 vs. 120.5 saccades recorded by EyeTribe and EyeLink respectively (paired t-test, p=0.001). There was no significant difference in the inter-saccadic interval, despite a discrepancy of 42ms between devices. Conclusions: The EyeTribe device was unable to capture valid saccade data during rapid number naming. Caution is advised regarding the implementation of eye trackers with low temporal resolution for objective saccade assessment or sideline concussion screening

Objective: To describe a case of gaze-position dependent opsoclonus and discuss potential localization. Background: Opsoclonus is characterized by bursts of involuntary, back-to-back saccades without an intersaccadic interval at frequency of 10-25 Hz in horizontal, vertical, and torsional planes. Opsoclonus with gaze-directional selectivity has been rarely described. Design/Methods: We report a 50 year-old man who sustained a concussion three years prior followed by postconcussive headaches and disequilibrium. Exam revealed very small amplitude oscillations in left gaze that could not be further characterized on clinical exam. Different larger amplitude horizontal oscillations were present with convergence. There were no other posterior fossa signs. Brain MRI was unremarkable. Results: Video-oculography demonstrated opsoclonus predominantly in left gaze [median amplitude 5 deg (range <1- 11 deg), frequency 30 Hz] and during leftward smooth pursuit, which improved [median amplitude 2 deg (range < 1-10 deg), frequency 10 Hz] as post-concussive symptoms improved. Conclusions: This case demonstrates opsoclonus with eye position selectivity in post-concussive syndrome. Various theories of opsoclonus exist, including lesions of saccade burst, omnipause, or cerebellar fastigial pause neurons which project to brainstem burst neurons. Ultimately, all of these lead to increased excitability in the inherently unstable saccade generators. Burst and omnipause neuron firing rates are not influenced by eye position. The leftward gaze-dependence in our case supports dysfunction of cerebellar dorsal vermis Purkinje cells leading to disinhibition of the fastigial ocular motor nucleus, as vermal pause neurons have gaze-directional selectivity. Vermal pause neurons exhibit a pause of discharge immediately before and during contralateral saccades. Thus, selective dysfunction, possibly related to concussion-related membrane instability, could create an imbalance in burst neuron excitability, resulting in triggering of unidirectional opsoclonus. Further, our patient's saccade system may be inherently prone to oscillations given the presence of larger amplitude horizontal oscillations consistent with 'voluntary flutter', which persisted when leftward opsoclonus improved

Objective: This study introduces the Mobile Universal Lexicon Evaluation System (MULES), a new vision-based test of rapid picture naming, in a cohort of youth and collegiate athletes at pre-season concussion testing. Background: Vision-based measures of rapid number naming (King-Devick [K-D]) have improved the sensitivity of sports-related concussion screening. K-D requires saccades and vergence, measuring aspects of frontal, parietal and brainstem centers. We developed the MULES to capture a more extensive vision network, integrating saccades, color perception, and object identification. Design/Methods: We administered MULES and K-D to youth and collegiate athletes during pre-season baseline testing. Sports for 2016-17 included ice hockey, football, soccer, volleyball and wrestling. Test administration order was randomized. Results: Among 165 athletes (age 14+/-5 years, range 6-24, 25% female), average K-D times (59.9+/-29.7 seconds) were similar to MULES (57.9+/-20.4 seconds). Higher K-D times predicted greater MULES times, accounting for age (p<0.001, linear regression). Age was itself a predictor of K-D and MULES time scores, with longer times noted for younger participants (p<0.001). Faster times with increasing age were noted primarily among athletes <16 years for K-D and <15 years for MULES. MULES showed greater degrees of improvement between two baseline trials (57.9 vs. 51.2 seconds, p<0.0001, paired t-test), vs. K-D (59.9 vs. 58.3 seconds, p=0.01). Conclusions: A complex task, the MULES test of rapid picture naming involves a more extensive visual network that captures not only rapid saccades but color perception and the characterization of objects. Color recognition is early in object processing and requires area V4 and the inferior temporal projections. In contrast, rapid number naming appears to engage a specific area of the inferior temporal cortex. Both tests use the centers responsible for initiating and sequencing saccadic eye movements, and will be further examined in our youth and collegiate cohorts during this athletic season for their ability to detect concussion

Acute and chronic disease processes that lead to cerebral injury can often be clinically challenging diagnostically, prognostically, and therapeutically. Neurodegenerative processes are one such elusive diagnostic group, given their often diffuse and indolent nature, creating difficulties in pinpointing specific structural abnormalities that relate to functional limitations. A number of studies in recent years have focused on eye-hand coordination (EHC) in the setting of acquired brain injury (ABI), highlighting the important set of interconnected functions of the eye and hand and their relevance in neurological conditions. These experiments, which have concentrated on focal lesion-based models, have significantly improved our understanding of neurophysiology and underscored the sensitivity of biomarkers in acute and chronic neurological disease processes, especially when such biomarkers are combined synergistically. To better understand EHC and its connection with ABI, there is a need to clarify its definition and to delineate its neuroanatomical and computational underpinnings. Successful EHC relies on the complex feedback- and prediction-mediated relationship between the visual, ocular motor, and manual motor systems and takes advantage of finely orchestrated synergies between these systems in both the spatial and temporal domains. Interactions of this type are representative of functional sensorimotor control, and their disruption constitutes one of the most frequent deficits secondary to brain injury. The present review describes the visually mediated planning and control of eye movements, hand movements, and their coordination, with a particular focus on deficits that occur following neurovascular, neurotraumatic, and neurodegenerative conditions. Following this review, we also discuss potential future research directions, highlighting objective EHC as a sensitive biomarker complement within acute and chronic neurological disease processes.

Introduction Disturbances of eye movements are infrequently encountered in motor neuron diseases or motor neuropathies, and there is no known syndrome that combines progressive muscle weakness with downbeat nystagmus. Methods To describe the core clinical features of a syndrome of motor neuron disease associated with downbeat nystagmus, clinical features were collected from 6 patients. Results All patients had slowly progressive muscle weakness and wasting, in combination with downbeat nystagmus, which was clinically most obvious in downward and lateral gaze. Onset was in the second to fourth decade, with finger extension weakness, progressing to other distal and sometimes more proximal muscles. Visual complaints were not always present. Electrodiagnostic testing showed signs of regional motor axonal loss in all patients. Discussion The etiology of this syndrome remains elusive. As finger extension weakness and downbeat nystagmus are the discriminating clinical features of this motor neuron disease, we propose the name FEWDON-MND syndrome

The King-Devick (K-D) test of rapid number naming is a visual performance measure that captures saccadic eye movements. Patients with multiple sclerosis (MS) have slowed K-D test times associated with neurologic disability and reduced quality of life. We assessed eye movements during the K-D test to identify characteristics associated with slowed times. Participants performed a computerized K-D test with video-oculography. The 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and its 10-Item Neuro-Ophthalmic Supplement measured vision-specific quality of life (VSQOL). Among 25 participants with MS (age 37 +/- 10 years, range 20-59) and 42 controls (age 33 +/- 9 years, range 19-54), MS was associated with significantly longer (worse) K-D times (58.2 +/- 19.8 vs. 43.8 +/- 8.6 s, P = 0.001, linear regression models, accounting for age). In MS, test times were slower among patients with higher (worse) Expanded Disability Status Scale scores (P = 0.01). Average inter-saccadic intervals (ISI) were significantly longer in MS participants compared to controls (362 +/- 103 vs. 286 +/- 50 ms, P = 0.001), and were highly associated with prolonged K-D times in MS (P = 0.006). MS participants generated greater numbers of saccades (P = 0.007). VSQOL scores were reduced in MS patients with longer (worse) K-D times (P = 0.04-0.001) and longer ISI (P = 0.002-0.001). Patients with MS have slowed K-D times that may be attributable to prolonged ISI and greater numbers of saccades. The K-D test and its requisite eye movements capture VSQOL and make rapid number naming a strong candidate efferent visual performance measure in MS.

While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy-related inflammation proven by brain biopsy, she was treated successfully with immunosuppression.

Saccades rapidly direct the line of sight to targets of interest to make use of the high acuity foveal region of the retina. These fast eye movements are instrumental for scanning visual scenes, foveating targets, and, ultimately, serve to guide manual motor control, including eye-hand coordination. Cerebral injury has long been known to impair ocular motor control. Recently, it has been suggested that alterations in control may be useful as a marker for recovery. We measured eye movement control in a saccade task in subjects with chronic middle cerebral artery stroke with both cortical and substantial basal ganglia involvement and in healthy controls. Saccade latency distributions were bimodal, with an early peak at 60 ms (anticipatory saccades) and a later peak at 250 ms (regular saccades). Although the latencies corresponding to these peaks were the same in the two groups, there were clear differences in the size of the peaks. Classifying saccade latencies relative to the saccade "go signal" into anticipatory (latencies up to 80 ms), "early" (latencies between 80 and 160 ms), and "regular" types (latencies longer than 160 ms), stroke subjects displayed a disproportionate number of anticipatory saccades, whereas control subjects produced the majority of their saccades in the regular range. We suggest that this increase in the number of anticipatory saccade events may result from a disinhibition phenomenon that manifests as an impairment in the endogenous control of ocular motor events (saccades) and interleaved fixations. These preliminary findings may help shed light on the ocular motor deficits of neurodegenerative conditions, results that may be subclinical to an examiner, but clinically significant secondary to their functional implications.