Saccadic Peak Velocity Research Articles

Characteristics of horizontal saccades in children with intermittent exotropia

PurposeTo analyze the peak velocity and gain of horizontal saccades in children diagnosed with intermittent exotropia (IXT) and to compare these measurements with those obtained from children without strabismus. MethodsParticipants included children ≤12 years of age with IXT and no history of strabismus surgery and children without strabismus. The peak velocity and gain of horizontal saccades recorded using an eye tracker were analyzed. ResultsA total of 48 children (including 38 with IXT) were included. In the IXT group, the angles of deviation at near were 30.3Δ ± 13.5Δ; at distance, 30.6Δ ± 10.5Δ. Stereopsis was ≤60 arcsec in 29 patients and 80–400 arcsec in 9 patients. In the IXT group, the peak velocity and gain of the adduction saccade tended to be greater than those of the abduction saccade, but not significantly. The no-strabismus group exhibited a similar trend, with a stronger tendency in the dominant eye, reaching statistical significance. ConclusionsBoth the children with IXT and children without strabismus showed a dominance of adduction in their saccades; however, this dominance was weaker in children with IXT.

Visual symptoms in postural tachycardia syndrome: An investigation of position-dependent visual exploration.

Patients with postural tachycardia syndrome report position-dependent visual symptoms. Despite their impact on daily life, these symptoms have remained largely unexplored in research. The aim of this study was to investigate the nature of visual symptoms in postural tachycardia syndrome and possible underlying pathophysiological mechanisms. Fifteen patients with postural tachycardia syndrome and 15 healthy controls were included in the study. Through a comprehensive array of measurements, including haemodynamics, subjective symptom assessments, eye movement tracking and pupil diameter analysis, participants were assessed during free image exploration in both supine and 60° head-up tilt positions. During head-up tilt, patients showed a decreased number and duration of fixations, as well as a decreased number, peak velocity and amplitude of saccades compared to the supine position and the control group. This reduction in visual exploration occurred primarily in the peripheral field of view and coincided with the occurrence of subjective visual symptoms. No significant differences in the saccade main sequence were observed between the two groups in either body position. Patients with postural tachycardia syndrome have a reduced exploration of the peripheral field of view when in an upright body position, potentially leading to tunnel vision. Since the normality of the saccade main sequence in patients combined with the focus on the centre of the field of view and the lower saccade amplitudes points to an intact brainstem function, the decrease in peripheral visual exploration may be attributed to a position-dependent dysfunction of the frontal eye field.

Video head impulse gain is impaired in myotonic dystrophy types 1 and 2.

This study was undertaken to examine vestibulo-ocular reflex (VOR) characteristics in myotonic dystrophy type 1 (DM1) and type 2 (DM2) using video head impulse testing (vHIT). VOR gain, refixation saccade prevalence, first saccade amplitude, onset latency, peak velocity, and duration were compared in DM1, DM2, age-matched normal controls, and patients with peripheral and central vestibulopathies. Fifty percent of DM1 and 37.5% of DM2 patients demonstrated reduced VOR gain. Refixation saccade prevalence for horizontal canal (HC) and posterior canal (PC) was significantly higher in DM1 (101 ± 42%, 82 ± 47%) and DM2 (70 ± 45%, 61 ± 38%) compared to controls (40 ± 28% and 43 ± 33%, p < 0.05). The first saccade amplitudes and peak velocities were higher in HC and PC planes in DM1 and DM2 compared to controls (p < 0.05). HC slow phase eye velocity profiles in DM1 showed delayed peaks. The asymmetry ratio, which represents the percentage difference between the first and second halves of the slow phase eye velocity response, was therefore negative (-22.5 ± 17%, -2.3 ± 16%, and - 4.7 ± 8% in DM1, DM2, and controls). HC VOR gains were lower and gain asymmetry ratio was larger and negative in patients with DM1 with moderate to severe ptosis and a history of imbalance and falls compared to the remaining DM1 patients (p < 0.05). In peripheral vestibulopathies, saccade amplitude was larger, peak velocity was higher, and onset latency was shorter (p < 0.05) than in DM1. In central vestibulopathy (posterior circulation strokes), saccade peak velocity was higher, but amplitude and onset latency were not significantly different from DM1. VOR impairment is common in DM1 and DM2. In DM1, refixation saccade characteristics are closer to central than peripheral vestibulopathies. Delayed peaks in the vHIT eye velocity profile observed in patients with DM1 may reflect extraocular muscle weakness. VOR impairment and VOR asymmetry in DM1 are associated with imbalance and falls.

Role of the video head impulse test in the evaluation of vestibulo-ocular reflex in individuals with Parkinson's disease.

<p>Parkinson&rsquo;s disease (PD) is the most common movement disorder and the second most common neu&shy;rodegenerative disease of the central ner&shy;vous system. Dizziness is frequently reported by PD patients, yet there is a paucity of research focusing on the vestibulo-ocular reflex (VOR) in this population using high-frequency vestibular testing. This study aims to investigate the VOR in individuals with PD using the video head thrust test with and without suppression.&nbsp;</p>. <p>Forty individuals with PD and 40 healthy individuals were included in the study. According to the Hoehn-Yahr Scale, individuals with PD were defined as early stage with a score of 1&ndash;2.5 and middle to late stage with a score of 3 to 5. The Head Impulse Testing Paradigm (HIMP) and Suppression Head Impulse Testing Paradigm (SHIMP) were applied to all individuals.</p>. <p>No statistically significant difference was observed between the PD group and the control group in terms of semicircular canal (SCC) gains in both HIMP and SHIMP tests. No catch-up saccades were observed in the right anterior, right posterior, left anterior, and left posterior SCC planes in the PD and control groups. However, in the right lateral SCC plane 32 patients in the PD group had saccades, while 8 patients in the control group had saccades. In the left lateral SCC plane, 32 patients in the PD group and 9 patients in the control group had catch-up saccades. A statistically significant difference was observed in the number and amplitude of saccades in the right and left lateral SCC planes compared to the control group (p&lt;0.05). In addition, in the PD group, the amplitude, peak velocity, and latency of the anticompensatory saccades seen in SHIMP showed a statistically significant difference compared to the control group (p&lt;0.05).</p>. <p>VOR in the vertical SCC plane was not affected in individuals with PD. However, VOR in the lateral SCC plane was affected. It was concluded that when evaluating VOR with both HIMP and SHIMP in individuals with PD, the presence of catch-up saccades should be focused on and evaluated for possible vestibular dysfunction, even though SCC gains are normal. This study will contribute to a deeper understanding of vestibular function in PD, potentially informing better management strategies for dizziness in this population.&nbsp;</p>.

Enhancing Imaging Anatomy Competency: Integrating Digital Imaging and Communications in Medicine (DICOM) Viewers Into the Anatomy Lab Experience.

Radiologic interpretation is a skill necessary for all physicians to provide quality care for their patients. However, some medical students are not exposed to Digital Imaging and Communications in Medicine (DICOM) imaging manipulation until their third year during clinical rotations. The objective of this study is to evaluate how medical students exposed to DICOM manipulation perform on identifying anatomical structures compared to students who were not exposed. This was a cross-sectional cohort study with 19 medical student participants organized into a test and control group. The test group consisted of first-year students who had been exposed to a new imaging anatomy curriculum (n = 9). The control group consisted of second-year students who had not had this experience (n = 10). The outcomes measured included quiz performance, self-reported confidence levels, and eye-tracking data. Students in the test group performed better on the quiz compared to students in the control group (p = 0.03). Confidence between the test and control groups was not significantly different (p = 0.16), though a moderate to large effect size difference was noted (Hedges' g = 0.75). Saccade peak velocity and fixation duration between the groups were not significantly different (p = 0.29, p = 0.77), though a moderate effect size improvement was noted in saccade peak velocity for the test group (Hedges' g = 0.49). The results from this study suggest that the early introduction of DICOM imaging into a medical school curriculum does impact students' performance when asked to identify anatomical structures on a standardized quiz.

Saccades and Microsaccades Coupling During Free-Throw Shots in Basketball Players.

We investigated the role of saccades and microsaccades when different levels of basketball players were engaged in an ecological free-throw condition. All participants made more correct than incorrect shoots, with a movement time initiation shorter in amateurs than in near-expert groups. Near-experts had more stable gaze fixation than amateurs, with higher microsaccade rate and duration and lower peak velocity. Amateurs showed higher saccade rate, peak velocity, and amplitude than near-experts. The temporal sequence of near-experts' microsaccade rate increased after the saccade peak; on the contrary, in amateurs, the saccade peak is shown after the decrement in microsaccade rates. The spatiotemporal characteristics of microsaccades and saccades may reflect an optimal sampling method by which the brain discretely acquires visual information and can differentiate between participants who use a fixation before the critical movement time and participants who move their eyes to catch more visual cues to make decisions.

Impairment of Visual Fixation and Preparatory Saccade Control in Borderline Personality Disorder With and Without Comorbid Attention-Deficit/Hyperactivity Disorder

BackgroundBorderline personality disorder (BPD) is associated with heightened impulsivity, evidenced by increased substance abuse, self-harm, and suicide attempts. Addressing impulsivity in individuals with BPD is a therapeutic objective, but its underlying neural basis in this clinical population remains unclear, partly due to its frequent comorbidity with attention-deficit/hyperactivity disorder (ADHD). MethodsWe used a response inhibition paradigm—the interleaved pro-/antisaccade task—among adolescents diagnosed with BPD with and without comorbid ADHD (n = 25 and n = 24, respectively) during concomitant video-based eye tracking. We quantified various eye movement response parameters reflective of impulsive action during the task, including delay to fixation acquisition, fixation breaks, anticipatory saccades, and direction errors with express saccade (saccade reaction time: 90–140 ms) and regular saccade latencies (saccade reaction time > 140 ms). ResultsIndividuals with BPD exhibited deficient response preparation, as evidenced by reduced visual fixation on task cues and greater variability of saccade responses (i.e., saccade reaction time and peak velocity). The ADHD/BPD group shared these traits and made more anticipatory responses and direction errors with express saccade latencies and reduced error correction. ConclusionsSaccadic deficits in BPD and ADHD/BPD stemmed not from an inability to execute antisaccades but rather from inadequate preparation for the upcoming task set. These distinctions may arise due to abnormal signaling in cortical areas like the frontal eye fields, posterior parietal cortex, and anterior cingulate cortex. Understanding these mechanisms could provide insights into targeted interventions focusing on task set preparation to manage response inhibition deficits in BPD and ADHD/BPD.

Elevated Smooth Pursuit Gain in Collegiate Athletes with Sport-related Concussion Immediately Following Injury.

Although there is evidence that sport-related concussion (SRC) affects oculomotor function and perceptual ability, experiments are often poorly controlled and are not replicable. This study aims to test the hypothesis that there are decreased values when assessing oculomotor impairment indicating poorer performance in SRC patients. Fifteen DI athletes presenting with SRC (7 females, 8 males) and 15 student volunteers (CON) (12 females, 3 males) completed a dynamic visual acuity (DVA) task that involved answering the direction of a moving stimulus (Landolt C) while wearing a head-mounted binocular eye tracker. There were 120 trials total with 60 trials presenting at 30º per second and 60 presenting at 90º per second. Various eye movement measurements, including horizontal smooth pursuit eye movements (SPEM) gain and saccadic peak velocity, were analyzed between groups using univariate ANOVAs. Saccade count in SPEM trials, accuracy, and vision were analyzed using Kruskal-Wallis tests. There was no statistical difference in saccadic peak velocity: SRC = 414.7 42º/s, CON = 406.6 40.6º/s. A significant difference was found between SRC patients and healthy controls in horizontal SPEM gain (SRC = 0.9 0.04, CON = 0.86 0.03, F(1,28) = 7.243, P = 0.012) indicating that patients demonstrated compensatory eye movements when tracking the target. There were significantly more saccades in all SPEM trials (P = 0.001). SRCoculomotor deficits manifest as elevated horizontal SPEM gain when assessed within 48 hours of injury and compared to healthy controls within the same age range. SRC demonstrates altered oculomotor ability. While accurate in tracking a stimulus, SRC patients may conduct less controlled eye movements.

Comparison of adaptation characteristics between visually and memory-guided saccades.

Saccade adaptation plays a crucial role in maintaining saccade accuracy. The behavioral characteristics and neural mechanisms of saccade adaptation for an externally cued movement, such as visually guided saccades (VGS), are well studied in nonhuman primates. In contrast, little is known about the saccade adaptation of an internally driven movement, such as memory-guided saccades (MGS), which are guided by visuospatial working memory. As the oculomotor plant changes because of growth, aging, or skeletomuscular problems, both types of saccades need to be adapted. Do both saccade types engage a common adaptation mechanism? In this study, we compared the characteristics of amplitude decrease adaptation in MGS with VGS in nonhuman primates. We found that the adaptation speed was faster for MGS than for VGS. Saccade duration changed during MGS adaptation, whereas saccade peak velocity changed during VGS adaptation. We also compared the adaptation field, that is, the gain change for saccade amplitudes other than the adapted. The gain change for MGS declines on both smaller and larger sides of adapted amplitude, more rapidly for larger than smaller amplitudes, whereas the decline in VGS was reversed. Thus, the differences between VGS and MGS adaptation characteristics support the previously suggested hypothesis that the adaptation mechanisms of VGS and MGS are distinct. Furthermore, the result suggests that the MGS adaptation site is a brain structure that influences saccade duration, whereas the VGS adaptation site influences saccade peak velocity. These results should be beneficial for future neurophysiological experiments.NEW & NOTEWORTHY Plasticity helps to overcome persistent motor errors. Such motor plasticity or adaptation can be investigated with saccades. Thus far our knowledge is primarily about visually guided saccades, an externally cued movement, which we can make only when the object is visible at the time of saccade. However, as the world is complex, we can make saccades even when the object is not visible. Here, we investigate the adaptation of an internally driven movement: the memory-guided saccade.

Quantification of saccadic fatigability and diagnostic efficacy for myasthenia gravis.

The diagnostic challenge of myasthenia gravis (MG) is exacerbated by the variable efficacy of current testing methodologies, necessitating innovative approaches to accurately identify the condition. This study aimed to assess ocular muscle fatigue in patients with MG using video-oculography (VOG) by examining repetitive saccadic eye movements and comparing these metrics to those of healthy control participants. This prospective, cross-sectional study was conducted at a tertiary care center and involved 62 patients diagnosed with MG (48 with ocular MG and 14 with generalized MG) and a control group of 31 healthy individuals, matched for age and sex. The assessment involved recording saccadic eye movements within a ± 15° range, both horizontally and vertically, at a rate of 15 saccades per minute over a 5-min period, resulting in 75 cycles. Participants were afforded a 3-min rest interval between each set to mitigate cumulative fatigue. The primary outcome was the detection of oculomotor fatigue, assessed through changes in saccadic waveforms, range, peak velocity, latency, and the duration from onset to target, with a focus on comparing the second saccade against the average of the last five saccades. In the evaluation of repetitive saccadic movements, patients with MG exhibited a reduced saccadic range and a prolonged duration to reach the target, compared to healthy subjects. Furthermore, a significant elevation in the frequency of multistep saccades was observed among MG patients, with a marked rise observed over consecutive trials. Receiver operating characteristic (ROC) analysis revealed the discriminative performance of multistep saccade frequency, in conjunction with variations in saccadic range and duration from onset to target achievement between the second saccade and the mean of the final five saccades, as effective in distinguishing MG patients from healthy subjects. Although alterations in peak saccadic velocity and latency were less pronounced, they were nevertheless detectable. The utilization of VOG for repetitive saccadic testing in the diagnosis of MG has demonstrated considerable diagnostic precision. This methodology affords significant accuracy in evaluating ocular muscle fatigue in MG patients, providing class III evidence supportive of its clinical application.

Post-Saccadic Oscillations of the Pupil and Lens Reduce Fixation Stability in Retinitis Pigmentosa and Age-Related Macular Degeneration.

Post-saccadic oscillations (PSOs) reflect movements of gaze that result from motion of the pupil and lens relative to the eyeball rather than eyeball rotations. Here, we analyzed the characteristics of PSOs in subjects with age-related macular degeneration (AMD), retinitis pigmentosa (RP), and normal vision (NV). Our aim was to assess the differences in PSOs between people with vision loss and healthy controls because PSOs affect retinal image stability after each saccade. Participants completed a horizontal saccade task and their gaze was measured using a pupil-based eye tracker. Oscillations occurring in the 80 to 200ms post-saccadic period were described with a damped oscillation model. We compared the amplitude, decay time constant, and frequency of the PSOs for the three different groups. We also examined the correlation between these PSO parameters and the amplitude, peak velocity, and final deceleration of the preceding saccades. Subjects with vision loss (AMD, n = 6, and RP, n = 5) had larger oscillation amplitudes, longer decay constants, and lower frequencies than subjects with NV (n = 7). The oscillation amplitudes increased with increases in saccade deceleration in all three groups. The other PSO parameters, however, did not show consistent correlations with either saccade amplitude or peak velocity. Post-saccadic fixation stability in AMD and RP is reduced due to abnormal PSOs. The differences with respect to NV are not due to differences in saccade kinematics, suggesting that anatomic and neuronal variations affect the suspension of the iris and the lens in the patients' eyes.

Evidence of elevated situational awareness for active duty soldiers during navigation of a virtual environment.

U.S. service members maintain constant situational awareness (SA) due to training and experience operating in dynamic and complex environments. Work examining how military experience impacts SA during visual search of a complex naturalistic environment, is limited. Here, we compare Active Duty service members and Civilians' physiological behavior during a navigational visual search task in an open-world virtual environment (VE) while cognitive load was manipulated. We measured eye-tracking and electroencephalogram (EEG) outcomes from Active Duty (N = 21) and Civilians (N = 15) while they navigated a desktop VE at a self-regulated pace. Participants searched and counted targets (N = 15) presented among distractors, while cognitive load was manipulated with an auditory Math Task. Results showed Active Duty participants reported significantly greater/closer to the correct number of targets compared to Civilians. Overall, Active Duty participants scanned the VE with faster peak saccade velocities and greater average saccade magnitudes compared to Civilians. Convolutional Neural Network (CNN) response (EEG P-300) was significantly weighted more to initial fixations for the Active Duty group, showing reduced attentional resources on object refixations compared to Civilians. There were no group differences in fixation outcomes or overall CNN response when comparing targets versus distractor objects. When cognitive load was manipulated, only Civilians significantly decreased their average dwell time on each object and the Active Duty group had significantly fewer numbers of correct answers on the Math Task. Overall, the Active Duty group explored the VE with increased scanning speed and distance and reduced cognitive re-processing on objects, employing a different, perhaps expert, visual search strategy indicative of increased SA. The Active Duty group maintained SA in the main visual search task and did not appear to shift focus to the secondary Math Task. Future work could compare how a stress inducing environment impacts these groups' physiological or cognitive markers and performance for these groups.

Vestibulo-ocular reflex dynamics with head-impulses discriminates Usher patients type 1 and 2

Usher Syndrome classification takes into account the absence of vestibular function but its correlation with genotype is not well characterized. We intend to investigate whether video Head Impulse Test (vHIT) is useful in screening and to differentiate Usher Syndrome types. 29 Usher patients (USH) with a genetically confirmed diagnosis and 30 healthy controls were studied with vHIT and dizziness handicap inventory questionnaire (DHI). Statistical significant differences between USH1, USH2 and controls were found in the vestibulo-ocular-reflex (VOR) gain of all SCCs, with USH1 patients consistently presenting smaller gains. VOR gain of the right lateral SCC could discriminate controls from USH1, and USH2 from USH1 with an overall diagnostic accuracy of 90%. USH1 DHI correlated with VOR (ρ = − 0,971, p = 0.001). Occurrence rate of covert and overt lateral semicircular canals refixation saccades (RS) was significantly different between groups, being higher in USH1 patients (p < 0.001). USH1 peak velocity of covert and overt saccades was higher for lateral semicircular canals (p < 0.05 and p = 0.001) compared with USH2 and controls. Covert saccades occurrence rate for horizontal SCCs could discriminate USH1 from USH2 patients and controls with a diagnostic accuracy of 85%. vHIT is a fast and non-invasive instrument which allowed us to screen and distinguish Usher patients from controls with a high precision. Importantly, its use allowed further discrimination between USH1 from USH2 groups. Moreover, VOR gain seems to correlate with vertigo-related quality of life in more severe phenotypes.

Eye Movement Correlates of Working Memory Capacity: Evidence from the Reading Span Task

In reading, eye movements are typically influenced by both higher-level and lower-level cognitive processes that are affected by individual differences such as working memory capacity. However, the extent to which working memory impacts reading under increasing task demands remains uncertain. Therefore, this study aimed to explore the influence of working memory capacity, assessed via the n-back task, on peak saccade velocity during reading when an additional memory task is introduced. Thirty-one healthy participants with normal or corrected-to-normal vision read sentences performing either comprehension task or dual task on comprehension and working memory span. The results of the comprehension task were used as a baseline to track the differences in eye movement measures in the dual task with the increasing task demand. Participants who performed well in the n-back task exhibited higher peak saccade velocity during both single and dual reading tasks, particularly as the task demands increased: reading for comprehension while simultaneously maintaining six items in working memory was associated with the highest peak saccade velocity. Conversely, those with n-back lower performance did not display significant changes in peak saccade velocity. This discrepancy is attributed to task-induced variations in arousal among high-performing individuals. The study underscores the importance of individual differences in working memory and suggests a potential link between arousal and cognitive processes involved in reading comprehension.

Determining Which Sine Wave Frequencies Correspond to Signal and Which Correspond to Noise in Eye-Tracking Time-Series.

The Fourier theorem states that any time-series can be decomposed into a set of sinusoidal frequencies, each with its own phase and amplitude. The literature suggests that some frequencies are important to reproduce key qualities of eye-movements ("signal") and some of frequencies are not important ("noise"). To investigate what is signal and what is noise, we analyzed our dataset in three ways: (1) visual inspection of plots of saccade, microsaccade and smooth pursuit exemplars; (2) analysis of the percentage of variance accounted for (PVAF) in 1,033 unfiltered saccade trajectories by each frequency band; (3) analyzing the main sequence relationship between saccade peak velocity and amplitude, based on a power law fit. Visual inspection suggested that frequencies up to 75 Hz are required to represent microsaccades. Our PVAF analysis indicated that signals in the 0-25 Hz band account for nearly 100% of the variance in saccade trajectories. Power law coefficients (a, b) return to unfiltered levels for signals low-pass filtered at 75 Hz or higher. We conclude that to maintain eyemovement signal and reduce noise, a cutoff frequency of 75 Hz is appropriate. We explain why, given this finding, a minimum sampling rate of 750 Hz is suggested.

The Effect of Stimulus Contrast and Spatial Position on Saccadic Eye Movement Parameters.

(1) Background: Saccadic eye movements are rapid eye movements aimed to position the object image on the central retina, ensuring high-resolution data sampling across the visual field. Although saccadic eye movements are studied extensively, different experimental settings applied across different studies have left an open question of whether and how stimulus parameters can affect the saccadic performance. The current study aims to explore the effect of stimulus contrast and spatial position on saccadic eye movement latency, peak velocity and accuracy measurements. (2) Methods: Saccadic eye movement targets of different contrast levels were presented at four different spatial positions. The eye movements were recorded with a Tobii Pro Fusion video-oculograph (250 Hz). (3) Results: The results demonstrate a significant effect of stimulus spatial position on the latency and peak velocity measurements at a medium grey background, 30 cd/m2 (negative and positive stimulus polarity), light grey background, 90 cd/m2 (negative polarity), and black background, 3 cd/m2 (positive polarity). A significant effect of the stimulus spatial position was observed on the accuracy measurements when the saccadic eye movement stimuli were presented on a medium grey background (negative polarity) and on a black background. No significant effect of stimulus contrast was observed on the peak velocity measurements under all conditions. A significant stimulus contrast effect on latency and accuracy was observed only on a light grey background. (4) Conclusions: The best saccadic eye movement performance (lowest latency, highest peak velocity and accuracy measurements) can be observed when the saccades are oriented to the right and left from the central fixation point. Furthermore, when presenting the stimulus on a light grey background, a very low contrast stimuli should be considered carefully.

Medication only improves limb movements while deep brain stimulation improves eye and limb movements during visually-guided reaching in Parkinson's disease.

Antiparkinson medication and subthalamic nucleus deep brain stimulation (STN-DBS), two common treatments of Parkinson's disease (PD), effectively improve skeletomotor movements. However, evidence suggests that these treatments may have differential effects on eye and limb movements, although both movement types are controlled through the parallel basal ganglia loops. Using a task that requires both eye and upper limb movements, we aimed to determine the effects of medication and STN-DBS on eye and upper limb movement performance. Participants performed a visually-guided reaching task. We collected eye and upper limb movement data from participants with PD who were tested both OFF and ON medication (n = 34) or both OFF and ON bilateral STN-DBS while OFF medication (n = 11). We also collected data from older adult healthy controls (n = 14). We found that medication increased saccade latency, while having no effect on reach reaction time (RT). Medication significantly decreased saccade peak velocity, while increasing reach peak velocity. We also found that bilateral STN-DBS significantly decreased saccade latency while having no effect on reach RT, and increased saccade and reach peak velocity. Finally, we found that there was a positive relationship between saccade latency and reach RT, which was unaffected by either treatment. These findings show that medication worsens saccade performance and benefits reaching performance, while STN-DBS benefits both saccade and reaching performance. We explore what the differential beneficial and detrimental effects on eye and limb movements suggest about the potential physiological changes occurring due to treatment.

Visual Exploration While Walking With and Without Visual Cues in Parkinson’s Disease: Freezer Versus Non-Freezer

Background Visual cues can improve gait in Parkinson’s disease (PD), including those experiencing freezing of gait (FOG). However, responses are variable and underpinning mechanisms remain unclear. Visuo-cognitive processing (measured through visual exploration) has been implicated in cue response, but this has not been comprehensively examined. Objective To examine visual exploration and gait with and without visual cues in PD who do and do not self-report FOG, and healthy controls (HC). Methods 17 HC, 21 PD without FOG, and 22 PD with FOG walked with and without visual cues, under single and dual-task conditions. Visual exploration (ie, saccade frequency, duration, peak velocity, amplitude, and fixation duration) was measured via mobile eye-tracking and gait (ie, gait speed, stride length, foot strike angle, stride time, and stride time variability) with inertial sensors. Results PD had impaired gait compared to HC, and dual-tasking made gait variables worse across groups (all P < .01). Visual cues improved stride length, foot strike angle, and stride time in all groups (P < .01). Visual cueing also increased saccade frequency, but reduced saccade peak velocity and amplitude in all groups (P < .01). Gait improvement related to changes in visual exploration with visual cues in PD but not HC, with relationships dependent on group (FOG vs non-FOG) and task (single vs dual). Conclusion Visual cues improved visual exploration and gait outcomes in HC and PD, with similar responses in freezers and non-freezers. Freezer and non-freezer specific associations between cue-related changes in visual exploration and gait indicate different underlying visuo-cognitive processing within these subgroups for cue response.

Compensatory saccade in the vestibular impaired monkey.

Loss of the vestibulo-ocular reflex (VOR) affects visual acuity during head movements. Patients with unilateral and bilateral vestibular deficits often use saccadic eye movements to compensate for an inadequate VOR. Two types of compensatory saccades have been distinguished, covert saccades and overt saccades. Covert saccades occur during head rotation, whereas overt saccades occur after the head has stopped moving. The generation of covert saccades is part of a central vestibular compensation process that improves visual acuity and suppresses oscillopsia. Understanding the covert saccade mechanism may facilitate vestibular rehabilitation strategies that can improve the patient's quality of life. To understand the brain mechanisms underlying covert saccades at the neural level, studies in an animal model are necessary. In this study, we employed non-human primates whose vestibular end organs are injured. We examined eye movement during the head-impulse test, which is a clinical test to evaluate the vestibulo-ocular reflex. During this test, the monkeys are required to fixate on a target and the head is rapidly and unexpectedly rotated to stimulate the horizontal semi-circular canals. Similar to human subjects, monkeys made compensatory saccades. We compared these saccades with catch-up saccades following a moving target that simulates the visual conditions during the head impulse test. The shortest latency of the catch-up saccades was 250 ms, which indicates that it requires at least 250 ms to induce saccades by a visual signal. The latency of some compensatory saccades is shorter than 250 ms during the head impulse test, suggesting that such short latency compensatory saccades were not induced visually. The peak velocity of the short latency saccades was significantly lower than that of longer latency saccades. The peak velocity of these longer latency saccades was closer to that of visually guided saccades induced by a stepping target. These results are consistent with studies in human patients. Thus, this study demonstrates, for the first time, compensatory covert saccades in vestibular impaired monkeys.

Neurocognitive effect of biased µ-opioid receptor agonist oliceridine, a utility function analysis and comparison with morphine.

Oliceridine (Olinvyk®) is a μ-opioid receptor agonist that in contrast to conventional opioids preferentially engages the G-protein-coupled signaling pathway. We determined the utility function of oliceridine versus morphine based on neurocognitive tests and cold pressor test. The study had a randomized, double-blind, placebo-controlled, partial block 3-way crossover design. Experiments were performed in 20 male and female volunteers. Subjects received intravenous oliceridine (1 or 3 mg; cohorts of 10 subjects/dose), morphine (5 or 10 mg; cohorts of 10 subjects/dose) or placebo on three separate occasions. Prior to and following dosing, neurocognitive tests, cold pressor test and plasma drug concentrations were obtained at regular intervals. Population pharmacokinetic-pharmacodynamic analyses served as basis for construction of a utility function, which is an objective function of probability of benefit minus probability of harm. Antinociception served as measure of benefit, slowing of saccadic peak velocity and increased body sway as measures of neurocognitive harm. The oliceridine and morphine C50's, i.e. the effect-site concentrations causing 50% effect, were: antinociception 13±2 and 23±7 ng/mL, saccadic peak velocity 90±14 and 54±15 ng/mL, and body sway 10±2 and 5.6±0.8 ng/mL, respectively. The ratio oliceridine/morphine of the therapeutic indices, C50(benefit)/C50(harm), were 0.34 (95% CI 0.17-0.7; p<0.01) for saccadic peak velocity and 0.33 (0.16-0.50; p<0.01) for body sway. The oliceridine utility was positive across the effect-site concentration 5-77 ng/mL, indicative of a greater probability of benefit than harm. The morphine utility was not significantly different from zero from 0-100 ng/mL. Over the concentration range 15-50 ng/mL the oliceridine utility was superior to that of morphine (p < 0.01). Similar observations were made for body sway. These data indicate that over the clinical concentration range, oliceridine is an analgesic with a favorable safety profile over morphine when considering analgesia and neurocognitive function.