Antisaccade Latency Research Articles

Oculomotor and Vestibular Deficits in Friedreich Ataxia - Systematic Review and Meta-Analysis of Quantitative Measurements

Disease-specific oculomotor assessments play a crucial role in the early diagnosis of hereditary cerebellar ataxias. Whereas several studies have reported on quantitative oculomotor and vestibular measurements in Friedreich’s Ataxia (FRDA), the value of specific oculomotor paradigms remains unclear. We aimed to address this knowledge gap through a systematic literature review and providing disease-specific recommendations for a tailored set of eye-movement recordings in FRDA. MEDLINE and Embase were searched for studies reporting on quantitative oculomotor and/or vestibular measurements in FRDA-patients. Data on oculomotor and vestibular parameters were extracted and correlations with a range of clinical parameters were sought. Included studies (n = 17) reported on 185 patients. Abnormalities observed included the presence of saccadic intrusions (143/161) such as square-wave jerks (SWJ, 90/109) and ocular flutter (21/43), impaired eccentric gaze-holding (40/104), abnormal pursuit (81/93) and angular vestibulo-ocular reflex (aVOR) deficits (39/48). For visually-guided saccades (VGS), we frequently observed increases in saccade latency (27/38) and dysmetric saccades (71/93), whereas saccade velocity was more often preserved (37/43). Augmented anti-saccade (AS) latency, downbeat nystagmus and frequent macro-SWJ correlated with disease duration. Increased AS-latency and VGS-latency, frequent macro-SWJ, reduced aVOR-gain and augmented aVOR peak-latency correlated with disease severity. A broad range of oculomotor and vestibular deficits are documented in the literature. Impairments in pursuit, saccades and aVOR-responses are most commonly reported, and as such, should be prioritized as disease markers. Quantitative oculomotor testing in FRDA may facilitate early diagnosis and prove valuable in monitoring disease progression and treatment response.

Effect of Repetitive Head Impacts on Saccade Performance in Canadian University Football Players.

Investigate the effect of cumulative head impacts on saccade latency and errors, measured across two successive football seasons. Participants were acquired from a sample of convenience-one Canadian university football team. Head impacts were collected during training camp, practices, eight regular season games, and four playoff games in each season. Saccade measurements were collected at five time points-before and after training camp, at midseason, after regular season, and after playoffs. Two seasons following players from a single USports football team during practices and games. Players who completed a baseline saccade measurement and a minimum of one follow-up measurement were included in the study. A total of 127 players were monitored across two competitive seasons, including 61 players who participated in both seasons. Head impact measurements were collected using helmet-mounted sensors. Saccade latency and number of errors were measured using high-speed video or electro-oculography. On average, each head impact increased prosaccade latency by 5.16 × 10-3 ms (95% confidence interval [CI], 2.26 × 10-4-1.00 × 10-2, P = 0.03) and antisaccade latency by 5.74 × 10-3 ms (95% CI, 7.18 × 10-4-1.06 × 10-2, P = 0.02). These latency increases did not decrease between the two seasons; in fact, prosaccade latencies were 23.20 ms longer (95% CI, 19.40-27.14, P < 0.001) at the second season's baseline measurement than the first. The number of saccade errors was not affected by cumulative head impacts. Repetitive head impacts in Canadian university football result in cumulative declines in brain function as measured by saccade performance. Football organizations should consider implementing policies focused on reducing head impacts to improve player safety.

Automating the analysis of eye movement for different neurodegenerative disorders

The clinical observation and assessment of extra-ocular movements is common practice in assessing neurodegenerative disorders but remains observer-dependent. In the present study, we propose an algorithm that can automatically identify saccades, fixation, smooth pursuit, and blinks using a non-invasive eye tracker. Subsequently, response-to-stimuli-derived interpretable features were elicited that objectively and quantitatively assess patient behaviors. The cohort analysis encompasses persons with mild cognitive impairment (MCI), Alzheimer’s disease (AD), Parkinson’s disease (PD), Parkinson’s disease mimics (PDM), and controls (CTRL). Overall, results suggested that the AD/MCI and PD groups had significantly different saccade and pursuit characteristics compared to CTRL when the target moved faster or covered a larger visual angle during smooth pursuit. These two groups also displayed more omitted antisaccades and longer average antisaccade latency than CTRL. When reading a text passage silently, people with AD/MCI had more fixations. During visual exploration, people with PD demonstrated a more variable saccade duration than other groups. In the prosaccade task, the PD group showed a significantly smaller average hypometria gain and accuracy, with the most statistical significance and highest AUC scores of features studied. The minimum saccade gain was a PD-specific feature different from CTRL and PDM. These features, as oculographic biomarkers, can be potentially leveraged in distinguishing different types of NDs, yielding more objective and precise protocols to diagnose and monitor disease progression.

Anti-saccade as a tool to evaluate cognitive impairment in vestibular migraine.

Vestibular migraine (VM), an intricate subtype of migraine, amalgamates the dual attributes of migraine and vestibular disorders. In clinical settings, individuals with VM frequently articulate concerns regarding the manifestation of subjective cognitive impairment. This cognitive dysfunction is intricately linked with diminished mobility, heightened susceptibility to falls, and increased absenteeism in afflicted patients. Consequently, comprehending the features of cognitive impairment in VM patients holds potential clinical significance. The pursuit of rapid and objective methods for detection and assessment is foundational and prerequisite for efficacious cognitive management of VM patients. The study encompassed 50 patients diagnosed with vestibular migraine and recruited 50 age-sex matched healthy controls. All participants underwent anti-saccade tasks, and cognitive evaluation was performed using the MMSE and MoCA to assess overall cognitive function. Additionally, RBANS scales were employed to measure specific cognitive domains. The VM patients and normal controls demonstrated statistical parity in terms of age, gender, education, weight, and BMI, with no significant differences observed. Analysis of cognitive scores divulged a marked increase in the incidence of Mild Cognitive Impairment (MCI) in VM patients compared to Healthy Controls (HCs). Both MMSE and MoCA scores were notably lower in VM patients compared to their healthy counterparts. The RBANS cognitive test indicated significant impairment in immediate memory, visuospatial construction, language, attention, and delayed memory among VM patients. Notably, the Trail Making Test and Stroop Color-Word Test revealed compromised processing speed and executive function cognitive domains. The anti-saccadic task highlighted significantly elevated anti-saccadic latency and frequency of direction errors in vestibular migraine patients. Symptom severity, illness duration, and episode frequency in VM patients positively correlated with counter-scanning errors and negatively correlated with cognitive performance across diverse cognitive domains. VM patients exhibit cognitive decline across multiple cognitive domains during the interictal period. This cognitive impairment may not be fully reversible, underscoring its potential clinical significance for cognitive management in VM patients. The sensitivity of anti-saccade tasks to the cognitive status of VM patients positions them as promising objective indicators for diagnosis, intervention, and evaluation of cognitive impairment effects in VM in future applications.

Inhibitory control and its modification in spider phobia - Study protocol for an antisaccade training trial.

Inhibitory control deficits are considered a key pathogenic factor in anxiety disorders. To assess inhibitory control, the antisaccade task is a well-established measure that assesses antisaccade performance via latencies and error rates. The present study follows three aims: (1) to investigate inhibitory control via antisaccade latencies and errors in an antisaccade task, and their associations with multiple measures of fear in patients with spider phobia (SP) versus healthy controls (HC), (2) to investigate the modifiability of antisaccade performance via a fear-specific antisaccade training in patients with SP and HC, and (3) to explore associations between putative training-induced changes in antisaccade performance in SPs and changes in diverse measures of fear. Towards aim 1, we assess antisaccade latencies (primary outcome) and error rates (secondary outcome) in an emotional antisaccade task. Further, the baseline assessment includes assessments of psychophysiological, behavioral, and psychometric indices of fear in patients with SP and HCs. To address aim 2, we compare effects of a fear-specific antisaccade training with effects of a prosaccade training as a control condition. The primary and secondary outcomes are reassessed at a post-1-assessment in both SPs and HCs. Aim 3 employs a cross-over design and is piloted in patients with SP, only. Towards this aim, primary and secondary outcomes, as well as psychophysiological, behavioral, and psychometric measures of fear are reassessed at a post-2-assessment after the second training block. This study aims to better understand inhibitory control processes and their modifiability in spider phobia. If successful, antisaccade training may assist in the treatment of specific phobia by directly targeting the putative underlying inhibitory control deficits. This study has been preregistered with ISRCTN (ID: ISRCTN12918583) on 28th February 2022.

Regional Brain Structure Mediates Age‐Related Decline in Eye Movement Control

AbstractBackgroundEye movements (EM) are considered potential biomarkers of neurodegeneration because they are altered in patients with neurodegenerative disease, including Alzheimer’s disease (AD). Alterations in EM control have also been observed in old age, with particularly strong age effects on saccadic latency, inhibitory errors in the antisaccade task, and smooth pursuit accuracy. The goal of our study was to characterize the neural pathways of age‐related changes in these EM outcomes.MethodThe analysis was based on 8,318 participants (aged 30 to 95 years) from the population‐based Rhineland Study. EMs were recorded using video‐based infrared oculography at 1,000 Hz. Volumes and thickness measures of selected brain structures were obtained using FreeSurfer from 3 Tesla T1‐weighted MR images. Relations of brain structure with EM outcomes were quantified using multivariable linear regression models. Brain structure variables were also analyzed as potential mediators in the relation between age and EM outcomes using causal mediation analysis under a counterfactual framework.ResultIn women, higher volume of the right thalamus and right globus pallidus was associated with lower antisaccade latency, whereas higher cortical thickness in the anterior cingulate cortex was associated with higher antisaccade latency. Higher cortical thickness in right supramarginal gyrus and right paracentral lobule and sulcus was associated with fewer antisaccade errors in women. There were no significant associations between regional brain structure and antisaccade performance in men. Higher cortical thickness in the right calcarine sulcus was associated with higher smooth pursuit velocity gain in both men and women. Additionally, individual brain structures mediated up to 11% of the age‐related decline in EM performance.ConclusionOur results support that EMs indeed reflect neurodegenerative processes as changes in brain structure partly account for age‐related decline in oculomotor performance. Relevant brain regions include both brain regions vulnerable to AD pathology and brain regions that are typically spared, suggesting that both “normal” age‐related and pathological mechanisms may be causative for decline in EM control. Our results highlight the importance of taking into account normal age‐related changes when considering EMs as early biomarkers for AD. Further work is needed to better distinguish normal age‐related changes from pathological change.

Sensorimotor and inhibitory control in aging FMR1 premutation carriers.

Aging FMR1 premutation carriers are at risk of developing neurodegenerative disorders, including fragile X-associated tremor/ataxia syndrome (FXTAS), and there is a need to identify biomarkers that can aid in identification and treatment of these disorders. While FXTAS is more common in males than females, females can develop the disease, and some evidence suggests that patterns of impairment may differ across sexes. Few studies include females with symptoms of FXTAS, and as a result, little information is available on key phenotypes for tracking disease risk and progression in female premutation carriers. Our aim was to examine quantitative motor and cognitive traits in aging premutation carriers. We administered oculomotor tests of visually guided/reactive saccades (motor) and antisaccades (cognitive control) in 22 premutation carriers (73% female) and 32 age- and sex-matched healthy controls. Neither reactive saccade latency nor accuracy differed between groups. FMR1 premutation carriers showed increased antisaccade latencies relative to controls, both when considering males and females together and when analyzing females separately. Reduced saccade accuracy and increased antisaccade latency each were associated with more severe clinically rated neuromotor impairments. Findings indicate that together male and female premutation carriers show a reduced ability to rapidly exert volitional control over prepotent responses and that quantitative differences in oculomotor behavior, including control of visually guided and antisaccades, may track with FXTAS - related degeneration in male and female premutation carriers.

Oculometric measures as a tool for assessment of clinical symptoms and severity of Parkinson’s disease

Abnormalities of oculometric measures (OM) are widely described in people with Parkinson's disease (PD). However, knowledge of correlations between abnormal OM, disease severity and clinical assessment in PD patients is still lacking. To evaluate these correlations, PD patients (215 patients, mean age 69 ± 9.1 years, 79 females) with severe (H&Y > 3) and mild to moderate (H&Y ≤ 2) disease, and 215 age-matched healthy subjects were enrolled. All patients were evaluated using MDS-UPDRS and an oculometric test using computer vision and deep learning algorithms. Comparisons of OM between groups and correlations between OM and MDS-UPDRS scores were calculated. Saccadic latency (ms) was prolonged in patients with severe compared with mild to moderate disease (pro-saccades: 267 ± 69 vs. 238 ± 53, p = 0.0011; anti-saccades: 386 ± 119 vs. 352 ± 106, p = 0.0393) and in patients with mild to moderate disease versus healthy subjects (pro-saccades: 238 ± 53 vs. 220 ± 45, p = 0.0003; anti-saccades: 352 ± 106 vs. 289 ± 71, p < 0.0001). Error rate (%) was higher among patients with severe (64.06 ± 23.08) versus mild to moderate disease (49.84 ± 24.81, p = 0.0001), and versus healthy subjects (49.84 ± 24.81 vs. 28.31 ± 21.72, p = 0.00001). Response accuracy (%) was lower for patients with severe (75.66 ± 13.11) versus mild to moderate disease (79.66 ± 13.56, p = 0.0462), and versus healthy subjects (79.66 ± 13.56 vs. 90.27 ± 8.79, p < 0.0001). Pro- and anti-saccadic latency, error rate and accuracy were correlated with MDS-UPDRS scores (r = 0.32, 0.28, 0.36 and -0.30, respectively, p < 0.0001) and similar correlations were found with its axial subscore (R = 0.38, 0.29, 0.44, and -0.30, respectively, p < 0.0001). Several OM were different in patients under levodopa treatment. OM worsened as PD severity increases, and were correlated with MDS-UPDRS scores. Using OM can be implemented for PD patients’ assessment as a tool to follow disease progression.

Anti-saccades reveal impaired attention control over negative social evaluation in individuals with depressive symptoms

Depressed individuals are excessively sensitive to negative information but blunt to positive information, which has been considered as vulnerability to depression. Here, we focused on inhibitory control over attentional bias on social evaluation in individuals with depression. We engaged individuals with and without depressive symptoms (categorized by Beck Depression Inventory-II) in a novel attention control task using positive and negative evaluative adjectives as self-referential feedback given by social others. Participants were instructed to look at sudden onset feedback targets (pro-saccade) or the mirror location of the targets (anti-saccade) when correct saccade latencies and saccade errors were collected. The two indices showed that while both groups displayed longer latencies and more errors for anti-saccade relative to pro-saccade responses depressed individuals spent more time reacting correctly and made more errors than non-depressed individuals in the anti-saccade trials and such group differences were not observed in the pro-saccade trials. Although group differences in correct anti-saccade latencies were found for both positive and negative stimuli, depressed individuals spent more time making correct anti-saccade responses to negative social feedback than to positive ones whereas non-depressed individuals featured longer correct anti-saccade latencies for positive relative to negative evaluations. Our results suggest that depressed individuals feature an impaired ability in attention control for self-referential evaluations, notably those of negative valence, shedding new light on depression-distorted self-schema and corresponding social dysfunctions.

Effect of habitual reading direction on saccadic eye movements: A pilot study.

Cognitive processes can influence the characteristics of saccadic eye movements. Reading habits, including habitual reading direction, also affect cognitive and visuospatial processes, favouring attention to the side where reading begins. Few studies have investigated the effect of habitual reading direction on saccade directionality of low-cognitive-demand stimuli (such as dots). The current study examined horizontal prosaccade, antisaccade, and self-paced saccade in subjects with two primary habitual reading directions. We hypothesised that saccades responding to the stimuli in subject's habitual reading direction would show a longer prosaccade latency and lower antisaccade error rate (errors being a reflexive glance to a sudden-appearing target, rather than a saccade away from it). Sixteen young Chinese participants with primary habitual reading direction from left to right and sixteen young Arabic and Persian participants with primary habitual reading direction from right to left were recruited. All subjects spoke/read English as their second language. Subjects needed to look towards a 5°/10° target in the prosaccade task or look towards the mirror image location of the target in the antisaccade task and look between two 10° targets in the self-paced saccade task. Only Arabic and Persian participants showed a shorter and directional prosaccade latency towards 5° stimuli against their habitual reading direction. No significant effect of reading direction on antisaccade latency towards the correct directions was found. Chinese readers were found to generate significantly shorter prosaccade latencies and higher antisaccade directional errors compared with Arabic and Persian readers for stimuli appearing at their habitual reading side. The present pilot study provides insights into the effect of reading habits on saccadic eye movements of low-cognitive-demand stimuli and offers a platform for future studies to investigate the relationship between reading habits and eye movement behaviours.

Evaluation of cognition with the eyelink: Saccadic eye movements in healthy subjects

AbstractBackgroundThe aim of this study is to determine the normative data of eye movements models for healthy individuals between the ages of 18‐77.Method76 healthy subjects were included in 3 age groups as 18‐44, 45‐59, 60+. Neuropsychological assessment with five cognitive domains, was applied. EyeLink 1000 Plus was used to record and pro‐saccade and anti‐saccade eye movement paradigms. Amplitude, latency, anticipatory saccades, express saccades, correct saccade response, corrected saccade and uncorrected saccade responses were analyzed.ResultIn antisaccade results, correct saccade response, latency, amplitude, anticipatory saccade, express saccade, corrected saccade response, uncorrected saccade were significantly different between the groups (p&lt;0.05). Significant difference was also found in prosaccade latency (p&lt;0.001). In the 18‐44 age group, executive functions were highly negatively correlated with antisaccade latency (r = ‐0.744, p = 0.000), and language was meanly negatively correlated with latency (r = ‐0.514, p = ‐0.010). In the 45‐59 age group, a medium level of negative correlation was observed between executive functions and latency (r = ‐0.501, p = 0.025). Language and express saccade (r = ‐0.515, p = 0.020) were meanly negatively correlated in the 45‐59 year age group. In the 60+ age group, a medium level of negative correlation was found between attention and latency (r = ‐0.414, p = 0.021). In this age group, executive functions and uncorrected saccade (r = ‐0.396, p = 0.027) were weakly negatively correlated.ConclusionDecline in cognitive functions that occur with aging might affect eye movements. The relationship between antisaccades and cognitive functions in our preliminary study may attract attention to antisaccades in evaluation of cognition.

Eye Movement Latency Coefficient of Variation as a Predictor of Cognitive Impairment: An Eye Tracking Study of Cognitive Impairment.

Studies demonstrated impairment in the control of saccadic eye movements in Alzheimer's disease (AD) and people with mild cognitive impairment (MCI) when conducting the pro-saccade and antisaccade tasks. Research showed that changes in the pro and antisaccade latencies may be particularly sensitive to dementia and general executive functioning. These tasks show potential for diagnostic use, as they provide a rich set of potential eye tracking markers. One such marker, the coefficient of variation (CV), is so far overlooked. For biological markers to be reliable, they must be able to detect abnormalities in preclinical stages. MCI is often viewed as a predecessor to AD, with certain classifications of MCI more likely than others to progress to AD. The current study examined the potential of CV scores on pro and antisaccade tasks to distinguish participants with AD, amnestic MCI (aMCI), non-amnesiac MCI (naMCI), and older controls. The analyses revealed no significant differences in CV scores across the groups using the pro or antisaccade task. Antisaccade mean latencies were able to distinguish participants with AD and the MCI subgroups. Future research is needed on CV measures and attentional fluctuations in AD and MCI individuals to fully assess this measure's potential to robustly distinguish clinical groups with high sensitivity and specificity.

Effects of deep brain stimulation frequency on eye movements and cognitive control

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson’s disease (PD). Varying the frequency DBS has differential effects on axial and distal limb functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson’s Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes.

Stimulation of non-motor subthalamic nucleus impairs selective response inhibition via prefrontal connectivity.

Given the inconsistent results in the past, there is an ongoing debate whether and how deep brain stimulation in the subthalamic nucleus modifies cognitive control processes like response inhibition in persons with Parkinson's disease. In this study, we examined how the location of the stimulation volume within the subthalamic nucleus affects the performance in an antisaccade task but also how its structural connectivity is related to response inhibition. Antisaccade error rates and latencies were collected in 14 participants on and off deep brain stimulation in a randomized order. Stimulation volumes were computed based on patient-specific lead localizations using preoperative MRI and postoperative CT scans. Structural connectivity of the stimulation volumes with pre-defined cortical oculomotor control regions as well as whole-brain connectivity was estimated using a normative connectome. We showed that the detrimental effect of deep brain stimulation on response inhibition, measured as antisaccade error rate, depended upon the magnitude of the intersection of volumes of activated tissue with the non-motor subregion of the subthalamic nucleus and on its structural connectivity with regions of the prefrontal oculomotor network including bilateral frontal eye fields and right anterior cingulate cortex. Our results corroborate previous recommendations for avoidance of stimulation in the ventromedial non-motor subregion of the subthalamic nucleus which connects to the prefrontal cortex to prevent stimulation-induced impulsivity. Furthermore, antisaccades were initiated faster with deep brain stimulation when the stimulation volume was connected to fibres passing the subthalamic nucleus laterally and projecting onto the prefrontal cortex, indicating that improvement of voluntary saccade generation with deep brain stimulation may be an off-target effect driven by stimulation of corticotectal fibres directly projecting from the frontal and supplementary eye fields onto brainstem gaze control areas. Taken together, these findings could help implement individualized circuit-based deep brain stimulation strategies that avoid impulsive side effects while improving voluntary oculomotor control.

Ocular motility as a measure of cerebral dysfunction in adults with focal epilepsy

ObjectiveUsing objective oculomotor measures, we aimed to: (1) compare oculomotor performance in patients with drug-resistant focal epilepsy to healthy controls, and (2) investigate the differential impact of epileptogenic focus laterality and location on oculomotor performance. MethodsWe recruited 51 adults with drug-resistant focal epilepsy from the Comprehensive Epilepsy Programs of two tertiary hospitals and 31 healthy controls to perform prosaccade and antisaccade tasks. Oculomotor variables of interest were latency, visuospatial accuracy, and antisaccade error rate. Linear mixed models were performed to compare interactions between groups (epilepsy, control) and oculomotor tasks, and between epilepsy subgroups and oculomotor tasks for each oculomotor variable. ResultsCompared to healthy controls, patients with drug-resistant focal epilepsy exhibited longer antisaccade latencies (mean difference = 42.8 ms, P = 0.001), poorer spatial accuracy for both prosaccade (mean difference = 0.4°, P = 0.002), and antisaccade tasks (mean difference = 2.1°, P < 0.001), and more antisaccade errors (mean difference = 12.6%, P < 0.001). In the epilepsy subgroup analysis, left-hemispheric epilepsy patients exhibited longer antisaccade latencies compared to controls (mean difference = 52.2 ms, P = 0.003), while right-hemispheric epilepsy was the most spatially inaccurate compared to controls (mean difference = 2.5°, P = 0.003). The temporal lobe epilepsy subgroup displayed longer antisaccade latencies compared to controls (mean difference = 47.6 ms, P = 0.005). SignificancePatients with drug-resistant focal epilepsy exhibit poor inhibitory control as evidenced by a high percentage of antisaccade errors, slower cognitive processing speed, and impaired visuospatial accuracy on oculomotor tasks. Patients with left-hemispheric epilepsy and temporal lobe epilepsy have markedly impaired processing speed. Overall, oculomotor tasks can be a useful tool to objectively quantify cerebral dysfunction in drug-resistant focal epilepsy.

Executive function and relation to static balance metrics in chronic mild TBI: A LIMBIC-CENC secondary analysis.

Among patients with traumatic brain injury (TBI), postural instability often persists chronically with negative consequences such as higher fall risk. One explanation may be reduced executive function (EF) required to effectively process, interpret and combine, sensory information. In other populations, a decline in higher cognitive functions are associated with a decline in walking and balance skills. Considering the link between EF decline and reduction in functional capacity, we investigated whether specific tests of executive function could predict balance function in a cohort of individuals with a history of chronic mild TBI (mTBI) and compared to individuals with a negative history of mTBI. Secondary analysis was performed on the local LIMBIC-CENC cohort (N = 338, 259 mTBI, mean 45 ± STD 10 age). Static balance was assessed with the sensory organization test (SOT). Hierarchical regression was used for each EF test outcome using the following blocks: (1) the number of TBIs sustained, age, and sex; (2) the separate Trail making test (TMT); (3) anti-saccade eye tracking items (error, latency, and accuracy); (4) Oddball distractor stimulus P300 and N200 at PZ and FZ response; and (5) Oddball target stimulus P300 and N200 at PZ and FZ response. The full model with all predictors accounted for between 15.2% and 21.5% of the variability in the balance measures. The number of TBI's) showed a negative association with the SOT2 score (p = 0.002). Additionally, longer times to complete TMT part B were shown to be related to a worse SOT1 score (p = 0.038). EEG distractors had the most influence on the SOT3 score (p = 0.019). Lastly, the SOT-composite and SOT5 scores were shown to be associated with longer inhibition latencies and errors (anti-saccade latency and error, p = 0.026 and p = 0.043 respectively). These findings show that integration and re-weighting of sensory input when vision is occluded or corrupted is most related to EF. This indicates that combat-exposed Veterans and Service Members have greater problems when they need to differentiate between cues when vision is not a reliable input. In sum, these findings suggest that EF could be important for interpreting sensory information to identify balance challenges in chronic mTBI.

High (130 Hz)- and mid (60 Hz)-frequency deep brain stimulation in the subthalamic nucleus differentially modulate response inhibition: A preliminary combined EEG and eye tracking study

While deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinson’s disease (PD), it may also increase impulsivity by interfering with the inhibition of reflexive responses. The aim of this study was to investigate if varying the pulse frequency of STN-DBS has a modulating effect on response inhibition and its neural correlates.For this purpose, 14 persons with PD repeated an antisaccade task in three stimulation settings (DBS off, high-frequency DBS (130 Hz), mid-frequency DBS (60 Hz)) in a randomized order, while eye movements and brain activity via high-density EEG were recorded.On a behavioral level, 130 Hz DBS stimulation had no effect on response inhibition measured as antisaccade error rate, while 60 Hz DBS induced a slight but significant reduction of directional errors compared with the DBS-off state and 130 Hz DBS. Further, stimulation with both frequencies decreased the onset latency of correct antisaccades, while increasing the latency of directional errors.Time-frequency domain analysis of the EEG data revealed that 60 Hz DBS was associated with an increase in preparatory theta power over a midfrontal region of interest compared with the off-DBS state which is generally regarded as a marker of increased cognitive control. While no significant differences in brain activity over mid- and lateral prefrontal regions of interest emerged between the 60 Hz and 130 Hz conditions, both stimulation frequencies were associated with a stronger midfrontal beta desynchronization during the mental preparation for correct antisaccades compared with DBS off-state which is discussed in the context of potentially enhanced proactive recruitment of the oculomotor network.Our preliminary findings suggest that mid-frequency STN-DBS may provide beneficial effects on response inhibition, while both 130 Hz- and 60 Hz STN-DBS may promote voluntary actions at the expense of slower reflexive responses.

Cluster analysis reveals distinct patterns of saccade impairment and their relation to cognitive profiles in Parkinson's disease.

Saccade performance has been reported to be altered in Parkinson's disease (PD), however, with a large variability between studies as both motor and cognitive impairment interfere with oculomotor control. The aim of this study was to identify different patterns in saccade alterations in PD using a data-driven approach and to explore their relationship with cognitive phenotypes. Sixty-one participants with PD and 25 controls performed eye-tracking (horizontal and vertical prosaccades, antisaccades) and neuropsychological testing. Hierarchical cluster analysis was applied to the eye-tracking data to subsequently compare the clusters based on demographical, clinical and cognitive characteristics. The three identified clusters of saccade alterations differed in cognitive profiles from healthy controls, but not in PD-related motor symptoms or demographics. The rate of directive errors in the antisaccade task was increased in clusters 1 and 2. Further, cluster 1 was defined by a general disinhibition of reflexive saccades and executive dysfunction in the neuropsychological evaluation. In cluster 2, prolonged saccade latencies and hypometria were accompanied by multidomain cognitive impairment. The cluster 3 showed increased antisaccade latency and vertical hypometria despite lack of evidence for cognitive impairment. Our results suggest that there may be at least two opposing patterns of saccade alterations associated with cognitive impairment in PD, which may explain some of the contradictory results of previous studies.

P021 Associations between Virtual Reality (VR) Ocular Assessments and Vigilance during Extended Wakefulness – Preliminary Analysis

Abstract Introduction Sustained vigilance is essential for safety in high-risk workplaces, making rapid and accessible alertness failure vulnerability assessments extremely desirable. We are piloting existing technology, the NeuroFlex® Platform, which takes ocular performance measurements of both prosaccade and antisaccade eye-movements using a portable Virtual Reality (VR) headset. We’ve conducted preliminary comparisons between these measures and Psychomotor Vigilance during extended wakefulness. Methods Sixteen young-adults (females= 8; age M= 25.13, SD= 4.30) completed five test batteries starting 1-hour post-wake where repeated testing encapsuled more than 24-hours of extended wakefulness. Each battery consisted of two 10-minute visual Psychomotor Vigilance Tasks, in addition to three administrations of 60-second prosaccade and antisaccade assessments using the NeuroFlex® VR platform. Results Time main effects occurred for reciprocal reaction time, F(3.83,57.37) = 20.54, p &amp;lt;.001, and proportions of lapses/trials, F(3.55,48.33) = 7.36, p &amp;lt;.001. Vigilance troughs occurred around the circadian nadir (19-hours post-wake) with some recovery at final administrations (25-hours post-wake). No associations were found between prosaccade latency and vigilance metrics. Moderate negative (r=-.63, p=.01 &amp; r=-.54, p=.03) associations were found between antisaccade latency and reciprocal reaction time near the nadir, but not the number of lapses per trial. Discussion This preliminary analysis has demonstrated potential sensitivity of the NeuroFlex® platforms ocular measurements to vigilance. Though we have not detected associations between lapses and eye-movement latency, we were limited to the existing output generation of the NeuroFlex® platform in this preliminary investigation. With refined data analyses, we see promise in the NeuroFlex® platforms capability of predicting alertness failure.

O064 A Portable Ocular Assessment for Predicting Fitness to Drive under Extended-Wakefulness Conditions – Preliminary Analysis

Abstract Introduction In response to the high incidence of fatigue-based vehicle accidents, roadside assessments of sleepiness are in significant demand. For this purpose, we’ve piloted the existing NeuroFlex® Platform, which takes ocular performance measurements of both prosaccade and antisaccade eye-movements using a portable Virtual Reality (VR) headset. We’ve conducted preliminary comparisons between these measures and simulated driving performance. Methods Sixteen young-adults (females= 8; age M= 25.13, SD= 4.30) completed five test batteries starting 1-hour post-wake where repeated testing encapsuled more than 24-hours of extended wakefulness. Each battery consisted of one 60-minute drive on the AusEd driving simulator, in addition to three administrations of 60-second prosaccade and antisaccade assessments using the NeuroFlex® VR platform. Results Steering deviations from the median lane position showed a time main effect, F(4,24.49) = 13.38, p &amp;lt;.001, with the most diminished performance occurring at 19 (M=59.50cm, SD=26.61cm) and 25-hours post-wake (M=72.88cm, SD= 40.09cm) (vs. peak performance @13-hours post-wake M=35.09, SD=12.81; M diff.= 24.41 and 37.79 respectively, p &amp;lt;.001). One moderate association between prosaccade latency and steering deviation was found in the final battery following 25-hours of wakefulness (r=.51, p= 0.04). No significant associations were found for antisaccade latency. Discussion Despite the lack of significant associations with steering deviations, eye-movement latency did demonstrate durational increases over extended wakefulness. In this preliminary investigation we were limited to the existing output generation of the NeuroFlex® platform. Therefore, with refined data analyses of ocular control, we see promise in the NeuroFlex® platforms capability of detecting road users’ fitness to drive.