Saccades Research Articles

Saccadic eye movement speed is related to variations in phantom array effect visibility

The phantom array effect is one of the temporal light artefacts that can decrease performance and increase fatigue. The phantom array effect visibility shows large individual differences; however, the dominant factors that can explain these individual differences remain unclear. We investigated the relationship between saccadic eye movement speed and phantom array visibility at two different angles and four different directions of saccadic eye movement. The peak speed of saccadic eye movement and the phantom array effect visibility were measured at different modulation frequencies of the light source. Our results show that phantom array visibility increased as eye movement speed increased; the phantom array visibility was higher at a wide viewing angle with fast eye movement speed than at a narrow viewing angle. Moreover, when clustered into subgroups according to individual eye movement speed, the mean speed of the saccadic eye movement of each subgroup is related to the variations in the visibility of the phantom array effect of the subgroup. Therefore, saccadic eye movement speed is related to variations in phantom array effect visibility.

Deviated Saccadic Trajectory as a Biometric Signature of Glaucoma.

To investigate whether the trajectories of saccadic eye movements (SEMs) significantly differ between glaucoma patients and controls. SEMs were recorded by video-based infrared oculography in 53 patients with glaucoma and 41 age-matched controls. Participants were asked to bilaterally view 24°-horizontal, 14°-vertical, and 20°-diagonal eccentric Goldmann III-sized stimuli. SEMs were evaluated with respect to the saccadic reaction time (SRT), the mean velocity, amplitude, and two novel measures: departure angle (DA) and arrival angle (AA). These parameters were compared between the groups and the associations of SEM parameters with glaucoma parameters and integrated visual field defects were investigated. Glaucoma patients exhibited increased mean SRT, DA, and AA values compared with controls for 14°-vertical visual targets (P = 0.05, P < 0.01, and P < 0.01, respectively). The SRT, DA, and AA were significantly associated with the mean and pattern standard deviations of perimetry and with the mean RNFL thickness by OCT (all P < 0.001). Glaucoma was associated with the AA (P = 0.05) and both the SRT (P = 0.01) and DA (P = 0.04) were associated with integrated visual field defects. The saccadic trajectories of glaucoma patients depart in an erroneous path and compensate the disparity by deviating the trajectory at arrival. The initial deviation that we observed (despite continuous exposure to the stimulus) suggests the disoriented spatial perception of glaucoma patients which may be relevant to difficulties encountered daily.

Investigation of saccadic eye movement abnormalities in children with HIV/AIDS on HAART

Reading is a complex psychological task that involves rapid movements of both eyes in the same direction (saccades) from one word to the next, or, occasionally, backwards to previously encountered text. Eye movement provides a sensitive window into cognitive processing during reading and reading skills are associated with various eye movement parameters, total number of saccades and saccadic amplitudes. This is due to the knowledge that brain areas compromised by HIV infection also control saccadic eye movements. The aim of this study was to investigate the relationship between saccadic eye movements in children with HIV/AIDS on Highly Active Antiretroviral Therapy (HAART). With a descriptive cross-sectional design, 128 conveniently accessed male and female participants of ages 6 years to 13 years 11 months had their saccadic eye movements evaluated. The tool used to screen for saccadic eye movement abnormalities was a numerical reading test called the Development Eye Movement (DEM) test. Descriptive and inferential statistics was developed using SAS. Seventy-eight percent (78%) of participants had minimal immunosuppression and 65% had undetectable viral loads. The DEM test classified participants into four Behaviour Types based on their performances in this timed reading test. Ninety-three percent (93%) had vertical times and 92% had horizontal times that were outside of the specified test norms. The Behaviour Types revealed that 53% had automaticity problems (Type 3), 22% had both eye movement and automaticity problems (Type 4), 8% had no problems (Type 1) and only 3% had eye movement problems (Type 2). The association between the viral load with Behaviour Types (p=0.2) and the CD4 count against the behaviour types (p=0.17) were not statistically significant, hence no relationship could be established. More than half of the sample population manifested automaticity problems. What could not be determined was whether the automaticity problems found in this population were related to the neurocognitive functioning or neurodevelopmental delays which are known to exist in children with HIV/AIDS despite being on HAART, or if it was due to other factors. No relationship could be established between the Behaviour Types specified in the DEM test and the HIV biomarkers despite the DEM performances being largely outside of the standardised norms.

Adaptive myriad filtering algorithms for removal of nonstationary noise in electrooculograms

Suppressing nonstationary noise present in biomedical signals is important to provide high-quality diagnoses. Nonstationary noise is difficult for removing due to its time-varying and previously unknown characteristics. The application of linear filtering to the electrooculograph (EOG) signals leads to the smoothing of diagnostically important rapid changes in a signal caused by saccadic eye movements. In this respect, for processing edges and other discontinuous transitions, nonlinear filters based on robust estimators are more appropriate. The paper introduces novel adaptive algorithms for real-time nonlinear filtering of nonstationary noise in EOG signal with a noise- and signal-dependent filter switching, which is more appropriate for processing a local vicinity of the current input signal sample. One of the algorithms is based on myriad filters and sub-filter weighted FIR (which inite Impulse Responce) myriad hybrid filters. It suggests replacing the median with a myriad operation, calculated by Newton¢s numerical technique with adaptive switching of window length and linearity parameter settings. The other algorithm adaptively switches sub-filter weighted FIR median hybrid and averaging filters with different window lengths, offering simpler calculations and high-speed performance. These algorithms do not require time for filter parameters modification and their exact tuning during real-time signal processing and a prior knowledge of the signal model and noise variance. Numerical simulations were conducted to evaluate the filtering quality based on criteria of mean-square error and signal-to-noise ratio for a model signal under different levels of Gaussian noise. The achieved results show good performance and algorithm high quality for suppression of nonstationary noise in EOG. The myriad type adaptive algorithm prevails over the median in effectiveness but requires a numerical technique for cost function minimization, however, myriad filtering real-time implementation is possible with utilization of high-speed computers. Suggested adaptive algorithms significantly improve the efficiency of nonadaptive filters.

Bayesian and Discriminative Models for Active Visual Perception across Saccades.

The brain interprets sensory inputs to guide behavior, but behavior itself disrupts sensory inputs. Perceiving a coherent world while acting in it constitutes active perception. For example, saccadic eye movements displace visual images on the retina and yet the brain perceives visual stability. Because this percept of visual stability has been shown to be influenced by prior expectations, we tested the hypothesis that it is Bayesian. The key prediction was that priors would be used more as sensory uncertainty increases. Humans and rhesus macaques reported whether an image moved during saccades. We manipulated both prior expectations and levels of sensory uncertainty. All psychophysical data were compared with the predictions of Bayesian ideal observer models. We found that humans were Bayesian for continuous judgments. For categorical judgments, however, they were anti-Bayesian: they used their priors less with greater uncertainty. We studied this categorical result further in macaques. The animals' judgments were similarly anti-Bayesian for sensory uncertainty caused by external, image noise, but Bayesian for uncertainty due to internal, motor-driven noise. A discriminative learning model explained the anti-Bayesian effects. We conclude that active vision uses both Bayesian and discriminative models depending on task requirements (continuous vs categorical) and the source of uncertainty (image noise vs motor-driven noise). In the context of previous knowledge about the saccadic system, our results provide an example of how the comparative analysis of Bayesian versus non-Bayesian models of perception offers novel insights into underlying neural organization.

Opsoclonus Myoclonus Syndrome Associated With a New Diagnosis of HIV

Abstract Opsoclonus myoclonus syndrome (OMS) is a rare neurological disorder characterized by rapid saccadic eye movements, focal myoclonus, and gait disturbances. Both neoplastic and infectious processes have been found to be associated with OMS. In this report, we present a case of OMS in the setting of a new diagnosis of HIV. After diagnosis, the patient was initiated on antiretroviral therapy in addition to clonazepam with some improvement in her neurological symptoms. It was not until she was started on prednisone as an outpatient that her symptoms completely resolved and she returned to her functional baseline.

Laminar mechanisms of saccadic suppression in primate visual cortex

Saccadic eye movements are known to cause saccadic suppression, a temporary reduction in visual sensitivity and visual cortical firing rates. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within visual area V4. We find subpopulation-specific differences in the magnitude and timing of peri-saccadic modulation. Input-layer neurons show changes in firing rate and inter-neuronal correlations prior to saccade onset, and putative inhibitory interneurons in the input layer elevate their firing rate during saccades. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input-layer-targeting pathway can initiate saccadic suppression by enhancing local inhibitory activity. Collectively, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.

Effects of Eye Movement Exercise on Cognitive Function and Prefrontal Cortex Connectivity for the Elderly with Mild Cognitive Impairment: An fNIRS Study

PURPOSE The purpose of this study was to examine the effects of an eye movement exercise intervention on cognitive function and prefrontal cortex connectivity in the elderly with mild cognitive impairment.METHODS Ten older adults with mild cognitive impairment participated in eye movement exercise consisting of saccadic eye movement, pursuit eye movement, vestibular-ocular eye movement, and vergence eye movement for 4 weeks. Cognitive function (MoCA-K), reaction time during stroop task, and prefrontal cortex connectivity were measured using the functional near-infrared spectrometric analyzer (fNIRS) before and after the intervention.RESULTS First, cognitive function of the elderly with mild cognitive impairment showed significant improvement after the eye movement exercise (p &lt; .05). Second, reaction time decreased significantly from 1.16 to 0.91 ms after eye movement exercise. Third, the strength of prefrontal cortex connectivity (left OFC - right FPC, right OFC - right FPC) increased after the intervention in the older adults with mild cognitive impairment.CONCLUSIONS The results of this study suggest that eye movement exercise is an effective intervention for improving cognitive function through improvement of brain functional connection in the elderly patients with mild cognitive impairment.

Velocity tracking control best explains the modulation of saccade kinematics during eye-hand coordination: Velocity-based control of saccades during eye-hand coordination.

Fast movements like saccadic eye movements that occur in the absence of sensory feedback are thought to be controlled by internal feedback. Such internal feedback provides an instantaneous estimate of the output, which serves as a proxy for sensory feedback, that can be used by the controller to correct deviations from the desired plan. In the predominant view, the desired plan/input is encoded in the form of a static displacement signal (endpoint model), believed to be encoded in the spatial map of the superior colliculus (SC). However, recent evidence has shown that SC neurons have a dynamic signal that correlates with saccade velocity, suggesting that information for velocity-based control is available for generating saccades. Motivated by this observation, we used a novel optimal control framework to test whether saccadic execution could be achieved by tracking a dynamic velocity signal at the input. We validated this velocity tracking model in a task where the peak saccade velocity was modulated by the speed of a concurrent hand movement independent of the saccade endpoint. A comparison showed that in this task, the velocity tracking model performed significantly better than the endpoint model. These results suggest that the saccadic system may have additional flexibility to incorporate a velocity-based internal feedback control when imposed by task goals or context.

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.

Saccadic eye movement in individuals with ultra high‐risk psychosis and bipolar disorder

AbstractBackgroundThe purpose of the study is to examine saccadic eye movements, and the relationship with motor functions based on the cerebellar connection among individuals with ultra‐high‐risk of psychosis and bipolar disorder (UHR‐P, UHR‐BD) and healthy controls (HC).MethodThe study included 20 UHR‐P (mean age 21.95±3.38), 20 UHR‐BD (mean age 21.45±4.27), and 19 HC (mean age 24.84±3.95). Participants had been selected from cases clinical‐high‐risk criteria in interviews made with The Structured Interview of Psychosis Risk Syndromes (SIPS) and Bipolar Prodrome Symptom Interview and Scale (BPSS). Correct and incorrect count, amplitude and latency of anti‐saccade were used to evaluate eye movements. Eye movement data were recorded from the right eye using an EyeLink 1000 Plus eye‐tracker. In addition, Brief Motor Scale (BMS) was used to evaluate motor functions.ResultThe number of correct saccade of anti‐saccade showed a significant difference between HC and UHR‐BD (p = 0.021). The Correct anti‐saccades were strongly correlated with motor function in UHR‐BD (r = ‐0.754, p&lt;0.000). There was a moderate positive correlation between incorrect responses of anti‐saccade and motor function in UHR‐BD. (r = 0.455, p = 0.044). Motor functions indicated statistically significant differences between HC and high‐risk groups (p = 0.002 and p&lt; 0.000). No significant relationship was found between anti‐saccade latency and amplitude and motor functions. (p&gt; 0.05).ConclusionWe indicated that patients with ultra‐high risk had saccadic inhibition and motor coordination‐sequencing problems. This may be related to the dysfunctions in the cerebellum. The results are preliminary data of an ongoing study.

Opsoclonus Induced by Head-Shaking in Vestibular Migraine.

Opsoclonus refers to saccadic oscillations without an intersaccadic interval occurring in multiple planes. Opsoclonus mostly indicates dysfunction of the brainstem or cerebellum. We report opsoclonus induced by horizontal head-shaking without other signs of brainstem or cerebellar dysfunction in two patients with vestibular migraine (VM). The development of opsoclonus after horizontal head-shaking indicates unstable or hyperactive neural circuits between the excitatory and inhibitory saccadic premotor burst neurons in these patients with VM.

Adaptive changes to saccade amplitude and target localization do not require pre-saccadic target visibility

The accuracy of saccadic eye movements is maintained by saccadic adaptation, a learning mechanism that is proposed to rely on visual prediction error, i.e., a mismatch between the pre-saccadically predicted and post-saccadically experienced position of the saccade target. However, recent research indicates that saccadic adaptation might be driven by postdictive motor error, i.e., a retrospective estimation of the pre-saccadic target position based on the post-saccadic image. We investigated whether oculomotor behavior can be adapted based on post-saccadic target information alone. We measured eye movements and localization judgements as participants aimed saccades at an initially invisible target, which was always shown only after the saccade. Each such trial was followed by either a pre- or a post-saccadic localization trial. The target position was fixed for the first 100 trials of the experiment and, during the following 200 trials, successively shifted inward or outward. Saccade amplitude and the pre- and post-saccadic localization judgements adjusted to the changing target position. Our results suggest that post-saccadic information is sufficient to induce error-reducing adaptive changes in saccade amplitude and target localization, possibly reflecting continuous updating of the estimated pre-saccadic target location driven by postdictive motor error.

Impact of depression and post-traumatic stress on manual and oculomotor performance in service members with a history of mild TBI

ABSTRACT Objective To determine the impact of depression and post-traumatic stress on an automated oculomotor and manual measure of visual attention, compared to conventional neuropsychological assessment. Setting: Military traumatic brain injury (TBI) rehabilitation program. Participants 188 Active Duty Service Members (ADSM) with a history of mild TBI. Design A cross-sectional and correlational study with data obtained through an IRB-approved data registry study. Main measures: Bethesda Eye & Attention Measure (BEAM); brief neuropsychological battery; self-reported symptom surveys including Neurobehavioral Symptom Inventory (NSI), Patient Health Questionnaire-8 (PHQ-8), and PTSD Checklist-5 (PCL-5). Results Small effect sizes were found for partial correlations between both depression and post-traumatic stress and key BEAM metrics. In contrast, small-to-medium effects sizes were found across all traditional neuropsychological test measures. Conclusion This study illustrates the profile of impairments associated with depression and post-traumatic stress on saccadic eye movements and manual responses to BEAM relative to conventional neuropsychological tests. Results demonstrated that among ADSM seen for mTBI, depression and PTS exert a significant negative impact on measures of processing speed, attention, executive function, and memory across saccadic, manual, and conventional neuropsychological tests. However, the unique psychometric features of each of these assessment approaches may assist in distinguishing the effects of psychiatric comorbidities within this population.

Vision impairment is common in non-hospitalised patients with post-COVID-19 syndrome

ABSTRACT Clinical relevance Vision-related problems can be part of longstanding sequelae after COVID-19 and hamper the return to work and daily activities. Knowledge about symptoms, visual, and oculomotor dysfunctions is however scarce, particularly for non-hospitalised patients. Clinically applicable tools are needed as support in the assessment and determination of intervention needs. Background The purpose of this study was to evaluate vision-related symptoms, assess visual and oculomotor function, and to test the clinical assessment of saccadic eye movements and sensitivity to visual motion in non-hospitalised post-COVID-19 outpatients. The patients (n = 38) in this observational cohort study were recruited from a post-COVID-19 clinic and had been referred for neurocognitive assessment. Methods Patients who reported vision-related symptoms reading problems and intolerance to movement in the environment were examined. A structured symptom assessment and a comprehensive vision examination were undertaken, and saccadic eye movements and visual motion sensitivity were assessed. Results High symptom scores (26–60%) and prevalence of visual function impairments were observed. An increased symptom score when reading was associated with less efficient saccadic eye movement behaviour (p < 0.001) and binocular dysfunction (p = 0.029). Patients with severe symptoms in visually busy places scored significantly higher on the Visual Motion Sensitivity Clinical Test Protocol (p = 0.029). Conclusion Vision-related symptoms and impairments were prevalent in the study group. The Developmental Eye Movement Test and the Visual Motion Sensitivity Clinical Test Protocol showed promise for clinical assessment of saccadic performance and sensitivity to movement in the environment. Further study will be required to explore the utility of these tools.

Development of a New Eye Movement Measurement Device Using Eye-Tracking Analysis Technology

Smooth pursuit eye movements and saccadic eye movements are vital for precise vision. Therefore, tests for eye movement are important for assessing nervous or muscular diseases. However, objective measurements are not frequently performed due to the need for a polygraph system, electrodes, amplifier, and personal computer for data analysis. To address this, we developed an all-in-one eye-movement-measuring device that simultaneously presents visual stimuli, records eye positions, and examines its feasibility for evaluating eye movements. This device generates stimulus that induces eye movements and records those movements continuously. The horizontal or vertical eye movements of 16 participants were measured at various visual target speeds of 20–100 deg/s. The maximum cross-correlation coefficient (rho max) between the eye and visual target positions was used as an index of eye movement accuracy. A repeated-measures multi-way analysis of variance was performed, with the main effect being that rho max significantly decreased as the visual target speed increased. The average (±standard deviation) rho max values across all velocities were 0.995 ± 0.008 and 0.967 ± 0.062 in the horizontal and vertical directions, respectively, and were significantly higher for horizontal eye movements than for vertical eye movements. Moreover, rho max and saccadic frequency were significantly correlated for the slowest and fastest visual target motions. These suggest that our device enables accurate measurements of eye movements. We believe our new measurement device can be applied clinically for easily and objectively evaluating eye movements.

Peripheral targets attenuate miniature eye movements during fixation

Fixating a small dot is a universal technique for stabilizing gaze in vision and eye movement research, and for clinical imaging of normal and diseased retinae. During fixation, microsaccades and drifts occur that presumably benefit vision, yet microsaccades compromise image stability and usurp task attention. Previous work suggested that microsaccades and smooth pursuit catch-up saccades are controlled by similar mechanisms. This, and other previous work showing fewer catch-up saccades during smooth pursuit of peripheral targets suggested that a peripheral target might similarly mitigate microsaccades. Here, human observers fixated one of three stimuli: a small central dot, the center of a peripheral, circular array of small dots, or a central/peripheral stimulus created by combining the two. The microsaccade rate was significantly lower with the peripheral array than with the dot. However, inserting the dot into the array increased the microsaccade rate to single-dot levels. Drift speed also decreased with the peripheral array, both with and without the central dot. Eye position variability was higher with the array than with the composite stimulus. The results suggest that analogous to the foveal pursuit, foveating a stationary target engages the saccadic system likely compromising retinal-image stability. In contrast, fixating a peripheral stimulus improves stability, thereby affording better retinal imaging and releasing attention for experimental tasks.

Posterior Parietal Cortex Plays a Causal Role in Abstract Memory-Based Visual Categorical Decisions.

Neural activity in the lateral intraparietal cortex (LIP) correlates with both sensory evaluation and motor planning underlying visuomotor decisions. We previously showed that LIP plays a causal role in visually-based perceptual and categorical decisions, and preferentially contributes to evaluating sensory stimuli over motor planning. In that study, however, monkeys reported their decisions with a saccade to a colored target associated with the correct motion category or direction. Since LIP is known to play a role in saccade planning, it remains unclear whether LIP's causal role in such decisions extend to decision-making tasks which do not involve saccades. Here, we employed reversible pharmacological inactivation of LIP neural activity while two male monkeys performed delayed match to category (DMC) and delayed match to sample (DMS) tasks. In both tasks, monkeys needed to maintain gaze fixation throughout the trial and report whether a test stimulus was a categorical match or nonmatch to the previous sample stimulus by releasing a touch bar. LIP inactivation impaired monkeys' behavioral performance in both tasks, with deficits in both accuracy and reaction time (RT). Furthermore, we recorded LIP neural activity in the DMC task targeting the same cortical locations as in the inactivation experiments. We found significant neural encoding of the sample category, which was correlated with monkeys' categorical decisions in the DMC task. Taken together, our results demonstrate that LIP plays a generalized role in visual categorical decisions independent of the task-structure and motor response modality.SIGNIFICANCE STATEMENT Neural activity in the lateral intraparietal cortex (LIP) correlates with perceptual and categorical decisions, in addition to its role in mediating saccadic eye movements. Past work found that LIP is causally involved in visual decisions that are rapidly reported by saccades in a reaction time based decision making task. Here we use reversible inactivation of LIP to test whether LIP is also causally involved in visual decisions when reported by hand movements during delayed matching tasks. Here we show that LIP inactivation impaired monkeys' task performance during both memory-based discrimination and categorization tasks. These results demonstrate that LIP plays a generalized role in visual categorical decisions independent of the task-structure and motor response modality.

The genetic spectrum of congenital ocular motor apraxia type Cogan: an observational study, continued

BackgroundThe term congenital ocular motor apraxia (COMA), coined by Cogan in 1952, designates the incapacity to initiate voluntary eye movements performing rapid gaze shift, so called saccades. While regarded as a nosological entity by some authors, there is growing evidence that COMA designates merely a neurological symptom with etiologic heterogeneity. In 2016, we reported an observational study in a cohort of 21 patients diagnosed as having COMA. Thorough re-evaluation of the neuroimaging features of these 21 subjects revealed a previously not recognized molar tooth sign (MTS) in 11 of them, thus leading to a diagnostic reassignment as Joubert syndrome (JBTS). Specific MRI features in two further individuals indicated a Poretti–Boltshauser syndrome (PTBHS) and a tubulinopathy. In eight patients, a more precise diagnosis was not achieved. We pursued this cohort aiming at clarification of the definite genetic basis of COMA in each patient.ResultsUsing a candidate gene approach, molecular genetic panels or exome sequencing, we detected causative molecular genetic variants in 17 of 21 patients with COMA. In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. In two individuals without MTS on MRI, pathogenic variants were detected in NPHP1 and KIAA0586, arriving at a diagnosis of JBTS type 4 and 23, respectively. Three patients carried heterozygous truncating variants in SUFU, representing the first description of a newly identified forme fruste of JBTS. The clinical diagnoses of PTBHS and tubulinopathy were confirmed by detection of causative variants in LAMA1 and TUBA1A, respectively. In one patient with normal MRI, biallelic pathogenic variants in ATM indicated variant ataxia telangiectasia. Exome sequencing failed to reveal causative genetic variants in the remaining four subjects, two of them with clear MTS on MRI.ConclusionsOur findings indicate marked etiologic heterogeneity in COMA with detection of causative mutations in 81% (17/21) in our cohort and nine different genes being affected, mostly genes associated with JBTS. We provide a diagnostic algorithm for COMA.