Navigating Visual Challenges: How Parkinson's Disease Alters Cognitive Priorities in Visual Search.

OBJECTIVE: Parkinson's disease (PD) hampers visual search tasks such as reading, driving, and navigation. We examined expectations from past experiences, guiding cognition and contextual priors, on visual search in PD. METHODS: We compared eye movements as PD and healthy participants searched for a hidden object (target) in cluttered real-world scenes. RESULTS: PD participants prolonged fixation on high-probability (high-prior) locations for the target, consistent across expected and unexpected scenario. Such emphasis on contextual visual priors, evidenced by high fixation duration on high-probability areas, was beneficial when the target was at the expected location but presented challenges when the target was situated in an unlikely place. CONCLUSION: This study contributes to understanding how PD impacts visual search behavior and cognitive processing. The findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. It provides insights for potential interventions targeting visuo-cognitive deficits in PD patients. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

Ion channel profiles of extraocular motoneurons and internuclear neurons in human abducens and trochlear nuclei.

Introduction: Extraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of singly-innervated fibers (SIF). Recently, it has been established by our research group that these motoneuron types of monkey abducens and trochlear nuclei express distinct ion channel profiles: SIF motoneurons, as well as abducens internuclear neurons (INT), express strong Kv1.1 and Kv3.1b immunoreactivity, indicating their fast-firing capacity, whereas MIF motoneurons do not. Moreover, low voltage activated cation channels, such as Cav3.1 and HCN1 showed differences between MIF and SIF motoneurons, indicating distinct post-inhibitory rebound characteristics. However, the ion channel profiles of MIF and SIF motoneurons have not been established in human brainstem tissue. Methods: Therefore, we used immunohistochemical methods with antibodies against Kv, Cav3 and HCN channels to (1) examine the human trochlear nucleus in terms of anatomical organization of MIF and SIF motoneurons, (2) examine immunolabeling patterns of ion channel proteins in the distinct motoneurons populations in the trochlear and abducens nuclei. Results: In the examination of the trochlear nucleus, a third motoneuron subgroup was consistently encountered with weak perineuronal nets (PN). The neurons of this subgroup had -on average- larger diameters than MIF motoneurons, and smaller diameters than SIF motoneurons, and PN expression strength correlated with neuronal size. Immunolabeling of various ion channels revealed that, in general, human MIF and SIF motoneurons did not differ consistently, as opposed to the findings in monkey trochlear and abducens nuclei. Kv1.1, Kv3.1b and HCN channels were found on both MIF and SIF motoneurons and the immunolabeling density varied for multiple ion channels. On the other hand, significant differences between SIF motoneurons and INTs were found in terms of HCN1 immunoreactivity. Discussion: These results indicated that motoneurons may be more variable in human in terms of histochemical and biophysiological characteristics, than previously thought. This study therefore establishes grounds for any histochemical examination of motor nuclei controlling extraocular muscles in eye movement related pathologies in the human brainstem.

A 360° View for Large Language Models: Early Detection of Amblyopia in Children using Multi-View Eye Movement Recordings.

Amblyopia is a neurodevelopmental visual disorder that affects approximately 3-5% of children globally and it can lead to vision loss if it is not diagnosed and treated early. Traditional diagnostic methods, which rely on subjective assessments and expert interpretation of eye movement recordings presents challenges in resource-limited eye care centers. This study introduces a new approach that integrates the Gemini large language model (LLM) with eye-tracking data to develop a classification tool for diagnosis of patients with amblyopia. The study demonstrates: (1) LLMs can be successfully applied to the analysis of fixation eye movement data to diagnose patients with amblyopia; and (2) Input of medical subject matter expertise, introduced in this study in the form of medical expert augmented generation (MEAG), is an effective adaption of the generic retrieval augmented generation (RAG) approach for medical applications using LLMs. This study introduces a new multi-view prompting framework for ophthalmology applications that incorporates fine granularity feedback from pediatric ophthalmologist together with in-context learning to report an accuracy of 80% in diagnosing patients with amblyopia. In addition to the binary classification task, the classification tool is generalizable to specific subpopulations of amblyopic patients based on severity of amblyopia, type of amblyopia, and with or without nystagmus. The model reports an accuracy of: (1) 83% in classifying patients with moderate or severe amblyopia, (2) 81% in classifying patients with mild or treated amblyopia; and (3) 85% accuracy in classifying patients with nystagmus. To the best of our knowledge, this is the first study that defines a multi-view prompting framework with MEAG to analyze eye tracking data for the diagnosis of amblyopic patients.

Exploring Heading Direction Perception in Cervical Dystonia, Tremor, and Their Coexistence.

OBJECTIVE: Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one's own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. We compare such perception behavior in visual and vestibular domains, predicting that visual heading perception would be superior to vestibular heading perception. METHODS: Following the focus on the perception of heading direction, we used psychophysics techniques, such as two-alternative-forced-choice task, to examine perception of direction of one's own movements as they see isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). We fitted a sigmoidal psychometric function curve to determine the threshold for visual or vestibular heading perception in our participants. RESULTS: Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions-isolated cervical dystonia, isolated tremor, and their combination. CONCLUSION: These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

Pallidal multifractal complexity is a new potential physiomarker of dystonia.

OBJECTIVE: Low-frequency 4-12 Hz pallidal oscillations are being considered as potential physiomarkers for dystonia. We suggest investigating the multifractal properties of pallidal activity as an additional marker. METHODS: We employed local field potentials (LFP) recordings from 23 patients with dystonia who were undergoing deep brain stimulation (DBS) surgery to explore the connection between disease severity and the multifractal characteristics of pallidal activity. Furthermore, we performed an analysis of LFP recordings from four patients, following the externalization of DBS lead electrodes, to investigate the impact of DBS and neck muscle vibration on multifractal parameters. RESULTS: Greater dystonia severity exhibited a correlation with a narrower multifractal spectrum width but higher multifractal spectral asymmetry. Both GPi DBS and muscle vibration in dystonia patients expanded the multifractal spectrum width while restoring multifractal spectral symmetry. Notably, the threshold peak intensities for an increase in multifractal spectrum width substantially overlapped with the optimal volume of tissue activated. A broader multifractal spectrum during DBS corresponded to more favorable clinical outcomes. CONCLUSIONS: Multifractal properties of pallidal neuronal activity serve as indicators of neural dysfunction in dystonia. SIGNIFICANCE: These findings suggest the potential of utilizing multifractal characteristics as predictive factors for the DBS outcome in dystonia.

Interdisciplinary insights into tremor in dystonia: Navigating clinical controversies, definitional challenges, and pathophysiological complexities.

This review delves into the historical evolution and ongoing controversy surrounding the relationship between tremor and dystonia. The Dystonia Consensus Panel and the International Parkinson's and Movement Disorders Society's Tremor Taskforce have attempted to define these entities, but the complexity arises when patients have a combination of both dystonia and tremor. The term "dystonic tremor" has sparked diverse interpretations, with debates over its clinical features and the need for more objectively defined characteristics. Logistic regression analyses in a large cohort of dystonia patients identified determinants such as body region affected by dystonia, dystonia severity, age, and recruitment site, with unexpected associations emphasizing the subjectivity in detecting and classifying tremor. The study further discovered diverse prevalence of "dystonic tremor" based on different definitions, revealing substantial variability among investigators. The recently convened Dystonia-Tremor panel aimed to address these challenges by proposing a more uniform nomenclature, emphasizing precise and descriptive terms. Despite the complexity, instrumented measures, such as electromyography, temporal discrimination threshold, blink reflex, and trajectory shape analysis, seem to be useful in distinguishing between tremor and dystonia. The pathophysiology debate centers around the involvement of the cerebello-thalamo-cortical and basal ganglia-thalamo-cortical circuits. Evidence supports the role of both circuits in driving the pathophysiology of dystonic tremor, challenging the notion of a clear dichotomy. The review concludes by emphasizing the need for a nuanced understanding, highlighting the intricate interplay between tremor and dystonia, and the potential of instrumental measures in advancing diagnostic accuracy.

Improved Side-Effect Stimulation Thresholds and Postoperative Transient Confusion With Asleep, Image-Guided Deep Brain Stimulation.

BACKGROUND AND OBJECTIVES: Asleep, image-guided deep brain stimulation (DBS) is a modern alternative to awake, microelectrode recording (MER) guidance. Studies demonstrate comparable efficacy and complications between techniques, although some report lower stimulation thresholds for side effects with image guidance. In addition, few studies directly compare the risk of postoperative transient confusion (pTC) across techniques. The purpose of this study was to compare clinical efficacy, stimulation thresholds for side effects, and rates of pTC with MER-guided DBS vs intraoperative 3D-fluoroscopy (i3D-F) guidance in Parkinson's disease and essential tremor. METHODS: Consecutive patients from 2006 to 2021 were identified from the departmental database and grouped as having either MER-guided DBS or i3D-F-guided DBS insertion. Directional leads were used once commercially available. Changes in Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, levodopa equivalent daily dose, Fahn-Tolosa-Marin scores, and stimulation thresholds were assessed, as were rates of complications including pTC. RESULTS: MER guidance was used to implant 487 electrodes (18 globus pallidus interna, GPi; 171 subthalamic nucleus; 76 ventrointermediate thalamus, VIM) in 265 patients. i3D-F guidance was used in 167 electrodes (19 GPi; 25 subthalamic nucleus; 41 VIM) in 85 patients. There were no significant differences in Unified Parkinson's Disease Rating III Scale, levodopa equivalent daily dose, or Fahn-Tolosa-Marin between groups. Stimulation thresholds for side effects were higher with i3D-F guidance in the subthalamic nucleus (MER, 2.80 mA ± 0.98; i3D-F, 3.46 mA ± 0.92; P = .002) and VIM (MER, 2.81 mA ± 1.00; i3D-F, 3.19 mA ± 1.03; P = .0018). Less pTC with i3D-F guidance (MER, 7.5%; i3D-F, 1.2%; P = .034) was also found. CONCLUSION: Although clinical efficacy between MER-guided and i3D-F-guided DBS was comparable, thresholds for stimulation side effects were higher with i3D-F guidance and the rate of pTC was lower. This suggests that image-guided DBS may affect long-term side effects and pose a decreased risk of pTC.

Does Vestibular Motion Perception Correlate with Axonal Pathways Stimulated by Subthalamic Deep Brain Stimulation in Parkinson's Disease?

Perception of our linear motion - heading - is critical for postural control, gait, and locomotion, and it is impaired in Parkinson's disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. Fourteen PD participants with bilateral STN DBS performed a two-alternative forced-choice discrimination task where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30° to the left or to the right with respect to the straight-ahead direction. Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts' involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways are thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases, there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN-induced modulation of vestibular heading perception in PD.

Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA).

Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies. Patients with IMCAs develop cerebellar symptoms, characterized mainly by gait ataxia, showing an acute or subacute clinical course. We present a novel concept of latent autoimmune cerebellar ataxia (LACA), analogous to latent autoimmune diabetes in adults (LADA). LADA is a slowly progressive form of autoimmune diabetes where patients are often initially diagnosed with type 2 diabetes. The sole biomarker (serum anti-GAD antibody) is not always present or can fluctuate. However, the disease progresses to pancreatic beta-cell failure and insulin dependency within about 5 years. Due to the unclear autoimmune profile, clinicians often struggle to reach an early diagnosis during the period when insulin production is not severely compromised. LACA is also characterized by a slowly progressive course, lack of obvious autoimmune background, and difficulties in reaching a diagnosis in the absence of clear markers for IMCAs. The authors discuss two aspects of LACA: (1) the not manifestly evident autoimmunity and (2) the prodromal stage of IMCA's characterized by a period of partial neuronal dysfunction where non-specific symptoms may occur. In order to achieve an early intervention and prevent cell death in the cerebellum, identification of the time-window before irreversible neuronal loss is critical. LACA occurs during this time-window when possible preservation of neural plasticity exists. Efforts should be devoted to the early identification of biological, neurophysiological, neuropsychological, morphological (brain morphometry), and multimodal biomarkers allowing early diagnosis and therapeutic intervention and to avoid irreversible neuronal loss.

Unraveling the Twist: Spatial Navigational Challenges in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is an intricate neurological condition with motor and nonmotor symptoms. These include disruptions in visual perception, self-orientation, visual working memory, and vestibular functions. However, the specific impact of CD on perceiving self-motion direction, especially with isolated visual or vestibular stimuli, remains largely unexplored. OBJECTIVE: This study aimed to examine the effects of CD on linear motion perception, hypothesizing impaired heading discrimination in both vestibular and visual tasks, and that such deficits correlate with the disease severity. METHODS: We employed a cutting-edge motion platform to precisely control whole-body linear motion. Through repeated two-alternative forced-choice tasks, we assessed vestibular heading direction discrimination. Participants observed dynamic star clouds in immersive virtual reality and indicated their perceived self-motion direction, evaluating visual heading direction discrimination. Sensitivity to direction variations and response accuracy errors were analyzed using robust Gaussian cumulative distribution psychometric functions. RESULTS: Heading perception is impaired in individuals with CD, particularly evident in vestibular heading discrimination. CD severity correlated with elevated thresholds for both vestibular and visual heading discrimination. Surprisingly, lateralized CD did not introduce bias in either system, suggesting widespread disruption over localized effects. CONCLUSIONS: Contrary to previous beliefs, our findings challenge the idea that CD-related heading discrimination issues mainly arise from peripheral vestibular effects. Instead, abnormal proprioceptive input from dystonic neck muscles introduces noise into the central mechanism integrating visual, vestibular, and proprioceptive signals. These insights into spatial navigation deficits have implications for future CD research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Objective assessment of eye alignment and disparity-driven vergence in Parkinson's disease.

Background: Self-reported diplopia is described in up to one-third of Parkinson's disease (PD) patients. Objective: The purpose of our study was to expand our understanding of the mechanistic underpinnings of diplopia in PD. We hypothesize that the time-based control of eye alignment and increased eye deviation under binocular viewing will be related to the fusion-initiating and fusion-maintaining component deficits of disparity-driven vergence in PD. Methods: We used high-resolution video-oculography to measure eye alignment under binocular and monocular viewing and disparity-driven vergence in 33 PD and 10 age-matched healthy participants. We computed eye deviation and time-based control of eye alignment, occurrence of conjugate saccadic eye movements, latency and gain of vergence (fusion initiation), and variance of eye position at the end of dynamic vergence (fusion maintenance). Results: We categorized PD subjects into three groups, considering their time-based control of eye alignment as compared to healthy controls in binocular viewing. Group 1 = 45% had good control and spent >80% of the time when the eyes were well-aligned, Group 2 = 26% had intermediate control and spent <80% but greater >5% of the time when the eyes were well-aligned, and Group 3 = 29% had very poor control with increased eye deviation majority of the times (<5% of the time when the eyes were well-aligned). All three groups exhibited greater eye deviation under monocular viewing than controls. PD subjects exhibited fusion-initiating and fusion-maintaining vergence deficits (prolonged latencies, reduced vergence gain, increased variance of fusion-maintaining component) with a greater probability of saccadic movements than controls. Group 2 and Group 3 subjects were more likely to exhibit failure to initiate vergence (>20%) than Group 1 (13%) and controls (0%) trials. No significant difference was found in the Unified Parkinson's Disease Rating Scale (UPDRS-a tool to measure the severity of PD) values between the three PD groups (Group 1 = 33.69 ± 14.22, Group 2 = 38.43 ± 22.61, and Group 3 = 23.44 ± 1, p > 0.05). Conclusion: The majority of PD subjects within our cohort had binocular dysfunction with increased eye deviation under monocular viewing and disparity-driven vergence deficits. PD subjects with intermediate or poor control of eye deviation under binocular viewing had greater fusion-initiating and fusion-maintaining vergence deficits. The study highlights the importance of assessing binocular dysfunction in PD subjects independent of the severity of motor symptoms.

Proprioceptive Modulation of Pallidal Physiology in Cervical Dystonia.

BACKGROUND: There is a growing body of evidence suggesting that botulinum toxin can alter proprioceptive feedback and modulate the muscle-spindle output for the treatment of dystonia. However, the mechanism for this modulation remains unclear. METHODS: We conducted a study involving 17 patients with cervical dystonia (CD), seven of whom had prominent CD and 10 with generalized dystonia (GD) along with CD. We investigated the effects of neck vibration, a form of proprioceptive modulation, on spontaneous single-neuron responses and local field potentials (LFPs) recorded from the globus pallidum externus (GPe) and internus (GPi). RESULTS: Our findings demonstrated that neck vibration notably increased the regularity of neck-sensitive GPi neurons in focal CD patients. Additionally, in patients with GD and CD, the vibration enhanced the firing regularity of non-neck-sensitive neurons. These effects on single-unit activity were also mirrored in ensemble responses measured through LFPs. Notably, the LFP modulation was particularly pronounced in areas populated with burst neurons compared to pause or tonic cells. CONCLUSION: The results from our study emphasize the significance of burst neurons in the pathogenesis of dystonia and in the efficacy of proprioceptive modulation for its treatment. Moreover, we observed that the effects of vibration on focal CD were prominent in the α band LFP, indicating modulation of pallido-cerebellar connectivity. Moreover, the pallidal effects of vibration in GD with CD involved modulation of cerebro-pallidal θ band connectivity. Our analysis provides insight into how vibration-induced changes in pallidal activity are integrated into the downstream motor circuit. © 2023 International Parkinson and Movement Disorder Society.

Monitoring Eye Movement in Patients with Parkinson's Disease: What Can It Tell Us?

Parkinson's disease (PD) affects approximately 10 million individuals worldwide. Visual impairments are a common feature of PD. Patients report difficulties with visual scanning, impaired depth perception and spatial navigation, and blurry and double vision. Examination of PD patients reveals abnormal fixational saccades, strabismus, impaired convergence, and abnormal visually-guided saccades. This review aims to describe objective features of abnormal eye movements in PD and to discuss the structures and pathways through which these abnormalities may manifest.

DYT1 dystonia: Neurophysiological properties of the pallidal activity.

OBJECTIVES: The aim of this paper is to find the differences in the physiology of the pallidal neurons in DYT1 and non-DYT1 dystonia. METHODS: We performed microelectrode recording of the single unit activity in both segments of the globus pallidus during stereotactic implantation of electrodes for deep brain stimulation (DBS). RESULTS: We found a reduced firing rate, reduced burst rate, and increased pause index in both pallidal segments in DYT1. Also, in DYT1 the activity in both pallidal segments was similar, but not so in non-DYT1. CONCLUSION: The results suggest a common pathological focus for both pallidal segments, located in the striatum. We also speculate that strong striatal influence on GPi and GPe overrides other input sources to the pallidal nuclei causing similarity in neuronal activity. SIGNIFICANCE: We found significant differences in neuronal activity between DYT1 and non-DYT1 neurons. Our findings shed light on the pathophysiology of DYT-1 dystonia which can be very different from non-DYT1 dystonia and have other efficient treatment tactics.

Physiological measures and anatomical correlates of subthalamic deep brain stimulation effect on gait in Parkinson's disease.

We examined whether conflicting visual and non-visual information leads to gait abnormalities and how the subthalamic deep brain stimulation (STN DBS) influences gait dysfunction in Parkinson's disease (PD). We used a motion capture system to measure the kinematics of the lower limbs during treadmill walking in immersive virtual reality. The visual information provided in the virtual reality paradigm was modulated to create a mismatch between the optic-flow velocity of the visual scene and the walking speed on the treadmill. In each mismatched condition, we calculated the step duration, step length, step phase, step height, and asymmetries. The key finding of our study was that mismatch between treadmill walking speed and the optic-flow velocity did not consistently alter gait parameters in PD. We also found that STN DBS improved the PD gait pattern by changing the stride length and step height. The effects on phase and left/right asymmetry were not statistically significant. The DBS parameters and location also determined its effects on gait. Statistical effects on stride length and step height were noted when the DBS volume of activated tissue (VTA) was in the dorsal aspect of the subthalamus. The statistically significant effects of STN DBS was present when VTA significantly overlapped with MR tractogrphically measured motor and pre-motor hyperdirect pathways. In summary, our results provide novel insight into ways for controlling walking behavior in PD using STN DBS.

Classics to Contemporary of Saccadic Dysmetria and Oscillations.

Clear vision requires accurate gaze shift from one object to the other and steadily maintaining it when eyes are at the target. The rapid gaze shifts are assured by the high-frequency burst in the brainstem neuronal firing, the mechanism relying on the tight cerebellar supervision. The cerebellar oversight is equally essential for maintaining gaze on the object of interest. The cerebellar significance on the motor control of gaze and the consequences of cerebellar illness are known for almost three quarters of the century - since David Cogan published the classic paper titled "Ocular Dysmetria, Flutter Like Oscillations of the Eyes, and Opsoclonus." In this classic series of cases, three disorders of gaze shifting and gaze holding were described in a number of etiologies, ultimately manifesting in a final common pathway involving the cerebellum. Since the 1950s, there had been substantial progress in contemporary neurology, experimental neuroscience literature has expanded, and computational models of ocular motor control have flourished in the field. In this short commentary, I will highlight Cogan's cerebellar classic in the context of contemporary research on motor control of saccades.

Scale for Ocular motor Disorders in Ataxia (SODA).

Eye movements are fundamental diagnostic and progression markers of various neurological diseases, including those affecting the cerebellum. Despite the high prevalence of abnormal eye movements in patients with cerebellar disorders, the traditional rating scales do not focus on abnormal eye movements. We formed a consortium of neurologists focusing on cerebellar disorders. The consortium aimed to design and validate a novel Scale for Ocular motor Disorders in Ataxia (SODA). The primary purpose of the scale is to determine the extent of ocular motor deficits due to various phenomenologies. A higher score on the scale would suggest a broader range of eye movement deficits. The scale was designed such that it is easy to implement by non-specialized neurological care providers. The scale was not designed to measure each ocular motor dysfunction's severity objectively. Our validation studies revealed that the scale reliably measured the extent of saccade abnormalities and nystagmus. We found a lack of correlation between the total SODA score and the total International Cooperative Ataxia Rating Scale (ICARS), Scale for Assessment and Rating of Ataxia (SARA), or Brief Ataxia Rating Scale (BARS). One explanation is that conventionally reported scales are not dedicated to eye movement disorders; and when present, the measure of ocular motor function is only one subsection of the ataxia rating scales. It is also possible that the severity of ataxias does not correlate with eye movement abnormalities. Nevertheless, the SODA met the consortium's primary goal: to prepare a simple outcome measure that can identify ocular motor dysfunction in patients with cerebellar ataxia.

Reading difficulties in amblyopia: Consequence of visual sensory and oculomotor dysfunction.

INTRODUCTION: Reading is a vision-reliant task, requiring sequential eye movements. Binocularly discordant input results in visual sensory and oculomotor dysfunction in amblyopia, which may contribute to reading difficulties. This study aims to determine the contributions of fixation eye movement (FEM) abnormalities, clinical type and severity of amblyopia to reading performance under binocular and monocular viewing conditions. METHODS: Twenty-three amblyopic patients and nine healthy controls were recruited. Eye movements elicited during fixation and reading of preselected passages were collected for each subject using infrared video-oculography. Subjects were classified as having no nystagmus (n = 9), fusion maldevelopment nystagmus (FMN, n = 5), or nystagmus without structural anomalies that does not meet criteria for FMN or infantile nystagmus (n = 9). Reading rate (words/min), the number of forward and regressive saccades (per 100 words) and fixation duration (s) were computed. RESULTS: Amblyopic patients with and without nystagmus exhibited greater vergence and fixation instability. In patients without nystagmus, the instability arises from increased amplitude and velocity of fast and slow FEMs respectively. Amblyopic patients with and without nystagmus exhibited lower reading speeds with increased fixation duration, regressive and progressive saccades than controls in all viewing conditions. Mixed etiology, greater amblyopic eye visual acuity and stereopsis deficits were associated with greater reading difficulties under binocular viewing. CONCLUSIONS: The presence of oculomotor dysfunction and the extent of visual acuity and stereoacuity deficits contribute to reading difficulties in patients with amblyopia, with and without nystagmus. The understanding of reading difficulties is essential to devise accommodations to limit long-term academic and vocational consequences of amblyopia.

Saccadic premotor burst neurons and histochemical correlates of their firing patterns in rhesus monkey.

Bursting behavior of brainstem premotor burst neurons (BNs) is essential for initiation of saccades and calibrating their metrics. Several ion channel families such as voltage-gated potassium (Kv) channels, low-voltage-activated calcium (Cav3) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are major regulators of the bursting in neurons. Therefore, it was speculated that ion channels with rapid kinematics are essential for characteristic firing patterns of the BNs and rapid saccade velocities. However, the expression patterns of ion channels are yet to be confirmed. Confirmation would not only support the neuromimetic model predictions for saccade generation in brainstem, but also contemporary views that channelopathies can cause saccade disorders in humans. As proof of concept, we examined excitatory BNs in the rostral interstitial nucleus of medial longitudinal fasciculus (RIMLF, vertical saccades) and inhibitory BNs in nucleus paragigantocellularis dorsalis (PGD, horizontal saccades) histochemically in macaque monkeys. We found strong expression of Kv channels, which enable rapid-firing, as well as HCN1&2 and Cav3.2&3.3, which enable post-inhibitory rebound bursting, in both BN populations. Moreover, PGD was found to host multiple neuron groups in terms of calretinin immunoreactivity. Our results provide histochemical evidence that supports models proposing post-inhibitory rebound facilitates bursting in BNs. Furthermore, our findings support the notion that deductions can be made about electrophysiological firing properties by histochemical examination of functional groups within the brainstem saccadic circuitry. This development is an important building block supporting the concept of channelopathies in saccadic disorders. Future histological studies in humans will confirm this approach for saccadic disorders.