Gaze Dysfunction Research Articles

Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis

BackgroundImpairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction in these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia. MethodsActivation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted. ResultsFifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal and frontotemporal circuitry. ConclusionAlterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia.

Special clinical features with a novel mutation site of CHN1 gene in a Chinese family with Duane retraction syndrome

ABSTRACT Purpose This study is to describe the special clinical and genotypic features of a Chinese family with variant types of Duane retraction syndrome and to present our experience on managing these cases. Methods Four individuals from one family were reviewed by ophthalmologic examinations, in which two affected and two unaffected individuals were revealed. MRI scans were performed on the two patients. Relevant gene mutations were screened by the next-generation sequencing technology and confirmed by Sanger sequencing technology. Results The six-year-old proband presented with special clinical features of severe horizontal gaze dysfunction, exotropia and mild scoliosis. His mother showed significantly limited binocular abductions, with retraction of eyeballs in adduction. From MRI scans, abducens nerves were not observed in both patients and the oculomotor nerve was slightly thin in the proband. The proband and his mother shared the same CHN1 gene mutation site (c. 62A>G; p.Y21C). Strabismus surgery was performed on the proband to correct the primary gaze exotropia. (NM_001822: exon3 or NM_001025201: exon4: c. 62A>G; p.Y21C) Conclusions A novel CHN1 gene mutation was revealed from a Chinese family with Duane retraction syndrome. Remarkably, the proband and his mother presented different clinical features of ocular motility disorder. Strabismus correction surgery and amblyopia training helped to improve the appearance and visual function of the proband.

Transcallosal Anterior Interforniceal Approach for Removal of Superior Midbrain Cavernous Malformations in Children: A Retrospective Series of 10 Cases in a Single Center

Surgical treatment of brainstem cavernous malformations (CMs) remains a great challenge for neurosurgeons. Several cases published in the literature have addressed surgical approaches. However, no surgical approach has been reported to provide better exposure for CMs located in the superior midbrain. We presented 10 cases of superior midbrain CMs in children treated in Beijing Tiantan Hospital from 2002 to 2016. The most common presenting signs and symptoms were hydrocephalus and cranial nerve deficit. We used the transcallosal anterior interforniceal approach in all patients to remove the CM lesion. Total resection was achieved in all patients. During the follow-up period, temporary short-term memory impairment was present in 5 patients, unilateral ptosis occurred in 1 patient, and upward gaze dysfunction occurred in 2 patients. There was complete neurologic functional improvement for cranial nerves. Exacerbation of hydrocephalus occurred in 4 patients requiring additional ventriculoperitoneal shunt postoperatively. The transcallosal anterior interforniceal approach can provide good exposure and direct visualization to superior midbrain CMs. Complications are short-term and reversible.

Role of neural integrators in oculomotor systems: asystematic narrative literature review.

To evaluate the role of neural integrators (NI) in the oculomotor system. A literature search was carried out using several electronic databases during the months of June 2014 to March 2015. The following keywords were used to generate focused results: 'neural integrators', 'gaze-holding', 'oculomotor integration', 'impaired gaze-holding', 'gaze evoked nystagmus' and 'gaze dysfunction'. Further materials were found through searching relevant articles within reference lists. Seventy-one articles were sourced for this review which analysed animal and human subjects and network models; 45 were studies of humans, 16 studies of primates, three studies of felines and one study from rats and network models. The remaining articles were literature reviews. The horizontal and vertical, including torsional, NI are located logically in the brainstem, nearby their appropriate target extraocular motoneuron nuclei for stable eye position in eccentric position. The nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN) are closely linked at the caudal pons and dorsal rostral medulla, integrating horizontal conjugate eye movement. The interstitial nucleus of Cajal (INC) integrates vertical and torsional eye movement at the upper midbrain. The integrator time constant is averaged to 25seconds in human horizontal and animal vertical NI to perform its function. Case reports revealed that dysfunction of horizontal NI also resulted in vertical ocular deviations, indicating some overlap of horizontal and vertical gaze control. Furthermore, pharmacological inactivation of NI exposed a population of inhibitory neurotransmitters that permits its mechanism of action; allowing for smooth conjugate movement. Neural integrators operate to integrate eye velocity and eye position information to provide signals to extraocular motoneurons to attain and maintain a new position. Therefore, NI allow image stabilization during horizontal and vertical eye movements at eccentric positions for comfortable single vision.

Games and Telerehabilitation for Balance Impairments and Gaze Dysfunction: Protocol of a Randomized Controlled Trial.

BackgroundDigital media and gaming have received considerable interest from researchers and clinicians as a model for learning a broad range of complex tasks and facilitating the transfer of skills to daily life. These emerging rehabilitation technologies have the potential to improve clinical outcomes and patient participation because they are engaging, motivating, and accessible. Our research goal is to develop preventative and therapeutic point-of-care eHealth applications that will lead to equivalent or better long-term health outcomes and health care costs than existing programs. We have produced a novel computer-aided tele-rehabilitation platform that combines computer game-based exercises with tele-monitoring.ObjectiveCompare the therapeutic effectiveness of an in-home, game-based rehabilitation program (GRP) to standard care delivered in an outpatient physical therapy clinic on measures of balance, gaze control, dizziness, and health-related quality of life.MethodsA randomized, controlled, single-blind pilot trial will be conducted. Fifty-six participants with a diagnosis of peripheral vestibular disorder will be randomly assigned to either usual physical therapy (comparator group) or to a game-based intervention (experimental group). Measures to be assessed will include gaze control, dynamic balance, and self-reported measures of dizziness.ResultsThe project was funded and enrollment was started in August 2014. To date, 36 participants have been enrolled. There have been 6 drop-outs. It is expected that the study will be completed January 2016 and the first results are expected to be submitted for publication in Spring of 2016.ConclusionsA successful application of this rehabilitation program would help streamline rehabilitation services, leverage therapist time spent with clients, and permit regular practice times at the client’s convenience.Trial RegistrationClinicaltrials.gov: NCT02134444; https://clinicaltrials.gov/ct2/show/NCT02134444 (Archived by WebCite at http://www.webcitation.org/6cE18bqqY)

Vertical gaze palsy in Parkinsonism: An alternative diagnosis to progressive supranuclear palsy

Vertical gaze palsy is a highly relevant clinical sign in Parkinsonian syndromes. As the eponymous sign of progressive supranuclear palsy (PSP), it is a core feature of this disease. However, the differential diagnosis of vertical gaze palsy in patients with Parkinsonism is rarely considered. We present the case of a 65-year-old gentleman with Parkinsonism who presented with diplopia secondary to oculomotor dysfunction and vertical gaze palsy. Computed tomography (CT) sacn demonstrated a thalamic haemorrhage with intraventricular extension. Neurosurgical intervention was not required. The patients spectacles were fitted with a temporary Fresnel prism over the left lens to relieve diplopia. This progressively improved without the need for strabismus surgery. Vertical gaze dysfunction occurs in patients with thalamic haemorrhage and is an important differential diagnosis of vertical gaze palsy in Parkinsonism.

Profile of Gaze Dysfunction following Cerebrovascular Accident

Aim. To evaluate the profile of ocular gaze abnormalities occurring following stroke. Methods. Prospective multicentre cohort trial. Standardised referral and investigation protocol including assessment of visual acuity, ocular alignment and motility, visual field, and visual perception. Results. 915 patients recruited: mean age 69.18 years (SD 14.19). 498 patients (54%) were diagnosed with ocular motility abnormalities. 207 patients had gaze abnormalities including impaired gaze holding (46), complete gaze palsy (23), horizontal gaze palsy (16), vertical gaze palsy (17), Parinaud's syndrome (8), INO (20), one and half syndrome (3), saccadic palsy (28), and smooth pursuit palsy (46). These were isolated impairments in 50% of cases and in association with other ocular abnormalities in 50% including impaired convergence, nystagmus, and lid or pupil abnormalities. Areas of brain stroke were frequently the cerebellum, brainstem, and diencephalic areas. Strokes causing gaze dysfunction also involved cortical areas including occipital, parietal, and temporal lobes. Symptoms of diplopia and blurred vision were present in 35%. 37 patients were discharged, 29 referred, and 141 offered review appointments. 107 reviewed patients showed full recovery (4%), partial improvement (66%), and static gaze dysfunction (30%). Conclusions. Gaze dysfunction is common following stroke. Approximately one-third of patients complain of visual symptoms, two thirds show some improvement in ocular motility.

Gaze-shift strategies during functional activity in progressive supranuclear palsy

The relative sparing of visual fixation in parallel with disruption of saccade function in progressive supranuclear palsy (PSP) creates a unique human model for the study of gaze-shift strategies which are adopted when vertical gaze palsy impairs primarily the eye-movement component of gaze control. It was hypothesized that people with PSP would rely on head pitch as a primary component of gaze shift during a platform stepping task and that there would be a predominance of fixation behavior (counter rotation of the eyes during head pitch) while attempting a down-gaze shift. Fourteen subjects with probable and 5 subjects with possible PSP participated in two experiments to measure visual fixation and gaze shift on the same continuum (using a derived vertical gaze fixation score, vGFS). Experiment #1 required gaze fixation during passive head pitch at 0.1-0.2 Hz, whereas experiment #2 required gaze shifts during a continuous platform step on, over, and off task. The primary gaze-shift strategy involved pitching the head downward to compensate for a loss in vertical saccade function. This strategy produced head pitch velocity that leads vertical eye velocity on the order of 200-500 ms. Gaze shifts during platform stepping showed greater fixation suppression (e.g., lower vGFS) in both groups of PSP compared to the visual stabilization task, but some subjects showed "fixation intrusion" during attempted gaze shift. The amount of eye movement was relatively constant when corrected for orbit height, whereas the extent of head pitch varied in proportion to the task demands. The mechanism controlling gaze in PSP, therefore appears to modulate head pitch independently of eye movement, but the gaze strategy seems dependent upon the extent of gaze dysfunction. These findings support the view that the desired gaze signal is parsed into separate eye and head pathways upstream from the burst neurons.

Modeling locomotor dysfunction following spaceflight with Galvanic vestibular stimulation

In this study locomotor and gaze dysfunction commonly observed in astronauts following spaceflight were modeled using two Galvanic vestibular stimulation (GVS) paradigms: (1) pseudorandom, and (2) head-coupled (proportional to the summed vertical linear acceleration and yaw angular velocity obtained from a head-mounted Inertial Measurement Unit). Locomotor and gaze function during GVS were assessed by tests previously used to evaluate post-flight astronaut performance; dynamic visual acuity (DVA) during treadmill locomotion at 80 m/min, and navigation of an obstacle course. During treadmill locomotion with pseudorandom GVS there was a 12% decrease in coherence between head pitch and vertical translation at the step frequency relative to the no GVS condition, which was not significantly different to the 15% decrease in coherence observed in astronauts following shuttle missions. This disruption in head stabilization likely resulted in a decrease in DVA equivalent to the reduction in acuity observed in astronauts 6 days after return from extended missions aboard the International Space Station (ISS). There were significant increases in time-to-completion of the obstacle course during both pseudorandom (21%) and head-coupled (14%) GVS, equivalent to an ISS astronaut 5 days post-landing. An attempt to suppress head movement was evident during both pseudorandom and head-coupled GVS while negotiating the obstacle course, with a 20 and 16%, decrease in head pitch and yaw velocity, respectively. The results of this study demonstrate that pseudorandom GVS generates many of the salient features of post-flight locomotor dysfunction observed in astronauts following short and long duration missions. An ambulatory GVS system may prove a useful adjunct to the current pre-flight astronaut training regimen.

Pharmacological therapy in progressive supranuclear palsy.

To our knowledge, previous reports on drug treatment in progressive supranuclear palsy have not evaluated autopsy-confirmed cases. To evaluate pharmacological treatment responses from detailed clinical records in patients with autopsy-confirmed progressive supranuclear palsy. We reviewed medical records for clinical presentation and pharmacological response in 12 patients with autopsy-confirmed progressive supranuclear palsy diagnosed using the National Institute of Neurological Disorders and Stroke pathologic criteria. For each drug class, exposure, global positive response, and specific positive response (parkinsonism, other movement disorders, or gaze dysfunction) were recorded. Drug classes examined were dopaminergics (all patients), tricyclics (3 patients), methysergide maleate (3 patients), 5-hydroxytryptophan (2 patients), and anticholinergics and selective serotonin inhibitors (1 patient). Positive clinical response was detected in 7 of the patients receiving dopaminergic drugs and in 1 patient each receiving tricyclics, methysergide, and 5-hydroxytryptophan, respectively. None of the patients responded markedly however, and there was no persistent beneficial effect. Use of dopaminergic drugs most frequently improved parkinsonian features, but disabling adverse effects included orthostatic hypotension (6 patients), hallucinations and delusions (3 patients), gastrointestinal complaints (3 patients), and dizziness (1 patient). Only 1 patient developed dyskinesia. Use of antiparkinsonian medications and other neurotransmitter replacement therapies was largely ineffective and caused frequent adverse effects in this series of patients with autopsy-confirmed with progressive supranuclear palsy.

Thalamic Hemorrhage

The clinical features of thalamic hemorrhage in terms of localization are of great interest in many studies. To better understand the relationship between the localization of thalamic hemorrhage and clinical features. we evaluated the characteristics of patients with four different topographic types of thalamic hemorrhage. We prospectively studied 100 patients with thalamic hemorrhage who were admitted consecutively to our primary care unit. We divided them into two groups according to large (> 2 cm in diameter and/or > 4 mL in volume) and small thalamic hemorrhage. Four topographic subgroups (large and small) were compared to identify clinical syndromes associated with distinct lesion locations. All patients with posterolateral thalamic hemorrhage had severe sensorimotor deficit. Neuropsychological disturbances in patients with posterolateral thalamic hemorrhage were prominent, with primarily transcortical aphasia in those with left-sided lesions and hemineglect and anosognosia in those with right-sided lesions. Several variants of vertical gaze dysfunction, skew ocular deviation, gaze preference toward the site of the lesion, and miotic pupils were frequent in posterolateral thalamic hemorrhage, particularly in the large type. Patients with small and large anterolateral thalamic hemorrhage were characterized by severe motor and sensory deficits; language and oculomotor disturbances were also observed, although less frequently than in posterolateral hemorrhage. Sensorimotor deficits were observed in patients with medial thalamic hemorrhage (moderate in small hemorrhages and severe in large hemorrhages because of involvement of the adjacent internal capsule). Language disturbances in patients with left-sided lesions and neglect in patients with right-sided lesions were seen only in large medial thalamic hemorrhage. Dorsal thalamic hemorrhage was rare and characterized by mild and transient sensorimotor disturbances. Among patients with dorsal thalamic hemorrhages, only those with large lesions had oculomotor and neuropsychological disturbances. We concluded that despite clinical similarity among the four types of thalamic hemorrhage, there was some discrepancy in the clinical features of small and large thalamic hemorrhages. The most important predictors of death were initial consciousness, nuchal rigidity, maximum size, volume and ventricular extension of hemorrhage, and occurrence of hydrocephalus.

Loss of psychic self-activation with bithalamic infarction

Two patients with bilateral thalamo-mesencephalic infarct in the paramedian territory developed vertical gaze dysfunction and marked behavioural changes, in the absence of significant motor inability and formal neuropsychological impairment. While they were physically and emotionally active before stroke, they became apathetic, aspontaneous, indifferent, and seemed to have lost motor and affectic drive, as well as the need itself for any psychic activity. However, this mental and motor inertia was reversible when the patients were repeatedly stimulated by another person. This need for constant external programming, together with a lack of emotional reactivity, made the patients resemble robots. CT and MRI suggested involvement of the dorsomedial and midline nuclei of the thalamus, and SPECT showed remote frontomesial hypoperfusion. A disturbance of the striatal-ventral pallidal-thalamic-frontomesial limbic loop is suggested by previous reports of a similar "loss of psychic self-activation", "pure psychic akinesia", or "athymhormia" with bipallidal, bistriatal, or subcortical bifrontal lesions.