Visuo-Cognitive Phenotypes in Early Multiple Sclerosis: A Multisystem Model of Visual Processing.

Background: Cognitive impairment can emerge in the earliest stages of multiple sclerosis (MS), with heterogeneity in cognitive deficits often hindering symptom identification and management. Sensory-motor dysfunction, such as visual processing impairment, is also common in early disease and can impact neuropsychological task performance in MS. However, cognitive phenotype research in MS does not currently consider the relationship between early cognitive changes and visual processing impairment.

Spike and wave discharges detection in genetic absence epilepsy rat from Strasbourg and patients with genetic generalized epilepsy.

Objective: Generalised spike and wave discharges (SWDs) are pathognomonic EEG signatures for diagnosing absence seizures in patients with Genetic Generalized Epilepsy (GGE). The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is one of the best-validated animal models of GGE with absence seizures.

Methods: We developed an SWDs detector for both GAERS rodents and GGE patients with absence seizures using a neural network method.

Behavioral measures of cortical hyperexcitability assessed in people who experience visual snow.

Objective: To determine whether visual perceptual measures in people who experience visual snow are consistent with an imbalance between inhibition and excitation in visual cortex.

Methods: Sixteen patients with visual snow and 18 controls participated. Four visual tasks were included: center-surround contrast matching, luminance increment detection in noise, and global form and global motion coherence thresholds.

Impairment of Smooth Pursuit as a Marker of Early Multiple Sclerosis.

Background: Multiple sclerosis (MS) is a diffuse disease that disrupts wide-ranging cerebral networks. The control of saccades and smooth pursuit are similarly dependent upon widespread networks, with the assessment of pursuit offering an opportunity to examine feedback regulation. We sought to characterize pursuit deficits in MS and to examine their relationship with disease duration.

Ocular motor signatures of cognitive dysfunction in multiple sclerosis.

The anatomical and functional overlap between ocular motor command circuitry and the higher-order networks that form the scaffolding for cognition makes for a compelling hypothesis that measures of ocular motility could provide a means to sensitively interrogate cognitive dysfunction in people with multiple sclerosis (MS). Such an approach may ultimately provide objective and reproducible measures of cognitive dysfunction that offer an innovative capability to refine diagnosis, improve prognostication, and more accurately codify disease burden. A further dividend may be the validation and application of biomarkers that can be used in studies aimed at identifying and monitoring preventative, protective and even restorative properties of novel neurotherapeutics in MS.

Ocular motor measures of cognitive dysfunction in multiple sclerosis I: inhibitory control.

Our ability to control and inhibit behaviours that are inappropriate, unsafe, or no longer required is crucial for functioning successfully in complex environments. Here, we investigated whether a series of ocular motor (OM) inhibition tasks could dissociate deficits in patients with multiple sclerosis (MS), including patients with only a probable diagnosis (clinically isolated syndrome: CIS), from healthy individuals as well as a function of increasing disease duration. 25 patients with CIS, 25 early clinically definite MS patients (CDMS: ≤7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis), and 25 healthy controls participated.

Ocular motor measures of cognitive dysfunction in multiple sclerosis II: working memory.

Our companion paper documents pervasive inhibitory deficits in multiple sclerosis (MS) using ocular motor (OM) measures. Here we investigated the utility of an OM working memory (WMem) task in characterising WMem deficits in these patients as a function of disease status and disease duration. 22 patients with CIS, 22 early clinically definite MS patients (CDMS: <7 years of diagnosis), 22 late CDMS patients (>7 years from diagnosis), and 22 healthy controls participated.

Saccade reprogramming in Friedreich ataxia reveals impairments in the cognitive control of saccadic eye movement.

Although cerebellar dysfunction has known effects on motor function in Friedreich ataxia (FRDA), it remains unclear the extent to which the reprogramming of eye movements (saccades) and inhibition of well-learned automatic responses are similarly compromised in affected individuals. Here we examined saccade reprogramming to assess the ability of people with FRDA to respond toward unexpected changes in either the amplitude or direction of an "oddball" target. Thirteen individuals with genetically confirmed FRDA and 12 age-matched controls participated in the study.

Saccade adaptation in autism and Asperger's disorder.

Autism and Asperger's disorder (AD) are neurodevelopmental disorders primarily characterized by deficits in social interaction and communication, however motor coordination deficits are increasingly recognized as a prevalent feature of these conditions. Although it has been proposed that children with autism and AD may have difficulty utilizing visual feedback during motor learning tasks, this has not been directly examined. Significantly, changes within the cerebellum, which is implicated in motor learning, are known to be more pronounced in autism compared to AD.

Ischaemic stroke: the ocular motor system as a sensitive marker for motor and cognitive recovery.

Objective: To evaluate the sensitivity of measuring cognitive processing in the ocular motor system as a marker for recovery of deficit in post stroke patients.

Methods: 15 patients (mean age 60.6 years, mean National Institutes of Health Stroke Scale (NIHSS) score 2.

A closer look at visually guided saccades in autism and Asperger's disorder.

Motor impairments have been found to be a significant clinical feature associated with autism and Asperger's disorder (AD) in addition to core symptoms of communication and social cognition deficits. Motor deficits in high-functioning autism (HFA) and AD may differentiate these disorders, particularly with respect to the role of the cerebellum in motor functioning. Current neuroimaging and behavioral evidence suggests greater disruption of the cerebellum in HFA than AD.

Longitudinal assessment of antisaccades in patients with multiple sclerosis.

We have previously demonstrated that assessment of antisaccades (AS) provides not only measures of motor function in multiple sclerosis (MS), but measures of cognitive control processes in particular, attention and working memory. This study sought to demonstrate the potential for AS measures to sensitively reflect change in functional status in MS. Twenty-four patients with relapsing-remitting MS and 12 age-matched controls were evaluated longitudinally using an AS saccade task.

Inhibitory control during smooth pursuit in Parkinson's disease and Huntington's disease.

The basal ganglia are involved in the preferential selection and suppression of competing responses. Parkinson's disease and Huntington's disease are 2 prototypical basal ganglia disorders that feature impaired inhibitory control, a function of poor conflict resolution. Previous saccadic studies showed that individuals with Parkinson's disease experience difficulty suppressing unwanted ocular motor responses, whereas evidence for a similar difficulty in Huntington's disease is more equivocal.

Ocular motor fixation deficits in Friedreich ataxia.

Friedreich ataxia (FRDA) is the most common genetic cause of ataxia with a prevalence of approximately 1 in 29,000. Ocular motor abnormalities are common in FRDA and include fixation instability, saccadic dysmetria, and vestibular dysfunction. It has not yet been determined whether aspects of spatial attention, which are closely coupled to eye movements, are similarly compromised in FRDA.

Disruption to higher order processes in Friedreich ataxia.

Friedreich ataxia (FRDA), the most common of the genetically inherited ataxias, is characterised by ocular motor deficits largely reflecting disruption to brainstem-cerebellar circuitry. These deficits include fixation instability, saccadic dysmetria, disrupted pursuit, and vestibular abnormalities. Whether higher order or cognitive control processes involved the generation of more volitional eye movements are similarly impaired, has not been explored previously.

Control of visually guided saccades in multiple sclerosis: Disruption to higher-order processes.

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing of behaviourally relevant information. The attentional control of eye movement was investigated in 25 individuals with MS and a comparable number of neurologically healthy individuals matched for age and IQ.

Antisaccade performance in patients with multiple sclerosis.

Commonly used measures of disability in patients with Multiple sclerosis (MS) inadequately reflect disease severity and progression. Further, cognitive deficits experienced by up to 70% of patients, are poorly represented by these measures. Saccadic eye movements may provide a powerful tool for the analysis of cognitive changes in MS, providing a surrogate measure of performance that extends more conventional measures.

Multiple sclerosis: Cognition and saccadic eye movements.

Ocular motor abnormalities are frequently reported in Multiple Sclerosis (MS), the most salient of which are well represented by the commonly used clinical measure, the EDSS. However, cognitive function, which is poorly represented by this scale, may also be ascertained from ocular motor measures, suggesting that an analysis of eye movements has the potential to extend and complement this more conventional measure. The generation of single and triple-step memory-guided saccades was investigated in 25 individuals with MS and a comparable number of neurologically healthy individuals matched for age and IQ.

Vestibular, saccadic and fixation abnormalities in genetically confirmed Friedreich ataxia.

Friedreich ataxia (FRDA), the commonest of the inherited ataxias, is a multisystem neurodegenerative condition that affects ocular motor function. We assessed eye movement abnormalities in 20 individuals with genetically confirmed FRDA and compared these results to clinical measures. All subjects were assessed with infrared oculography.

Inhibitory control and spatial working memory: a saccadic eye movement study of negative symptoms in schizophrenia.

The negative symptoms of schizophrenia are perhaps the most unremitting and burdensome features of the disorder. Negative symptoms have been associated with distinct motor, cognitive and neuropathological impairments, possibly stemming from prefrontal dysfunction. Eye movement paradigms can be used to investigate basic sensorimotor functions, as well as higher order cognitive aspects of motor control such as inhibition and spatial working memory - functions subserved by the prefrontal cortex.

Inhibitory control and spatial working memory in Parkinson's disease.

Patients with Parkinson's disease (PD) have difficulty performing tasks relying on inhibitory control and working memory, functions of the prefrontal cortex. Eye movement paradigms can be used to investigate basic sensorimotor functions and higher order cognitive aspects of motor control. This study investigated inhibitory control and spatial working memory in the saccadic system of 13 individuals with mild-moderate PD and 13 age-matched controls.

Saccadic trajectory in Huntington's disease.

Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG.

Self-paced and reprogrammed saccades: differences between melancholic and non-melancholic depression.

Motor disturbances in major depressive disorder (MDD) are increasingly recognized and may differentiate melancholic, from non-melancholic depression. Motor impairments in melancholic depression have been likened to Parkinson's disease and proposed to have a frontostriatal basis. This study investigated self-pacing and reprogramming skills, thought to rely on frontostriatal functioning, in groups of healthy individuals (n=15), non-melancholic depression patients (n=10) and melancholic depression patients (n=9) using ocular motor tasks.

Self-paced saccades and saccades to oddball targets in Parkinson's disease.

Patients with Parkinson's disease (PD) manifest difficulty in initiation and execution of movements, particularly when movements are sequential, simultaneous or repetitive. Eye movements are particularly effective in evaluating motor impairments. We utilized a series of saccadic eye movement paradigms to explore the ability of 13 patients with mild-moderate PD and 13 age-matched healthy controls to self-pace saccades between two continuously illuminated targets, before and after an externally cued tracking period, and respond to unexpected changes in task demand.

Ocular motor differences between melancholic and non-melancholic depression.

Background: Major depressive disorder may be a heterogeneous disorder, yet melancholic depression is the most consistently described subtype, regarded as qualitatively different to non-melancholic depression in terms of cognitive and motor impairments. Eye movement studies in depression are infrequent and findings are inconclusive.

Methods: This study employed a battery of saccadic eye movement tasks to explore reflexive saccades, as well as higher order cognitive aspects of saccades including inhibitory control and spatial working memory.