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. OBJECTIVES: This study explored the relationship between cognition and visual processing in early MS by adopting a three-system model of afferent sensory, central cognitive and efferent ocular motor visual processing to identify distinct visuo-cognitive phenotypes. METHODS: Patients with clinically isolated syndrome and relapsing-remitting MS underwent neuro-ophthalmic, ocular motor and neuropsychological evaluation to assess each visual processing system. The factor structure of ocular motor variables was examined using exploratory factor analysis, and phenotypes were identified using latent profile analysis. RESULTS: Analyses revealed three ocular-motor constructs (cognitive control, cognitive processing speed and basic visual processing) and four visuo-cognitive phenotypes (early visual changes, efferent-cognitive, cognitive control and afferent-processing speed). While the efferent-cognitive phenotype was present in significantly older patients than was the early visual changes phenotype, there were no other demographic differences between phenotypes. The efferent-cognitive and cognitive control phenotypes had poorer performance on the Symbol Digit Modalities Test compared to that of other phenotypes; however, no other differences in performance were detected. CONCLUSION: Our findings suggest that distinct visual processing deficits in early MS may differentially impact cognition, which is not captured using standard neuropsychological evaluation. Further research may facilitate improved symptom identification and intervention in early disease.

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. We included 192 24-hour EEG sessions recorded from 18 GAERS rats, and 24-hour scalp-EEG data collected from 11 GGE patients. RESULTS: The SWDs detection performance on GAERS showed a sensitivity of 98.01% and a false positive (FP) rate of 0.96/hour. The performance on GGE patients showed 100% sensitivity in five patients, while the remaining patients obtained over 98.9% sensitivity. Moderate FP rates were seen in our patients with 2.21/hour average FP. The detector trained within our patient cohort was validated in an independent dataset, TUH EEG Seizure Corpus (TUSZ), that showed 100% sensitivity in 11 of 12 patients and 0.56/hour averaged FP. CONCLUSIONS: We developed a robust SWDs detector that showed high sensitivity and specificity for both GAERS rats and GGE patients. SIGNIFICANCE: This detector can assist researchers and neurologists with the time-efficient and accurate quantification of SWDs.

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. This study investigated inhibitory control and spatial working memory in the saccadic system of 21 patients with schizophrenia (10 with high negative symptoms scores and 11 with low negative symptom scores) and 14 healthy controls. Tasks explored suppression of reflexive saccades during qualitatively different tasks, the generation of express and anticipatory saccades, and the ability to respond to occasional, unpredictable ("oddball") targets that occurred during a sequence of well-learned, reciprocating saccades between horizontal targets. Spatial working memory was assessed using a single and a two-step memory-guided task (involving a visually-guided saccade during the delay period). Results indicated significant increases in response suppression errors, as well as increased response selection impairments, during the oddball task, in schizophrenia patients with prominent negative symptoms. The variability of memory-guided saccade accuracy was also increased in patients with prominent negative symptom scores. Collectively, these findings provide further support for the proposed association between prefrontal dysfunction and negative symptoms.

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. Tasks explored suppression of reflexive saccades during qualitatively different tasks, generation of express and anticipatory saccades, and the ability to respond to occasional, unpredictable ("oddball") targets that occurred during a sequence of well-learned, reciprocating saccades between horizontal targets. Spatial working memory was assessed using single and two-step (involving a visually guided saccade during the delay period) memory-guided tasks. Results for the PD group indicated an increased percentage of response selection errors during an oddball task, reduced suppression of inappropriate reflexive saccades during memory-guided tasks (but not during fixation or saccade-engagement tasks), and an increased percentage of express and anticipatory saccades. Spatial working memory was preserved in the PD group during single and two-step memory-guided tasks. These findings are consistent with dysfunction within fronto-striatal and prefrontal-collicular pathways influencing suppression and selection of eye movements.

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 were requested to be performed at a rhythm of 1 Hz between two continuously illuminated targets, before and after external cueing. Saccade reprogramming, for direction and amplitude, was explored using a saccadic "oddball" task. Results indicated no group differences for accuracy, intersaccadic intervals (during the self-paced task), latency or peak velocity. However, the melancholic group showed greater intrasubject variability of latencies than the control group, lower peak saccade velocities compared to the non-melancholic group, and reduced accuracy of the primary saccade when compared to the control and the non-melancholic groups. These findings provide further support for distinct motor impairments associated with melancholia that may reflect frontostriatal abnormalities.