The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Adverse drug reactions induced by valproic acid

The neural pathways and brain regions involved in eye movements during ocular fixation and gaze control include the cerebrum, brainstem and cerebellum, and abnormal eye movements can indicate the presence of neurodegeneration. In some patients, oculomotor signs are key to making a diagnosis. Careful clinical examination of eye movements in patients with neurodegenerative disorders is, therefore, an invaluable adjunct to neurological and cognitive assessments. Eye movement recordings in the laboratory are generally not necessary for diagnostic purposes, but can be a useful addition to the clinical examination. Laboratory recordings of eye movements can provide valuable information about disease severity, progression or regression in neurodegenerative disease, and hold particular promise for objective evaluation of the efficacy of putative neuroprotective and neurorestorative therapies. For example, aspects of saccade performance can be tested to probe both motor and cognitive aspects of oculomotor behaviour. This Review describes the oculomotor features of the major age-related movement disorders, including Parkinson disease, Huntington disease, dementia and other neurodegenerative disorders. Findings in presymptomatic individuals and changes associated with disease progression are discussed.

https://nzbri.org/resources/publications/68/Anderson_Nature_Reviews_Neurology_2013.pdf

Eye movements in patients with neurodegenerative disorders

An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy.

A review of quality of life after predictive testing for and earlier identification of neurodegenerative diseases

Reflexive and Volitional Saccades: Biomarkers of Huntington Disease Severity and Progression

Social orienting: reflexive versus voluntary control.

A Neurophysiological Correlate and Model of ReflexiveSpatial Attention

We created a novel eye movement version of the n-back task to measure spatial working memory (WM). Rather than one continuous trial, discrete trials were presented in order to develop a simpler WM task. In Experiment 1, we varied the visibility of the final stimulus to maximize the difference in performance between 0-back and 1-back tasks (WM effect). In Experiment 2, we administered the optimized task to children. In Experiment 3, we further simplified the task. Both adults and children easily completed our task, displaying significant WM effects. Further, similar WM effects were obtained in our original and simplified n-back spatial WM tasks, demonstrating flexibility. Because WM deficits are often an early feature of disease and a marker of disease progression, our saccadic measure of spatial WM may be particularly useful in hard-to-test populations, such as patients and children, and may have application in brain-imaging studies that require discrete trials.

/pdf/novel-n-back-spatial-working-memory-task-using-eye-movement-465y7vahyg.pdf

Novel n-back spatial working memory task using eye movement response

Objective Valproic acid (VPA) has been suggested as a potential adjunct therapy in schizophrenia for the treatment of clinical symptoms and cognitive deficits. Here, we investigate the effects of VPA on clinical symptoms and saccadic eye movements while controlling for multiple medication effects. Methods Remitted and first-episode schizophrenia patients taking haloperidol were given adjunct VPA for approximately 2weeks and tested using a measure of clinical symptoms (Positive and Negative Syndrome Scale) and saccadic eye movement tasks over three testing periods. The effects of VPA were compared with schizophrenia patients medicated with equivalent doses of haloperidol alone (HAL group) and normal controls. Results Schizophrenia patients had higher error rates on the antisaccade task (AS task) compared with normal controls. Adjunct VPA did not affect AS task error rates but was associated with an increase in response times for both saccade and AS tasks, with a significantly greater and dose-dependent increase in response times for the AS task. There were no differences in clinical improvement between VPA and HAL schizophrenia patient groups when controlling for haloperidol medication state. Conclusions These results suggest that adjuvant VPA therapy results in both sensorimotor and cognitive slowing but does not either help or further impair inhibitory control in schizophrenia, as measured by the elevated AS task errors. Copyright © 2011 John Wiley & Sons, Ltd. key words—saccade; antisaccade; valproic acid; schizophrenia; haloperidol

Saumil S. Patel

Papers

Reflexive and Volitional Saccades: Biomarkers of Huntington Disease Severity and Progression

Social orienting: reflexive versus voluntary control.

A Neurophysiological Correlate and Model of ReflexiveSpatial Attention

Novel n-back spatial working memory task using eye movement response

Effects of adjunct valproic acid on clinical symptoms and saccadic eye movements in schizophrenia.