Pharmacological treatment effects on eye movement control

Abstract

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second-generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson's disease, and Huntington's disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.

Analysis of exploratory eye movements in patients with schizophrenia during visual scanning of projective tests' figures

“…Studies correlating eye movement properties, symptomatology and medication dose have shown discordant results 6,[11][12][13]23,28 . Controlled studies comparing the effects of risperidone and olanzapine have found a decrease in the mean length of the saccadic movements in schizophrenia patients compared to controls but no difference was found among patients due to the medication type 30 .…”

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements

“…The use of oculomotor tasks offers an advantageous tool to evaluate pharmacological effects on cognitive and motor functions (Reilly et al, 2008). The smooth pursuit eye movement (SPEM) task requires a mechanism to track a moving object in extra-personal space without head movement and draws upon attention, motion processing and temporo-spatial prediction (Barnes, 2008).…”

Review: Managing posttraumatic stress disorder in combat veterans with comorbid traumatic brain injury

“…Intravenous administration of fentanyl 100 µg adversely affected oculomotor function, but the effect does not last more than 15 to 30 min [72]. Oculomotor function is not known to be affected by serotonin-specific reuptake inhibitor (SSRI) antidepressants, indicating that these medications should not produce a false positive reading of abnormal function [73]. The lack of oculomotor effect from SSRI antidepressants is important because these medications are first-line pharmacotherapy agents in PTSD and major depression.…”