Assessing seizure susceptibility using visual psychophysical tests

PhD ThesisThe spread of epileptic activity within the cortex is opposed by a powerful inhibitory restraint. We hypothesized that the same inhibitory mechanisms are likely also to underlie the phenomenon of centre-surround suppression. In this thesis, I used different non-invasive visual psychophysical assays of surround suppression to answer whether they can be used as a measurement of network state in epilepsy and as a way of predicting seizures. We recruited 146 healthy volunteer controls and 54 patients with clinically confirmed epilepsy. Three different stimulus paradigms (motion direction discrimination, contrast detection and orientation discrimination tasks) were used to derive surround suppression indices which are believed to reflect the strength of cortical inhibition. Our results suggest that motion and contrast surround suppression phenomena are not related. We found that suppression indices for the different tests in individual participants were not significantly correlated. In addition, multivariate regression analyses showed that motion suppression index was predicted strongly by age and seizure type, but not by seizure frequency. Specifically, we found that patients with exclusively focal epilepsy, and no history of generalization, showed significantly stronger cortical inhibition as measured by the surround suppression index compared to all other groups, including controls. In contrast, patients with focal seizures evolving into generalised seizures, and patients with generalised genetic epilepsy, showed a similar level of cortical inhibition to controls. To answer whether psychophysical tests can be used as a way of predicting seizures, a longitudinal study was designed, deriving repeated measures of suppression indices in individuals. The results indicated no strong link between timing of seizures and suppression indices in patients. iii In conclusion, visual psychophysics provides a simple and non-invasive means of assessing the state of inhibitory networks involved in the pathophysiology of epilepsy. The inability to increase activity in inhibitory networks in response to focal epileptic seizure may predict the risk of generalised seizures, which may in turn allow stratification of SUDEP risk.Epilepsy Actio

Two common psychophysical measures of surround suppression reflect independent neuronal mechanisms.

Psychophysical surround suppression is believed to reflect inhibitory neuronal mechanisms in visual cortex. In recent years, two psychophysical measures of surround suppression have been much studied: (i) duration thresholds on a motion-discrimination task (which are worse for larger than for smaller stimuli) and (ii) contrast thresholds on a contrast-detection task (which are worse when grating stimuli are surrounded by a stimulus of the same orientation than when they are presented in isolation or surrounded by a stimulus of orthogonal orientation). Changes in both metrics have been linked to several different human conditions, including aging, differences in intelligence, and clinical disorders such as schizophrenia, depression, and autism. However, the exact nature of the neuronal correlate underlying these phenomena remains unclear. Here, we use an individual-differences approach to test the hypothesis that both measures reflect the same property of the visual system, e.g., the strength of GABA-ergic inhibition across visual cortex. Under this hypothesis we would expect the two measures to be significantly positively correlated across individuals. In fact, they are not significantly correlated. In addition, we replicate the previously reported correlation between age and motion-discrimination surround suppression, but find no correlation between age and contrast-detection surround suppression. We conclude that the two forms of psychophysical surround suppression arise independently from different cortical mechanisms

Moderate acute alcohol intoxication has minimal effect on surround suppression measured with a motion direction discrimination task.

A well-studied paradox of motion perception is that, in order to correctly judge direction in high-contrast stimuli, subjects need to observe motion for longer in large stimuli than in small stimuli. This effect is one of several perceptual effects known generally as "surround suppression." It is usually attributed to center-surround antagonism between neurons in visual cortex, believed to be mediated by GABA-ergic inhibition. Accordingly, several studies have reported that this index of surround suppression is reduced in groups known to have reduced GABA-ergic inhibition, including older people and people with schizophrenia and major depressive disorder. In this study, we examined the effect on this index of moderate amounts of ethanol alcohol. Among its many effects on the nervous system, alcohol potentiates GABA-ergic transmission. We therefore hypothesized that it should further impair the perception of motion in large stimuli, resulting in a stronger surround-suppression index. This prediction was not borne out. Alcohol consumption slightly worsened duration thresholds for both large and small stimuli, but their ratio did not change significantly