Abstracts

Rationale: Idiopathic generalized epilepsies (IGEs) constitute approximately 30-40% of all epilepsies. Compared to healthy individuals, patients with IGEs demonstrate increased cortical excitability (i.e. hyperexcitability) as well as poorer attention, executive functioning, and mood. We previously conducted an explorative study investigating the natural relationship between cortical excitability and cognition in healthy individuals. Preliminary results from this study provided evidence that hyperexcitability is associated with poorer cognitive functioning and mood. The aim of the present study is to characterize the relationship between cortical excitability, cognitive functioning, and mood in a sample of patients with IGEs.  Methods: Ten patients with IGEs (mean age = 30.30, SD = 9.21; 50% male, 80% Caucasian) were recruited for the study. Single-pulse and paired-pulse transcranial magnetic stimulation (TMS) were applied to all participants to measure resting motor threshold and long-interval intracortical inhibition (LICI), repectively. LICI protocol consisted of stimuli delivered in 30-ms increments at ISIs of 50-290ms. LICI recovery curves were constructed for each participant and used to calculate area under the curve (AUC). A higher AUC represents a less inhibitory, or even an excitatory response to the LICI paradigm, which is an indication of hyperexcitability and more specifically, GABAB network dysfunction. A neuropsychological battery was administered to assess aspects of attention (Digit Span Forwards; Digit Span Backwards; Trails A; Flanker), executive function (Trails B; Stroop Color and Word Test; WCST), and mood (POMS).  Results: Total AUC was negatively correlated with both Digit Span Forwards (r = -0.773, p = 0.009) and Digit Span Backwards (r = -0.639, p = 0.047), indicating that decreased inhibition on the LICI paradigm is related to poorer performance on these tasks. Individual correlational analyses were then conducted to assess the relationship between each AUC and neuropsychological outcome measures. Analyses revealed negative correlations between the AUC at 50-80ms and Digit Span Backwards (r = -0.658, p = 0.039), and 110-140ms AUC and Digit Forwards (r = -0.725, p = 0.018). The AUC between 140-170ms was positively correlated with the POMS total mood disturbance score (r = 0.696, p = 0.025) and the Flanker task (r = 0.653, p = 0.041), indicating decreased inhibition at these ISIs is related to more negative mood states, but better performance on the Flanker task.  Conclusions: Overall, cortical hyperexcitability (likely GABAB network dysfunction) is associated with poorer attention and mood in patients with IGEs. These results provide preliminary evidence for a relationship between cortical excitability and cognition/mood in IGE. Furthermore, these findings suggest that modulating cortical excitability may improve attention and mood in patients with IGEs, and serve as a physiological basis for treatment development in these areas via neuromodulatory interventions.  Funding: UAB Department of Neurology