Cortical excitability and seizure control influence attention performance in patients with idiopathic generalized epilepsies (IGEs)

We recently found that higher cortical excitability is associated with poorer attention performance in healthy adults. While patients with idiopathic generalized epilepsies (IGEs), previously termed genetic generalized epilepsies, are known to demonstrate increased cortical excitability and cognitive deficits, a relationship between these variables in IGEs has not been investigated. Therefore, we aimed to characterize the effects of cortical excitability and seizure control on cognitive performance in IGEs. We studied 30 patients with IGEs (16 patients with controlled IGEs (cIGEs) and 14 patients with treatment-resistant IGEs (trIGEs)) and 24 healthy controls (HCs). Transcranial magnetic stimulation (TMS) was used to measure cortical excitability, including long-interval intracortical inhibition (LICI). Attention was assessed with the Digit Span Forwards, Digit Span Backwards, Trails A, and Flanker tasks. Executive functioning was assessed using Trails B, Stroop Color and Word, and the Wisconsin Card Sorting Task. Two-way multivariate analyses of variance (MANOVAs) were conducted to assess the influences of seizure control (HCs vs. cIGEs vs. trIGEs) and cortical excitability (inhibitory vs. excitatory) on composite measures of attention and executive functions. Attention performance was significantly affected by cortical excitability and seizure control. Participants with primarily excitatory LICI responses, indicating higher cortical excitability, performed worse than inhibitory responders on composite attention (Wilks' lambda = 0.748, F(4, 44) = 3.72, p = 0.011). While participants with cIGEs and trIGEs did not significantly differ in attention performance, participants with trIGEs performed worse on the Digit Forwards (False Discovery Rate (FDR)p < 0.001), Digit Backwards (FDRp = 0.015), and Flanker (FDRp = 0.0075) tasks compared with HCs. These results provide support for the relationship between cortical excitability and attention dysfunction in IGEs. Further investigation is needed to determine whether there is a causal relationship between these variables and whether intracortical gamma-aminobutyric acid (GABA)_B networks may be targeted to improve attention deficits in clinical populations with decreased LICI. Findings also suggest that additional research directly comparing cognition in patients with cIGEs and trIGEs is warranted.