Objective: ADHD is common in patients with epilepsy, but adult patients with possible epilepsy are not routinely screened for ADHD. We aimed to characterize the results of two validated screening tools in the setting of an Epilepsy Monitoring Unit (EMU). Method: This study utilized the validated Adult ADHD Self-Report Scale version 1.1 (ASRS) and Conners Continuous Performance Test, third edition (CPT-III) to screen patients who were admitted to the EMU at a Level 4 epilepsy center. Patients with epileptic seizures (ES) were compared with patients with psychogenic nonepileptic seizures (PNES). Results: In all, 40.6% of patients screened positive using the ASRS. A significantly greater proportion of patients with PNES (63.6%) screened positive compared with patients with ES (27.8%, Fisher’s exact test, p = .005). Positive ASRS screens showed no significant association with positive CPT screens (chi-square test, p = .146). Conclusion: Adult patients admitted to the EMU are at a high risk of comorbid attention deficits.

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Most anti-seizure drugs (ASDs) achieve their effects by suppressing neuronal excitability through various drug targets. However, these drug targets are widely expressed in both excitatory and inhibitory neurons. Here, we investigate whether the efficacy of the ASD retigabine (RTG) is altered after removal of the potassium channel subunit KCNQ2, one of its drug targets, from parvalbumin-expressing interneurons (PV-INs). Parvalbumin-Cre (PV-Cre) mice were crossed with Kcnq2-floxed (Kcnq2fl/fl) mice to conditionally delete Kcnq2, the gene encoding KCNQ2, from PV-INs. The efficacy of RTG (10 mg/kg, i.p.) in preventing seizures induced by picrotoxin (PTX, 10 mg/kg, i.p.) and kainic acid (KA, 30mg/kg, i.p.) in conditional knockout mice (cKO, PV-Kcnq2fl/fl) was tested. Immunostaining for KCNQ2 and KCNQ3 and in vitro pharmacological studies with whole-cell recordings were also performed. The cKO mice had no significant change in appearance, body mass, balance, heat sensitivity, depressive behavior, mortality, or EEG spectral power. RTG significantly delayed the onset of PTX- and KA-induced convulsive seizures in cKO mice, but not in wild-type littermates (WT). The expression of both KCNQ2 and KCNQ3 subunits was specifically enriched at the distal axon initial segments (AISs) of hippocampal CA1 PV-INs. In cKO mice, this specific expression and the potassium currents mediated by these subunits were greatly reduced in PV-INs, while their expression in CA1 pyramidal cells (CA1-PCs) remained unchanged. Accordingly, while the ability of RTG to suppress CA1-PC spike activity was unchanged in cKO mice, its suppressive effect on high-frequency spike activity of CA1 PV-INs (elicited by >540pA depolarizing currents) was significantly reduced compared with WT mice. In addition, the RTG-induced suppressive effect on intrinsic membrane excitability of PV-INs in WT mice became absent or decreased in cKO mice. These findings suggest that reducing the suppression of PV-INs by RTG improves its anticonvulsant effect.Key Points(3-5 bullets, no longer than 85 characters each)RTG was effective for seizures only after Kcnq2 was removed from PV-INs.KCNQ2/KCNQ3 was enriched at PV-IN AISs, sites of AP initiation.Kcnq2 removal greatly reduced KCNQ2/KCNQ3 expression and function in CA1 PV-INs.The suppressive effect of RTG on hippocampal PV-INs was blunted in cKO mice.Therefore, the efficacy of RTG may improve with partial sparing of interneurons.

1Sustained attention is supported by circuits in the frontoparietal attention network. In human 2 and primate studies, the right posterior parietal cortex (PPC) shows dominance for sustained attention, 3 and phase-amplitude coupling (PAC) throughout the frontoparietal network correlates with 4 performance on attention tasks. Here we evaluate oscillatory dynamics of bilateral PPC in mice during 5 the 5-Choice Serial Reaction Time Task (5-CSRTT). Right PPC theta-gamma PAC (TG-PAC) and gamma 6 power were independently elevated to a greater degree than the left PPC during the period prior to a 7 correct response and were significantly correlated with accuracy in both simple and difficult tasks. 8Greater task difficulty was also associated with greater hemispheric asymmetry in TG-PAC, favoring the 9 right PPC. These findings highlight the engagement of PPC with sustained attention in mice, reflected by 10 increases in TG-PAC and gamma power, with maximal expression in the right hemisphere. 11 12