Cortical excitability affects mood state in patients with idiopathic generalized epilepsies (IGEs).

Previously, we demonstrated an association between cortical hyperexcitability and mood disturbance in healthy adults. Studies have documented hyperexcitability in patients with idiopathic generalized epilepsies (IGEs; long-interval intracortical inhibition [LICI]) and high prevalence of mood comorbidities. This study aimed to investigate the influences of cortical excitability and seizure control on mood state in patients with IGEs. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to 30 patients with IGEs (16 controlled IGEs [cIGEs], 14 with treatment-resistant IGEs [trIGEs]), and 22 healthy controls (HCs) to assess cortical excitability with LICI. The Profile of Mood Sates (POMS) questionnaire was used to assess total mood disturbance (TMD), as well as, six mood domains: Depression, Confusion, Anger, Anxiety, Fatigue, and Vigor. To assess the effects of seizure control (HC vs. cIGEs vs. trIGEs) and LICI response (inhibitory vs. excitatory) on TMD, a two-way multivariate analysis of variance (MANOVA) was performed. Analyses revealed a significant main effect of long-interval intracortical inhibition (LICI) response on TMD (F(1, 46) = 4.69, p = 0.04), but not seizure control (F(2, 46) = 0.288, p = 0.75). Excitatory responders endorsed significantly higher TMD scores, indicating greater mood disturbance, than inhibitory responders (MD = -2.12; T (50) = -2.47, p = 0.04). Also, excitatory responders endorsed more items than inhibitory responders on the Depression (MD = -2.12; T (50) = -2.47, p = 0.04) and Fatigue (MD = -3.42; T (50) = -2.96, p = 0.03) subscales of the POMS. These findings provide further evidence of a relationship between hyperexcitability and mood disturbance, and indicate that cortical excitability may have greater influence on mood state than seizure control in patients with IGEs. Results also support theories for the underlying role of gamma-aminobutyric acid (GABA) network dysfunction in the etiology of depression. To better understand the clinical relevance and causal nature of these relationships, further investigation is warranted.

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.

Neuropsychological consequences of sleep disturbance in children with epilepsy.

A growing body of research reveals strong relationships between sleep disturbance, sleep architecture, and neuropsychological functioning in children. Children with epilepsy experience numerous neuropsychological comorbidities, including cognitive deficiencies and emotional/behavioral difficulties; thus, it is reasonable to consider the moderating role of sleep in this population. This review summarizes findings involving the prevalence and characteristics of sleep problems often experienced by children with epilepsy. The complex and bidirectional relationship between sleep and seizure frequency is discussed. Research pertaining to the relationship between sleep disturbance and daytime cognition as well as behavior reveals a substantial association between these variables. Clinically relevant practices related to the assessment and treatment of sleep-related complications are reviewed, and directions for further research involving intervention and assessment are also reviewed.

Cortical excitability and neuropsychological functioning in healthy adults.

Evidence from clinical populations, such as epilepsy and attention deficit/hyperactivity disorder, suggests a relationship between hyperexcitability and cognitive impairment, but this relationship has not been demonstrated in healthy individuals. Here, we investigate the relationship between cortical excitability and cognitive functioning in healthy adults. Single- and paired-pulse TMS was applied to 20 healthy adults to measure cortical excitability and long-interval intracortical inhibition (LICI). A neuropsychological battery was administered to assess aspects of attention, executive function, and mood. Participants with primarily excitatory responses to the LICI paradigm performed worse on a composite measure of attention and reported more negative mood states than participants with primarily inhibitory responses. Thus, differences in attention and mood among healthy adults are related to differences in cortical excitability as measured by LICI. This is consistent with a role for GABAB inhibitory circuits in regulating attention and mood, and suggests that individual variability in these domains may reflect variability in cortical excitability. This study demonstrates preliminary evidence that increased cortical excitability is associated with poorer cognition and mood in healthy adults. These findings provide new insight into the presence of cognitive dysfunction in several patient populations with hyperexcitability and support the development of neurostimulation interventions for clinical use.