Epilepsy often occurs with other neurological disorders, such as autism, affective disorders, and cognitive impairment. Research indicates that many neurological disorders share a common pathophysiology of dysfunctional energy metabolism, neuroinflammation, oxidative stress, and gut dysbiosis. The past decade has witnessed a growing interest in the use of metabolic therapies for these disorders with or without the context of epilepsy. Over one hundred years ago, the high-fat, low-carbohydrate ketogenic diet (KD) was formulated as a treatment for epilepsy. For those who cannot tolerate the KD, other diets have been developed to provide similar seizure control, presumably through similar mechanisms. These include, but are not limited to, the medium-chain triglyceride diet, low glycemic index diet, and calorie restriction. In addition, dietary supplementation with ketone bodies, polyunsaturated fatty acids, or triheptanoin may also be beneficial. The proposed mechanisms through which these diets and supplements work to reduce neuronal hyperexcitability involve normalization of aberrant energy metabolism, dampening of inflammation, promotion of endogenous antioxidants, and reduction of gut dysbiosis. This raises the possibility that these dietary and metabolic therapies may not only exert anti-seizure effects, but also reduce comorbid disorders in people with epilepsy. Here, we explore this possibility and review the clinical and preclinical evidence where available.

Higher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in the CA3 region and are regulated by multiple synaptic inputs. Here, we used a multi-electrode array to determine the effects of CBZ on SPW-Rs and synaptic transmission at multiple hippocampal synapses. Our results demonstrate that CBZ reduced SPW-Rs at therapeutically relevant concentrations (IC₅₀ = 37 μM) and altered the core characteristics of ripples, important for information processing and consolidation. Moreover, CBZ inhibited neurotransmission in a synapse-specific manner. CBZ inhibition was most potent at the medial-perforant-path-to-CA3 and mossy-fiber-to-CA3 synapses (IC₅₀s ~ 30 and 60 μM, respectively) and least potent at medial-perforant-path-to-dentate granule cell synapses (IC₅₀ ~ 120 μM). These results suggest that the synapse-specific CBZ inhibition of neurotransmission reduces SPW-Rs and that the CBZ inhibition of SPW-Rs may underlie the cognitive impairments observed with therapeutic doses of CBZ.

Background/Objectives: We examined the effects of cardiovascular exercise on verbal fluency using a between-groups design. Methods: Within our experimental (i.e., exercise) group, participants performed phonemic and semantic verbal fluency tasks (VFTs) before, during, and after a vigorous 30 min bout of cycling. Participants within our control group also completed these VFTs before, during, and after a non-physical activity. We compared the VFT performance of the experimental (exercise) and control (no-exercise) groups of participants in terms of the characteristics of the words that they produced within the VFTs. In addition, we examined these aspects of VFT performance for each participant group across time within the experiment session. Conclusions: From these comparisons, we see that exercise influenced VFT performance. Most notably, participants engaged in exercise changed their VFT performance over time, while control group participants did not. Exercising participants produced more words over the course of their exercise session that contained fewer letters over time and were lower in frequency during and after exercise as compared to before exercise. Additionally, topic switches in the VFTs increased after exercise as compared to before exercise. Participants in the control group did not change their VFT performance over time according to any of these measures. These findings indicate that exercise impacted participants’ lexical access and that these VFT performance changes were not due to practice effects.