Absence seizures: Update on signaling mechanisms and networks

Absence seizures (AS) are a hallmark of genetic generalized epilepsies (GGE), characterized by brief episodes of impaired consciousness accompanied by electroencephalographic spike-and-wave discharges (SWDs). Traditionally attributed to cortico-thalamo-cortical (CTC) dysrhythmia, emerging evidence suggests a more intricate pathophysiological framework involving high-order thalamic nuclei, the basal ganglia, limbic structures, and the cerebellum. Rather than arising abruptly from a discrete cortical event, SWDs appear to develop progressively through dynamic network interactions. This paradigm shift underscores the necessity of a network-based approach to comprehensively understand AS pathophysiology. Concurrently, advances in electrophysiology and neuroimaging are refining our understanding of the signaling mechanisms that drive AS generation. This review explores the network dynamics underlying AS, synthesizing recent experimental and clinical findings to provide an integrative framework for future research and the development of novel therapeutic strategies in absence epilepsy. PLAIN LANGUAGE SUMMARY: Absence seizures are brief episodes of staring and unresponsiveness, often beginning in childhood, and are caused by abnormal rhythmic activity in the brain. This review summarizes recent research on how specific brain circuits generate and maintain these seizures. While most studies have focused on the cortex and thalamus, we also highlight the contributions of other regions such as the basal ganglia, cerebellum, and limbic structures. Understanding how these brain networks interact may help explain seizure patterns and guide the development of improved treatments.