Syndrome-specific and familial imaging traits in juvenile absence epilepsy

Juvenile absence epilepsy (JAE) is an idiopathic generalized epilepsy characterized by absences, generalized tonic-clonic seizures, and cognitive difficulties. In contrast to juvenile myoclonic epilepsy (JME), where distinct functional and structural brain alterations are well established, it remains unclear whether comparable changes are identifiable in absence-predominant syndromes. We aimed to delineate functional and structural correlates of the cognitive profile in people with JAE and to explore potential familial imaging traits.

We acquired working memory functional magnetic resonance imaging (MRI) and high-resolution T1-weighted MRI in 23 individuals with JAE, 18 unaffected siblings, and 28 controls.

Compared with both siblings and controls, patients showed increased motor cortex activation during the attention-only condition, but relative suppression of motor activity and inadequate default mode network deactivation with increasing working memory demand. Gray matter volume was reduced in sensorimotor regions and in the left inferior and middle frontal gyri in patients. Larger volumes in these frontal regions correlated with better language function. In contrast, increased gray matter volume in the dorsal midcingulate cortex was present in both patients and their siblings relative to controls.

Our findings in JAE differ from the patterns of functional reorganization reported in JME, indicating that each syndrome involves distinct motor-cognitive pathophysiological mechanisms aligned with its seizure profile. Inferior frontal structural abnormalities likely contribute to the well-recognized language difficulties in JAE, whereas increased midcingulate gray matter volume may serve as a familial marker linked to attentional vulnerability.