Abstracts

Rationale: Juvenile Myoclonic Epilepsy (JME) is the most common idiopathic generalised epilepsy (IGE), characterised by frequent myoclonic jerks, generalised tonic-clonic seizures and, less commonly, absences. Neuropsychological and, less consistently, anatomical studies have indicated frontal lobe dysfunction in the disease (e.g. Ronan et al, 2011). However, IGEs probably involve large-scale network phenomena rather than localised regional abnormalities (Avanzini et al, 2012). Given its assumed thalamocortical basis, here we investigated thalamo-cortical structural and functional network connectivity in JME. Methods: Structural connectivity, as measured by diffusion tensor imaging (DTI) tractography, was assessed in a cohort of patients with JME (n=28, M:F 12:16, mean age 33.61 years) compared to a large sample of healthy controls (n=38, M:F 17:21, mean age 31.74 years). White matter bundles passing through the thalamus were parcellated using independent component analysis (ICA; O'Muircheartaigh et al, 2011) and the resulting bundles were compared. From regions of reduced thalamocortical structural connectivity, task modulated functional connectivity from the thalamus was then investigated using psychophysiological interactions (PPI, Friston et al, 1997) during a verbal fluency fMRI task to investigate the effect of abnormal structural connectivity on neuropsychological function. Results: We found reduced representation of an anterior thalamocortical bundle in JME (figure 1, p<0.05, corrected for 27 multiple comparisons using the Bonferroni method). We then investigated task-modulated functional connectivity using fMRI from the same anterior thalamic region. We demonstrated an alteration in task-modulated connectivity in the JME group in a region of frontal cortex directly connected to the thalamus via the same anatomical bundle (figure 2; p<0.05 corrected for multiple comparisons across the whole brain using cluster correction). Functional connectivity with the thalamus in this medial frontal region was increased during the phonemic fluency task in JME compared with controls. Connectivity of this region correlated with the number of generalised seizures in the previous year (p<0.05). Connectivity also related to out-of-scanner performance in verbal fluency differentially between JME patients with and without seizures (figure 2, panels b and c). Conclusions: By integrating methods examining structural and effective inter-regional connectivity, these results provide convincing evidence for abnormalities in a specific thalamo-cortical circuit, with reduced structural and task-induced functional connectivity, which may underlie the neuropsychological changes in JME.