Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study

Abstract

Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

Thalamic volume reduction in drug‐naive patients with new‐onset genetic generalized epilepsy

“…These areas connect to cingulate, caudate, putamen, frontal cortex, supplementary motor area, postcentral cortex, and occipital cortex,41 all cortical areas that are associated with GGE 36, 42, 43…”

Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy

“…In an fMRI study using an executive frontal lobe paradigm, patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and the frontoparietal cognitive networks, providing an explanation for how cognitive effects can cause myoclonic jerks in juvenile myoclonic epilepsy. 24 It was suggested that the SMA, as a connector linking prefrontal cognitive areas and the motor system, may facilitate the occurrence of generalized seizures, a notion supported by alterations in anatomic connectivity of the SMA in juvenile myoclonic epilepsy. 25 To estimate the corticothalamic connectivity in juvenile myoclonic epilepsy, we parcellated the thalamus into several nuclei connected to different cortices by using probabilistic tractography.…”

Besondere bildgebende Befunde bei primär generalisierten Epilepsien

“…Abb. 2e, f; [17]), die mit einer mittels DTI nachgewiesenen ebenfalls erhöhten strukturellen Konnektivität korrelierte [18]. Diese Befunde boten eine schlüssige Erklärung für das JMEspezifische Phänomen der Praxisinduktion, bei der eine Kombination aus kognitiver und manueller Tätigkeit motorische Anfälle triggern kann (über eine pathologische Hyperkonnektivität zwischen ansonsten getrennten funktionellen Systemen; .…”

“…Diese Befunde bieten eine Erklärung für die typische Anfallstriggerung durch Praxisinduktion bei der JME. Ähnliche Befunde bei gesunden Geschwistern sprechen dafür, dass dieses fMRT-Merkmal erblich ist und somit als Endophä-notyp dienen kann ( [17,19], L links, R rechts) …”