Altered thalamocortical functional connectivity in idiopathic generalized epilepsy

Abstract

SUMMARYObjective: Aberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed-based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics. Methods: Forty-nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic-clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel-based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between-group comparison of thalamocortical FC was then carried out using resting-state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables. Results: Neuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE. Significance: Our results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/ posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long-standing burden of the disease.

Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy

“…However, another study found a different pattern of connectivity by using a similar analytic strategy. 21 This inconsistency is at least partly due to the different locations of seed regions in these studies. To avoid the bias of a predefined seed region in the present study, we performed a voxelwise functional connectivity analysis (expressed as FCS) between the thalamus and cortex.…”

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

“…For example, patients with generalized tonic–clonic seizures only (GTCSO) revealed reduced gray matter in the ventral anterior and lateral nuclei of the thalamus compared to healthy controls 3, 23, 24. In a group of patients with juvenile myoclonic epilepsy (JME), shape analysis showed surface reduction in the medial and lateral nuclei of bilateral thalami25 and decreased gray matter volume in the anteromedial thalamus has also been found in patients with JME11 and in a group of mixed GGE patients 26. Similarly, gray matter volume reduction in bilateral thalami has been reported in patients with CAE 9.…”

Frequency-specific Alterations of Functional Hub in Generalized Tonic-clonic Seizure

“…To date, the majority of previous studies have predominately detected abnormal epileptic at a conventional lowfrequency range (0.01-0.08 Hz) because the lowfrequency range was thought to be linked to neuronal intrinsic fluctuations, which may ignore some meaningful information associated with frequencyspecific spontaneous blood oxygen level-dependent (BOLD) fluctuation [5][6][7][8] . Besides, neighboring frequency bands within the same neuronal network may compete or interact with each other, which means that the brain intrinsic resting-state functional networks are frequency-dependent 9,10 .…”