Sleep onset uncovers thalamic abnormalities in patients with idiopathic generalised epilepsy

Abstract

The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE.

Objective and subjective measures of prior sleep–wake behavior predict functional connectivity in the default mode network during NREM sleep

“…Our observations may suggest that FC differences in insomnia could be more pronounced during sleep rather than in wake. While a different pathology, the idea that the change in state from wakefulness to sleep can uncover FC differences between patient groups and healthy participants is supported by our recent work in idiopathic generalized epilepsy (Bagshaw et al, 2017). Additionally, the current study was limited in not being able to assess slow wave sleep, which is understood to be both important for memory consolidation and is influenced by insomnia (Diekelmann & Born, 2010).…”

Computer modelling of connectivity change suggests epileptogenesis mechanisms in idiopathic generalised epilepsy

“…Several studies have shown that pathological use of this circuitry results in manifestation of generalised spike-wave discharges (Gloor, 1968; Meeren, 2002; Meeren et al, 2005; van Luijtelaar and Sitnikova, 2006; Huguenard and McCormick, 2007; Beenhakker and Huguenard, 2009; Lacey et al, 2012). Recently, EEG-fMRI analysis performed on IGE patients during early sleep stages revealed enhanced functional connectivity between thalamus and somatomotor region (which include precentral gyrus), amongst other regions (Bagshaw et al, 2017). These reports essentially complement our finding on abnormally high cortico-reticular anatomical connectivity as one of the contributory structures involved in mechanising epilepsy.…”

Brain functional connectivity in sleep-related hypermotor epilepsy

“…The role of the thalamus in the pathophysiology of different forms of epilepsy is well known, and previous studies have shown altered thalamic FC in temporal lobe epilepsy ( Chen et al, 2015 ) and idiopathic generalized epilepsy ( Kim et al, 2014 , Masterton et al, 2012 , Moeller et al, 2011 ). A recent EEG-fMRI study ( Bagshaw et al, 2017 ) specifically demonstrated alterations in thalamic functional connectivity in idiopathic generalized epilepsy patients, showing a higher thalamocortical connectivity in patients. However, when thalamic functional connectivity was investigated in non-SHE frontal lobe epilepsy patients, no significant differences with healthy controls were found ( Dong et al, 2016 ).…”