Thalamus and focal to bilateral seizures

Abstract

ObjectiveTo investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE), using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. As the thalamus modulates propagation of temporal-lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized, i.e.,. focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity and whole-brain network centrality.MethodsFBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multi-scale approach, entailing analysis of SPM12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiological interaction), and graph-theoretical metrics of centrality.ResultsIndividuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamo-motor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS.ConclusionsIn TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.

Altered Relationship Between Heart Rate Variability and fMRI-Based Functional Connectivity in People With Epilepsy

“…Allen et al ( 32 ), using resting-state fMRI, showed that the nodal participation of thalamus, a measure that reflects the connectivity strength of a region with regions from separate large-scale networks, was increased in epilepsy patients compared to healthy controls, and particularly in patients that succumbed to SUDEP or were at high-risk. Similarly, two recent studies reported altered thalamocortical connectivity ( 61 ) as well as impaired connectivity between thalamus and basal ganglia ( 62 ) in individuals with focal to bilateral tonic-clonic seizures (FBTCS), a group of epilepsy patients associated with increased risk of seizure-related injuries and sudden unexpected death. Structural studies have revealed association of thalamic volume loss with SUDEP and high-risk patients ( 63 ) as well as with patients that present severe hypoxia during generalized tonic-clonic seizures ( 64 ).…”

Altered structural connectome in non-lesional newly diagnosed focal epilepsy: Relation to pharmacoresistance

“…The thalamus, which has important roles in seizure initiation, propagation and modulation of focal seizures ( Blumenfeld et al, 2009 , Guye et al, 2006 , Filipescu et al, 2019 , Wykes et al, 2019 , Keller et al, 2015 , Caciagli et al, 2020 , He et al, 2020 ), may be a crucial structural hub as an imaging marker of pharamacoresistance or FBTCS. Studies in genetic generalized epilepsy have demonstrated altered thalamic connectivity ( Sinha et al, 2019 , Wang et al, 2019a , Wang et al, 2019b ), which measured shortly after diagnosis, could be related to AED treatment outcomes ( Wang et al, 2019a , Wang et al, 2019b ).…”

“…One study related altered thalamocortical circuits to disorder severity and demonstrated a relationship between the extent of impaired connectivity and the number of generalized seizures in juvenile myoclonic epilepsy ( O'Muircheartaigh et al, 2012 ). Caciagli et al, 2020 have proposed altered thalamic functional profiles as imaging biomarkers of active secondary generalization. Sinha et al (2020, PREPRINT) have demonstrated greater and more widespread structural network alteration in patients with temporal lobe epilepsy and FBTCS when compared to patients without FBTCS.…”

The cerebellum contributes to tonic-clonic seizures by altering neuronal activity in the ventral posteromedial nucleus (VPM) of the thalamus

“…The thalamus is a critical structure in the seizure network [20][21][22] , although the contribution of its different nuclei to mediating seizures is not fully understood. Using the Ntsr1 Cre ;ChR2 mice, we targeted blue light to manipulate the thalamic nuclei, as each of its major divisions were densely innervated by a convergence of axons from multiple Cre-expressing brain regions.…”

“…Other regions, such as the cerebellum, are thought to play some role in seizures, but the extent of their contribution is controversial 19 . The majority of these regions project to the thalamus, which is not only a well-established area of information integration, but is also understood to serve as a key gateway for mediating seizures that depend upon these various regions [20][21][22] . Yet, the precise role of individual thalamic nuclei and their unique combination of inputs on the generation of (which was not certified by peer review) is the author/funder.…”