Altered brain connectivity in sudden unexpected death in epilepsy (SUDEP) revealed using resting-state fMRI

Abstract

HighlightsThe functional architecture among regulatory structures, and the whole brain, is less modular in confirmed cases of SUDEP and those at high-risk.Altered functional organisation may mean potential impairment of communication among key regulatory circuits.SUDEP is associated with regional connectivity disruptions among cortical and sub-cortical regulatory sites.Medial thalamic connectivity was significantly altered in SUDEP compared with all control groups, including those at high-risk.Increases in the number, and a shift in organisation, of hubs appears to relate to lower mortality risk.

Regional microglial populations in central autonomic brain regions in SUDEP

“…Functional MRI also shows reduced connectivity between the left and right thalamus, brainstem, and cingulate cortex, 13 and particularly between the putamen, with the cingulate cortex in epilepsy patients considered at risk for SUDEP 11 . In a retrospective functional MRI (fMRI) analysis comparing actual SUDEP cases with those considered at high‐risk, the medial thalamus showed proportionally more inter‐nodal connectivity, suggesting that this may be a critical region 10 . The thalamus is known to have roles in respiratory control during hypoxia 43‐45 as well as sympathetic autonomic regulatory functions 7 .…”

“…11 In a retrospective functional MRI (fMRI) analysis comparing actual SUDEP cases with those considered at high-risk, the medial thalamus showed proportionally more inter-nodal connectivity, suggesting that this may be a critical region. 10 The thalamus is known to have roles in respiratory control during hypoxia [43][44][45] as well as sympathetic autonomic regulatory functions. 7 There are direct efferent projections from pre-Bötzinger complex neurons to thalamic nuclei, in particular the dorsomedial region.…”

“…8,9 Recent functional MRI analyses from SUDEP cases, in addition to people with epilepsy considered at higher risk, have shown altered connectivity between autonomic cortical and subcortical cardiac and respiratory regulatory regions, including the thalamus, suggesting disorganization of interconnections. [10][11][12][13] Structural MRI analyses from large data sets (ENIGMA-epilepsy consortium) recognize stereotypical regional patterns of cortical thinning in epilepsy syndromes. 14 Regional patterns of increased or decreased MRI gray matter volumes have also been observed in SUDEP or at-risk patients, including the pulvinar, parahippocampal gyrus, and other CAN regions.…”

“…Knowledge of their interconnectivity and function associated with specific regions continues to evolve 8,9 . Recent functional MRI analyses from SUDEP cases, in addition to people with epilepsy considered at higher risk, have shown altered connectivity between autonomic cortical and subcortical cardiac and respiratory regulatory regions, including the thalamus, suggesting disorganization of interconnections 10‐13 …”

Peri‐ictal hypoxia is related to extent of regional brain volume loss accompanying generalized tonic‐clonic seizures

“…Widespread volume loss appeared in subjects whose seizures were accompanied by severe hypoxia, especially in GM sites previously shown to exhibit loss in patients with SUDEP and those at highest risk (thalamus, cerebellum, vermis, and PAG) 16 . In addition, we found GM loss in the hypothalamus and temporal pole, and white matter reductions in the medulla and pons of the brainstem, regions known to be associated with SUDEP 17 .…”