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

Allen LA; Harper RM; Guye M; Kumar R; Ogren JA; Vos SB; Ourselin S; Scott CA; Lhatoo SD; Lemieux L; Diehl B

NeuroImage: Clinical (Jan 2019)

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

Allen LA,
Harper RM,
Guye M,
Kumar R,
Ogren JA,
Vos SB,
Ourselin S,
Scott CA,
Lhatoo SD,
Lemieux L,
Diehl B

Affiliations

Allen LA: Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; Epilepsy Society MRI Unit, Chalfont St Peter, Buckinghamshire, UK; The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Corresponding author at: Clinical & Experimental Epilepsy, Queen Square, London, United Kingdom.
Harper RM: The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; UCLA Brain Research Institute, Los Angeles, CA, USA; Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Guye M: Aix Marseille University, CNRS, CRMBM UMR 7339, Marseille, France
Kumar R: The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Bioengineering, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Ogren JA: The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; UCLA Brain Research Institute, Los Angeles, CA, USA
Vos SB: The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; UCLA Brain Research Institute, Los Angeles, CA, USA; Wellcome / EPSRC Centre Interventional and Surgical Sciences, UCL, London, UK; Translational Imaging Group, Centre for Medical Image Computing, UCL, London, UK
Ourselin S: School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, King's College London, London, UK
Scott CA: Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Lhatoo SD: Department of Neurology, University of Texas Health Sciences Center at Houston, Houston, TX, USA
Lemieux L: Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; Epilepsy Society MRI Unit, Chalfont St Peter, Buckinghamshire, UK
Diehl B: Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; Epilepsy Society MRI Unit, Chalfont St Peter, Buckinghamshire, UK; The Center for SUDEP Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA

Journal volume & issue: Vol. 24

Abstract

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The circumstances surrounding SUDEP suggest autonomic or respiratory collapse, implying central failure of regulation or recovery. Characterisation of the communication among brain areas mediating such processes may shed light on mechanisms and noninvasively indicate risk.We used rs-fMRI to examine network properties among brain structures in people with epilepsy who suffered SUDEP (n = 8) over an 8-year follow-up period, compared with matched high- and low-risk subjects (n = 16/group) who did not suffer SUDEP during that period, and a group of healthy controls (n = 16). Network analysis was employed to explore connectivity within a ‘regulatory-subnetwork’ of brain regions involved in autonomic and respiratory regulation, and over the whole-brain.Modularity, the extent of network organization into separate modules, was significantly reduced in the regulatory-subnetwork, and the whole-brain, in SUDEP and high-risk. Increased participation, a local measure of inter-modular belonging, was evident in SUDEP and high-risk groups, particularly among thalamic structures. The medial prefrontal thalamus was increased in SUDEP compared with all other control groups, including high-risk. Patterns of hub topology were similar in SUDEP and high-risk, but were more extensive in low-risk patients, who displayed greater hub prevalence and a radical reorganization of hubs in the subnetwork.SUDEP is associated with reduced functional organization among cortical and sub-cortical brain regions mediating autonomic and respiratory regulation. Living high-risk subjects demonstrated similar patterns, suggesting such network measures may provide prospective risk-indicating value, though a crucial difference between SUDEP and high-risk was altered connectivity of the medial thalamus in SUDEP, which was also elevated compared with all sub-groups. Disturbed thalamic connectivity may reflect a potential non-invasive marker of elevated SUDEP risk. Keywords: SUDEP, Rs-fmri, Graph theory, Amygdala, Thalamus

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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