Network localisation of cardiorespiratory dysfunction in focal epilepsy
Abstract number :
965
Submission category :
5. Neuro Imaging / 5B. Functional Imaging
Year :
2020
Submission ID :
2423298
Source :
www.aesnet.org
Presentation date :
12/7/2020 1:26:24 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Eugenio Abela, King's College London; Nira Futter - King's College London; Andrea Biondi - King's College London; Pedro Viana - King's College London; Mark Richardson - King's College London;;
Rationale:
Cardiorespiratory dysfunction (CRD) is the likely culprit behind sudden unexpected death in epilepsy (SUDEP), but its neuroanatomical substrates remain unclear. Here, we use functional connectomics to test the hypothesis that cortical sites associated with stimulation- or seizure-induced CRD are connected to cardiorespiratory brainstem centers via an unique brain network. We also tested whether this network was enriched for serotonergic (5-HT) neurotransmission, which seems to be deficient in SUDEP, and for SCN1A gene expression, which associates with SUDEP in animal models.
Method:
Through a systematic literature search, we identified 140 patients with focal epilepsy in which electrical stimulation of 148 intracranial electrodes elicited CRD. We calculated seed-to-voxel functional connectivity networks from each of these electrodes using a large normative resting-state fMRI database (n=1000) and applied nonparametric statistics to identify brainstem areas connected to them. Non-responsive electrodes were used as control sites to assess anatomical specificity. We then investigated cases of ictal CRD associated with 18 epileptogenic lesions and 6 seizure-onset electrodes and tested whether these sites were connected to this network. Finally, we assessed whether cardiorespiratory sites had higher 5-HT transporter densities and SCN1A expression compared to control regions, using openly available PET and gene expression atlases.
Results:
Cardiorespiratory sites were connected to midbrain raphe, inferior ventral pons, and upper medulla oblongata. Epileptogenic lesions and seizure onset electrodes were significantly connected to these nodes (p = 0.001, mean r = 0.34 [95.0%CI 0.21,0.68]). Compared to control sites, cardiorespiratory electrodes and brainstem nodes had substantially higher 5-HT transporter densities (p = 0.0145, mean Cohen’s d = 1.68 [0.798, 2.61]), and brainstem nodes showed increased SCN1A expression levels (p< 0.001, d = 0.38 [0.326, 0.442]).
Conclusion:
A large-scale serotonergic network, potentially susceptible to SCN1A mutations, connects supratentorial regions to cardiorespiratory brainstem centers and might underpin acute cardiorespiratory dysfunction in SUDEP.
Funding:
:Marie-Curie Fellowship (EU Horizon 2020)
Neuro Imaging