Regional cortical thickness changes accompanying generalized tonic-clonic seizures

Affiliations

¹ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
² Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA.
³ UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
⁴ Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
⁵ Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
⁶ Institute of Neurology, University College London, London, United Kingdom.
⁷ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
⁸ Epilepsy Center, UH Case Medical Center, Cleveland, OH, USA.
⁹ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: rharper@ucla.edu.

PMID: 30094170
PMCID: PMC6073085
DOI: 10.1016/j.nicl.2018.07.015

Regional cortical thickness changes accompanying generalized tonic-clonic seizures

Jennifer A Ogren et al. Neuroimage Clin. 2018.

. 2018 Jul 18:20:205-215.

doi: 10.1016/j.nicl.2018.07.015. eCollection 2018.

Authors

Affiliations

¹ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
² Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA.
³ UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
⁴ Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
⁵ Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
⁶ Institute of Neurology, University College London, London, United Kingdom.
⁷ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA.
⁸ Epilepsy Center, UH Case Medical Center, Cleveland, OH, USA.
⁹ Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: rharper@ucla.edu.

PMID: 30094170
PMCID: PMC6073085
DOI: 10.1016/j.nicl.2018.07.015

Abstract

Objective: Generalized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms.

Methods: High-resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic-clonic seizures (Mean age ± SD: 37.1 ± 12.6 years, 22 male) at Case Western Reserve University, University College London, and the University of California at Los Angeles. Control data included 530 healthy individuals (37.1 ± 12.6 years; 220 male) from UCLA and two open access databases (OASIS and IXI). Cortical thickness group differences were assessed at all non-cerebellar brain surface locations (P < 0.05 corrected).

Results: Increased cortical thickness appeared in post-central gyri, insula, and subgenual, anterior, posterior, and isthmus cingulate cortices. Post-central gyri increases were greater in females, while males showed more extensive cingulate increases. Frontal and temporal cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital cortices showed thinning. The extents of thickness changes were sex- and hemisphere-dependent, with only males exhibiting right-sided and posterior cingulate thickening, while females showed only left lateral orbitofrontal thinning. Regional cortical thickness showed modest correlations with seizure frequency, but not epilepsy duration.

Significance: Cortical thickening and thinning occur in patients with generalized tonic-clonic seizures, in cardiovascular and somatosensory areas, with extent of changes sex- and hemisphere-dependent. The data show injury in key autonomic and respiratory cortical areas, which may contribute to dysfunctional cardiorespiratory patterns during seizures, as well as to longer-term SUDEP risk.

Keywords: ACC, anterior cingulate cortex; Autonomic; CWRU, Case Western Reserve University; Cingulate; GTCS, generalized tonic-clonic seizures; Insula; OASIS, Open Access Series of Imaging Studies; PCC, posterior cingulate cortex; ROI, region of interest; Respiratory; SUDEP; SUDEP, sudden unexpected death in epilepsy; UCL, University College London; UCLA, University of California Los Angeles..

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Figures

**Fig. 1**
Regions of significant group difference overlaid on “pial” views (A & B: showing topical view of sulci and gyri) and “inflated” views (C & D: sulci expanded and gyri flattened) for combined male and female cortical thickness data of left and right lateral (A & C) and medial (B & D) brain views of cortical thickness differences in 53 GTCS patients vs 530 age- and gender-matched controls, using sex as a covariate. t-statistic thresholds set using FDR (Rate: p = 0.05) Blue scale represents thinning, red-yellow scales indicate cortical thickening in GTCS patients over controls. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 2**
Regions of significant group difference overlaid on “pial” views (showing topical view of sulci and gyri) and “inflated” views (i.e. sulci expanded and gyri flattened) for data from 31 female GTCS patients vs 310 age-matched female controls (Female, A-D) and from 22 male GTCS vs. 220 age-matched male controls (Male, E-H). Lateral views (A, C, E, F) and medial views (B, D, F, H) in left and right brain views show areas of cortical thinning (blue scale) and thickening (red-yellow scales) in GTCS patients over controls, partitioned by sex. t-statistic thresholds (FDR Rate: p = 0.05) set in the combined male-female analysis (Fig. 1) were maintained here for consistency. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

See this image and copyright information in PMC

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Regional cortical thickness changes accompanying generalized tonic-clonic seizures

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Regional cortical thickness changes accompanying generalized tonic-clonic seizures

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Abstract

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