Convergent Evidence for a Premotor Cortical Hotspot in Lennox-gastaut Syndrome
Abstract number :
2.199
Submission category :
5. Neuro Imaging / 5B. Functional Imaging
Year :
2022
Submission ID :
2204788
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School; Christopher Butson, PhD – b) Normal Fixel Institute for Neurological Diseases – University of Florida; Matthew Hook, MSc – Normal Fixel Institute for Neurological Diseases – University of Florida; Linda Dalic, PhD, FRACP – Neurology – Austin Health; Emma Macdonald-Laurs, MBChB – Neurology – The Royal Children's Hospital; John Archer, PhD, FRACP – Medicine (Austin Health) – The University of Melbourne; John Rolston, PhD, MD – Neurosurgery – Brigham and Women's Hospital
Rationale: Simultaneous thalamocortical responsive neurostimulation (RNS), where stimulation is delivered to the thalamus, cortex, or both upon detection of epileptiform activity, is an emerging treatment strategy for Lennox-Gastaut syndrome (LGS) (Ann Clin Transl Neurol 2020;7(10):2035-2040). Thalamic targets for LGS have been explored, including the centromedian nucleus. However, a cortical target is less defined, partly due to the generalized nature of this epilepsy. We aimed to localize cortical “hotspots” in LGS by integrating results from prior neuroimaging studies, and investigating the functional connectivity of these hotspots using normative connectome data.
Methods: Statistical brain maps from 3 prior group-level studies were integrated (Figure 1): (i) a combined EEG-functional MRI (EEG-fMRI) study of blood-oxygen-level-dependent (BOLD) activation patterns during bursts of interictal generalized paroxysmal fast activity (n=25 LGS patients) (Neurology 2019;93(3):e215-e226); (ii) an 18F-FDG-PET study of interictal cerebral glucose hypometabolism (n=21 LGS patients vs n=18 controls) (AES Poster 2019); and (iii) a diffusion MRI study of structural connectivity patterns associated with seizure reduction in the ESTEL trial of centromedian thalamic deep brain stimulation (DBS; n=19 LGS patients) (Ann Neurol 2022; In press). To define areas of peak cortical overlap, the 3 maps were: warped to a common template brain surface, converted to z-scores, averaged together, and thresholded to show the top 5% of average z-score values. The resulting “hotspots” were used as seed regions in a whole-brain functional connectivity analysis using normative resting-state fMRI data of 100 healthy adults from the Human Connectome Project.
Results: In both hemispheres, the peak cortical overlap was in caudal middle frontal gyrus (dorsal premotor cortex/Brodmann area 6), immediately anterior to precentral sulcus, with limited and less significant spread to neighboring caudal inferior and superior frontal gyri (Figure 2A). Normative functional connectivity analysis (seeded from the hotspots) revealed distributed connectivity with a bilateral network of frontoparietal and lateral temporal cortex (Figure 2B) resembling the distributed areas of epileptic involvement identified by EEG-fMRI and 18F-FDG-PET (Figure 1A).
Conclusions: We show convergent evidence for a potential hotspot in LGS located in the caudal middle frontal gyrus/dorsal premotor cortex, where there is peak epileptic involvement on EEG-fMRI and 18F-FDG-PET, and where thalamic DBS connections yield therapeutic benefit. Furthermore, normative functional connectivity of this region recapitulates abnormal EEG-fMRI and 18F-FDG-PET patterns in LGS, suggesting it is ideally positioned to modulate the wider epileptic network underlying this syndrome. Hence, premotor cortex may be a discrete target for simultaneous thalamocortical RNS and other emerging cortically based therapies including targeted drug delivery devices and non-invasive transcranial stimulation.
Funding: Not applicable
Neuro Imaging