Mapping the Cortex-wide Propagation of Direct Electrical Stimulation in Focal Cortical Dysplasia Type II
Abstract number :
2.058
Submission category :
3. Neurophysiology / 3E. Brain Stimulation
Year :
2023
Submission ID :
495
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School
Emma Macdonald-Laurs, MBChB, FRACP – Neurology – Royal Children's Hospital; Melissa Chua, MD – Neurosurgery – Brigham and Women's Hospital, Harvard Medical School; Alexander Yearley, BA – Harvard Medical School; Hargunbir Singh, MBBS – Neurosurgery – Brigham and Women's Hospital, Harvard Medical School; Michaela Stamm, MS – Neurosurgery – Brigham and Women's Hospital, Harvard Medical School; John Rolston, MD, PhD – Neurosurgery – Brigham and Women's Hospital, Harvard Medical School
Rationale:
Focal cortical dysplasia type II (FCDII) is a common cause of drug-resistant focal epilepsy. There is increasing recognition that FCDII are nonuniformly distributed in the cortex, and that the specific location may influence patient outcomes including seizure onset age and response to therapy (Epilepsia 2022;63(1):61-74). However, the neurophysiologic mechanisms linking FCDII location to the development of focal epilepsy are unclear. We studied the inter-areal effective connectivity of FCDII locations using an atlas of cortex-wide intracranial EEG recordings representing ~30,000 single-pulse electrical stimulations of the human brain from ~600 individuals.
Methods: A total of 170 patients with focal epilepsy and FCDII were studied (median age=7 years; 58% male). FCDII locations were manually segmented using patients’ anatomical MRI scans, then warped to a template cortical surface (FreeSurfer’s fsaverage_sym). Using intracranial EEG data from the F-TRACT project (Brain 2022;145(5):1653-1667), we derived whole-brain maps of evoked responses to focal stimulation, parcellated by the Destrieux atlas (containing 74 cortical parcels per hemisphere). For each parcel, we calculated (i) average probability that stimulation of the parcel evoked a significant excitatory response in other parcels, and (ii) average amplitude of the evoked response in other parcels. Permutation tests were used to correlate each metric with the number of FCDs observed at each parcel. Associations were also explored between F-TRACT metrics and patient clinical variables including seizure onset age (years), scalp EEG patterns (focal vs diffuse interictal epileptiform discharges [IEDs]), and surgical outcome (seizure free vs not seizure free).
Results:
Median age of seizure onset was 5.8 years. A total of 83% of patients had predominantly focal IEDs on scalp EEG, whereas the remainder showed more diffuse IEDs. A total of 63% of patients underwent resective surgery, 85% of these becoming seizure free. FCDII were most frequently found in the caudal and anterior middle frontal gyrus and anterior insula/circular sulcus; they were less common in the temporal, occipital, and parietal lobes (Fig. 1). Analysis of F-TRACT stimulation data revealed a significant positive correlation between FCDII occurrence and the probability of those anatomical sites evoking an excitatory response elsewhere in the brain (Fig. 2). In contrast, no association was found with evoked response amplitude. No associations were found with seizure onset age (p=0.4), scalp EEG patterns (p=0.6), or surgical outcome (p=0.2).
Conclusions:
FCDII are nonuniformly distributed, being most common in the frontal lobe and anterior insula. Surgical resection is associated with a high chance of seizure freedom. They occur in regions with greater probability of evoking significant excitatory responses elsewhere. The strong, widespread excitatory connections may contribute to the striking epileptogenicity and resultant drug-resistant epilepsy associated with these small, discrete lesions.
Funding:
NIH/NINDS career development award (K23 NS114178).
Neurophysiology