Authors :
Presenting Author: Leigh Sepeta, PhD – Children's National Hospital
Samantha Werner, MA – Children's National Hospital
Sienna Williams, BS – Children's National Medical Center
Priyanka Venkata Sita Illapani, MSc – Children's National Hospital
Sonya Leikin, BS – Children's National Hospital
Cemal Karakas, MD – Children's National Hospital
Ana Moreno Chaza, BS – Children's National Hospital
Madison Berl, PhD – Children's National Hospital
Nishant Sinha, PhD – University of Pennsylvania
Mohamad Koubeissi, MD, MA, FAAN, FANA, FAES – George Washington University
Nathan Cohen, MD – Children's National Hospital
William Gaillard, MD – Children's National Hospital
Nunthasiri Wittayanakorn, MD – Children's National Hospital, George Washington University
Chima Oluigbo, MD – Children's National Hospital, George Washington University
Hua Xie, PhD – Children's National Hospital
Rationale:
Epilepsy and autism spectrum disorders (ASD) frequently co-occur, with up to 30% overlap in both populations and increasing prevalence into adulthood. Although reasons for this remain unknown, shared genetic and neuroanatomical substrates are suspected. The hippocampus and amygdala, key regions in social and emotional processing, may underlie the overlap. This co-occurrence provides a model to directly investigate neural circuitry in ASD using stereoelectroencephalography (sEEG). We aim to examine functional disruptions in these regions using sEEG to better understand neural correlates of autistic traits in epilepsy patients with ASD.
Methods:
sEEG data were recorded using a Nihon Kohden system with a 1-kHz sampling rate. Ten-minute epochs were randomly selected from long-term sEEG recordings during interictal periods when the patient was at rest and awake. All selected recordings were between 10:00AM and 2:00PM on the second or third day following the eletrodes implantation, and at least 1h away from an ictal event. We used Brainstorm to locate sEEG electrodes by overlaying pre-implantation MRI and post-implantation CT scans. The accuracy of this process was visually confirmed by a board-certified neurosurgeon. Freesurfer was used to identify electrodes targeting the hippocampus and amygdala. We used EEGLAB to preprocess sEEG recordings. Data was high-pass filtered ( >0.5Hz) and the 60Hz line noise was removed, followed by bipolar referencing, and were epoched into 30s segments without overlap. The amygdala-hippocampal synchrony was measured by coherence across five frequency band: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), and gamma (30-80 Hz) and averaged across epochs. Social Responsive Scale (SRS) was used to measure the autism symptom severity, and higher SRS indicates greater severity. We fitted a linear regression model using coherence to predict SRS scores, controlling for pairwise channel distance.
Results:
Eight patients with ASD (2 females, 6 with left foc) undergoing routine epilepsy care were used, with 20 and 15 channels targeting hippocampus and amygdala, respectively. We found that weaker gamma coherence between hippocampus and amygdala was related to greater autism severity measured by the total score of SRS (t = -2.2, p = 0.04).
Conclusions:
In a patient population with epilepsy and ASD, stronger gamma coherence between the hippocampus and amygdala was related to reduced social deficits. Gamma activity is implicated in various cognitive processes, including perceptual binding, social behavior and emotion processing. Abnormalities in gamma band has been linked to dysfunctions of inhibitory interneuron signaling as a potential marker of ASD. Our findings reinforce previous studies and confirm our initial hypothesis that altered hippocampal-amygdala synchrony may underly autistic traits in epilepsy patients with ASD. Future studies should examine epilepsy patients without autism and high gamma band ( >80Hz), as well as noninvasive neuromodulatory interventions that target hippocampus-amygdala gamma synchrony.
Funding:
This work is supported by the District of Columbia Intellectual and Developmental Disabilities Research Center Pilot Award.