Gamma Suppression on Somatosensory Evoked Potentials using High-Density EEG in Patients with SSADHD Deficiency, a hyper-GABAergic Condition
Abstract number :
242
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2020
Submission ID :
2422588
Source :
www.aesnet.org
Presentation date :
12/6/2020 12:00:00 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Christos Papadelis, Cook Children's Health Care System; Georgios Ntolekras - Boston Children's Hospital, Harvard Medical School; Melissa L. DiBacco - Boston Children's Hospital; Matthew Pesce - Boston Children’s Hospital, Harvard Medical School; Jean-Bapt
Rationale:
SSADHD is a rare disorder of GABA degradation. Physiological fluids show elevation of the neurotransmitter GABA, and PET imaging studies indicate down-regulation of brain GABAA receptors. Physiological fluids show elevation of the inhibitory neurotransmitter GABA, and earlier PET imaging studies have shown down-regulation of brain GABA(A) receptors. Together with evidence of increased levels of excitatory neurotransmitter glutamate in the brain, the research suggests that impaired GABA and GABAAR signaling is a major pathogenic factor underlying the neurological and psychiatric manifestations of this disorder. However, to date this hypothesis still needs experimental validation. In this study, we aim to expand our understanding of GABAergic activity in children with SSADHD by evaluating somatosensory evoked responses recorded with high-density electroencephalography (HD-EEG). We hypothesize that brain oscillatory activity in the gamma frequency band that depends on GABAergic neurotransmission will be altered in patients with SSADHD compared to healthy controls.
Method:
We recorded somatosensory evoked potentials (SEPs) from 17 children with SSADHD and 10 healthy controls using HD-EEG (64 channels) (Fig. 1a). We obtained the SEPs after stimulation of both left and right upper extremities (i.e. thumb, index finger, and pinkie) with pneumatic stimulation (800 trials each) (Fig. 1b). We performed electric source imaging on the averaged data of each participant using standardized Low-Resolution Electromagnetic Tomography (sLORETA), which estimates the 3-D distribution of electric neuronal activity in the brain. In order to estimate the forward model, we built realistic head models using the Boundary Element Model (BEM) based on each participant’s MRI. With sLORETA, we localized the neural activity at the peak of the first cortical response after the stimulus’ onset (Fig. 1c). We then estimated the virtual channel in the left and right S1 (Fig. 1d). We performed time-frequency analysis on the virtual channel signals of each participant using Morlet wavelet between 1-100 Hz. Finally, we applied a permutation independent t-test to time-frequency magnitude estimates in order to compare differences between the two groups.
Results:
The first cortical responses were localized within the primary somatosensory cortex (S1) for both hemispheres of patients with SSADHD and healthy controls. Wavelet analysis at the virtual channels in S1 revealed suppressed gamma and beta activity in the SSADHD cohort compared to controls contralateral to the stimulated side between 50 and 120 ms after the stimulus onset (p< 0.05; corrected for multiple comparisons by controlling the false discovery rate).
Conclusion:
We present for the first time evidence of suppressed gamma and beta activity in the SEPs elicited from tactile stimulation of the upper extremities of patients with SSADHD compared to healthy controls. Decreased gamma activity is consistent with the downregulation of the GABA and GABAAR signaling previously demonstrated using clinical flumazenil PET imaging and animal slide electrophysiology and immunohistochemistry.
Funding:
:SSADH Natural History Study (PI: Phillip L. Pearl)
Translational Research