Abstract Details

Title Functional Neuronal Networks After Cortical Spreading Depolarizations

Topic General Neurology

Presentation(s) P10 - Poster Session 10 (11:45 AM-12:45 PM)

Poster/Presentation
Number 4-007

Objective To study the effect of unilateral cortical spreading depolarizations (CSD) on resting state functional connectivity (RSFC).

Background CSDs are implicated in the pathophysiology of several neurological conditions including traumatic brain injury (TBI). Previous work has suggested that CSDs induced in one hemisphere increase intrahemispheric RSFC and decrease interhemispheric RSFC using hemodynamic measures of RSFC. We sought to determine the effect of CSDs on neuronally-derived RSFC in a mouse model and apply our analysis approach to a patient with lateralizing TBI.

Design/Methods We utilized Thy1-ChR2 mice to non-invasively induce unilateral CSDs with optogenetics in mice with chronic, intact skull imaging windows. We then determined hemodynamically-based RSFC at baseline, immediately following CSD, and at 1, 12, and 24 hours post-CSD using optical intrinsic signal imaging under tribromoethanol anesthesia. We performed neuronal calcium imaging in a separate cohort of Thy1-GCaMP6f animals to determine neuronally-based RSFC after a CSD. We used global regression and a novel local-regression approach where the CSD hemisphere was regressed separately from the contralateral hemisphere. Finally, we analyzed fMRIs from a patient with lateralizing TBI and a healthy control patient using analogous regression approaches.

Results CSD disrupted hemodynamic and neuronal metrics of RSFC. Furthermore, we found that this effect was exaggerated by global signal regression. We developed a novel local regression processing technique (hemispheric regression) which mitigated these differences. Our results showed differences between these two signal processing techniques. Finally, we applied the hemispheric regression approach to a patient with lateralizing TBI and found analogous differences.

Conclusions We found considerable dynamic changes after CSD both in neuronal and hemodynamic-derived RSFC. Furthermore, a local hemispheric regression approach led to differences in connectivity patterns compared to the commonly used global signal regression.

Authors/Disclosures
Miran Oncel, MD PRESENTER	Mr. Oncel has nothing to disclose.
James H. Lai	Mr. Lai has nothing to disclose.
Jian Li (Massachusetts General Hospital)	No disclosure on file
Sanem Aykan (MGH, HMS)	No disclosure on file
Joanna Yang	No disclosure on file
Tao Qin	No disclosure on file
Andrea Harriott, MD (Massachusetts General Hospital)	Dr. Harriott has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Theranica. Dr. Harriott has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Headache Cooperative of New England. The institution of Dr. Harriott has received research support from Electrocore. Dr. Harriott has a non-compensated relationship as a Author agreement with Abbvie that is relevant to AAN interests or activities. Dr. Harriott has a non-compensated relationship as a Researcher/Receipt of drug with Praxis that is relevant to AAN interests or activities.
David Boas (Boston University)	No disclosure on file
Sava Sakadzic (Massachusetts General Hospital)	No disclosure on file
Cenk Ayata, MD (Massachusetts General Hospital)	Dr. Ayata has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quris. Dr. Ayata has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurelis. The institution of Dr. Ayata has received research support from NIH. The institution of Dr. Ayata has received research support from Takeda. The institution of Dr. Ayata has received research support from Neurelis.
Brian Edlow, MD	Dr. Edlow has received research support from NIH.
David Y. Chung, MD (Massachusetts General Hospital)	The institution of Dr. Chung has received research support from NIH/NINDS. The institution of Dr. Chung has received research support from Brain Aneurysm Foundation. The institution of Dr. Chung has received research support from Angea Biotherapeutics.

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