Abstract Details

Title Hidden Markov Model Reveals Dynamic Limbic-prefrontal Network States Associated with Depression in Temporal Lobe Epilepsy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S29 - Epilepsy: Basic Science and Mechanisms (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Objective In this study, we investigated whether dynamic patterns of large-scale limbic-prefrontal synchrony using hidden Markov models (HMM) are associated with depression severity and assessed how epileptiform activity modulates these dynamic connectivity patterns.

Background Depression has been linked to altered communication within the limbic and prefrontal networks. Dynamic approaches, such as HMM can capture transient network states and provide insight into how brain connectivity unfolds over time.

Design/Methods We analyzed two-hour continuous iEEG recordings from 12 subjects with depth electrodes implanted in the amygdala, hippocampal head, hippocampal tail, orbitofrontal cortex, and anterior cingulate cortex. Interregional dynamic functional connectivity (dFC) was calculated using the imaginary part of the phase locking value (iPLV) for each 5-second epoch of EEG data for each canonical frequency band. HMM was applied to the dFC to identify recurring network states, with the optimal number of states determined via the Akaike Information Criteria (AIC). Fractional occupancy and mean dwelling time were correlated with depression severity scores. False discovery rate (FDR) correction was applied for multiple comparisons.

Results Among the four inferred states, one state that was characterized by significant involvement of the beta-band iPLV showed a significant association with depression severity. Fractional occupancy (r = -0.70, p(FDR) = 0.04) and mean dwell time (r = -0.69, p(FDR) = 0.05) of this state decreased with higher depression scores. Epileptiform discharges were associated with reduced dwell time and decreased self-transition probability in this state, suggesting that interictal activity disrupts the stability of beta-dominated network configurations.

Conclusions These findings indicate that reduced stability of a beta-dominated network state within the broader limbic-prefrontal cortical networks is linked to greater depression severity. Epileptiform discharges appear to destabilize this state, potentially exacerbating mood dysregulation. HMM-based analysis of iEEG connectivity provides a promising framework for identifying dynamic neural signatures of mood disorders.

Authors/Disclosures
Justin Liao PRESENTER	Mr. Liao has nothing to disclose.
Sebastian Hanna, MD	Mr. Hanna has nothing to disclose.
Victoria Ho, MD, PhD (UCLA Neurology)	The institution of Dr. Ho has received research support from NIH.
Doris Deng, MD (Johns Hopkins University)	Dr. Deng has nothing to disclose.
Kurt Y. Qing, MD, PhD (New York Presbyterian Hospital, Weill Cornell Medical Center)	Dr. Qing has nothing to disclose.
Melanie Lucas, PhD	Dr. Lucas has nothing to disclose.
Sumeet Vadera, MD	Dr. Vadera has nothing to disclose.
David King-Stephens, MD (University of California, Irvine)	Dr. King-Stephens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. King-Stephens has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. King-Stephens has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelis.
Mona Sazgar, MD (University of California, Irvine)	Dr. Sazgar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Sazgar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xenon. Dr. Sazgar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for UCB. Dr. Sazgar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurelis. Dr. Sazgar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai. Dr. Sazgar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Lifesciences. The institution of Dr. Sazgar has received research support from UCB. Dr. Sazgar has received publishing royalties from a publication relating to health care.
Lilit Mnatsakanyan, MD (UC Irvine Medical Center)	Dr. Mnatsakanyan has nothing to disclose.
Diego A. Pizzagalli, PhD	Prof. Pizzagalli has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alkermes. Prof. Pizzagalli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead Pharmaceuticals. Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neumora. Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Boehringer. Prof. Pizzagalli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Circular Genomics. Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Compass Pathway. Prof. Pizzagalli has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Engrail. Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine . Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuroscience Software. Prof. Pizzagalli has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Psychonomic Society. Prof. Pizzagalli has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Psychological Association. Prof. Pizzagalli has stock in Ceretype Neuromedicine. Prof. Pizzagalli has stock in Compass Pathway. Prof. Pizzagalli has stock in Engrail Therapeutics. Prof. Pizzagalli has stock in Neumora Therapeutics. Prof. Pizzagalli has stock in Neuroscience Software.
Beth Lopour	The institution of Dr. Lopour has received research support from NIH. The institution of Dr. Lopour has received research support from Department of Defense. The institution of Dr. Lopour has received research support from John C. Hench Foundation. Dr. Lopour has received personal compensation in the range of $500-$4,999 for serving as a grant reviewer with NIH.
Brian Jung, MD	Dr. Jung has nothing to disclose.

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