MSTPublications: June 2024
The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.
Doss DJ, Shless JS, Bick SK, Makhoul GS, Negi AS, Bibro CE, Rashingkar R, Gummadavelli A, Chang C, Gallagher MJ, Naftel RP, Reddy SB, Williams-Roberson S, Morgan VL, Johnson GW, Englot DJ.
Brain. 2024 Jun 14:awae189. doi: 10.1093/brain/awae189. Online ahead of print.
Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient’s connectivity matrix. Each patient’s components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.
A novel mouse home cage lickometer system reveals sex- and housing-based influences on alcohol drinking.
Petersen N, Adank DN, Quan Y, Edwards CM, Taylor A, Winder DG, Doyle MA.
bioRxiv [Preprint]. 2024 May 23:2024.05.22.595186. doi: 10.1101/2024.05.22.595186.
Alcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment. We developed LIQ PARTI (Lick Instance Quantifier with Poly-Animal RFID Tracking Integration), an open-source tool to examine home cage continuous access two-bottle choice drinking behavior in a group-housed setting, investigating the influence of sex and social isolation on ethanol consumption and bout microstructure in C57Bl/6J mice. LIQ PARTI, based on our previously developed single-housed LIQ HD system, accurately tracks drinking behavior using capacitive-based sensors and RFID technology. Group-housed female mice exhibited higher ethanol preference than males, while males displayed a unique undulating pattern of ethanol preference linked to cage changes, suggesting a potential stress-related response. Chronic ethanol intake distinctly altered bout microstructure between male and female mice, highlighting sex and social environmental influences on drinking behavior. Social isolation with the LIQ HD system amplified fluid intake and ethanol preference in both sexes, accompanied by sex- and fluid-dependent changes in bout microstructure. However, these effects largely reversed upon resocialization, indicating the plasticity of these behaviors in response to social context. Utilizing a novel group-housed home cage lickometer device, our findings illustrate the critical interplay of sex and housing conditions in voluntary alcohol drinking behaviors in C57Bl/6J mice, facilitating nuanced insights into the potential contributions to AUD etiology.
Clinical associations with a polygenic predisposition to benign lower white blood cell counts.
Mosley JD, Shelley JP, Dickson AL, Zanussi J, Daniel LL, Zheng NS, Bastarache L, Wei WQ, Shi M, Jarvik GP, Rosenthal EA, Khan A, Sherafati A, Kullo IJ, Walunas TL, Glessner J, Hakonarson H, Cox NJ, Roden DM, Frangakis SG, Vanderwerff B, Stein CM, Van Driest SL, Borinstein SC, Shu XO, Zawistowski M, Chung CP, Kawai VK.
Nat Commun. 2024 Apr 22;15(1):3384. doi: 10.1038/s41467-024-47804-5.
This article was highlighted in VUMC News!
Computer-Aided Design and Biological Evaluation of Diazaspirocyclic D4R Antagonists.
Jones CAH, Brown BP, Schultz DC, Engers J, Kramlinger VM, Meiler J, Lindsley CW.
ACS Chem Neurosci. 2024 Jun 19;15(12):2396-2407. doi: 10.1021/acschemneuro.4c00086. Epub 2024 Jun 7.
Wnt/β-catenin signaling is a therapeutic target in anaplastic thyroid carcinoma.
Diaz D, Bergdorf K, Loberg MA, Phifer CJ, Xu GJ, Sheng Q, Chen SC, Byrant JM, Tigue ML, Hartmann H, Rohde SL, Netterville JL, Baregamian N, Goettel JA, Ye F, Lee E, Weiss VL.
Endocrine. 2024 May 28. doi: 10.1007/s12020-024-03887-0. Online ahead of print.
Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate.
Mack TM, Raddatz MA, Pershad Y, Nachun DC, Taylor KD, Guo X, Shuldiner AR, O’Connell JR, Kenny EE, Loos RJF, Redline S, Cade BE, Psaty BM, Bis JC, Brody JA, Silverman EK, Yun JH, Cho MH, DeMeo DL, Levy D, Johnson AD, Mathias RA, Yanek LR, Heckbert SR, Smith NL, Wiggins KL, Raffield LM, Carson AP, Rotter JI, Rich SS, Manichaikul AW, Gu CC, Chen YI, Lee WJ, Shoemaker MB, Roden DM, Kooperberg C, Auer PL, Desai P, Blackwell TW, Smith AV, Reiner AP, Jaiswal S, Weinstock JS, Bick AG.
Nat Aging. 2024 Jun 4. doi: 10.1038/s43587-024-00647-7. Online ahead of print.
This article was highlighted in the VUMC News here!
Transcriptome-Wide Association Analysis Identifies Candidate Susceptibility Genes for Prostate-Specific Antigen Levels in Men Without Prostate Cancer.
Chen DM, Dong R, Kachuri L, Hoffmann T, Jiang Y, Berndt SI, Shelley JP, Schaffer KR, Machiela MJ, Freedman ND, Huang WY, Li SA, Lilja H, Justice A, Madduri R, Rodriguez A, Van Den Eeden SK, Chanock S, Haiman CA, Conti DV, Klein RJ, Mosley JD, Witte JS, Graff RE.
HGG Adv. 2024 Jun 5:100315. doi: 10.1016/j.xhgg.2024.100315. Online ahead of print.
Attitudes of autistic adults toward genetic testing for autism.
Gallion T, Williams ZJ, Niarchou M, Duncan L, Hooker G, Taylor KA.
J Genet Couns. 2024 May 25. doi: 10.1002/jgc4.1918. Online ahead of print.
Comparison of Outcomes for Abdominoperineal Resection versus Low Anterior Resection for Very-Low Rectal Cancer.
Muldoon RL, Bethurum AJ, Gamboa AC, Zhang K, Ye F, Regenbogen SE, Abdel-Misih S, Ejaz A, Wise PE, Silviera M, Holder-Murray J, Balch GC, Hawkins AT.
J Gastrointest Surg. 2024 Jun 17:S1091-255X(24)00500-6. doi: 10.1016/j.gassur.2024.06.008. Online ahead of print.