MSTPublications: July 2024
A transcriptomic atlas of the human brain reveals genetically determined aspects of neuropsychiatric health.
Bledsoe X, Gamazon ER.
Am J Hum Genet. 2024 Jun 19:S0002-9297(24)00208-8. doi: 10.1016/j.ajhg.2024.06.002. Online ahead of print.
Regulation of gene expression is a vital component of neurological homeostasis. Cataloging the consequences of endogenous gene expression on the physical structure and connectivity of the brain offers a means of unifying trait-associated genetic variation with trait-associated neurological features. We perform tissue-specific transcriptome-wide association studies (TWASs) on over 3,400 neuroimaging phenotypes in the UK Biobank (N = 33,224) using our joint-tissue imputation (JTI)-TWAS method. We identify highly significant associations between predicted expression for 7,192 genes and a wide variety of measures of the brain derived from magnetic resonance imaging (MRI). Our approach generates reproducible results in internal and external replication datasets. Genetically determined expression alone is sufficient for high-fidelity reconstruction of brain structure and organization. We demonstrate complementary benefits of cross-tissue and single-tissue analyses toward an integrated neurobiology and provide evidence that gene expression outside the central nervous system provides unique insights into brain health. As an application, we provide evidence suggesting that the genetically regulated expression of schizophrenia risk genes causally affects over 73% of neurological phenotypes that are altered in individuals with schizophrenia (as identified by neuroimaging studies). Imaging features associated with neuropsychiatric traits can provide valuable insights into underlying pathophysiology. By linking neuroimaging-derived phenotypes with expression levels of specific genes, this resource represents a powerful gene prioritization schema that can improve our understanding of brain function, development, and disease. The use of multiple different cortical and subcortical atlases in the resource facilitates direct integration of these data with findings from a diverse range of clinical neuroimaging studies.
Network signatures define consciousness state during focal seizures.
Doss DJ, Johnson GW, Makhoul GS, Rashingkar RV, Shless JS, Bibro CE, Paulo DL, Gummadavelli A, Ball TJ, Reddy SB, Naftel RP, Haas KF, Dawant BM, Constantinidis C, Williams Roberson S, Bick SK, Morgan VL, Englot DJ.
Epilepsia. 2024 Jul 26. doi: 10.1111/epi.18074. Online ahead of print.
Objective: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal-to-bilateral tonic-clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally.
Methods: We obtained electrographic data from 74 patients with stereoelectroencephalography (SEEG). Sliding window band power, functional connectivity, and segregation were computed on preictal, ictal, and postictal data. Five-minute epochs of wake, rapid eye movement sleep, and deep sleep were also extracted. Connectivity of subcortical arousal structures was analyzed in a cohort of patients with both SEEG and functional magnetic resonance imaging (fMRI). Given that custom neuromodulation of seizures is predicated on detection of seizure type, a convolutional neural network was used to classify seizure types.
Results: We found that in the frontoparietal association cortex, an area associated with consciousness, both consciousness-impairing seizures (FIASs and FBTCSs) and deep sleep had increases in slow wave delta (1-4 Hz) band power. However, when network measures were employed, we found that only FIASs and deep sleep exhibited an increase in delta segregation and a decrease in gamma segregation. Furthermore, we found that only patients with FIASs had reduced subcortical-to-neocortical functional connectivity with fMRI versus controls. Finally, our deep learning network demonstrated an area under the curve of .75 for detecting consciousness-impairing seizures.
Significance: This study provides novel insights into ictal network measures in FASs, FIASs, and FBTCSs. Importantly, although both FIASs and FBTCSs result in loss of consciousness, our results suggest that ictal network changes in FIASs uniquely resemble those that occur during deep sleep. Our results may inform novel neuromodulation strategies for preservation of consciousness in epilepsy.
Obesity is associated with muscle atrophy in rotator cuff tear.
Herzberg SD, Zhao Z, Freeman TH, Prakash R, Baumgarten KM, Bishop JY, Carey JL, Jones GL, McCarty EC, Spencer EE, Vidal AF, Jain NB, Giri A, Kuhn JE, Khazzam MS, Matzkin EG, Brophy RH, Dunn WR, Ma CB, Marx RG, Poddar SK, Smith MV, Wolf BR, Wright RW.
BMJ Open Sport Exerc Med. 2024 Jun 28;10(2):e001993. doi: 10.1136/bmjsem-2024-001993. eCollection 2024.
Objective: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears.
Methods: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis.
Results: A total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2 increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01-1.81) increased odds among individuals with full-thickness tear.
Conclusions: Higher BMI was associated with significantly higher odds of muscle atrophy in patients with rotator cuff tears. More study is needed to understand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients.
Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system./
Sorets AG, Schwensen KR, Francini N, Kjar A, Abdulrahman AM, Shostak A, Katdare KA, Schoch KM, Cowell RP, Park JC, Ligocki AP, Ford WT, Ventura-Antunes L, Hoogenboezem EN, Prusky A, Castleberry M, Michell DL, Miller TM, Vickers KC, Schrag MS, Duvall CL, Lippmann ES.
bioRxiv [Preprint]. 2024 Jun 10:2024.06.09.598079. doi: 10.1101/2024.06.09.598079.
Optimizing cystoscopy and TURBT: enhanced imaging and artificial intelligence.
Shkolyar E, Zhou SR, Carlson CJ, Chang S, Laurie MA, Xing L, Bowden AK, Liao JC.
Nat Rev Urol. 2024 Jul 9. doi: 10.1038/s41585-024-00904-9. Online ahead of print.
Diversity of Research Participant Gender, Race, and Ethnicity in Communication Sciences and Disorders: A Systematic Review and Quantitative Synthesis of American Speech-Language-Hearing Association Publications in 2020.
Millager RA, Feldman JI, Williams ZJ, Shibata K, Martinez-Torres KA, Bryan KM, Pruett DG, Mitchell JT, Markfeld JE, Merritt B, Daniels DE, Jones RM, Woynaroski T.
Perspect ASHA Spec Interest Groups. 2024 Jun;9(3):836-852. doi: 10.1044/2024_PERSP-23-00204. Epub 2024 May 7.
Unveiling Cellular Identities and Gene Expression Pathways in Overlapping Myocarditis and Myositis.
Fankhauser RG, Johnson DB, Moslehi JJ, Balko JM.
Cancer Immunol Res. 2024 Jul 5:OF1-OF2. doi: 10.1158/2326-6066.CIR-24-0506. Online ahead of print.