Neurosciences Commons^™

Generation Of Five Induced Pluripotent Stem Cell Lines From Patients With Mecp2 Duplication Syndrome, Danielle Mendonca, Gerarda Cappuccio, Jennifer Sheppard, Magdalena Delacruz, Jesse Bengtsson, Claudia M B Carvalho, Aleksandar Bajic, Hyekyung Park, Jean J Kim, Paymaan Jafar-Nejad, Christine Coquery, Davut Pehlivan, Bernhard Suter, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.

Novel Hemizygous Single-Nucleotide Duplication In Rpgr In A Patient With Retinal Dystrophy And Sensorineural Hearing Loss, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Nichole Owen, Richard A Lewis, Lisa Saba, Texome Project, Michael F Wangler, Sandesh Nagamani

Duncan NRI Faculty and Staff Publications

Background: The RPGR gene has been associated with X-linked cone-rod dystrophy. This report describes a variant in RPGR detected with exome sequencing (ES). Genes like RPGR have not always been included in panel-based testing and thus genome-wide tests such as ES may be required for accurate diagnosis.

Methods: The Texome Project is studying the impact of ES in medically underserved patients who are in need of genomic testing to guide diagnosis and medical management. The hypothesis is that ES could uncover diagnoses not made by standard medical care.

Results: A 58-year-old male presented with retinitis pigmentosa, sensorineural hearing loss, and …

Matr3 Pathogenic Variants Differentially Impair Its Cryptic Splicing Repression Function, Mashiat Khan, Xiao Xiao Lily Chen, Michelle Dias, Jhune Rizsan Santos, Sukhleen Kour, Justin You, Rebekah Van Bruggen, Mohieldin M M Youssef, Ying-Wooi Wan, Zhandong Liu, Jill A Rosenfeld, Qiumin Tan, Udai Bhan Pandey, Hari Krishna Yalamanchili, Jeehye Park

Duncan NRI Faculty and Staff Publications

Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research …

Generation Of A Dcx-Creert2 Knock-In Mouse For Genetic Manipulation Of Newborn Neurons, Gabriella A Perez, Kyung-Won Park, Denise Lanza, Jenna Cicardo, M Danish Uddin, Joanna L Jankowsky

Faculty, Staff and Students Publications

A wide variety of CreERT2 driver lines are available for genetic manipulation of adult-born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult-born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreERT2 driver line targeted to the endogenous mouse …

The Importance Of Considering Competing Risks In Recurrence Analysis Of Intracranial Meningioma, Christian Mirian, Lasse Rehné Jensen, Tareq A Juratli, Andrea Daniela Maier, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Fuyou Guo, Pedro Góes, Manoel Antonio De Paiva Neto, Aria Jamshidi, Ricardo Komotar, Michael Ivan, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Anders Broechner, Mathias Jacobsen Bach, Ian Law, David Scheie, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.

METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage …

Deepvelo: Deep Learning Extends Rna Velocity To Multi-Lineage Systems With Cell-Specific Kinetics, Haotian Cui, Hassaan Maan, Maria C Vladoiu, Jiao Zhang, Michael D Taylor, Bo Wang

Faculty, Staff and Students Publications

Existing RNA velocity estimation methods strongly rely on predefined dynamics and cell-agnostic constant transcriptional kinetic rates, assumptions often violated in complex and heterogeneous single-cell RNA sequencing (scRNA-seq) data. Using a graph convolution network, DeepVelo overcomes these limitations by generalizing RNA velocity to cell populations containing time-dependent kinetics and multiple lineages. DeepVelo infers time-varying cellular rates of transcription, splicing, and degradation, recovers each cell's stage in the differentiation process, and detects functionally relevant driver genes regulating these processes. Application to various developmental and pathogenic processes demonstrates DeepVelo's capacity to study complex differentiation and lineage decision events in heterogeneous scRNA-seq data.

Comparative Transcriptomic Analysis Of Cerebellar Astrocytes Across Developmental Stages And Brain Regions, Wookbong Kwon, Dong-Joo Choi, Kwanha Yu, Michael R Williamson, Sanjana Murali, Yeunjung Ko, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expressed genes (DEGs) published for the cortex, hippocampus, and olfactory bulb revealed cerebellar-specific gene signature across these …

Single-Cell Multi-Omic Analysis Of The Vestibular Schwannoma Ecosystem Uncovers A Nerve Injury-Like State, Thomas F Barrett, Bhuvic Patel, Saad M Khan, Riley D Z Mullins, Aldrin K Y Yim, Sangami Pugazenthi, Tatenda Mahlokozera, Gregory J Zipfel, Jacques A Herzog, Michael R Chicoine, Cameron C Wick, Nedim Durakovic, Joshua W Osbun, Matthew Shew, Alex D Sweeney, Akash J Patel, Craig A Buchman, Allegra A Petti, Sidharth V Puram, Albert H Kim

Faculty, Staff and Students Publications

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, …

Multi-Site Benchmark Classification Of Major Depressive Disorder Using Machine Learning On Cortical And Subcortical Measures, Vladimir Belov, Tracy Erwin-Grabner, Moji Aghajani, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Robin Bülow, Christopher R K Ching, Colm G Connolly, Kathryn Cullen, Christopher G Davey, Danai Dima, Annemiek Dols, Jennifer W Evans, Cynthia H Y Fu, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke Groenewold, J Paul Hamilton, Ben J Harrison, Tiffany C Ho, Benson Mwangi, Natalia Jaworska, Neda Jahanshad, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Elisa Melloni, Bryon A Mueller, Amar Ojha, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Elena Pozzi, Liesbeth Reneman, Matthew D Sacchet, Philipp G Sämann, Anouk Schrantee, Kang Sim, Jair C Soares, Dan J Stein, Sophia I Thomopoulos, Aslihan Uyar-Demir, Nic J A Van Der Wee, Steven J A Van Der Werff, Henry Völzke, Sarah Whittle, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Roberto Goya-Maldonado, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy …

Tfeb Drives Mtorc1 Hyperactivation And Kidney Disease In Tuberous Sclerosis Complex, Nicola Alesi, Damir Khabibullin, Dean M Rosenthal, Elie W Akl, Pieter M Cory, Michel Alchoueiry, Samer Salem, Melissa Daou, William F Gibbons, Jennifer A Chen, Long Zhang, Harilaos Filippakis, Laura Graciotti, Caterina Miceli, Jlenia Monfregola, Claudia Vilardo, Manrico Morroni, Chiara Di Malta, Gennaro Napolitano, Andrea Ballabio, Elizabeth P Henske

Duncan NRI Faculty and Staff Publications

Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient …

The Immune System And Metabolic Products In Epilepsy And Glioma-Associated Epilepsy: Emerging Therapeutic Directions, Shashwat Tripathi, Cody L Nathan, Matthew C Tate, Craig M Horbinski, Jessica W Templer, Joshua M Rosenow, Timothy L Sita, Charles D James, Benjamin Deneen, Stephen D Miller, Amy B Heimberger

Faculty, Staff and Students Publications

Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. …

Developmental Basis Of Shh Medulloblastoma Heterogeneity, Maxwell P Gold, Winnie Ong, Andrew M Masteller, David R Ghasemi, Julie Anne Galindo, Noel R Park, Nhan C Huynh, Aneesh Donde, Veronika Pister, Raul A Saurez, Maria C Vladoiu, Grace H Hwang, Tanja Eisemann, Laura K Donovan, Adam D Walker, Joseph Benetatos, Christelle Dufour, Livia Garzia, Rosalind A Segal, Robert J Wechsler-Reya, Jill P Mesirov, Andrey Korshunov, Kristian W Pajtler, Scott L Pomeroy, Olivier Ayrault, Shawn M Davidson, Jennifer A Cotter, Michael D Taylor, Ernest Fraenkel

Faculty, Staff and Students Publications

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different …

Development Of A Rabbit Human Glioblastoma Model For Testing Of Endovascular Selective Intra-Arterial Infusion (Esia) Of Novel Stem Cell-Based Therapeutics, Peter Kan, Visish M Srinivasan, Joy Gumin, Roberto Garcia, Stephen R Chen, Jeremiah N Johnson, Dalis E Collins, Melissa M Chen, Daniel Ledbetter, Jason Huse, Zean Aaron Evan Luna, Ariadna Robledo, Viren Vasandani, Abhijit Rao, Sanjay K Singh, Elizabeth J Shpall, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang

Faculty, Staff and Student Publications

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24).

METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on …

A Retrospective Genomic Landscape Of 661 Young Adult Glioblastomas Diagnosed Using 2016 Who Guidelines For Central Nervous System Tumors, James F Haberberger, Worthy Pegram, Nicholas Britt, Kelsie Schiavone, Eric Severson, Radwa Sharaf, Lee A Albacker, Erik Williams, Mirna Lechpammer, Amanda Hemmerich, Douglas Lin, Richard S P Huang, Matthew Hiemenz, Julia Elvin, Ryon Graf, Glenn Lesser, David Kram, Roy Strowd, Wenya Linda Bi, Lori A Ramkissoon, Michael B Cohen, Prasanth Reddy, James Creeden, Jeffrey S Ross, Brian M Alexander, Shakti H Ramkissoon

Faculty, Staff and Student Publications

The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Doxycycline For Transgene Control Disrupts Gut Microbiome Diversity Without Compromising Acute Neuroinflammatory Response, Emily J Koller, Caleb A Wood, Zoe Lai, Ella Borgenheimer, Kristi L Hoffman, Joanna L Jankowsky

Faculty, Staff and Students Publications

The tetracycline transactivator (tTA) system provides controllable transgene expression through oral administration of the broad-spectrum antibiotic doxycycline. Antibiotic treatment for transgene control in mouse models of disease might have undesirable systemic effects resulting from changes in the gut microbiome. Here we assessed the impact of doxycycline on gut microbiome diversity in a tTA-controlled model of Alzheimer's disease and then examined neuroimmune effects of these microbiome alterations following acute LPS challenge. We show that doxycycline decreased microbiome diversity in both transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite the change in microbiome composition, doxycycline treatment …

Gene Regulation And Speciation In A Migratory Divide Between Songbirds, Matthew I M Louder, Hannah Justen, Abigail A Kimmitt, Koedi S Lawley, Leslie M Turner, J David Dickman, Kira E Delmore

Faculty, Staff and Students Publications

Behavioral variation abounds in nature. This variation is important for adaptation and speciation, but its molecular basis remains elusive. Here, we use a hybrid zone between two subspecies of songbirds that differ in migration - an ecologically important and taxonomically widespread behavior---to gain insight into this topic. We measure gene expression in five brain regions. Differential expression between migratory states was dominated by circadian genes in all brain regions. The remaining patterns were largely brain-region specific. For example, expression differences between the subspecies that interact with migratory state likely help maintain reproductive isolation in this system and were documented in …

Mechanosensory Encoding In Ex Vivo Muscle–Nerve Preparations, Stephen N. Housley, Evelyn A. Gardolinski, Paul Nardelli, J'Ana Reed, Mark M. Rich, Timothy C. Cope

Neuroscience, Cell Biology & Physiology Faculty Publications

Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs). Specifically, we aimed to assess how well the ex vivo preparation represents in vivo firing behaviours of the three major LTMR subtypes of muscle primary sensory afferents, namely type Ia and II muscle spindle (MS) afferents and type Ib tendon organ afferents. Using published procedures for ex vivo study of LTMRs in mouse hindlimb muscles, we replicated earlier reports on afferent firing in response to conventional stretch paradigms applied to non-contracting, that is passive, muscle. Relative to in vivo …

Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: In the United States (U.S.), falls are the leading cause of injury among adults 65 and over, resulting in 36 million falls yearly (Moreland et al., 2020). According to the Centers for Disease Control and Prevention (CDC, 2023), one in four older adults experiences a fall each year. Falls are the world's second most prominent cause of accidental deaths (World Health Organization [WHO], 2021). Falls are the leading cause of both fatal and non-fatal injuries among older adults (Moreland et al., 2020).

Methods: A quality improvement project that included a fall bundle was implemented in a primary clinic. A …

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …

Addressing Healthcare Disparities Faced By Aging Down Syndrome Populations, Rhea Mistry

Pitzer Senior Theses

Down syndrome (DS) is a chromosomal genetic condition that impacts the development of the body and brain. The life expectancy of individuals with DS has drastically improved over the decades, increasing from 9 years in 1929 to 25 years in 1983 and further reaching 60 years by 2002. Individuals with DS face a variety of prominent co-occurring health conditions that are subject to change over time, including cognitive, visual, and hearing impairments, sleep apnea, cardiovascular defects, Down syndrome regression disorder, and dementia. Despite this increase in life span, DS is still most familiar to pediatric care providers, resulting in healthcare …

Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang

Faculty, Staff and Student Publications

OBJECTIVE: Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients.

METHODS: We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS …

Management Of Anhedonia After Epilepsy Surgery, Gerardo Maria De Araujo Filho, Antonio L Teixeira

Faculty, Staff and Student Publications

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling …

Multimodal Prediction Of Obsessive-Compulsive Disorder And Comorbid Depression Severity And Energy Delivered By Deep Brain Electrodes, Saurabh Hinduja, Ali Darzi, Itir Onal Ertugrul, Nicole Provenza, Ron Gadot, Eric A Storch, Sameer A Sheth, Wayne K Goodman, Jeffrey F Cohn

Faculty, Staff and Students Publications

To develop reliable, valid, and efficient measures of obsessive-compulsive disorder (OCD) severity, comorbid depression severity, and total electrical energy delivered (TEED) by deep brain stimulation (DBS), we trained and compared random forests regression models in a clinical trial of participants receiving DBS for refractory OCD. Six participants were recorded during open-ended interviews at pre- and post-surgery baselines and then at 3-month intervals following DBS activation. Ground-truth severity was assessed by clinical interview and self-report. Visual and auditory modalities included facial action units, head and facial landmarks, speech behavior and content, and voice acoustics. Mixed-effects random forest regression with Shapley feature …

Scan-Less Microscopy Based On Acousto-Optic Encoded Illumination, Andrea Marchese, Pietro Ricci, Peter Saggau, Martí Duocastella

Faculty, Staff and Students Publications

Several optical microscopy methods are now available for characterizing scientific and industrial processes at sub-micron resolution. However, they are often ill-suited for imaging rapid events. Limited by the trade-off between camera frame-rate and sensitivity, or the need for mechanical scanning, current microscopes are optimized for imaging at hundreds of frames-per-second (fps), well-below what is needed in processes such as neuronal signaling or moving parts in manufacturing lines. Here, we present a scan-less technology that allows sub-micrometric imaging at thousands of fps. It is based on combining a single-pixel camera with parallelized encoded illumination. We use two acousto-optic deflectors (AODs) placed …

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Cristin G Welle, Kevin B Wilkins, Helen M Bronte-Stewart, Valerie Voon, Takashi Morishita, Yuki Sakai, Amanda R Merner, Gabriel Lázaro-Muñoz, Theresa Williamson, Andreas Horn, Ro'ee Gilron, Jonathan O'Keeffe, Aryn H Gittis, Wolf-Julian Neumann, Simon Little, Nicole R Provenza, Sameer A Sheth, Alfonso Fasano, Abbey B Holt-Becker, Robert S Raike, Lisa Moore, Yagna J Pathak, David Greene, Sara Marceglia, Lothar Krinke, Huiling Tan, Hagai Bergman, Monika Pötter-Nerger, Bomin Sun, Laura Y Cabrera, Cameron C Mcintyre, Noam Harel, Helen S Mayberg, Andrew D Krystal, Nader Pouratian, Philip A Starr, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …

Co-Occurrence Of Autism Spectrum Disorder And Attention-Deficit/Hyperactivity Disorder With Idiopathic Hypersomnia: Data From The Hypersomnia Foundation Registry, Sophie Sevan Mikkelsen

Honors Undergraduate Theses

In recent years, hypersomnia patients and researchers alike have increasingly discussed the possibility of heightened comorbidities, or co-occurrences, of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) with the central disorders of hypersomnolence: idiopathic hypersomnia (IH) and narcolepsy (N). While a few scarce studies have investigated a link between ADHD and N, there has been no research on the co-occurrence of these conditions with IH. This study, using data from the Hypersomnia Foundation’s CoRDS Patient Registry, is the first to identify self-reported rates of ASD and ADHD diagnoses by people with idiopathic hypersomnia. Four chi-square tests were conducted to determine …

Editorial: Symmetry As A Guiding Principle In Artificial And Brain Neural Networks, Volume Ii, Fabio Anselmi, Ankit B Patel

Faculty, Staff and Students Publications

No abstract provided.

Dimensionality Reduction And Nearest Neighbors For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Austin Castelo, Mais Al Taie, Mohamed Eltaher, Joshua P Yung, Tucker J Netherton, Tiffany L Calderone, Jessica I Sanchez, Darrel W Cleere, Ahmed Elsaiey, Nakul Gupta, David Victor, Laura Beretta, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

Clinically deployed deep learning-based segmentation models are known to fail on data outside of their training distributions. While clinicians review the segmentations, these models tend to perform well in most instances, which could exacerbate automation bias. Therefore, detecting out-of-distribution images at inference is critical to warn the clinicians that the model likely failed. This work applied the Mahalanobis distance (MD) post hoc to the bottleneck features of four Swin UNETR and nnU-net models that segmented the liver on T1-weighted magnetic resonance imaging and computed tomography. By reducing the dimensions of the bottleneck features with either principal component analysis or uniform …

Functional Genomics And Small Molecules In Mitochondrial Neurodevelopmental Disorders, Daniel G Calame, Lisa T Emrick

Faculty, Staff and Students Publications

Mitochondria are critical for brain development and homeostasis. Therefore, pathogenic variation in the mitochondrial or nuclear genome which disrupts mitochondrial function frequently results in developmental disorders and neurodegeneration at the organismal level. Large-scale application of genome-wide technologies to individuals with mitochondrial diseases has dramatically accelerated identification of mitochondrial disease-gene associations in humans. Multi-omic and high-throughput studies involving transcriptomics, proteomics, metabolomics, and saturation genome editing are providing deeper insights into the functional consequence of mitochondrial genomic variation. Integration of deep phenotypic and genomic data through allelic series continues to uncover novel mitochondrial functions and permit mitochondrial gene function dissection on an …