Neurosciences Commons^™

Psychiatric Manifestations Of Encephalitis, Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. …

All Three Supersystems-Nervous, Vascular, And Immune-Contribute To The Cortical Infarcts After Subarachnoid Hemorrhage, Jens P Dreier, Alexander Joerk, Hiroki Uchikawa, Viktor Horst, Coline L Lemale, Helena Radbruch, Devin W Mcbride, Peter Vajkoczy, Ulf C Schneider, Ran Xu

Faculty, Staff and Student Publications

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical …

Predictors Of Bi-Directional Transitions From Mild Cognitive Impairment In A Diverse Cohort, Mitzi M. Gonzales, Roman Fernandez, Sarah Kremen, Zaldy S. Tan, Amy E. Werry, Xueqiu Jian, John Hart, Donald Royall, Gladys Maestre, Sara Espinoza

School of Medicine Publications

Trajectories following a diagnosis of mild cognitive impairment (MCI) are varied and may fluctuate over time. Among diverse ethnic and racial groups, social factors, medical comorbidities, and biases in assessment procedures may contribute to greater heterogeneity in the MCI diagnostic category and affect its prognostic significance for dementia. The study goal was to evaluate the frequency and variables associated with MCI transitions among non-Hispanic White (NHW) and Latinx older adults. Multistate Markov models characterized transitions across diagnostic states (cognitively unimpaired (CU), MCI, dementia) over ten years. Variables associated with transitions were assessed using hazard ratios (HR) and 95% confidence intervals …

Defining Neonatal Status Epilepticus: A Scoping Review From The Ilaee Neonatal Task Force, Magda L Nunes, Elissa G Yozawitz, Courtney J Wusthoff, Renée A Shellhaas, Efraín Olivas-Peña, Jo M Wilmshurst, Ronit M Pressler, Chahnez C Triki, Hans Hartmann, Terrie Inder, Geraldine B Boylan, Kette Valente, Solomon L Moshe, Eli M Mizrahi, Nicholas S Abend

Faculty, Staff and Students Publications

Objective: To review the available literature concerning the definition of neonatal status epilepticus (SE) and/or seizure burden.

Methods: The International League Against Epilepsy Neonatal Task Force performed a scoping review of the definitions of neonatal SE. Following a systematic literature review, articles were screened and data were abstracted regarding: (1) article characteristics (author identification, publication year, journal name, digital object identifier, title, objective, and study design); (2) cohort characteristics (sample size, gestational age, seizure etiology); (3) definition of SE and/or seizure burden; and (4) the method used to identify and classify SE, including routine EEG (EEG), continuous EEG monitoring (cEEG), …

Synaptic Alterations In Pyramidal Cells Following Genetic Manipulation Of Neuronal Excitability In Monkey Prefrontal Cortex, Guillermo Gonzalez-Burgos, Takeaki Miyamae, Yosuke Nishihata, Olga L Krimer, Kirsten Wade, Kenneth N Fish, Dominique Arion, Zhao-Lin Cai, Mingshan Xue, William R Stauffer, David A Lewis

Duncan NRI Faculty and Staff Publications

The primate dorsolateral prefrontal cortex (DLPFC) displays unique in vivo activity patterns, but how in vivo activity regulates DLPFC pyramidal neuron (PN) properties remains unclear. We assessed the effects of in vivo Kir2.1 overexpression, a genetic silencing tool, on synapses in monkey DLPFC PNs. We show for the first time that recombinant ion channel expression successfully modifies the excitability of primate cortex neurons, producing effects on synaptic properties apparently different from those in the rodent cortex.

Investigating The Impact Of Sorghum On Tau Protein Phosphorylation And Mitochondrial Dysfunction Modulation In Alzheimer’S Disease: An In Vitro Study, Nasim Rezaee, Eugene Hone, Hamid Sohrabi, Rasheed Abdulraheem, Stuart K. Johnson, Stuart Gunzburg, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with poorly understood pathology. Elevated tau, phospho-tau and mitochondrial dysfunction are significantly correlated with an increased risk of AD and are therefore targets for disease-modifying therapy. In this study, we examined the effects of polyphenolic extracts from six different varieties of sorghum: Shawaya short black-1 (Black), IS1311C (Brown), QL33/QL36 (Red), B923296 (Red), QL12 (White), and QL33 (Red) on the attenuation of beta amyloid-induced phospho-tau levels, total tau levels, and mitochondrial dysfunction in neuronal cells. Method: Tau proteins (231 (pT231), Serine- 199 (pS199), and total tau proteins (T-tau)) were detected and quantified …

Differential Effects Of Stimulation Waveform And Intensity On The Neural Structures Activated By Lumbar Transcutaneous Spinal Cord Stimulation, Harrison T. Finn, Marel Parono, Elizabeth A. Bye, Janet L. Taylor, Simon C. Gandevia, Martin E. Héroux, Jane E. Butler

Research outputs 2022 to 2026

Lumbar transcutaneous spinal cord stimulation (TSS) evokes synchronized muscle responses, termed spinally evoked motor response (sEMR). Whether the structures TSS activates to evoke sEMRs differ when TSS intensity and waveform are varied is unknown. In 15 participants (9 F, 6 M), sEMRs were evoked by TSS over L1–L3 (at sEMR threshold and suprathreshold intensities) with conventional (one 400-ls biphasic pulse) or high-frequency burst (ten 40-ls biphasic pulses at 10 kHz) stimulus waveforms in vastus medialis (VM), tibialis anterior (TA), and medial gastrocnemius (MG) muscles. TSS was paired with transcranial magnetic stimulation (TMS) over the contralateral motor cortex at relative interstimulus …

Comprehensive Assessment Reveals Numerous Clinical And Neurophysiological Differences Between Mecp2-Allelic Disorders, Davut Pehlivan, Chengjun Huang, Holly K Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G Glaze, Charles S Layne, Leonardo Sahelijo, Huda Y Zoghbi, Matthew J Mcginley, Bernhard Suter

Faculty, Staff and Students Publications

OBJECTIVE: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

MATERIALS AND METHODS: We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart.

RESULTS: We identified numerous clinical and physiological …

Exploring Individual Differences In Amygdala-Mediated Memory Modulation, Martina K Hollearn, Joseph R Manns, Lou T Blanpain, Stephan B Hamann, Kelly Bijanki, Robert E Gross, Daniel L Drane, Justin M Campbell, Krista L Wahlstrom, Griffin F Light, Aydin Tasevac, Phillip Demarest, Peter Brunner, Jon T Willie, Cory S Inman

Faculty, Staff and Students Publications

Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without …

Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou

School of Medicine Faculty Publications

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. …

Behavioral And Neuroactivational Correlates Of Psychosocial Stress-Induced Cocaine Seeking In The Rat, Nicole Hinds

Theses and Dissertations

Abstract Nicole Maria Hinds BEHAVIORAL AND NEUROACTIVATIONAL CORRELATES OF PSYCHOSOCIAL STRESS-INDUCED COCAINE SEEKING IN THE RAT 2024 Molecular Cell Biology & Neuroscience Doctor of Philosophy Cocaine Use Disorder is characterized by a high risk for relapse that can persist over extended periods of abstinence. Psychosocial stressors are well-established to promote drug craving and relapse in humans but have rarely been employed in preclinical relapse models. Consequently, the underlying neural circuitry by which these stressors drive cocaine seeking has not yet been thoroughly explored. This project aimed to identify brain regions recruited during psychosocial stress-induced cocaine seeking in rats, with a …

Robust Cluster Prediction Across Data Types Validates Association Of Sex And Therapy Response In Gbm, David L Gibbs, Gino Cioffi, Boris Aguilar, Kristin A Waite, Edward Pan, Jacob Mandel, Yoshie Umemura, Jingqin Luo, Joshua B Rubin, David Pot, Jill Barnholtz-Sloan

Faculty, Staff and Students Publications

Background: Previous studies have described sex-specific patient subtyping in glioblastoma. The cluster labels associated with these "legacy data" were used to train a predictive model capable of recapitulating this clustering in contemporary contexts.

Methods: We used robust ensemble machine learning to train a model using gene microarray data to perform multi-platform predictions including RNA-seq and potentially scRNA-seq.

Results: The engineered feature set was composed of many previously reported genes that are associated with patient prognosis. Interestingly, these well-known genes formed a predictive signature only for female patients, and the application of the predictive signature to male patients produced unexpected results. …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …

The Quic-Sp: A Spanish Language Tool Assessing Unpredictability In Early Life Is Linked To Physical And Mental Health, Sabrina R. Liu, Natasha A. Bailey, Sara Romero-González, Amy Moors, Belinda Campos, Elysia P. Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Accumulating evidence indicates that unpredictable signals in early life represent a unique form of adverse childhood experiences (ACEs) associated with disrupted neurodevelopmental trajectories in children and adolescents. The Questionnaire of Unpredictability in Childhood (QUIC) was developed to assess early life unpredictability, encompassing social, emotional, and physical unpredictability in a child’s environment, and has been validated in three independent cohorts. However, the importance of identifying ACEs in diverse populations, including non-English speaking groups, necessitates translation of the QUIC. The current study aims to translate and validate a Spanish language version of the QUIC (QUIC-SP) and assess its associations with mental and …

The Biological Intersection Between Chemotherapy-Related Cognitive Impairment And Alzheimer Disease, Matthew Torre, Camila A Zanella, Mel B Feany

Duncan NRI Faculty and Staff Publications

Alzheimer disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority. In parallel with the number of patients with AD, the number of cancer survivors is estimated to increase significantly, and up to 80% of cancer patients treated with chemotherapy will develop cognitive deficits, termed chemotherapy-related cognitive impairment. This review discusses biologically plausible pathways underlying both disorders, with the goal of …

Advances In Multiple Sclerosis, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is the most common demyelinating and inflammatory disease of the CNS; it has a global distribution with increasing prevalence [...].

High Cellular Plasticity State Of Medulloblastoma Local Recurrence And Distant Dissemination, Hailong Liu, Jing Zhang, Ziwei Wang, Wei Wang, Dongming Han, Xuan Chen, Yu Su, Jiao Zhang, Craig Daniels, Olivier Saulnier, Zeyuan John Wang, Chunyu Gu, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yahui Zhao, Yifei Jiang, Yu Gao, Zijia Liu, Mingxu Ma, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yanfeng Shi, Tao Yang, Wenxing Li, Xueling Qi, Zejun Duan, Junping Zhang, Mingshan Zhang, Chunjiang Yu, Wei Jin, Xinguang Yu, Yu Tian, Shuaicheng Li, Chunde Li, Michael D Taylor, Jiankang Li, Yong-Qiang Liu, Xiaoguang Qiu, Tao Jiang

Faculty, Staff and Students Publications

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 …

Evaluating Sympton Clusters In First-Time Ischemic Stroke Survivors Who Discharge From The Hospital To Home, Paula De La Pena

Dissertations

The purpose of this study was to examine symptoms and relationships between those symptoms in first-time ischemic stroke survivors who discharge home after their initial stroke. Current measurement of recovery after stroke places emphasis on the physical aspects of recovery when current literature suggests that other, more subtle symptoms may be equally contributory to recovery. This descriptive, exploratory research study was conducted via a secondary analysis of both structured and unstructured data in a study cohort of 115 first-time ischemic stroke survivors from a tertiary academic medical center in the Midwest. Unstructured clinical notes were analyzed for the presence of …