Neurosciences Commons^™

Multiple Gene Variants Linked To Alzheimer's-Type Clinical Dementia Via Gwas Are Also Associated With Non-Alzheimer's Neuropathologic Entities, Yuriko Katsumata, Lincoln M. P. Shade, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Walter A. Kukull, David W. Fardo, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The classic pathologic hallmarks of Alzheimer’s disease (AD) are amyloid plaques and neurofibrillary tangles (AD neuropathologic changes, or ADNC). However, brains from individuals clinically diagnosed with “AD-type” (amnestic) dementia usually harbor heterogeneous neuropathologies in addition to, or other than, ADNC. We hypothesized that some AD-type dementia associated genetic single nucleotide variants (SNVs) identified from large genomewide association studies (GWAS) were associated with non-ADNC neuropathologies. To test this hypothesis, we analyzed data from multiple studies with available genotype and neuropathologic phenotype information. Clinical AD/dementia risk alleles of interest were derived from the very large GWAS by Bellenguez et al. (2022) who …

All The Brain's A Stage For Serotonin: The Forgotten Story Of Serotonin Diffusion Across Cell Membranes, Paul W. Andrews, Catherine Bosyj, Luke Brenton, Laura Green, Paul J. Gasser, Christopher A. Lowry, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite …

Representational Coding Of Overt And Covert Orienting Of Visuospatial Attention In The Frontoparietal Network, Tingting Wu, Melissa-Ann Mackie, Chao Chen, Jin Fan

Publications and Research

Orienting of visuospatial attention refers to reallocation of attentional focus from one target or location to another and can occur either with (overt) or without (covert) eye movement. Although it has been demonstrated that both types of orienting commonly involve frontal and parietal brain regions as the frontoparietal network (FPN), the underlying representational coding of these two types of orienting remains unclear. In this functional magnetic resonance imaging study, participants performed a task that elicited overt and covert orienting to endogenously or exogenously cued targets with eye-tracking to monitor eye movement. Although the FPN was commonly activated for both overt …

Clinical Significance And Potential Role Of Trimethylamine N-Oxide In Neurological And Neuropsychiatric Disorders, Sowjanya Mudimela, Narahari Koppa Vishwanath, Anilkumar Pillai, Rodrigo Morales, Sean P Marrelli, Tatiana Barichello, Vijayasree V Giridharan

Faculty, Staff and Student Publications

Research in the last three decades has attracted the attention of many scientists and industrialists on the gut microbiome and its metabolites. Among many of these metabolites, trimethylamine oxide. Dietary choline, phosphatidylcholine, carnitine, and betaine produces TMAO that with other gut metabolites such as TMA (trimethylamine), and short-chain fatty acids (SCFA) enter the circulation. Finally they reach the brain through the blood-brain barrier (BBB) where they are involved in several physiological functions such as brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age resulting in dysbiosis. Several studies have confirmed that altered TMAO levels …

Cerebellar Coordination Of Neuronal And Behavioral Rhythms, Brittany Correia Chapman

Theses and Dissertations (ETD)

Long known for its role in motor control, it is increasingly clear that the cerebellum is also involved in numerous cognitive and affective behaviors. Though the neuronal mechanism for the role of the cerebellum in cognition is still unclear, there is a consensus that it involves cerebellar interactions with the cerebral cortex. Recent studies suggest that the cerebellum monitors, and possibly coordinates, the precise phase alignment or coherence of neuronal oscillations in cerebral cortical areas. Here, we asked how loss of cerebellar function affects respiratory rhythms and the interactions of local field potential (LFP) oscillations between the lobulus simplex (LS) …

Olfactory Processing In The Piriform Cortex Of Awake, Freely Moving Mice, Ian F. Chapman

Theses and Dissertations (ETD)

The piriform cortex (PC) has long been established as the primary cortical recipient of olfactory information in the mammalian brain. In rodents, information extracted from recordings of PC neurons can accurately decode the identity of odors, leading to delineation of PC as the primary cortical region involved in the formation of odor perception. Unfortunately, due to technical limitations, many of the prior studies establishing these coding principles were performed without the ability to track the responses of the same cells over time. Additionally, recordings have often relied on head-fixation to minimize diffusion of odor stimuli, limiting movement range and natural …

Assessing Naming Errors Using An Automated Machine Learning Approach, Tatiana T Schnur, Chia-Ming Lei

Faculty, Staff and Student Publications

OBJECTIVE: After left hemisphere stroke, 20%-50% of people experience language deficits, including difficulties in naming. Naming errors that are semantically related to the intended target (e.g., producing "violin" for picture HARP) indicate a potential impairment in accessing knowledge of word forms and their meanings. Understanding the cause of naming impairments is crucial to better modeling of language production as well as for tailoring individualized rehabilitation. However, evaluation of naming errors is typically by subjective and laborious dichotomous classification. As a result, these evaluations do not capture the degree of semantic similarity and are susceptible to lower interrater reliability because of …

Oxytocin Signaling Is Necessary For Synaptic Maturation Of Adult-Born Neurons, Brandon T Pekarek, Mikhail Kochukov, Brittney Lozzi, Timothy Wu, Patrick J Hunt, Burak Tepe, Elizabeth Hanson Moss, Evelyne K Tantry, Jessica L Swanson, Sean W Dooling, Mayuri Patel, Benjamin D W Belfort, Juan M Romero, Suyang Bao, Matthew C Hill, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial …

Distinct Organization Of Two Cortico-Cortical Feedback Pathways, Shan Shen, Xiaolong Jiang, Federico Scala, Jiakun Fu, Paul Fahey, Dmitry Kobak, Zhenghuan Tan, Na Zhou, Jacob Reimer, Fabian Sinz, Andreas S Tolias

Duncan NRI Faculty and Staff Publications

Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase–followed by a prolonged decrease–in pyramidal …

Cluster Analysis Of Short Sensory Profile Data Reveals Sensory-Based Subgroups In Autism Spectrum Disorder, Ariel M Lyons-Warren, Michael F Wangler, Ying-Wooi Wan

Duncan NRI Faculty and Staff Publications

Autism spectrum disorder is a common, heterogeneous neurodevelopmental disorder lacking targeted treatments. Additional features include restricted, repetitive patterns of behaviors and differences in sensory processing. We hypothesized that detailed sensory features including modality specific hyper- and hypo-sensitivity could be used to identify clinically recognizable subgroups with unique underlying gene variants. Participants included 378 individuals with a clinical diagnosis of autism spectrum disorder who contributed Short Sensory Profile data assessing the frequency of sensory behaviors and whole genome sequencing results to the Autism Speaks’ MSSNG database. Sensory phenotypes in this cohort were not randomly distributed with 10 patterns describing 43% (162/378) …

Transcriptional Profiles In Olfactory Pathway-Associated Brain Regions Of African Green Monkeys: Associations With Age And Alzheimer’S Disease Neuropathology, Jacob D Negrey, Dorothy L Dobbins, Timothy D Howard, Karin E Borgmann-Winter, C G Hahn, Sergey Kalinin, Douglas L Feinstein, Suzanne Craft, Carol A Shively, Thomas C Register

Department of Neuroscience Faculty Papers

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, Chlorocebus aethiops sabaeus), a well-described model of early AD-like neuropathology.

Methods: Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (Aβ) plaque load in …

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …

Anterior Connectivity Critical For Recovery Of Connected Speech After Stroke, Junhua Ding, Tatiana T Schnur

Faculty, Staff and Student Publications

Connected speech recovers to different degrees across people after left hemisphere stroke, but white matter predictors of differential recovery from the acute stage of stroke are unknown. We assessed changes in lexical-syntactic aspects of connected speech in a longitudinal analysis of 40 individuals (18 females) from the acute stage of left hemisphere stroke (within an average of 4 days post-stroke) to subacute (within 2 months) and chronic stages (early: 6 months, late: 1 year) while measuring the extent of acute lesions on white matter tracts to identify tracts predictive of recovery. We found that acute damage to the frontal aslant …

Sugammadex To Facilitate Neurologic Assessment In Severely Brain-Injured Patients: A Retrospective Analysis And Practical Guidance., Sara J Hyland, Punit A Pandya, Cameron J Mei, David C Yehsakul

Neuroscience Articles

Background Widely used in anesthetic management, sugammadex is increasingly employed in the reversal of neuromuscular blocking agents (NMBAs) in the emergency department and critical care arena, where little evaluative data currently exists. This study explored the utility and safety of using sugammadex to facilitate neurologic assessments in critically ill, NMBA-exposed patients. Methods We pursued a retrospective case series and single-arm cohort analysis of all brain-injured patients receiving sugammadex to facilitate neurologic evaluation during one year at a high-volume Level 1 trauma center. The primary outcome was the qualitative impact of sugammadex administration on neurosurgeon decision-making. Secondary outcomes included the change …

Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or …

Does Integrated Information Theory Make Testable Predictions About The Role Of Silent Neurons In Consciousness?, Gary Bartlett

All Faculty Scholarship for the College of Arts and Humanities

Tononi et al. claim that their integrated information theory of consciousness makes testable predictions. This article discusses two of the more startling predictions, which follow from the theory’s claim that conscious experiences are generated by inactive as well as active neurons. The first prediction is that a subject’s conscious experience at a time can be affected by the disabling of neurons that were already inactive at that time. The second is that even if a subject’s entire brain is “silent,” meaning that all of its neurons are inactive (but not disabled), the subject can still have a conscious experience. …

Chronic Stress May Disrupt Covariant Fluctuations Of Vitamin D And Cortisol Plasma Levels And Placentome Formation In Pregnant Sheep During The Last Trimester: A Methodological Approach And Preliminary Report, Colin Wakefield

Tower Health Research Day

No abstract provided.

Occupational Therapists And Physiotherapists Weighing Up The Dignity Of Risk For People Living With A Brain Injury: Grounded Theory, Mandy Stanley, Gisela Van Kessel, Carolyn M. Murray, Deborah Forsythe, Shylie Mackintosh

Research outputs 2014 to 2021

Purpose:

Following a brain injury survivors may have physical, or cognitive changes or behaviours which bring safety risks into play when engaging in activities. Therapists experience tensions in enabling the dignity of participation in the context of managing risk.

Materials and methods:

Ten occupational therapists and seven physiotherapists participated in a grounded theory study utilising semi-structured in-depth interviews to explore the tensions between dignity and management of safety risks. Data were analysed using constant comparative method and a process of moving from open coding to categories to theory development.

Results:

The process of weighing up was central to the therapists’ …

Brain Age Predicts Long-Term Recovery In Post-Stroke Aphasia, Sigfus Kristinsson, Natalie Busby, Christopher Rorden, Roger Newman-Norlund, Dirk B. Den Ouden, Sigridur Magnusdottir, Haukur Hjaltason, Helga Thors, Argye E. Hillis, Olafur Kjartansson, Leonardo Bonilha, Julius Fridriksson

Communication Sciences and Disorders Faculty Articles and Research

The association between age and language recovery in stroke remains unclear. Here, we used neuroimaging data to estimate brain age, a measure of structural integrity, and examined the extent to which brain age at stroke onset is associated with (i) cross-sectional language performance, and (ii) longitudinal recovery of language function, beyond chronological age alone. A total of 49 participants (age: 65.2 ± 12.2 years, 25 female) underwent routine clinical neuroimaging (T1) and a bedside evaluation of language performance (Bedside Evaluation Screening Test-2) at onset of left hemisphere stroke. Brain age was estimated from enantiomorphically reconstructed brain scans using a machine …

De Novo Variants In Frmd5 Are Associated With Developmental Delay, Intellectual Disability, Ataxia, And Abnormalities Of Eye Movement, Shenzhao Lu, Mengqi Ma, Xiao Mao, Carlos A Bacino, Joseph Jankovic, V Reid Sutton, James A Bartley, Xueying Wang, Jill A Rosenfeld, Ana Beleza-Meireles, Jaynee Chauhan, Xueyang Pan, Megan Li, Pengfei Liu, Katrina Prescott, Sam Amin, George Davies, Michael F Wangler, Yuwei Dai, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was …