Neuroscience and Neurobiology Commons^™

Apathy And Striatal Gray Matter Patterns In Schizophrenia And Huntington’S Disease, Gabriel Martinez, Skylar Walters, J S. Paulsen, Vince Calhoun, Jessica Turner

Neuroscience Institute Faculty Publications

Apathy is a symptom of many neurodegenerative and neuropsychiatric disorders, such as Huntington's disease and schizophrenia. Apathy is often conceptualized as a combination of three domains, cognitive, behavioral, and emotional, characterized by impaired goal-directed behavior. The striatum has been shown to be significantly associated with executive functions and planned motor behavior via projection to the prefrontal cortex (PFC). Due to its connection to the PFC and its involvement in the basal ganglia motor circuit, the striatum is thought to be a significant part of the circuit that controls goal-directed behavior. The purpose of this study was to investigate the relationship …

Handedness For Unimanual Grasping In 564 Great Apes: The Effect On Grip Morphology And A Comparison With Hand Use For A Bimanual Coordinated Task, Adrien Meguerditchian, Kimberley A. Phillips, Amandine Chapelain, Lindsay M. Mahovetz, Scott Milne, Tara Stoinski, Amanda Bania, Elizabeth Lonsdorf, Jennifer A. Schaeffer, Jamie L. Russell, William D. Hopkins

Neuroscience Institute Faculty Publications

A number of factors have been proposed to influence within and between species variation in handedness in non-human primates. In the initial study, we assessed the influence of grip morphology on hand use for simple reaching in a sample of 564 great apes including 49 orangutans Pongo pygmaeus, 66 gorillas Gorilla gorilla, 354 chimpanzees Pan troglodytes and 95 bonobos Pan paniscus. Overall, we found a significant right hand bias for reaching. We also found a significant effect of the grip morphology of hand use. Grasping with the thumb and index finger was more prevalent in the right compared to left …

Editorial: Mental Practice: Clinical And Experimental Research In Imagery And Action Observation, Magdalena Ietswaart

Neuroscience Institute Faculty Publications

No abstract provided.

Perceptual Decision-Making Difficulty Modulates Feedforward Effective Connectivity To The Dorsolateral Prefrontal Cortex, Bidhan Lamichhane, Mukesh Dhamala

Neuroscience Institute Faculty Publications

Diverse cortical structures are known to coordinate activity as a network in relaying and processing of visual information to discriminate visual objects. However, how this discrimination is achieved is still largely unknown. To contribute to answering this question, we used face-house categorization tasks with three levels of noise in face and house images in functional magnetic resonance imaging (fMRI) experiments involving thirty-three participants. The behavioral performance error and response time (RT) were correlated with noise in face-house images. We then built dynamical causal models (DCM) of fMRI blood-oxygenation level dependent (BOLD) signals from the face and house category-specific regions in …

Meta Gene Set Enrichment Analyses Link Mir-137-Regulated Pathways With Schizophrenia Risk, Carrie Wright, Vince D. Calhoun, Stefan Ehrlich, Lei Wang, Jessica A. Turner, Nora I. Perrone-Bizzozero

Neuroscience Institute Faculty Publications

Background: A single nucleotide polymorphism (SNP) within MIR137, the host gene for miR-137, has been identified repeatedly as a risk factor for schizophrenia. Previous genetic pathway analyses suggest that potential targets of this microRNA (miRNA) are also highly enriched in schizophrenia-relevant biological pathways, including those involved in nervous system development and function.
Methods: In this study, we evaluated the schizophrenia risk of miR-137 target genes within these pathways. Gene set enrichment analysis of pathway-specific miR-137 targets was performed using the stage 1 (21,856 subjects) schizophrenia genome wide association study data from the Psychiatric Genomics Consortium and a small independent replication …

Genetic Markers Of White Matter Integrity In Schizophrenia Revealed By Parallel Ica, Cota Navin Gupta, Jiayu Chen, Jingyu Liu, Eswar Damaraju, Carrie Wright, Nora I. Perrone-Bizzozero, Godfrey Pearlson, Li Lou, Andrew Michael, Jessica A. Turner, Vince D. Calhoun

Neuroscience Institute Faculty Publications

It is becoming a consensus that white matter integrity is compromised in schizophrenia (SZ), however the underlying genetics remains elusive. Evidence suggests a polygenic basis of the disorder, which involves various genetic variants with modest individual effect sizes. In this work, we used a multivariate approach, parallel independent component analysis (P-ICA), to explore the genetic underpinnings of white matter abnormalities in SZ. A pre-filtering step was first applied to locate 6527 single nucleotide polymorphisms (SNPs) discriminating patients from controls with a nominal uncorrected p-value of 0.01. These potential susceptibility loci were then investigated for associations with fractional anisotropy (FA) images …

Deep Mrna Sequencing Of The Tritonia Diomedea Brain Transcriptome Provides Access To Gene Homologues For Neuronal Excitability, Synaptic Transmission And Peptidergic Signalling, Adriano Senatore, Neranjan Edirisinghe, Paul S. Katz

Neuroscience Institute Faculty Publications

The sea slug Tritonia diomedea (Mollusca, Gastropoda, Nudibranchia), has a simple and highly accessible nervous system, making it useful for studying neuronal and synaptic mechanisms underlying behavior. Although many important contributions have been made using Tritonia, until now, a lack of genetic information has impeded exploration at themolecular level.
We performed Illumina sequencing of central nervous system mRNAs from Tritonia, generating 133.1 million 100 base pair, paired-end reads. De novo reconstruction of the RNA-Seq data yielded a total of 185,546 contigs, which partitioned into 123,154 non-redundant gene clusters (unigenes). BLAST comparison with RefSeq and Swiss-Prot protein databases, as well as …

Contextual Modulation Of Social And Endocrine Correlates Of Fitness: Insights From The Life History Of A Sex Changing Fish, Devaleena S. Pradhan

Neuroscience Institute Faculty Publications

Steroid hormones are critical regulators of reproductive life history, and the steroid sensitive traits (morphology, behavior, physiology) associated with particular life history stages can have substantial fitness consequences for an organism. Hormones, behavior and fitness are reciprocally associated and can be used in an integrative fashion to understand how the environment impacts organismal function. To address the fitness component, we highlight the importance of using reliable proxies of reproductive success when studying proximate regulation of reproductive phenotypes. To understand the mechanisms by which the endocrine system regulates phenotype, we discuss the use of particular endocrine proxies and the need for …

The Association Between Imitation Recognition And Socio-Communicative Competencies In Chimpanzees (Pan Troglodytes), Sarah Pope, Jamie L. Russell, William D. Hopkins

Neuroscience Institute Faculty Publications

Imitation recognition provides a viable platform from which advanced social cognitive skills may develop. Despite evidence that non-human primates are capable of imitation recognition, how this ability is related to social cognitive skills is unknown. In this study, we compared imitation recognition performance, as indicated by the production of testing behaviors, with performance on a series of tasks that assess social and physical cognition in 49 chimpanzees. In the initial analyses, we found that males were more responsive than females to being imitated and engaged in significantly greater behavior repetitions and testing sequences. We also found that subjects who consistently …

Sex Differences In The Brain: A Whole Body Perspective, Geert De Vries, Nancy Forger

Neuroscience Institute Faculty Publications

Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other organs when considering neural sex differences is that we …

Cell-Type Specific Transcriptomic Profiling To Dissect Mechanisms Of Differential Dendritogenesis, Surajit Bhattacharya, Eswar Prasad R. Iyer, Srividya Chandramouli Iyer, Daniel N. Cox

Neuroscience Institute Faculty Publications

The establishment, maintenance and modulation of cell-type specific neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the specification of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from purified populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression profiling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with …

Deep Learning For Neuroimaging: A Validation Study, Sergey M. Plis, Devon R. Hjelm, Ruslan Salakhutdinov, Elena A. Allen, Henry J. Bockholt, Jeffrey D. Long, Hans J. Johnson, Jane S. Paulsen, Jessica A. Turner, Vince D. Calhoun

Neuroscience Institute Faculty Publications

Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager’s toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building …

Interdisciplinary Perspectives On The Development, Integration, And Application Of Cognitive Ontologies, Janna Hastings, Gwen A. Frishkoff, Barry Smith, Mark Jensen, Russell A. Poldrack, Jane Lomax, Anita Bandrowski, Fahim Imam, Jessica Turner, Maryann E. Martone

Neuroscience Institute Faculty Publications

We discuss recent progress in the development of cognitive ontologies and summarize three challenges in the coordinated development and application of these resources. Challenge 1 is to adopt a standardized definition for cognitive processes. We describe three possibilities and recommend one that is consistent with the standard view in cognitive and biomedical sciences. Challenge 2 is harmonization. Gaps and conflicts in representation must be resolved so that these resources can be combined for mark-up and interpretation of multi-modal data. Finally, Challenge 3 is to test the utility of these resources for large- scale annotation of data, search and query, and …

Hidden Synaptic Differences In A Neural Circuit Underlie Differential Behavioral Susceptibility To A Neural Injury, Akira Sakurai, Arianna Tamvacakis, Paul Katz

Neuroscience Institute Faculty Publications

Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animals within the neural circuit underlying swimming behavior had no behavioral relevance under normal conditions but caused differential vulnerability of the behavior to a particular brain lesion. The extent of motor impairment correlated with the site of spike initiation in a specific neuron in the neural circuit, which was determined by the strength of an …

Hidden Synaptic Differences In A Neural Circuit Underlie Differential Behavioral Susceptibility To A Neural Injury, Akira Sakurai, Arianna Tamvacakis, Paul S. Katz

Neuroscience Institute Faculty Publications

Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animals within the neural circuit underlying swimming behavior had no behavioral relevance under normal conditions but caused differential vulnerability of the behavior to a particular brain lesion. The extent of motor impairment correlated with the site of spike initiation in a specific neuron in the neural circuit, which was determined by the strength of an …

Sharing Privacy-Sensitive Access To Neuroimaging And Genetics Data: A Review And Preliminary Validation, Anand D. Sarwate, Sergey M. Plis, Jessica A. Turner, Mohammad R. Arbabshirani, Vince D. Calhoun

Neuroscience Institute Faculty Publications

The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; …

Sharing Privacy-Sensitive Access To Neuroimaging And Genetics Data: A Review And Preliminary Validation, Anand D. Sarwate, Sergey M. Plis, Jessica Turner, Mohammad R. Arbabshirani, Vince D. Calhoun

Neuroscience Institute Faculty Publications

The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; …

Key Bifurcations Of Bursting Polyrhythms In 3-Cell Central Pattern Generators, Jeremy Wojcik, Justus Schwabedal, Robert Clewley, Andrey L. Shilnikov

Neuroscience Institute Faculty Publications

We identify and describe the key qualitative rhythmic states in various 3-cell network motifs of a multifunctional central pattern generator (CPG). Such CPGs are neural microcircuits of cells whose synergetic interactions produce multiple states with distinct phase-locked patterns of bursting activity. To study biologically plausible CPG models, we develop a suite of computational tools that reduce the problem of stability and existence of rhythmic patterns in networks to the bifurcation analysis of fixed points and invariant curves of a Poincare´ return maps for phase lags between cells. We explore different functional possibilities for motifs involving symmetry breaking and heterogeneity. This …

Sexually Dimorphic Role For Vasopressin In The Development Of Social Play, Matthew J. Paul, Joseph I. Terranova, Clemens K. Probst, Elaine K. Murray, Nafissa I. Ismail, Geert De Vries

Neuroscience Institute Faculty Publications

Despite the well-established role of arginine vasopressin (AVP) in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of …

Nih Initiative To Balance Sex Of Animals In Preclinical Studies: Generative Questions To Guide Policy, Implementation, And Metrics, Louise Mccullough, Geert De Vries, Virginia M. Miller, Jill Becker, Kathryn Sandberg, Margaret M. Mccarthy

Neuroscience Institute Faculty Publications

In May of 2014, the NIH Director together with the Director of the Office of Research on Women’s Health announced plans to take a multi-dimensional approach to address the over reliance on male cells and animals in preclinical research. The NIH is engaging the scientific community in the development of policies to improve the sex balance in research. The present, past, and future presidents of the Organization for the Study of Sex Differences, in order to encourage thoughtful discussion among scientists, pose a series of questions to generate ideas in three areas: 1. research strategies, 2. educational strategies, and 3. …

The Effects Of Perinatal Testosterone Exposure On The Dna Methylome Of The Mouse Brain Are Late-Emerging, Negar M. Ghahramani, Tuck Ngun, Pao-Yang Chen, Yuan Tian, Sangitha Krishnan, Stephanie Muir, Liudmilla Rubbi, Arthur P. Arnold, Geert De Vries, Nancy Forger, Matteo Pellegrini, Eric Vilain

Neuroscience Institute Faculty Publications

Background

The biological basis for sex differences in brain function and disease susceptibility is poorly understood. Examining the role of gonadal hormones in brain sexual differentiation may provide important information about sex differences in neural health and development. Permanent masculinization of brain structure, function, and disease is induced by testosterone prenatally in males, but the possible mediation of these effects by long-term changes in the epigenome is poorly understood.

Methods

We investigated the organizational effects of testosterone on the DNA methylome and transcriptome in two sexually dimorphic forebrain regions—the bed nucleus of the stria terminalis/preoptic area and the striatum. To …

The Rise Of Large-Scale Imaging Studies In Psychiatry, Jessica Turner

Neuroscience Institute Faculty Publications

From the initial arguments over whether 12 to 20 subjects were sufficient for an fMRI study, sample sizes in psychiatric neuroimaging studies have expanded into the tens of thousands. These large-scale imaging studies fall into several categories, each of which has specific advantages and challenges. The different study types can be grouped based on their level of control: meta-analyses, at one extreme of the spectrum, control nothing about the imaging protocol or subject selection criteria in the datasets they include, On the other hand, planned multi-site mega studies pour intense efforts into strictly having the same protocols. However, there are …

Poor Receptive Joint Attention Skills Are Associated With Atypical Gray Matter Asymmetry In The Posterior Superior Temporal Gyrus Of Chimpanzees (Pan Troglodytes), William D. Hopkins, Maria Misiura, Lisa A. Reamer, Jennifer A. Schaeffer, Mary C. Mareno, Steven J. Schapiro

Neuroscience Institute Faculty Publications

Clinical and experimental data have implicated the posterior superior temporal gyrus as an important cortical region in the processing of socially relevant stimuli such as gaze following, eye direction, and head orientation. Gaze following and responding to different socio-communicative signals is an important and highly adaptive skill in primates, including humans. Here, we examined whether individual differences in responding to socio- communicative cues was associated with variation in either gray matter (GM) volume and asymmetry in a sample of chimpanzees. Magnetic resonance image scans and behavioral data on receptive joint attention (RJA) was obtained from a sample of 191 chimpanzees. …

Genetic Influences On Receptive Joint Attention In Chimpanzees (Pan Troglodytes), William D. Hopkins, Alaine C. Keebaugh, Lisa A. Reamer, Jennifer Schaefer, Steven J. Schapiro, Larry J. Young

Neuroscience Institute Faculty Publications

Despite their genetic similarity to humans, our understanding of the role of genes on cognitive traits in chimpanzees remains virtually unexplored. Here, we examined the relationship between genetic variation in the arginine vasopressin V1a receptor gene (AVPR1A) and social cognition in chimpanzees. Studies have shown that chimpanzees are polymorphic for a deletion in a sequence in the 59 flanking region of the AVPR1A, DupB, which contains the variable RS3 repetitive element, which has been associated with variation in social behavior in humans. Results revealed that performance on the social cognition task was significantly heritable. Furthermore, males with one DupB1 allele …

Neuroanatomical Domain Of The Foundational Model Of Anatomy Ontology, B Nolan Nichols, Jose Lv Mejino, Landon T. Detwiler, Trond T. Nilsen, Maryann E. Martone, Jessica Turner, Daniel L. Rubin, James F. Brinkley

Neuroscience Institute Faculty Publications

Background: The diverse set of human brain structure and function analysis methods represents a difficult challenge for reconciling multiple views of neuroanatomical organization. While different views of organization are expected and valid, no widely adopted approach exists to harmonize different brain labeling protocols and terminologies. Our approach uses the natural organizing framework provided by anatomical structure to correlate terminologies commonly used in neuroimaging. Description: The Foundational Model of Anatomy (FMA) Ontology provides a semantic framework for representing the anatomical entities and relationships that constitute the phenotypic organization of the human body. In this paper we describe recent enhancements to the …

A Codimension-2 Bifurcation Controlling Endogenous Bursting Activity And Pulse-Triggered Responses Of A Neuron Model, William Halbert Barnett, Gennady Cymbalyuk

Neuroscience Institute Faculty Publications

The dynamics of individual neurons are crucial for producing functional activity in neuronal networks. An open question is how temporal characteristics can be controlled in bursting activity and in transient neuronal responses to synaptic input. Bifurcation theory provides a framework to discover generic mechanisms addressing this question. We present a family of mechanisms organized around a global codimension-2 bifurcation. The cornerstone bifurcation is located at the intersection of the border between bursting and spiking and the border between bursting and silence. These borders correspond to the blue sky catastrophe bifurcation and the saddle-node bifurcation on an invariant circle (SNIC) curves, …

Automated Annotation Of Functional Imaging Experiments Via Multi-Label Classification, Matthew Turner, Chayan Chakrabarti, Thomas B. Jones, Jiawei F. Xu, Peter T. Fox, George F. Luger, Angela R. Laird, Jessica A. Turner

Neuroscience Institute Faculty Publications

Identifying the experimental methods in human neuroimaging papers is important for grouping meaningfully similar experiments for meta-analyses. Currently, this can only be done by human readers. We present the performance of common machine learning (text mining) methods applied to the problem of automatically classifying or labeling this literature. Labeling terms are from the Cognitive Paradigm Ontology (CogPO), the text corpora are abstracts of published functional neuroimaging papers, and the methods use the performance of a human expert as training data. We aim to replicate the expert’s annotation of multiple labels per abstract identifying the experimental stimuli, cognitive paradigms, response types, …

Stress And Serial Adult Metamorphosis: Multiple Roles For The Stress Axis In Socially Regulated Sex Change, Tessa Solomon-Lane, Erica J. Crespi, Matthew S. Grober

Neuroscience Institute Faculty Publications

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses …

Persistent Peripheral Inflammation Attenuates Morphine-Induced Periaqueductal Gray Glial Cell Activation And Analgesic Tolerance In The Male Rat, Lori N. Eidson, Anne Z. Murphy Phd

Neuroscience Institute Faculty Publications

Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that CNS glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG‐glia. Here we test the hypothesis that morphine‐induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of …

Dopaminergic Tone Regulates Transient Potassium Current Maximal Conductance Through A Translational Mechanism Requiring D1rs, Camp/Pka, Erk And Mtor, Edmund William Rodgers, Wulf-Dieter C. Krenz, Xiaoyue Jiang, Lingjun Li, Deborah J. Baro

Neuroscience Institute Faculty Publications

Background: Dopamine (DA) can produce divergent effects at different time scales. DA has opposing immediate and long-term effects on the transient potassium current (IA) within neurons of the pyloric network, in the Panulirus interruptus stomatogastric ganglion. The lateral pyloric neuron (LP) expresses type 1 DA receptors (D1Rs). A 10 min application of 5-100 μM DA decreases LP IA by producing a decrease in IA maximal conductance (Gmax) and a depolarizing shift in IA voltage dependence through a cAMP-Protein kinase A (PKA) dependent mechanism. Alternatively, a 1 hr application of DA (≥5 nM) generates a persistent (measured 4 hr after DA …