Digital Commons Network^™

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation For Oromotor Feeding Problems In Newborns: An Open-Label Pilot Study, Bashar W. Badran, Dorothea D. Jenkins, Daniel Cook, Sean Thompson, Morgan Darcy, William H. Devries, Georgia Mappin, Philipp Summers, Marom Bikson, Mark S. George

Publications and Research

Neonates born premature or who suffer brain injury at birth often have oral feeding dysfunction and do not meet oral intake requirements needed for discharge. Low oral intake volumes result in extended stays in the hospital (>2 months) and can lead to surgical implant and explant of a gastrostomy tube (G-tube). Prior work suggests pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke, and transcutaneous auricular VNS (taVNS) has emerged as promising noninvasive form of VNS. Pairing taVNS with bottle-feeding rehabilitation may improve oromotor coordination and lead to improved oral intake volumes, ultimately avoiding the …

Enhanced Tes And Tdcs Computational Models By Meninges Emulation, Jimmy Jiang, Dennis Q. Truong, Zeinab Esmaeilpour, Yu Huang, Bashar W. Badran, Marom Bikson

Publications and Research

Objective. Understanding how current reaches the brain during transcranial electrical stimulation (tES) underpins efforts to rationalize outcomes and optimize interventions. To this end, computational models of current flow relate applied dose to brain electric field. Conventional tES modeling considers distinct tissues like scalp, skull, cerebrospinal fluid (CSF), gray matter and white matter. The properties of highly conductive CSF are especially important. However, modeling the space between skull and brain as entirely CSF is not an accurate representation of anatomy. The space conventionally modeled as CSF is approximately half meninges (dura, arachnoid, and pia) with lower conductivity. However, the resolution …

Cis-Regulatory Analysis Of Onecut1 Expression In Fate-Restricted Retinal Progenitor Cells, Sruti Patoori, Nathalie Jean-Charles, Ariana Gopal, Sacha Sulaiman, Sneha Gopal, Brian Wang, Benjamin Souferi, Mark Emerson

Publications and Research

Background: The vertebrate retina consists of six major classes of neuronal cells. During development, these cells are generated from a pool of multipotent retinal progenitor cells (RPCs) that express the gene Vsx2. Fate-restricted RPCs have recently been identified, with limited mitotic potential and cell fate possibilities compared to multipotent RPCs. One population of fate-restricted RPCs, marked by activity of the regulatory element ThrbCRM1, gives rise to both cone photoreceptors and horizontal cells. These cells do not express Vsx2, but co-express the transcription factors (TFs) Onecut1 and Otx2, which bind to ThrbCRM1. The components of the gene regulatory networks that control …

A Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Neural Development In Mice, Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg

Publications and Research

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse …

Polygenic Risk Score Analysis Revealed Shared Genetic Background In Attention Deficit Hyperactivity Disorder And Narcolepsy, Nagahide Takahashi, Tomoko Nishimura, Taeko Harada, Akemi Okumura, Damee Choi, Toshiki Iwabuchi, Hitoshi Kuwabara, Shu Takagi, Yoko Nomura, Jeffrey H. Newcorn, Nori Takei, Kenji J. Tsuchiya

Publications and Research

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between …

Barrels Xxxii Meeting Report: Whiskers In The Windy City, Giuseppe Cataldo, Chia-Chien Chen, Alicia C. Barrientos, Joshua C. Brumberg

Publications and Research

The 32^nd Annual Barrels meeting was hosted at the Northwestern University Feinberg School of Medicine in Chicago, Illinois on October 17^th and 18^th, 2019. The annual meeting brings together researchers who utilize the rodent whisker-to-barrel system as a means to understand cortical function and development. This year’s meeting focused on social behaviors, development and cerebellar functions within the barrel system and beyond.

Learning And Motivation For Rewards In Schizophrenia: Implications For Behavioral Rehabilitation, Victoria Martin, Alexandra Brereton, Jicheng Tang

Publications and Research

Purpose of review: Impaired reward processing and amotivation are well documented in schizophrenia. We aim to review the current state of neuroimaging and behavioral research addressing components of motivational deficits in this complex and impairing syndrome. Evidence will be integrated to inform the ongoing development of effective strategies for behavioral rehabilitation. Recent findings: While striatal dopamine and aberrant reward prediction errors have been connected to amotivation in schizophrenia, they are not sufficiently full explanations of reward processing impairments. Frontal dysfunction and associated cognitive control deficits also have evidenced involvement in atypical reward prediction, learning, and valuation. Ongoing work supports the …

Visual Modulation Of Resting State Α Oscillations, Kelly Webster, Tony Ro

Publications and Research

Once thought to simply reflect passive cortical idling, recent studies have demonstrated that α oscillations play a causal role in cognition and perception. However, whether and how cognitive or sensory processes modulate various components of the α rhythm is poorly understood. Sensory input and resting states were manipulated in human subjects while electroencephalography (EEG) activity was recorded in three conditions: eyes-open fixating on a visual stimulus, eyes-open without visual input (darkness), and eyes-closed without visual input (darkness). We show that α power and peak frequency increase when visual input is reduced compared to the eyes open, fixating condition. These results …

From The Human To The Planetary: Speculative Futures Of Care, Miriam Ticktin

Publications and Research

This is largely a theoretical, speculative essay that takes on the question of what ‘care’ looks like at a moment when climate change is increasingly taking center stage in public and political discussions. Starting with two new practices, namely, humanitarian care for nonhumans and One Health collaborations, I seek to determine what forms of political care can incorporate the well-being of future generations and future iterations of the earth. After an exploration of One Health as an approach to planetary care, I ask what its parts enable us to think, despite its limitations; I focus on the new human-nonhuman assemblages …

Neural Correlates Of Decision Making Related To Information Security: Self-Control And Moral Potency, Robert West, Emily Budde, Qing Hu

Publications and Research

Security breaches of digital information represent a significant threat to the wellbeing of individuals, corporations, and governments in the digital era. Roughly 50% of breaches of information security result from the actions of individuals inside organizations (i.e., insider threat), and some evidence indicates that common deterrence programs may not lessen the insiders’ intention to violate information security. This had led researchers to investigate contextual and individual difference variables that influence the intention to violate information security policies. The current research builds upon previous studies and explores the relationship between individual differences in self-control and moral potency and the neural correlates …

Development And Sensory Experience Dependent Regulation Of Microglia In Barrel Cortex, Joshua C. Brumberg, John Kalambogias, Chia-Chien Chen, Safraz Khan, Titus Son, Carolyn Headlam, Cindy Lin

Publications and Research

The barrel cortex is within the primary somatosensory cortex of the rodent, and processes signals from the vibrissae. Much focus has been devoted to the function of neurons, more recently, the role of glial cells in the processing of sensory input has gained increasing interest. Microglia are the principal immune cells of the nervous system that survey and regulate the cellular constituents of the dynamic nervous system. We investigated the normal and disrupted development of microglia in barrel cortex by chronically depriving sensory signals via whisker trimming for the animals’ first postnatal month. Using immunohistochemistry to label microglia, we performed …

Alpha Oscillations And Feedback Processing In Visual Cortex For Conscious Perception, Tony Ro

Publications and Research

Variability in perception between individuals may be a consequence of different inherent neural processing speeds. To assess whether alpha oscillations systematically reflect a feedback pacing mechanism for cortical processing during visual perception, comparisons were made between alpha oscillations, visual suppression from TMS, visual evoked responses, and metacontrast masking. Peak alpha oscillation frequencies, measured through scalp EEG recordings, significantly correlated with the optimum latencies for visual suppression from TMS of early visual cortex. Individuals with shorter alpha periods (i.e., higher peak alpha frequencies) processed visual information faster than those with longer alpha periods (i.e., lower peak alpha frequencies). Moreover, peak alpha …

Epigenetic Modifications In Alzheimer’S Neuropathology And Therapeutics, Michelle Esposito, Goldie Libby Sherr

Publications and Research

Transcriptional activation is a highly synchronized process in eukaryotes that requires a series of cis- and trans-acting elements at promoter regions. Epigenetic modifications, such as chromatin remodeling, histone acetylation/deacetylation, and methylation, have frequently been studied with regard to transcriptional regulation/dysregulation. Recently however, it has been determined that implications in epigenetic modification seem to expand into various neurodegenerative disease mechanisms. Impaired learning and memory deterioration are cognitive dysfunctions often associated with a plethora of neurodegenerative diseases, including Alzheimer’s disease. Through better understanding of the epigenetic mechanisms underlying these dysfunctions, new epigenomic therapeutic targets, such as histone deacetylases, are being explored. Here …

Modeling Changes In Cellular Micro-Environment In Mild To Moderate Head Trauma, Xiangfu Zhang, Subhendra N. Sarkar Phd, Rt

Publications and Research

Our work aims to connect and model multiple small, inter-related tissue injuries as a consequence of mild traumatic brain injuries (mTBI). It has been shown that frontal and temporal lobes are vulnerable regions for brain traumatic injury. A brain injury from a blow or high-speed impact can cause undersurface of the frontal and temporal lobes to deform against the anterior and cranial fossae. This deformation can often trigger damage to the cerebral vasculature, which is ill-understood and can result in chronic damage to larger vessels over time. These physiological injuries can be manifested psychologically; such as patients’ sleep-wake disturbances. The …

Neural Indices Of Vowel Discrimination In Monolingual And Bilingual Infants And Children, Yan H. Yu, Carol Tessel, Henry Han, Luca Campanelli, Nancy Vidal, Jennifer Gerometta, Karen Garrido-Nag, Hia Datta, Valerie L. Shafer

Publications and Research

Objectives: To examine maturation of neural discriminative responses to an English vowel contrast from infancy to 4 years of age and to determine how biological factors (age and sex) and an experiential factor (amount of Spanish versus English input) modulate neural discrimination of speech.

Design: Event-related potential (ERP) mismatch responses (MMRs) were used as indices of discrimination of the American English vowels [ε] versus [I] in infants and children between 3 months and 47 months of age. A total of 168 longitudinal and cross-sectional data sets were collected from 98 children (Bilingual Spanish–English: 47 male and 31 female …

Synchronicity: The Role Of Midbrain Dopamine In Whole-Brain Coordination, Jeff A. Beeler, Jakob Kiskye Dreyer

Publications and Research

Midbrain dopamine seems to play an outsized role in motivated behavior and learning. Widely associated with mediating reward-related behavior, decision making, and learning, dopamine continues to generate controversies in the field. While many studies and theories focus on what dopamine cells encode, the question of how the midbrain derives the information it encodes is poorly understood and comparatively less addressed. Recent anatomical studies suggest greater diversity and complexity of afferent inputs than previously appreciated, requiring rethinking of prior models. Here, we elaborate a hypothesis that construes midbrain dopamine as implementing a Bayesian selector in which individual dopamine cells sample afferent …

Neuromeasure: A Software Package For Quantification Of Cortical Motor Maps Using Frameless Stereotaxic Transcranial Magnetic Stimulation, Michael B. Gerber, Alasdair C. Mclean, Samuel J. Stephen, Alex G. Chalco, Usman M. Arshad, Gary W. Thickbroom, Josh Silverstein, K. Zoe Tsagaris, Amy Kuceyeski, Kathleen Friel, Taiza E. G. Santos, Dylan J. Edwards

Publications and Research

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make …

The Serial Blocking Effect: A Testbed For The Neural Mechanisms Of Temporal-Difference Learning, Ashraf Mahmud, Petio Petrov, Guillem R. Esber, Mihaela D. Iordanova

Publications and Research

Temporal-difference (TD) learning models afford the neuroscientist a theory-driven roadmap in the quest for the neural mechanisms of reinforcement learning. The application of these models to understanding the role of phasic midbrain dopaminergic responses in reward prediction learning constitutes one of the greatest success stories in behavioural and cognitive neuroscience. Critically, the classic learning paradigms associated with TD are poorly suited to cast light on its neural implementation, thus hampering progress. Here, we present a serial blocking paradigm in rodents that overcomes these limitations and allows for the simultaneous investigation of two cardinal TD tenets; namely, that learning depends on …

Influence Of Stimulus Intensity On Multimodal Integration In The Startle Escape System Of Goldfish, Camille Mcintyre, Thomas Preuss

Publications and Research

Processing of multimodal information is essential for an organism to respond to environmental events. However, how multimodal integration in neurons translates into behavior is far from clear. Here, we investigate integration of biologically relevant visual and auditory information in the goldfish startle escape system in which paired Mauthner-cells (M-cells) initiate the behavior. Sound pips and visual looms as well as multimodal combinations of these stimuli were tested for their effectiveness of evoking the startle response. Results showed that adding a low intensity sound early during a visual loom (low visual effectiveness) produced a supralinear increase in startle responsiveness as compared …

Commentary: Sugar Metabolism Regulates Flavor Preferences And Portal Glucose Sensing, Anthony Sclafani, Karen Acroff

Publications and Research

No abstract provided.

Cortical And Subcortical Contributions To Neuroplasticity After Repetitive Transspinal Stimulation In Humans, Lynda M. Murray, Anamul Islam Md., Maria Knikou

Publications and Research

The objectives of this study were to establish cortical and subcortical contributions to neuroplasticity induced by noninvasive repetitive transspinal stimulation in human subjects free of any neurological disorder. To meet our objectives, before and after 40 minutes of transspinal stimulation we established changes in tibialis anterior (TA) motor-evoked potentials (MEPs) in response to paired transcranial magnetic stimulation (TMS) pulses at interstimulus intervals (ISIs) consistent with I-wave periodicity. In order to establish to what extent similar actions are exerted at the spinal cord and motor axons, changes in soleus H-reflex and transspinal evoked potential (TEP) amplitude following transspinal and group Ia …

Changes In Functional Connectivity Following Treatment With Emotion Regulation Therapy, Matthew A. Scult, David M. Fresco, Faith M. Gunning, Conor Liston, Saren H. Seeley, Emmanuel Garcia, Douglas S. Mennin

Publications and Research

Emotion regulation therapy (ERT) is an efficacious treatment for distress disorders (i.e., depression and anxiety), predicated on a conceptual model wherein difficult to treat distress arises from intense emotionality (e.g., neuroticism, dispositional negativity) and is prolonged by negative self-referentiality (e.g., worry, rumination). Individuals with distress disorders exhibit disruptions in two corresponding brain networks including the salience network (SN)reflecting emotion/motivation and the default mode network (DMN) reflecting self-referentiality. Using resting-state functional connectivity (rsFC) analyses, seeded with primary regions in each of these networks, we investigated whether ERT was associated with theoretically consistent changes across nodes of these networks and whether these …

Immediate Neurophysiological Effects Of Transcranial Electrical Stimulation, Anli Liu, Mihály Vöröslakos, Gregory Kronberg, Simon Henin, Matthew R. Krause, Yu Huang, Alexander Opitz, Ashesh Mehta, Christopher C. Pack, Bart Krekelberg, Antal Berényi, Lucas C. Parra, Lucia Melloni, Orrin Devinsky, György Buzsáki

Publications and Research

Noninvasive brain stimulation techniques are used in experimental and clinical fields for their potential effects on brain network dynamics and behavior. Transcranial electrical stimulation (TES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), has gained popularity because of its convenience and potential as a chronic therapy. However, a mechanistic understanding of TES has lagged behind its widespread adoption. Here, we review data and modelling on the immediate neurophysiological effects of TES in vitro as well as in vivo in both humans and other animals. While it remains unclear how typical TES protocols affect neural activity, we …

Contextual Fear Memory Modulates Psd95 Phosphorylation, Ampar Subunits, Pkmζ And Pi3k Differentially Between Adult And Juvenile Rats, Roseanna M. Zanca, Shirley Sanay, Jorge A. Avila, Edgar Rodriguez, Harry N. Shair, Peter A. Serrano

Publications and Research

It is well known that young organisms do not maintain memories as long as adults, but the mechanisms for this ontogenetic difference are undetermined. Previous work has revealed that the α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acidreceptor (AMPAr)subunits aretraffickedinto the synaptic membranefollowing memory retrieval in adults. Additionally, phosphorylated PSD-95-pS295 promotes AMPAr stabilization at the synapse. We investigated these plasticity related proteins as potential mediators in the differential contextual stress memory retrieval capabilities observed between adult and juvenile rats. Rats were assigned to either pedestal stress (1h) or no stress control (home cage). Each animal was placed alone in an open field for 5minat the base …

Identification And Characterization Of Early Photoreceptor Cis-Regulatory Elements And Their Relation To Onecut1, Nathalie Jean-Charles, Diego F. Buenaventura, Mark M. Emerson

Publications and Research

Background: Cone and rod photoreceptors are two of the primary cell types affected in human retinal disease. Potential strategies to combat these diseases are the use of gene therapy to rescue compromised photoreceptors or to generate new functional photoreceptors to replace those lost in the diseased retina. Cis-regulatory elements specific to cones, rods, or both types of photoreceptors are critical components of successful implementation of these two strategies. The purpose of this study was to identify and characterize the cell type specificity and activity of cis-regulatory elements active in developing photoreceptors.

Methods: Cis-regulatory elements were introduced into the developing chicken …

Association Of The Haptoglobin Gene Polymorphism With Cognitive Function And Decline In Elderly African American Adults With Type 2 Diabetes: Findings From The Action To Control Cardiovascular Risk In Diabetes–Memory In Diabetes (Accord-Mind) Study, Michael Beeri, Hung-Mo Lin, Mary Sano, Ramit Ravona-Springer, Xiaoyu Liu, Barbara B. Bendlin, Carey E. Gleason, Elizabeth Guerrero-Berroa, Laili Soleimani, Lenore J. Launer, Scott Ehrenberg, Orit Lache, Yaakov K. Seligman, Andrew P. Levy

Publications and Research

IMPORTANCE African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with greater risk ofmyocardial infarction and mortality). An additional polymorphism in the promoter region of the Hp 2 allele, restricted to individuals of African descent, yields a fourth …

Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E. G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Quangvinh Truong, Alexandre C. B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards

Publications and Research

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.

Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.

Methods: …

Hyperphosphorylation Of Tau Associates With Changes In Its Function Beyond Microtubule Stability, Alejandra D. Alonso, Leah S. Cohen, Christopher Corbo, Viktoriya Morozova, Abdeslem Elldrissi, Greg R. Phillips, Frida E. Kleiman

Publications and Research

Tau is a neuronal microtubule associated protein whose main biological functions are to promote microtubule self-assembly by tubulin and to stabilize those already formed. Tau also plays an important role as an axonal microtubule protein. Tau is an amazing protein that plays a key role in cognitive processes, however, deposits of abnormal forms of tau are associated with several neurodegenerative diseases, including Alzheimer disease (AD), the most prevalent, and Chronic Traumatic Encephalopathy (CTE) and Traumatic Brain Injury (TBI), the most recently associated to abnormal tau. Tau post-translational modifications (PTMs) are responsible for its gain of toxic function. Alonso et al. …

Developmental Transitions In Amygdala Pkc Isoforms And Ampa Receptor Expression Associated With Threat Memory In Infant Rats, Maya Opendak, Roseanna M. Zanca, Eben Anane, Peter Serrano, Regina M. Sullivan

Publications and Research

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our …

The Impact Of Perineuronal Net Digestion Using Chondroitinase Abc On The Intrinsic Physiology Of Cortical Neurons, Philip Chu, Reena Abraham, Kumarie Budhu, Usma Khan, Natalie De Marco Garcia, Joshua C. Brumberg

Publications and Research

Perineuronal nets (PNNs) are a form of aggregate Extracellular Matrix (ECM) in the brain. Recent evidence suggests that the postnatal deposition of PNNs may play an active role in regulating neuroplasticity and, potentially, neurological disorders. Observations of high levels of PNNs expression around somas, proximal dendrites, and axon initial segments of a subtype of neurons have also led to proposals that PNNs may modulate the intrinsic properties of the neurons they ensheathe. While high levels of PNNs are postnatally expressed throughout the neocortex, it is still unclear how they impact the neuronal physiology of the many classes and subtypes of …