Neurosciences Commons^™

Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Neural plasticity plays a critical role in mediating short- and long-term brain responses to environmental stimuli. A major effector of plasticity throughout many regions of the brain is stress. Activation of the locus coeruleus (LC) is a critical step in mediating the neuroendocrine and behavioral limbs of the stress response. During stressor exposure, activation of the hypothalamic-pituitary-adrenal axis promotes release of corticotropin-releasing factor in LC, where its signaling promotes a number of physiological and cellular changes. While the acute effects of stress on LC physiology have been described, its long-term effects are less clear. This review will describe how stress …

A Gut Feeling: A Hypothesis Of The Role Of The Microbiome In Attention-Deficit/Hyperactivity Disorders., Xue Ming, Neil Chen, Carly Ray, Gretchen Brewer, Jeffrey Kornitzer, Robert A Steer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Attention-deficit/hyperactivity disorder (ADHD) is a neurologic disorder characterized by hyperactivity/impulsivity and/or inattentiveness, with genetic and environmental factors contributing to the disorder. With the growing recognition of the microbiome's role in many neurological disorders, the authors propose that it may also be implicated in ADHD. Here, we describe several evolving areas of research to support this hypothesis. First, a unique composition of gut bacteria has been identified and linked to behaviors in ADHD. Second, our research found an increased incidence of 2 gastrointestinal symptoms (constipation and flatulence) in children with ADHD, as compared to controls. Finally, emerging data may be interpreted …

Targeted Delivery Of A Therapeutic Protein For The Treatment Of Alzheimer's Disease, Heather Holman

Honors Undergraduate Theses

Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of α-synuclein. Our goal is to develop an effective method for delivery of TOM40 protein to the brain.

Previous studies have used lentiviruses to carry TOM40 into the hippocampus of α-synuclein transgenic mice. The disadvantage of lentiviral transfection is the random insertions of the target gene into the host …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Assessing Working Memory In Mild Cognitive Impairment With Serial Order Recall., Sheina Emrani, David J Libon, Melissa Lamar, Catherine C Price, Angela L Jefferson, Katherine A Gifford, Timothy J Hohman, Daniel A Nation, Lisa Delano-Wood, Amy Jak, Katherine J Bangen, Mark W Bondi, Adam M Brickman, Jennifer Manly, Rodney Swenson, Rhoda Au, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda)

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat …

Human Neuroimaging Reveals The Subcomponents Of Grasping, Reaching And Pointing Actions., Cristiana Cavina-Pratesi, Jason D Connolly, Simona Monaco, Teresa D Figley, A David Milner, Thomas Schenk, Jody C Culham

Brain and Mind Institute Researchers' Publications

Although the neural underpinnings of visually guided grasping and reaching have been well delineated within lateral and medial fronto-parietal networks (respectively), the contributions of subcomponents of visuomotor actions have not been explored in detail. Using careful subtraction logic, here we investigated which aspects of grasping, reaching, and pointing movements drive activation across key areas within visuomotor networks implicated in hand actions. For grasping tasks, we find activation differences based on the precision required (fine > coarse grip: anterior intraparietal sulcus, aIPS), the requirement to lift the object (grip + lift > grip: aIPS; dorsal premotor cortex, PMd; and supplementary motor area, SMA), …

Cross-Script Orthographic And Phonological Preview Benefits, Olessia Jouravlev, Debra Jared

Brain and Mind Institute Researchers' Publications

The present experiment examined the use of parafoveally presented first-language (LI) orthographic and phonological codes during reading of second-language (L2) sentences in proficient Russian-English bilinguals. Participants read English sentences containing a Russian preview word that was replaced by the English target word when the participant’s eyes crossed an invisible boundary located before the preview word. The use of English and Russian allowed us to manipulate orthographic and phonological preview effects independently of one another. The Russian preview words overlapped with English target words in (a) orthography (ВЕЛЮР [vʲɪˈlʲʉr]–BERRY), (b) phonology (БЛАНК [blank]–BLOOD), or (c) had no orthographic or phonological overlap …

Registered Reports: Introducing A New Article Format In Developmental Science, Daniel Ansari, Judit Gervain

Brain and Mind Institute Researchers' Publications

No abstract provided.

Understanding The Effects Of Education Through The Lens Of Biology, H Moriah Sokolowski, Daniel Ansari

Brain and Mind Institute Researchers' Publications

Early educational interventions aim to close gaps in achievement levels between children. However, early interventions do not eliminate individual differences in populations and the effects of early interventions often fade-out over time, despite changes of the mean of the population immediately following the intervention. Here, we discuss biological factors that help to better understand why early educational interventions do not eliminate achievement gaps. Children experience and respond to educational interventions differently. These stable individual differences are a consequence of biological mechanisms that support the interplay between genetic predispositions and the embedding of experience into our biology. Accordingly, we argue that …

Recording Neuronal Activity Using Miniscopes, Brainscan , Western University, Marco Prado, Sylvian Williams, Vania Prado, Salah El Mestikawy

Project Summaries

Our overarching goal is to understand how the striatum can select between competing options to favor goal-directed behaviors or the establishment of habitual control. This will provide fundamental and transformational insights into the regulation of cognitive functions by co-transmission.

Investigating Vta, Snc And Dopamine Projections In The Brain Using Mri, Brainscan , Western University, Penny Macdonald, Ali Khan, Adrian Owen, Ravi Menon

Project Summaries

By using a multi-modal imaging approach - combining a number of different imaging techniques - we will seek to understand the dopaminergic pathways of the brain. While all neurons depend on neurotransmitters such as dopamine to communicate (since neurotransmitters are responsible for transmitting signals between neurons in the brain), very few neurons actually produce dopamine.

Characterizing Auditory Cortical Receptive Fields, Brainscan , Western University, Ingrid Johnsrude, Alex Billig, Matthew A. Howard Iii, David Steven, Jorge Burneo

Project Summaries

Through this research we have a unique opportunity to explore how auditory cortices respond to naturalistic stimuli and how that response changes with different tasks. This foundational work is critical if we are to understand abnormality in auditory cortices in disorders such as autism, specific language impairment, auditory processing disorders and prolonged auditory deprivation (due to hearing loss).

State-Of-The-Art Clinical Assessment Of Hand Function, Brainscan , Western University, Joern Diedrichsen, Naveed Ejaz, John W. Krakauer, Kevin Olds, Robert Teasell, Neil Duggal, Andrew Pruszynski

Project Summaries

We have assembled a multi-disciplinary team of engineers, surgeons, clinicians and neuroscientists from Johns Hopkins School of Medicine and Western University to develop a new device for assessing hand function. It will be capable of sensitively measuring fingertip forces across all five fingers and along all movement directions. Then we can use this device to develop and validate a clinical hand assessment for patients with brain injuries.

Single-Photon Calcium Imaging For Interrogating The Circuitry Of The Frontoparietal Cognitive Control Network, Brainscan , Western University, Stefan Everling, Ravi Menon, Liya Ma

Project Summaries

We will use miniscopes to detect activities in the frontal eye field, a brain region responsible for voluntary eye movements and perception and awareness in the field of vision. The detection of neuronal activity with calcium imaging can then be compared with the visual stimuli and eye movements expected. If successful, this project will show the feasibility of calcium imaging using miniscopes in this way and open the door for future work to expand our understanding of frontoparietal cortical circuits.

Development Of Fmri Compatible Reversible Deactivation To Examine Cerebral Networks, Brainscan , Western University, Stephen Lomber, Blake Butler, Stefan Everling, Blaine Chronik

Project Summaries

This study will permit us, for the first time, to examine the effects of deactivation of one cortical site on large-scale neural networks. It will permit neural networks to be functionally disassembled and the consequences of 'reversible' lesions, strokes or tumors to be assessed and modeled before they occur.

Using Automated Touchscreen Tasks For Cognitive Assessment In A Novel Model Of Parkinson's Disease, Brainscan, Western University, Flavio Henrique Beraldo De Paiva, Marco Prado, Vania Prado

Project Summaries

This research will focus specifically on evaluating cognitive flexibility (the ability to respond and adapt behaviours to changes in the environment), cognitive dysfunction (changes in the intellectual processing and reasoning that impact daily functions, to a greater severity than what might be expected from typical age-related decline) and long-term memory in a PD model using touchscreens.

Imaging Visually-Evoked Cortical Activity, Brainscan, Western University, Blake E. Butler, Stephen Lomber, Kyle Gilbert, Mathias Dietz

Project Summaries

This work will significantly inform our understanding of 'neural plasticity', the ability of the brain to respond and reorganize to environmental changes or following an injury or disorder. It is also our hope that the results of this program will inform the design of devices to restore hearing - it might enable tuning of those devices to restore sensory representations in the brain in a patient-specific manner. We believe this will significantly reduce the impact of cognitive disorders that arise as a result of abnormal perception both in children and in older adults.

The Impact Of Maternal Immune Activation On Fetal Brain Development, Brainscan , Western University, Stephen Renaud, Susanne Schmid

Project Summaries

We will be studying the contribution of two distinct immune cell subtypes to fetal brain development: the mother's main immune cells present in the uterus (known as uterine natural killer cells), and the fetal brain's main immune cells (fetal microglial cells).

Evaluating Cognitive Impairment, Imaging And Blood Biomarkers In A Pre-Clinical Model Of Concussion, Brainscan, Western University, Arthur Brown, Marco Prado, Rob Bartha, Ravi Menon, Mark Daley

Project Summaries

The foundational milestone for the research, that we are addressing in this project, is to demonstrate that cognitive impairments in mouse models and humans are similar by using touchscreen technology. We will also be applying fMRI and MRS analyses to mouse models since they are analogous to that used in human studies - it will help us establish relevant endpoints for the studies as part of understanding the underlying characteristics, pathways and effects of concussion.

Genetic Manipulation Of Lactate Metabolism To Regulate Memory And Alzheimer's Disease Pathogenesis, Brainscan , Western University, Robert Cumming, Robert Bartha, Tim Scholl

Project Summaries

Our project will attempt to determine the relative importance of astrocyte or neuronal directed lactate generation on memory by modifying mouse models to either suppress or overexpress the lactate producing enzyme in either cell type. Using these newly created transgenic mouse models, we aim to understand the processes of production and utilization of lactate and its effect on memory and cognition in health and in AD across the lifespan. The outcome of our study may lead to entirely new clinical approaches to treating cognitive and neurodegenerative disorders via drugs which alter lactate metabolism.