Neurosciences Commons^™

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Self-Injurious Behaviours Are Associated With Alterations In The Somatosensory System In Children With Autism Spectrum Disorder., Emma G Duerden, Dallas Card, S Wendy Roberts, Kathleen M Mak-Fan, M Mallar Chakravarty, Jason P Lerch, Margot J Taylor

Brain and Mind Institute Researchers' Publications

Children with autism spectrum disorder (ASD) frequently engage in self-injurious behaviours, often in the absence of reporting pain. Previous research suggests that altered pain sensitivity and repeated exposure to noxious stimuli are associated with morphological changes in somatosensory and limbic cortices. Further evidence from postmortem studies with self-injurious adults has indicated alterations in the structure and organization of the temporal lobes; however, the effect of self-injurious behaviour on cortical development in children with ASD has not yet been determined. Thirty children and adolescents (mean age = 10.6 ± 2.5 years; range 7-15 years; 29 males) with a clinical diagnosis of …

Continuous Executive Function Disruption Interferes With Application Of An Information Integration Categorization Strategy., Sarah J Miles, Kazunaga Matsuki, John Paul Minda

Brain and Mind Institute Researchers' Publications

Category learning is often characterized as being supported by two separate learning systems. A verbal system learns rule-defined (RD) categories that can be described using a verbal rule and relies on executive functions (EFs) to learn via hypothesis testing. A nonverbal system learns non-rule-defined (NRD) categories that cannot be described by a verbal rule and uses automatic, procedural learning. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of EFs, but …

Overt Responses During Covert Orienting., Brian D Corneil, Douglas P Munoz

Brain and Mind Institute Researchers' Publications

A distributed network of cortical and subcortical brain areas controls our oculomotor behavior. This network includes the superior colliculus (SC), which coordinates an ancient visual grasp reflex via outputs that ramify widely within the brainstem and spinal cord, accessing saccadic and other premotor and autonomic circuits. In this Review, we discuss recent results correlating subliminal SC activity in the absence of saccades with diverse components of the visual grasp reflex, including neck and limb muscle recruitment, pupil dilation, and microsaccade propensity. Such subtle manifestations of covert orienting are accessible in the motor periphery and may provide the next generation of …

Examining Dorsal Striatum In Cognitive Effort Using Parkinson's Disease And Fmri., Alex A Macdonald, Ken N Seergobin, Ruzbeh Tamjeedi, Adrian M Owen, Jean-Sebastien Provost, Oury Monchi, Hooman Ganjavi, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

OBJECTIVE: Understanding cognition mediated by the striatum can clarify cognitive deficits in Parkinson's disease (PD). Previously, we claimed that dorsal striatum (DS) mediates cognitive flexibility. To refute the possibility that variation in cognitive effort confounded our observations, we reexamined our data to dissociate cognitive flexibility from effort. PD provides a model for exploring DS-mediated functions. In PD, dopamine-producing cells supplying DS are significantly degenerated. DS-mediated functions are impaired off and improved on dopamine replacement medication. Functional magnetic resonance imaging (fMRI) can confirm striatum-mediated functions.

METHODS: Twenty-two PD patients, off-on dopaminergic medication, and 22 healthy age-matched controls performed a number selection …

The Reversal Effects Of Curcumin, An Herbal Remedy, On The Impairments Induced By Vmat-2 Inhibitor Tetrabenazine, Emily Qian, Samantha E. Yohn

Honors Scholar Theses

Substantial evidence has shown that dopamine (DA), particularly in the nucleus accumbens (NAc), is involved in behavioral activation and effort-related processes, such as overcoming work related response costs. Interference with accumbens DA transmission through administration of the vesicular monoamine transportor-2 (VMAT-2) inhibitor tetrabenazine (TBZ) produces an alteration of response allocation in the concurrent FR5/chow choice procedure, biasing animals toward the lower effort alternative. It has been suggested that these drug-induced shifts in effort-related choice behavior seen in rodents are analogous to symptoms such as psychomotor retardation, anergia, and fatigue, which can be observed in people with depression and other related …

Effector-Independent Motor Sequence Representations Exist In Extrinsic And Intrinsic Reference Frames., Tobias Wiestler, Sheena Waters-Metenier, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences …

A Dedicated Binding Mechanism For The Visual Control Of Movement., Alexandra Reichenbach, David W Franklin, Peter Zatka-Haas, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

The human motor system is remarkably proficient in the online control of visually guided movements, adjusting to changes in the visual scene within 100 ms [1-3]. This is achieved through a set of highly automatic processes [4] translating visual information into representations suitable for motor control [5, 6]. For this to be accomplished, visual information pertaining to target and hand need to be identified and linked to the appropriate internal representations during the movement. Meanwhile, other visual information must be filtered out, which is especially demanding in visually cluttered natural environments. If selection of relevant sensory information for online control …

Gene Co-Citation Networks Associated With Worker Sterility In Honey Bees., Emma Kate Mullen, Mark Daley, Alanna Gabrielle Backx, Graham James Thompson

Brain and Mind Institute Researchers' Publications

BACKGROUND: The evolution of reproductive self-sacrifice is well understood from kin theory, yet our understanding of how actual genes influence the expression of reproductive altruism is only beginning to take shape. As a model in the molecular study of social behaviour, the honey bee Apis mellifera has yielded hundreds of genes associated in their expression with differences in reproductive status of females, including genes directly associated with sterility, yet there has not been an attempt to link these candidates into functional networks that explain how workers regulate sterility in the presence of queen pheromone. In this study we use available …

Investigating The Relation Between Striatal Volume And Iq., Penny A Macdonald, Hooman Ganjavi, D Louis Collins, Alan C Evans, Sherif Karama

Brain and Mind Institute Researchers' Publications

The volume of the input region of the basal ganglia, the striatum, is reduced with aging and in a number of conditions associated with cognitive impairment. The aim of the current study was to investigate the relation between the volume of striatum and general cognitive ability in a sample of 303 healthy children that were sampled to be representative of the population of the United States. Correlations between the WASI-IQ and the left striatum, composed of the caudate nucleus and putamen, were significant. When these data were analyzed separately for male and female children, positive correlations were significant for the …

Activation Of Mglur2/3 Receptors In The Ventro-Rostral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By Systemic Nmda Receptor Antagonists., Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …

Direct Control Of Visual Perception With Phase-Specific Modulation Of Posterior Parietal Cortex, Andrew Jaegle, Tony Ro

Publications and Research

We examined the causal relationship between the phase of alpha oscillations (9–12 Hz) and conscious visual perception using rhythmic TMS (rTMS) while simultaneously recording EEG activity. rTMS of posterior parietal cortex at an alpha frequency (10 Hz), but not occipital or sham rTMS, both entrained the phase of subsequent alpha oscillatory activity and produced a phase-dependent change on subsequent visual perception, with lower discrimination accuracy for targets presented at one phase of the alpha oscillatory waveform than for targets presented at the opposite phase. By extrinsically manipulating the phase of alpha before stimulus presentation, we provide direct evidence that the …

Bihemispheric Transcranial Direct Current Stimulation Enhances Effector-Independent Representations Of Motor Synergy And Sequence Learning., Sheena Waters-Metenier, Masud Husain, Tobias Wiestler, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Complex manual tasks-everything from buttoning up a shirt to playing the piano-fundamentally involve two components: (1) generating specific patterns of muscle activity (here, termed "synergies"); and (2) stringing these into purposeful sequences. Although transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has been found to increase the learning of motor sequences, it is unknown whether it can similarly facilitate motor synergy learning. Here, we determined the effects of tDCS on the learning of motor synergies using a novel hand configuration task that required the production of difficult muscular activation patterns. Bihemispheric tDCS was applied to M1 of …

Allocating Structure To Function: The Strong Links Between Neuroplasticity And Natural Selection, Michael Anderson, Barbara L. Finlay

Brain and Mind Institute Researchers' Publications

A central question in brain evolution is how species-typical behaviors, and the neural function-structure mappings supporting them, can be acquired and inherited. Advocates of brain modularity, in its different incarnations across scientific subfields, argue that natural selection must target domain-dedicated, separately modifiable neural subsystems, resulting in genetically-specified functional modules. In such modular systems, specification of neuron number and functional connectivity are necessarily linked. Mounting evidence, however, from allometric, developmental, comparative, systems-physiological, neuroimaging and neurological studies suggests that brain elements are used and reused in multiple functional systems. This variable allocation can be seen in short-term neuromodulation, in neuroplasticity over the …

The Impact Of Multisensory Integration Deficits On Speech Perception In Children With Autism Spectrum Disorders., Ryan A Stevenson, Magali Segers, Susanne Ferber, Morgan D Barense, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Speech perception is an inherently multisensory process. When having a face-to-face conversation, a listener not only hears what a speaker is saying, but also sees the articulatory gestures that accompany those sounds. Speech signals in visual and auditory modalities provide complementary information to the listener (Kavanagh and Mattingly, 1974), and when both are perceived in unison, behavioral gains in in speech perception are observed (Sumby and Pollack, 1954). Notably, this benefit is accentuated when speech is perceived in a noisy environment (Sumby and Pollack, 1954). To achieve a behavioral gain from multisensory processing of speech, however, the auditory and visual …

Diffusion Tensor Imaging And White Matter Abnormalities In Patients With Disorders Of Consciousness., Carlo Cavaliere, Marco Aiello, Carol Di Perri, Davinia Fernandez-Espejo, Adrian M Owen, Andrea Soddu

Brain and Mind Institute Researchers' Publications

Progress in neuroimaging has yielded new powerful tools which, potentially, can be applied to clinical populations, improve the diagnosis of neurological disorders and predict outcome. At present, the diagnosis of consciousness disorders is limited to subjective assessment and objective measurements of behavior, with an emerging role for neuroimaging techniques. In this review we focus on white matter alterations measured using Diffusion Tensor Imaging on patients with consciousness disorders, examining the most common diffusion imaging acquisition protocols and considering the main issues related to diffusion imaging analyses. We conclude by considering some of the remaining challenges to overcome, the existing knowledge …

Bilateral Saccadic Deficits Following Large And Reversible Inactivation Of Unilateral Frontal Eye Field., Tyler R Peel, Kevin Johnston, Stephen G Lomber, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Inactivation permits direct assessment of the functional contribution of a given brain area to behavior. Previous inactivation studies of the frontal eye field (FEF) have either used large permanent ablations or reversible pharmacological techniques that only inactivate a small volume of tissue. Here we evaluated the impact of large, yet reversible, FEF inactivation on visually guided, delayed, and memory-guided saccades, using cryoloops implanted in the arcuate sulcus. While FEF inactivation produced the expected triad of contralateral saccadic deficits (increased reaction time, decreased accuracy and peak velocity) and performance errors (neglect or misdirected saccades), we also found consistent increases in reaction …

Short-Duration Stimulation Of The Supplementary Eye Fields Perturbs Anti-Saccade Performance While Potentiating Contralateral Head Orienting., Brendan B Chapman, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Many forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro- and anti-saccades, we show a surprising diversity of state-dependent effects of ICMS-SEF. Short-duration ICMS-SEF passed around cue presentation selectively disrupted anti-saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti-saccade trials. These results are consistent with the functional relevance of the …

An Invitation To The Study Of Brain Networks, With Some Statistical Analysis Of Thresholding Techniques, Mark Daley

Brain and Mind Institute Researchers' Publications

We provide a brief introduction to the nascent application of network theory to mesoscale networks in the human brain. Following an overview of the typical data-gathering, processing, and analysis methods employed in this field, we describe the process for inferring a graph from neural time series. A crucial step in the construction of a graph from time series is the thresholding of graph edges to ensure that the graphs represent physiological relationships rather than artifactual noise. We discuss the most popular currently employed methodologies and then introduce one of our own, based on the theory of random matrices. Finally, we …

Observing Object Lifting Errors Modulates Cortico-Spinal Excitability And Improves Object Lifting Performance., Gavin Buckingham, Jeremy D Wong, Minnie Tang, Paul L Gribble, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

Observing the actions of others has been shown to modulate cortico-spinal excitability and affect behaviour. However, the sensorimotor consequences of observing errors are not well understood. Here, participants watched actors lift identically weighted large and small cubes which typically elicit expectation-based fingertip force errors. One group of participants observed the standard overestimation and underestimation-style errors that characterise early lifts with these cubes (Error video--EV). Another group watched the same actors performing the well-adapted error-free lifts that characterise later, well-practiced lifts with these cubes (No error video--NEV). We then examined actual object lifting performance in the subjects who watched the EV …

Sign Language Ability In Young Deaf Signers Predicts Comprehension Of Written Sentences In English., Kathy N Andrew, Jennifer Hoshooley, Marc F Joanisse

Brain and Mind Institute Researchers' Publications

We investigated the robust correlation between American Sign Language (ASL) and English reading ability in 51 young deaf signers ages 7;3 to 19;0. Signers were divided into 'skilled' and 'less-skilled' signer groups based on their performance on three measures of ASL. We next assessed reading comprehension of four English sentence structures (actives, passives, pronouns, reflexive pronouns) using a sentence-to-picture-matching task. Of interest was the extent to which ASL proficiency provided a foundation for lexical and syntactic processes of English. Skilled signers outperformed less-skilled signers overall. Error analyses further indicated greater single-word recognition difficulties in less-skilled signers marked by a higher …

Links Between White Matter Microstructure And Cortisol Reactivity To Stress In Early Childhood: Evidence For Moderation By Parenting., Haroon I Sheikh, Marc F Joanisse, Sarah M Mackrell, Katie R Kryski, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at …

Sensitivity Of Human Auditory Cortex To Rapid Frequency Modulation Revealed By Multivariate Representational Similarity Analysis., Marc F Joanisse, Diedre D Desouza

Brain and Mind Institute Researchers' Publications

Functional Magnetic Resonance Imaging (fMRI) was used to investigate the extent, magnitude, and pattern of brain activity in response to rapid frequency-modulated sounds. We examined this by manipulating the direction (rise vs. fall) and the rate (fast vs. slow) of the apparent pitch of iterated rippled noise (IRN) bursts. Acoustic parameters were selected to capture features used in phoneme contrasts, however the stimuli themselves were not perceived as speech per se. Participants were scanned as they passively listened to sounds in an event-related paradigm. Univariate analyses revealed a greater level and extent of activation in bilateral auditory cortex in response …

Dopaminergic Medication Impairs Feedback-Based Stimulus-Response Learning But Not Response Selection In Parkinson's Disease., Andrew Vo, Nole M Hiebert, Ken N Seergobin, Stephanie Solcz, Allison Partridge, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

Cognitive dysfunction is a feature of Parkinson's Disease (PD). Some cognitive functions are impaired by dopaminergic medications prescribed to address the movement symptoms that typify PD. Learning appears to be the cognitive function most frequently worsened by dopaminergic therapy. However, this result could reflect either impairments in learning (i.e., acquisition of associations among stimuli, responses, and outcomes) or deficits in performance based on learning (e.g., selecting responses). We sought to clarify the specific effects of dopaminergic medication on (a) stimulus-response association learning from outcome feedback and (b) response selection based on learning, in PD. We tested 28 PD patients on …

Rule-Based Category Learning In Children: The Role Of Age And Executive Functioning., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Rule-based category learning was examined in 4-11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working …

Accumulation Of Subcortical Iron As A Modifier Of Volumetric And Cognitive Decline In Healthy Aging: Two Longitudinal Studies, Ana Marie Daugherty

Wayne State University Dissertations

Accumulation of non-heme iron in the brain has been theorized as a cellular mechanism underlying global neural and cognitive decline in normal aging and neurodegenerative disease. Relatively few studies of brain iron in normal aging exist and extant studies are almost exclusively cross-sectional. Here, I estimated iron content via T2* and measured volumes in several brain regions in two independent samples of healthy adults. The first sample (N = 89) was measured twice with a two-year delay; and the second sample (N = 32) was assessed four times over a span of 7 years. Latent models estimated change in iron …

Longitudinal Change In Regional Cortices And Fluid Intelligence, Peng Yuan

Wayne State University Dissertations

Fluid intelligence (Gf) and crystalized intelligence (Gc) are two factors of the general intelligence. They have distinct age-related trajectories of change. Jung and Haier proposed Parieto-Frontal Integration Theory (P-FIT, 2007) to account for the inter-person variance in reasoning intelligence. Some brain regions such as prefrontal, parietal, temporal and anterior cingulate cortices were included in the P-FIT model and were hypothesized to be involved in fluid reasoning task. Therefore, in the current study, we examined latent growth curves (LGC) of longitudinal change in Gf, Gc, prefrontal cortex, parietal cortex, anterior cingulate, temporal cortex and primary visual cortex. Forty-six healthy middle-aged and …

The Effect Of Gaba A Antagonism On Locomotor Activity And Dopamine Release In The Mouse Caudate Putamen Following Acute Toluene Inhalation: An In-Vivo Microdialysis Study, Sean Callan

Wayne State University Theses

Toluene is ubiquitous solvent commonly inhaled recreationally. Despite its frequency of misuse, there is little understanding of how toluene acts within the brain. To examine this, this master's thesis examined the impact of acutely inhaled toluene on dopamine (DA) release in the mouse CPu in vivo using microdialysis techniques. Toluene inhalation produced dose-dependent increases in DA levels as well as changes in locomotor activity. These effects were potentiated by pre-treatment with the GABAA antagonist bicuculline via reverse microdialysis delivery. These results suggest that the DA dynamics of toluene abuse are related to toluene's previously explored effects on the GABA system. …

Inattention And Hyperactivity Among Preschool Age Children Born Prematurely, Andrew Heitzer

Wayne State University Theses

A large body of literature shows that compared to children born at term, preterm- children are at increased risk for difficulties with inattention and hyperactivity. Less consistency exists, however, in the limited body of research exploring the contribution of early biological risk to behavioral disinhibition within the population of children born prematurely. Therefore, our goal was to examine perinatal variables that may influence activity level and hyperactivity among preterm preschoolers. Ninety-eight preterm (23.4 - 33.9 weeks gestation) preschoolers (3-4 years) participated in the study. Direct measures of inattention and hyperactivity as well as parental ratings were used to evaluate behavior. …

The Quetiapine Active Metabolite N-Desalkylquetiapine And The Neurotensin Nts1 Receptor Agonist Pd149163 Exhibit Antidepressant-Like Effects On Operant Responding In Male Rats, Todd M. Hillhouse, Zachary Shankland, Katelin S. Matazel, Ashley Keiser, Adam J. Prus

Journal Articles

Major depressive disorder (MDD) is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that are apparent following one week of quetiapine treatment, and it is possible that the active metabolite N-Desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS₁ receptor agonist PD149163 are suggestive of antidepressant efficacy, but the effects of a NTS …