Neuroscience and Neurobiology Commons^™

Characterization Of The Behavioral, Biochemical And Molecular Indices Of Stress Produced By Nicotine Exposure And Withdrawal In Male And Female Rats, Oscar Valentin Torres

Open Access Theses & Dissertations

Introduction: Tobacco use is a major economic and health problem. Particularly concerning is that women consume more tobacco products, have a more difficult time quitting, and are less likely to benefit from cessation therapies than men. As a result, women are at higher risk of developing tobacco-related diseases. Women are generally more susceptible to stress and are more likely to cope with stress by smoking as compared to men. During abstinence, women also experience intense anxiety as compared to men and report that the anxiety-reducing effects of smoking are the main reason for continued use and relapse. Thus, stress produced …

Maternal Separation Affects Dopamine Transporter Function In The Spontaneously Hypertensive Rat: An In Vivo Electrochemical Study, Jacqueline S. Womersley, Jennifer H. Hsieh, Lauriston A. Kellaway, Greg A. Gerhardt, Vivienne A. Russell

Neuroscience Faculty Publications

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR …

Synaptic Reorganization Of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury In Mice, Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Physiology Faculty Publications

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found …

Aging Is Associated With Positive Responding To Neutral Information But Reduced Recovery From Negative Information, Carien M. Van Reekum, Stacey M. Schaefer, Regina C. Lapate, Catherine J. Norris, Lawrence L. Greischar, Richard J. Davidson

Dartmouth Scholarship

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 …

Mind Perception: Real But Not Artificial Faces Sustain Neural Activity Beyond The N170/Vpp, Thalia Wheatley, Anna Weinberg, Christine Looser, Tim Moran, Greg Hajcak

Dartmouth Scholarship

Faces are visual objects that hold special significance as the icons of other minds. Previous researchers using event-related potentials (ERPs) have found that faces are uniquely associated with an increased N170/vertex positive potential (VPP) and a more sustained frontal positivity. Here, we examined the processing of faces as objects vs. faces as cues to minds by contrasting images of faces possessing minds (human faces), faces lacking minds (doll faces), and non-face objects (i.e., clocks). Although both doll and human faces were associated with an increased N170/VPP from 175–200 ms following stimulus onset, only human faces were associated with a sustained …

Common And Distinct Mechanisms Of Cognitive Flexibility In Prefrontal Cortex, Chobok Kim, Nathan F. Johnson, Sara E. Cilles, Brian T. Gold

Neuroscience Faculty Publications

The human ability to flexibly alternate between tasks represents a central component of cognitive control. Neuroimaging studies have linked task switching with a diverse set of prefrontal cortex (PFC) regions, but the contributions of these regions to various forms of cognitive flexibility remain largely unknown. Here, subjects underwent functional brain imaging while they completed a paradigm that selectively induced stimulus, response, or cognitive set switches in the context of a single task decision performed on a common set of stimuli. Behavioral results indicated comparable reaction time costs associated with each switch type. Domain-general task-switching activation was observed in the inferior …

Alterations In Multiple Measures Of White Matter Integrity In Normal Women At High Risk For Alzheimer's Disease, Brian T. Gold, David K. Powell, Anders H. Andersen, Charles D. Smith

Neuroscience Faculty Publications

There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging …

Differential Activation Of Frontoparietal Attention Networks By Social And Symbolic Spatial Cues, Andrew D. Engell, Lauri Nummenmaa, Nikolaas N. Oosterhof, Richard N. Henson, James V. Haxby, Andrew J. Calder

Dartmouth Scholarship

Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer’s attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a ‘special’ category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non-biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain’s response during target localization in which laterally …

Behind The Mask: The Influence Of Mask-Type On Amygdala Response To Fearful Faces, M Justin Kim, Rebecca A. Loucks, Maital Neta, F. Caroline Davis, Jonathan A. Oler, Emily C. Mazzulla, Paul J. Whalen

Dartmouth Scholarship

In this study, we compared the effects of using neutral face masks vs non-face pattern masks on amygdala activity to masked fearful faces. Twenty-seven subjects viewed 18 s blocks of either fearful or happy faces masked with either neutral faces or patterns, while their brain activity was measured using functional magnetic resonance imaging. Results replicated increased amygdala activation to face-masked fearful vs happy faces. In the pattern mask condition, the amygdala discriminated between masked fearful and happy faces, but this effect manifested as a decrease in activation to fearful faces compared to happy faces. This interactive effect between facial expression …

Dopamine D1 Receptor-Mediated Nmda Receptor Insertion Depends On Fyn But Not Src Kinase Pathway In Prefrontal Cortical Neurons, Jian-Li Hu, Gang Liu, Yan-Chun Li, Wen-Jun Gao, Yueqiao Huang

PCOM Scholarly Papers

Background. Interactions between dopamine and glutamate in the prefrontal cortex are essential for cognitive functions such as working memory. Modulation of N-methyl-D-aspartic acid (NMDA) receptor functions by dopamine D1 receptor is believed to play a critical role in these functions. The aim of the work reported here is to explore the signaling pathway underlying D1 receptor-mediated trafficking of NMDA receptors in cultured rat prefrontal cortical neurons. Results. Activation of D1 receptor by selective agonist SKF-81297 significantly increased the expression of NR2B subunits. This effect was completely blocked by small interfering RNA knockdown of Fyn, but not Src. Under control conditions, …

Aging Influences The Neural Correlates Of Lexical Decision But Not Automatic Semantic Priming, Brian T. Gold, Anders H. Andersen, Greg A. Jicha, Charles D. Smith

Neuroscience Faculty Publications

Human behavioral data indicate that older adults are slower to perform lexical decisions (LDs) than young adults but show similar reaction time gains when these decisions are primed semantically. The present study explored the functional neuroanatomic bases of these frequently observed behavioral findings. Young and older groups completed unprimed and primed LD tasks while functional magnetic resonance imaging (fMRI) was recorded, using a fully randomized trial design paralleling those used in behavioral research. Results from the unprimed task found that age-related slowing of LD was associated with decreased activation in perceptual extrastriate regions and increased activation in regions associated with …

Microsaccade Rate Varies With Subjective Visibility During Motion-Induced Blindness, Po-Jang Hsieh, Peter U. Tse

Dartmouth Scholarship

Motion-induced blindness (MIB) occurs when a dot embedded in a motion field subjectively vanishes. Here we report the first psychophysical data concerning effects of microsaccade/eyeblink rate upon perceptual switches during MIB. We find that the rate of microsaccades/eyeblink rises before and after perceptual transitions from not seeing to seeing the dot, and decreases before perceptual transitions from seeing it to not seeing it. In addition, event-related fMRI data reveal that, when a dot subjectively reappears during MIB, the blood oxygen-level dependent (BOLD) signal increases in V1v and V2v and decreases in contralateral hMT+. These BOLD signal changes observed upon perceptual …

Medial Temporal Lobe Bold Activity At Rest Predicts Individual Differences In Memory Ability In Hhealthy Young Adults, Gagan S. Wig, Scott T. Grafton, Kathryn E. Demos, George L. Wolford, Steven E. Petersen, William M. Kelley

Dartmouth Scholarship

Human beings differ in their ability to form and retrieve lasting long-term memories. To explore the source of these individual differences, we used functional magnetic resonance imaging to measure blood-oxygen-level-dependent (BOLD) activity in healthy young adults (n = 50) during periods of resting fixation that were interleaved with periods of simple cognitive tasks. We report that medial temporal lobe BOLD activity during periods of rest predicts individual differences in memory ability. Specifically, individuals who exhibited greater magnitudes of task-induced deactivations in medial temporal lobe BOLD signal (as compared to periods of rest) demonstrated superior memory during offline testing. This relationship …

Switching Language Switches Mind: Linguistic Effects On Developmental Neural Bases Of ‘Theory Of Mind’, Chiyoko Kobayashi, Gary H. Glover, Elise Temple

Dartmouth Scholarship

Theory of mind (ToM)—our ability to predict behaviors of others in terms of their underlying intentions—has been examined through false-belief (FB) tasks. We studied 12 Japanese early bilingual children (8−12 years of age) and 16 late bilingual adults (18−40 years of age) with FB tasks in Japanese [first language (L1)] and English [second language (L2)], using fMRI. Children recruited more brain regions than adults for processing ToM tasks in both languages. Moreover, children showed an overlap in brain activity between the L1 and L2 ToM conditions in the medial prefrontal cortex (mPFC). Adults did not show such a convergent activity …

Detecting Agency From The Biological Motion Of Veridical Vs Animated Agents, Raymond A. Mar, William M. Kelley, Todd F. Heatherton, C. Neil Macrae

Dartmouth Scholarship

The ability to detect agency is fundamental for understanding the social world. Underlying this capacity are neural circuits that respond to patterns of intentional biological motion in the superior temporal sulcus and temporoparietal junction. Here we show that the brain's blood oxygenation level dependent (BOLD) response to such motion is modulated by the representation of the actor. Dynamic social interactions were portrayed by either live-action agents or computer-animated agents, enacting the exact same patterns of biological motion. Using an event-related design, we found that the BOLD response associated with the perception and interpretation of agency was greater when identical physical …

Functional Dissociation In Frontal And Striatal Areas For Processing Of Positive And Negative Reward Information, Xun Liu, David K. Powell, Hongbin Wang, Brian T. Gold, Christine R. Corbly, Jane E. Joseph

Neuroscience Faculty Publications

Reward-seeking behavior depends critically on processing of positive and negative information at various stages such as reward anticipation, outcome monitoring, and choice evaluation. Behavioral and neuropsychological evidence suggests that processing of positive (e.g., gain) and negative (e.g., loss) reward information may be dissociable and individually disrupted. However, it remains uncertain whether different stages of reward processing share certain neural circuitry in frontal and striatal areas, and whether distinct but interactive systems in these areas are recruited for positive and negative reward processing. To explore these issues, we used a monetary decision-making task to investigate the roles of frontal and striatal …

Prior Experience As A Stimulus Category Confound: An Example Using Facial Expressions Of Emotion, Leah H. Somerville, Paul J. Whalen

Dartmouth Scholarship

Facial expressions of emotion represent a stimulus set widely used to assess a broad range of psychological processes. However, a consideration of systematic differences between expression categories, other than differences relating to characteristics of the expressions themselves, has remained largely unaddressed. By collecting experience rankings in a large sample of undergraduates, we observed that the amount of reported experience individuals have had with different facial expressions of emotion systematically differed between all expression categories. These findings shed light on the potential for identifying confounds inherent to comparing some stimulus categories and, in this case, may aid in the interpretation of …

Dissociation Of Automatic And Strategic Lexical-Semantics: Functional Magnetic Resonance Imaging Evidence For Differing Roles Of Multiple Frontotemporal Regions, Brian T. Gold, David A. Balota, Sara J. Jones, David K. Powell, Charles D. Smith, Anders H. Andersen

Neuroscience Faculty Publications

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and …

Medial Prefrontal Activity Differentiates Self From Close Others, Todd F. Heatherton, Carrie L. Wyland, C. Neil Macrae, Kathryn E. Demos, Bryan T. Denny, William M. Kelley

Dartmouth Scholarship

No abstract provided.

Prenatal Cocaine Exposure Alters Alpha2 Receptor Expression In Adolescent Rats, Rosemarie M. Booze, David R. Wallace, Janelle M. Silvers, Barbara J. Strupp, Diane M. Snow, Charles F. Mactutus

Neuroscience Faculty Publications

BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured alpha2-adrenergic receptor (alpha2-AR) density in adolescent (35-days-old) rats, using [3H]RX821002 (5 nM).

RESULTS: Sex-specific alterations of alpha2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of alpha2-AR in parietal cortex.

CONCLUSION: These data suggest that prenatal cocaine exposure results in a persistent alteration …

Visibility, Visual Awareness, And Visual Masking Of Simple Unattended Targets Are Confined To Areas In The Occipital Cortex Beyond Human V1/V2, Peter U. Tse, Susanna Martinez-Conde, Alexander A. Schlegel, Stephen L. Macknik

Dartmouth Scholarship

In visual masking, visible targets are rendered invisible by modifying the context in which they are presented, but not by modifying the targets themselves. Here, we localize the neuronal correlates of visual awareness in the human brain by using visual masking illusions. We compare monoptic visual masking activation, which we find within all retinotopic visual areas, with dichoptic masking activation, which we find only in those retinotopic areas downstream of V2. Because monoptic and dichoptic masking are equivalent in magnitude perceptually, the present results establish a lower bound for maintenance of visual awareness of simple unattended targets. Moreover, we find …

Donepezil Effects On Mood In Patients With Schizophrenia And Schizoaffective Disorder, S Craig Risch, Michael D. Horner, Susan R. Mcgurk, Simmy Palecko, John S. Markowitz, Ziad Nahas, C. Lindsay Devane

Dartmouth Scholarship

Donepezil, 5 mg/d for 6 wk then 10 mg/d for 6 wk, and placebo daily for 12 wk in a double-blind cross-over paradigm, was added to the therapeutic regimen of 13 patients with schizophrenia or schizoaffective disorders, clinically stable on atypical antipsychotic medications. Patients had varying degrees of depressive symptoms, ranging from no depression to clinically significant depression. There was no worsening or induction of depression in individual patients or the group as a whole. In addition there was a statistically significant antidepressant effect in the group as a whole during the donepezil condition and a clinically significant antidepressant effect …

Il-23 Produced By Cns-Resident Cells Controls T Cell Encephalitogenicity During The Effector Phase Of Experimental Autoimmune Encephalomyelitis, Burkhard Becher, Brigit G. Durell, Randolph J. Noelle

Dartmouth Scholarship

CNS-resident cells, in particular microglia and macrophages, are a source of inflammatory cytokines during inflammation within the CNS. Expression of IL-23, a recently discovered cytokine, has been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE) in mice. Expression of the p40 subunit of IL-12 and IL-23 by microglia has been shown in situ and in vitro, but direct evidence for a functional significance of p40 expression by CNS cells during an immune response in vivo is still lacking. Here we report that p40 plays a critical role in maintaining encephalitogenicity during the disease course. By using …

Distinct Neural Systems Subserve Person And Object Knowledge, Jason P. Mitchell, Todd F. Heatherton, C. Neil Macrae

Dartmouth Scholarship

Studies using functional neuroimaging and patient populations have demonstrated that distinct brain regions subserve semantic knowledge for different classes of inanimate objects (e.g., tools, musical instruments, and houses). What this work has yet to consider, however, is how conceptual knowledge about people may be organized in the brain. In particular, is there a distinct functional neuroanatomy associated with person knowledge? By using event-related functional magnetic resonance imaging (fMRI), we measured neural activity while participants made semantic judgments about people or objects. A unique pattern of brain activity was associated with person judgments and included brain regions previously implicated in other …