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Cognitive and Neurobiological Approaches to Plasticity

Cognitive & Neurobiological Approaches to Plasticity

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Kansas State University
Department of Psychological Sciences
492 Bluemont Hall
1114 Mid-Campus Drive
Manhattan,KS 66506
Phone: (785) 532-6850

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P20GM113109

Pilot Grants

Stephanie HallMitochondrial dysfunction and its role in Alzheimer's disease

Stephanie Hall, Ph.D.
Assistant Professor, Department of Anatomy & Physiology

Nearly 6 million Americans suffer from Alzheimer’s disease (AD) and that number is expected to rise to 14 million by 2050. Currently there is no cure or even a treatment to slow its progression; however, exercise has been proven to reduce risk. Several studies have linked exercise to improved cognition and increased brain volume for people with AD. This project will establish the degree of mitochondrial function and oxidative damage protection provided by exercise. This will provide an essential step to next evaluating the role of mitochondrial dysfunction in a novel transgenic rat model (TgF344-AD). This project is the necessary first step in understanding the exercise-induced mitochondrial function changes in both the brain and skeletal muscle. The results of this experiment will lead to future extramural research proposals utilizing the novel transgenic rat model, TgF344-AD. The implications of this project could establish mitochondrial function as a pharmacological approach of interest in the treatment of this devastating disease. 

Mentor: Dr. David Poole (K-State)

                                               

 

Barbara PittsThe Effects of Reduced Inhibition on Memory for Complex Stimuli in Older Adults

Barbara Pitts, Ph.D.
Research Assistant Professor, Department of Psychological Sciences

The overall goal of this research is to determine the effects of reduced inhibitory control on older adults’ memory for complex, real-world events. The ability to inhibit irrelevant perceptual information and focus on relevant information is important to the process of understanding and remembering what is happening. Unfortunately, inhibition declines with age. In fact, older adults are more likely than young adults to remember task-irrelevant words and still images; the result of a process called hyperbinding. Currently, our knowledge of this phenomenon is limited to findings using static images and words, which are difficult to relate to the continuous stream of information we face in the real world. The aim of this proposed project is to evaluate age-related differences in the extent to which young and older adults represent task-irrelevant information in their event models of real-world events. This project will feed into the long-term research goal of understanding how event processing and memory are changed by healthy aging and is a first step towards developing a novel research program designed to identify the real-world effects of reduced inhibition on older adults’ memory.

Mentor: Dr. Karen Campbell (Brock University)

 

 

Abbie ViscardiThe impact of early life stress on brain development, immune function, and behavior

Abbie Viscardi, Ph.D.
Research Assistant Professor, Department of Anatomy & Physiology

The overarching goal of this research program is to improve lifelong brain health. To do so, we must first understand the early life origins of psychological resilience and susceptibility to declines in mental health. This project will examine how early life stress changes brain development and neural plasticity, using a swine model. Significant stress in early life alters neurodevelopmental processes and later brain function, putting individuals at greater risk of developing psychiatric disorders. The mechanisms by which these brain alterations contribute to the development of psychopathology are complex and difficult to study in humans. Pigs are increasingly being used as models of human brain disorders, as the anatomy, growth and development of the swine brain is very similar to humans. The central hypothesis of this project is that reducing early life stress will lead to a reduction in damaging agonistic behavior, a stronger immune system, sustained brain development and improved brain function later in life. This pilot project aims to develop an “early life stress” animal model for future studies exploring effective interventions, treatments or therapies to reduce the development of human psychiatric disorders.

Mentor: Dr. Johann Coetzee(K-State)

 

 

Matthew WisniewskiAuditory alpha rhythms: an independent component analysis (ICA) approach

Matthew Wisniewski, Ph.D.
Assistant Professor, Department of Psychological Sciences

Standard electroencephalogram (EEG) analysis practices in auditory science leave many task-related brain dynamics invisible to researchers. Importantly, temporal lobe "auditory alpha" oscillations (~7-13 Hz) are absent from event-related potentials (ERPs) and can be easily masked by more powerful non-auditory rhythms using traditional time-frequency analyses. As a result, theory on alpha oscillations in the brain is informed disproportionately by visual and motor studies. Progress is also limited in the study of disorders (e.g., schizophrenia and tinnitus) known to have abnormal auditory alpha as quantified with the magnetoencephalogram (MEG) and intracranial recordings. The aim of this project is to develop a measure of auditory alpha in EEG data. Independent component analysis (ICA) will be used to identify temporally independent brain dynamics localized to the temporal lobes in human subjects. A variety of parameters (e.g., high-pass filtering, low-pass filtering, channel count, ICA model) will be tested on the same data. This will identify procedural/analysis parameters yielding independent components (ICs) that most adequately characterize auditory alpha. The project will have a strong theoretical and health-relevant impact by giving scientists a well characterized measure to examine auditory alpha dynamics with EEG.

Mentors: Drs. Gary Brase (K-State) and Scott Makeig (University of California, San Diego)

 
Previous Pilot Grants

Cognitive flexibility in an animal model of autism spectrum disorder and changes in the cerebellum

Bethany Plakke, Ph.D.
Assistant Professor, Department of Psychological Sciences

Autism spectrum disorder (ASD) is a pervasive developmental disorder where children exhibit deficits in social interactions and communication abilities, as well as increases in repetitive behaviors. In addition, individuals with ASD frequently have impairments on tasks that test cognitive flexibility. While some progress has been made in understanding the neural networks involved in ASD, very little is understood about cognitive deficits and their underlying neurobiology. Current research in our lab is examining changes in cognitive flexibility in a rodent model of ASD using an attentional set-shifting task (SST). In humans, pregnant woman that took medication containing valproic acid (VPA) had children that developed ASD at a rate 4-8 times higher than that in the general population. This project utilizes a VPA rodent model which mimics human fetal exposure by introducing VPA into the system of a pregnant dam and then testing the offspring. The aim of this proposal is to examine cerebellar changes in VPA treated animals and to use those changes as a histological marker to determine if these histological markers are related to cognitive flexibility in the SST. 

Mentors: Drs. William DeCoteau (St. Lawrence University) and Adam Fox (St. Lawrence University)

 

Effects of Exercise on Animal Cognition

David Jarmolowicz, Ph.D.
Associate Professor, University of Kansas

Over 20 million Americans suffer from substance use disorder (SUD) costing the U.S. economy over $740 billion per year. These individuals often want to stop using, yet a hallmark of SUD is its resistance to treatment. Thus, there is a critical need to develop effective treatments for SUD. The success of substance abuse treatments may be improved by restoring the balance between two brain systems – the executive and impulsive systems. Targeted improvement of this balance, however, requires that we understand how therapeutic approaches impact the health of each of these brain systems. We will determine how a promising approach – physical exercise – impacts the health of these brain systems. The long term objective of this research is to leverage our understanding of the competing neurobehavioral decision systems to improve SUD treatment outcomes.

Mentor: Dr. Michael Johnson (University of Kansas)

 

Neural circuits of associative emotional learning in a zebrafish autism model

Thomas Mueller, Ph.D.
Research Assistant Professor, Division of Biology

Altered brain plasticity and impairments of socio-emotional behaviors are hallmarks of spectrum autism disorders alongside elevated anxiety and fear responses (which are typical comorbidities in in 50-80% of autism patients). Current research posits an imbalance of excitatory (E; glutamatergic) and inhibitory (I; GABAergic) signaling as central for the neuropathology of autism disorders. A major question in autism research is how alterations of specific neurons contribute to the E/I imbalance. The project will initiate a neural systems approach to address this question in a zebrafish model of autism. The results of the study will provide a critical foundation for subsequent functional studies on identified candidate neurons and their contribution to the pathophysiology of autism. 

Mentor: Dr. Stefan Bossmann (University of Kansas Medical Center)

 

Optimizing auditory training for beneficial outcomes

Matthew Wisniewski, Ph.D.
Assistant Professor, Department of Psychological Sciences

This project will improve the prevention and treatment of auditory disorders by informing auditory training regimen design. People receive detailed information via sound that is important for survival (e.g., identification of sounds that cannot be seen), communication (e.g., speech), and quality of life (e.g., music listening). Approximately 30 million individuals aged 12 years or older in the U.S. have hearing loss (HL) in both ears that degrades this information. Such listeners must employ extensive mental effort to deal with the problems that come with these disorders. Explicit auditory training can increase the amount of detail extracted from sound and may potentially reduce a reliance on mental effort. However, little is known about how training regimens should be designed to maximize benefits. This project takes the critical step of determining how the parameters of training impact outcomes. Here, a joint behavioral and neurophysiological approach will be taken to assess the outcomes of the some of the most popular auditory training regimens. Thus, this work will yield information about how training can maximally benefit the processing of speech under conditions of hearing protection (which is necessary to avoid hearing-loss) and hearing loss itself.

Mentor: Dr. Barbara Church (Georgia State University)

 

Neural Correlates of Metacognitive Accuracy using Electroencephalography

Alexandria Zakrzewski, Ph.D.
Research Assistant Professor, Department of Psychological Sciences

The overall goal of this proposal is to identify the neural correlates of metacognitive accuracy (i.e., how accurately we monitor our cognitive processes) to develop a rehabilitative method based in electroencephalography (EEG). Humans make metacognitive judgments about their cognitive processes (e.g., memory, perception, and learning). How well these judgments evaluate cognitive abilities (i.e., metacognitive accuracy) is crucial for effective regulation of one’s thoughts and behavior. Recent research shows feedback can improve metacognitive abilities; however, it is unclear how long this improvement lasts. Neurofeedback could increase brain responses associated with improved metacognitive accuracy, just as it has been used to change neural activity to decrease symptoms of ADHD.  Understanding the degree to which neural responses are related to metacognitive accuracy may produce new types of treatments for poor metacognition. This is especially important because poor metacognition impacts individuals’ ability to gauge their physical and mental health. Training regimens would allow individuals to better monitor and regulate behavior and the EEG methods studied here can strengthen this training.

Mentor: Dr. Brian Maniscalco (University of California-Irvine)

 

Neural Plasticity after Exercise in Teens (NPET)

Amanda Bruce, Ph.D.
Assistant Professor, University of Kansas Medical Center

Physical activity improves cognition and results in neural plasticity. The positive effects of exercise on brain health have been shown in older adults, but fewer studies have demonstrated the effects of exercise on neural plasticity in youth.  Some studies have found that greater hippocampal and basal ganglia volume was associated with better aerobic fitness, while other studies demonstrated improved cognition after an acute bout of exercise and a prolonged exercise program. Neural mechanisms are key in food decisions and these differ between normal weight (higher self-control) and obese adolescents (higher reward).  There is a critical need to better understand how exercise impacts cognition, as well as reward, control, and decision neural pathways in overweight/obese (OW/OB) youth. This study’s short-term goal is to assess executive functioning and neural mechanisms of food and activity decision-making in sedentary OW/OB youth, and to quantify changes following an exercise intervention. The long-term goal is to develop and promote effective, evidence-based interventions to prevent and treat childhood obesity. 

Mentor: Dr. Ann Davis (University of Kansas Medical Center)


Amygdala Circuits of Associate Learning and Reward Behavior in Zebrafish: An MRI Approach

Thomas Mueller, Ph.D.
Research Assistant Professor, Division of Biology

Modern Magnetic Resonance Imaging (MRI) methods such as Diffusion Tension Imaging (DTI) allow researchers to study intact whole brains, revealing neural circuits of behavior in natural three-dimensional complexity. This pilot project builds the  foundation for an interdisciplinary zebrafish-focused MRI approach by studying how the brain mediates learning and motivated behavior in health and disease. Specifically, the project will establish a combination of behavioral paradigms and DTI methodology targeting zebrafish to examine how the amygdala, the quintessential core of the emotional brain, controls associative learning and motivation. The results of the study will establish feasibility for comparative MRI functional connectivity studies using zebrafish as a model for human affective disorders and addiction.  The pilot project results will also provide the basis for future MRI studies on amygdala function in zebrafish wildtype, transgenic, and mutant lines to investigate the physiological roles of dopamine, serotonin and other neuroactive substances during associative learning. Ultimately, the established behavioral and MRI protocols will be adapted to study neurotransmitter and neuropeptide function across multiple levels of organization, from whole brain activity to cellular and synaptic circuitry. 

Mentor: Dr. Stefan Bossmann (University of Kansas Medical Center)

 


Understanding ArfGAP1 function in LRRK2-linked neuronal plasticity in Parkinson’s disease

Yulan Xiong, Ph.D.
Assistant Professor, University of Connecticut Health Center

Parkinson's disease (PD) is the most common movement disorder and is caused by a combination of risk factors including environmental exposure, age, and a positive family history for disease. Several genes have been unambiguously identified from the families with heritable PD. Mutations in the protein coding gene LRRK2 are the most common genetic cause of PD. Given its strong genetic links, LRRK2 represents a clear and compelling target for therapeutic development to treat PD. However, the mechanisms that regulate LRRK2 function and the LRRK2-linked disease remain unclear. In this proposal, we will acutely overexpress or knock down of ArfGAP1 in our newly developed LRRK2 mouse models and determine ArfGAP1 function in regulating LRRK2-linked neuronal plasticity in vivo including behavioral deficits and dopamine neurodegeneration. The overall goal of our proposal is to determine whether reciprocal interaction between ArfGAP1 and LRRK2 controls neurodegeneration. New knowledge regarding this aspect of LRRK2 biology will advance our understanding of the physiologic and pathophysiologic actions of LRRK2 as well as potential identification of novel targets for future pharmacologic intervention.

Mentor: Dr. Philine Wangemann (K-State)