Portrait of Dr. Bethany Plakke

Altered frontal cortex function in aged Fmr1 KOs

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

Mentors: Dr. Mary Cain (Kansas State University) & Dr. Michael E Ragozzino (University of Illinois Chicago)

"Alterations in the FMR1 gene causes both a neurodevelopmental disorder known as fragile X-syndrome (FXS) and fragile X-associated ataxia (FXTAS). FXS results in loss of the FMR1 protein (FMRP), causing autism spectrum disorder in most individuals; whereas FXTAS begins in middle age and leads to cerebellar ataxia. These disorders run in families as the premutation carrier (which can develop FXTAS) is the parent of the FXS individual. However, not many studies have been completed to understand the trajectory of cognitive decline across the lifespan. An animal model has been created which replicates the FXS outcomes by knocking out part of the FMR1 gene and causes a loss of FMRP. The heterozygous females used to breed the knockout will serve as a model of FXTAS (they carry the PM). This proposal would age the Fmr1 KO rats (FXS model) and the heterozygous females (PM model) to examine underlying pathology that could impact cognitive decline and coordination that occurs in both disorders with age. Aim 1 will examine decayed neural function by recording from medial prefrontal regions while animals perform cognitive tasks. Cognitive decline occurs for both FXS and FXTAS individuals but studies examining how aging impacts neural activity during cognitive performance have not been completed. Recording from medial prefrontal cortex during learning will elucidate how neural function is altered in aged subjects and impacted within FXS and FXTAS. Aim 2 will examine biomarkers associated with neurodegeneration related to neuroinflammation and oxidative stress. In tandem, these experiments will examine different mechanisms that could be contributing to cognitive decline and altered coordination in FXS and FXTAS. A better understanding of these mechanisms could assist in targeting treatments for the impacts of aging and assist other clinical populations with similar deficits such as those with Schizophrenia or Parkinson's."

- Dr. Plakke

Portrait of Dr. Meena KumariExosomes and modulation of neuroplasticity by oxycodone using 3D human brain cell culture

Meena Kumari, Ph.D.
Associate Professor, Department of Anatomy and Physiology, Kansas State University

Mentor: Dr. Hans Coetzee (Kansas State University)

"The long-term goals of this project are to understand how exosomes mediate chronic oxycodone effects on functional and structural neuroplasticity and identify biomarkers for oxycodone abuse to provide early therapeutic interventions to patients. In this application, goals are to determine 1) impact of chronic oxycodone on RNA cargo of exosomes from astrocytes, neurons, and microglia of human cortex origin as cortex expresses the highest level of opioid receptors and is highlighted in MRI scans as one of the areas responding to chronic oxycodone; 2) effects of chronic oxycodone on structural neuroplasticity using in vitro triple-cell (3D) cultures mimicking brain architecture; and 3) develop a micro-fluidic device based automated three-dimensional digital hydrogel (3DHC) system containing triple cell cultures for studying cell-cell communication and high throughput drug testing."

- Dr. Kumari

Portrait of Dr. Tianjun SunBuilding AI conversational agents to assess cognitive functioning in older adults

Tianjun Sun, Ph.D.
Assistant Professor, Department of Psychological Sciences, Kansas State University

Mentors: Drs. Heather Bailey (Kansas State University) & Doina Caragea (Kansas State University)

"The goal of the pilot project is to develop a prototype for a cost-efficient, scalable, and personalized screening tool for cognitive decline—in the form of an Artificial Intelligence (AI) conversational agent—that can be used to assess cognitive functioning in older adults. Upon further development from the pilot prototype, the tool will eventually be able to validly detect the subtle indicators of cognitive decline well before older individuals have started to experience the negative effects of cognitive impairment. The AI agent can be used as a computer-mediated approach to gathering information on a person to monitor their cognitive functioning development. The AI agent uses a one-on-one, text-based interview to interact with a user in a human-like, relational, and engaging manner. The AI system automatically derives the user's characteristics using a criterion-based computational assessment approach based on natural language processing (NLP) and machine learning (ML) techniques guided by psychometric principles. It is expected that the text generated from the conversation can be used for assessing cognitive functioning in older adults to facilitate screening for MCI, given the evidence that those who are suffering from cognitive decline show altered language output. To create and validate this initial pilot prototype, I propose to test if the existing interview protocol on life history and experiences used by the AI can differentiate individual differences in cognitive functioning in older adults."

- Dr. Sun

Quan LeiUse Virtual Reality Games to Train Scotoma Awareness and Visual Search in Central Vision Loss

Quan Lei, Ph.D.
Assistant Professor, Department of Psychology, Wichita State University

Mentor: Dr. Gordon Legge (University of Minnesota)


"The goal of this project is to design a training program using virtual reality (VR) games to improve functional vision in patients with age-related macular degeneration (AMD). Due to central vision loss, AMD patients rely on peripheral retina for daily tasks including visual search, which is largely inefficient due to poor acuity and suboptimal eye movement control. With limited success, previous research explored methods of training AMD patients to adopt a reliable peripheral retinal locus (PRL) for fixation and develop an efficient scanning strategy in order to improve visual search performance. One factor that potentially limits the training effect but has not been examined closely is scotoma awareness. AMD patients are generally not aware of the presence or properties (location and size) of their scotomas, which may have impeded the development of PRL and an efficient scanning strategy. Previous training research also suffered from poor generalizability to relevant daily tasks, presumably due to the use of simple and artificial stimuli presented on a 2-D screen that lack the richness and structure of daily scenes. The recent rise of virtual reality (VR) may play a transformative role in improving the ecological validity of such training studies. Within the scope of a pilot grant, the proposed project is intended to address these gaps by using simulated scotomas as a model system to explore the feasibility of using VR games to train individuals with central vision loss on visual search of daily scenes."

- Dr. Lei

Previous Pilot Grants

Mitochondrial 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 sought to 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)

The 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 was 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)

The 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 was 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)

Auditory 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)

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)