Neurosciences Commons^™

Modulation In Nmda Receptor Function Alleviates Safety Learning Deficit In Females Who Experienced Chronic Stress During Adolescence, Zuby C. Okafor

Theses and Dissertations

Anxiety disorders disproportionately impact women and are more prevalent in people with a history of chronic stress. Post-traumatic stress disorder (PTSD) is a type of stress and trauma-related disorder that is largely characterized by hyperarousal to fear-based cues. The inability to dissociate the fear-response from a non-threatening cue is known as impaired safety learning. Given that N-methyl-D-aspartate (NMDA) receptors are key mediators of learning behaviors, we examined the role of NMDAr function in deficient safety learning. Previous studies have shown that female rats with a history of stress have altered NMDAr gene expression and altered glutamatergic signaling; therefore, we hypothesized …

Glycosaminoglycan Modulation Of Key Proteins In Alzheimer's Disease, Tamim Chiba

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar (D-glucosamine) and either uronic acid (D-glucuronic acid or L-iduronic acid) or galactose. Nearly all GAGs (with the exception of hyaluronic acid) are covalently attached to proteins, forming proteoglycans, and are ubiquitous in nature. The monomeric units, chain length, degree and pattern of sulfation, and epimerization are important properties that determine the influence of these molecules. Through Coulombic forces, hydrogen bonds and hydrophobic interactions, they regulate many physiological and pathophysiological processes such as blood coagulation, cell growth and differentiation, inflammatory processes, host defense and viral infection mechanisms. …

Cue Polarization And Representation In Mouse Home-Base Establishment, Ericka Ann Schaeffer

Graduate Research Theses & Dissertations

Many individuals suffer from navigational deficits and subsequent topographical disorientation, yet there is debate over how navigation to a goal is represented within the brain. Early research suggests animals represent their environment in a Cartesian coordinate system which manifests into a cognitive map. Current research suggests animals use a vector-based system which gives rise to a directional response. These studies examined responses to the environment when there was a specific end goal (i.e., hidden platform, food reward, etc.), versus an animal’s internal goal, home-base. The first study used mice to examine the influence of visual and tactile cues on the …

Vasopressin Regulates Daily Rhythms And Circadian Clock Circuits In A Manner Influenced By Sex, Kayla Rohr, Adam Telega, Alexandra Savaglio, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Arginine vasopressin (AVP) is a neurohormone that alters cellular physiology through both endocrine and synaptic signaling. Circadian rhythms in AVP release and other biological processes are driven by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Loss of vasopressin signaling alters circadian behavior, but the basis of these effects remains unclear. Here we investigate the role of AVP signaling in circadian timekeeping by analyzing behavior and SCN function in a novel AVP-deficient mouse model. Consistent with previous work, loss of AVP signaling increases water consumption and accelerates recovery to simulated jetlag. We expand on these results to show that loss …

Therapeutic Potential Of Mitophagy-Inducing Microflora Metabolite, Urolithin A For Alzheimer’S Disease, Dona Pamoda W. Jayatunga, Eugene Hone, Harjot Khaira, Taciana Lunelli, Harjinder Singh, Gilles J. Guillemin, Binosha Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins

Research outputs 2014 to 2021

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neuro-degenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bi-oactive food components, known as nutraceuticals, may serve as such agents to combat AD. Uro-lithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, …

Investigating Auditory Electrophysiological Measures Of Participants With Mild Cognitive Impairment And Alzheimer's Disease: A Systematic Review And Meta-Analysis Of Event-Related Potential Studies, Hadeel Y. Tarawneh, Wilhelmina H. A. M. Mulders, Hamid R. Sohrabi, Ralph N. Martins, Dona M. P. Jayakody

Research outputs 2014 to 2021

Background: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer's disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD. Objective: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i.e., mild cognitive impairment (MCI) and subjective cognitive decline. Methods: The search was performed on six major electronic databases (Ovid MEDLINE, OVID EMBASE, PsycINFO, PubMed, Scopus, …

Spon1 Is Associated With Amyloid-Β And Apoe Ε4-Related Cognitive Decline In Cognitively Normal Adults, Shane Fernandez, Samantha C. Burnham, Lidija Milicic, Greg Savage, Paul Maruff, Madeline Peretti, Hamid R. Sohrabi, Yen Ying Lim, Michael Weinborn, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, David Groth, Giuseppe Verdile, Victor L. Villemagne, Tenielle Porter, Simon M. Laws

Research outputs 2014 to 2021

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β …

Foveal Avascular Zone And Choroidal Thickness Are Decreased In Subjects With Hard Drusen And Without High Genetic Risk Of Developing Alzheimer’S Disease, Inés López-Cuenca, Rosa De Hoz, Celia Alcantara-Rey, Elena Salobrar-García, Lorena Elvira-Hurtado, José A. Fernández-Albarral, Ana Barabash, Federico Ramírez-Toraño, Jaisalmer De Frutos-Lucas, Juan J. Salazar, Ana I. Ramírez, José M. Ramírez

Research outputs 2014 to 2021

A family history (FH+) of Alzheimer’s disease (AD) and ɛ4 allele of the ApoE gene are the main genetic risk factors for developing AD, whereas ɛ4 allele plays a protective role in age-related macular degeneration. Ocular vascular changes have been reported in both pathologies. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT-angiography and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD) in 184 cognitively healthy subjects. Choroidal thickness was statistically significantly different in the (FH−, ɛ4−, HD+) group compared with …

Visual Perception And Action In Reaching During Upper Limb Obstacle Avoidance, Nondon Chakraborty

Theses and Dissertations (Comprehensive)

During everyday activities, people reach to specific objects with their hands and avoid obstacles. For people to move successfully through an obstacle gap, it is necessary to be able to accurately perceive the actions that the surroundings afford and adjust hand movements accordingly. Reaching behaviours, including planning (perception) and execution (action), depend on visual information. This study aimed to understand and detect the differences between perceptual judgment and actual performance of both hands during a reaching task at the time of obstacle avoidance by using a hand-scaled approach. Participants were young adults (male (n=7) and female (n=10) aged 18 to …

Association Of Β-Amyloid Level, Clinical Progression And Longitudinal Cognitive Change In Normal Older Individuals, Laura M. Van Der Krall, Thanh Truong, Samantha C. Burnham, Vincent Doré, Rachel S. Mulligan, Svetlana Bozinovski, Fiona Lamb, Pierrick Bourgeat, Jurgen Fripp, Stephanie Schultz, Yen Y. Lim, Simon M. Laws, David Ames, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Olivier Salvado, Joanne Robertson, Paul Maruff, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2014 to 2021

Objective To determine the effect of β-amyloid (Aβ) level on progression risk to mild cognitive impairment (MCI) or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals. Methods All CN from the Australian Imaging Biomarkers and Lifestyle study with Aβ PET and ≥ 3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aβ positive; follow-up 5.3 ± 1.7 years). Aβ level was divided using the standardized 0–100 Centiloid scale: < 15 CL negative, 15–25 CL uncertain, 26–50 CL moderate, 51–100 CL high, > 100 CL very high, noting > 25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess …

Prevention Of Dementia Using Mobile Phone Applications (Prodemos): Protocol For An International Randomised Controlled Trial, Esmé Eggink, Melanie Hafdi, Marieke P. Hoevenaar-Blom, Manshu Song, Sandrine Andrieu, Linda E. Barnes, Cindy Birck, Rachael L. Brooks, Nicola Coley, Elizabeth Ford, Jean Georges, Abraham Van Der Groep, Willem A. Van Gool, Ron Handels, Haifeng Hou, Dong Li, Hongmei Liu, Jihui Lyu, Harm Van Marwijk, Mark Van Der Meijden, Yixuan Niu, Shanu Sadhwani, Wenzhi Wang, Youxin Wang, Anders Wimo, Xiaoyan Ye, Yueyi Yu, Qiang Zeng, Wei Wang, Carol Brayne, Eric P. Moll Van Charante, Edo Richard

Research outputs 2014 to 2021

Introduction Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a …

Intake Of Products Containing Anthocyanins, Flavanols, And Flavanones, And Cognitive Function: A Narrative Review, Samantha L. Gardener, Stephanie R. Rainey-Smith, Michael Weinborn, Catherine P. Bondonno, Ralph N. Martins

Research outputs 2014 to 2021

The purpose of this review is to examine human research studies published within the past 6 years which evaluate the role of anthocyanin, flavanol, and flavanone consumption in cognitive function, and to discuss potential mechanisms of action underlying any observed benefits. Evidence to date suggests the consumption of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive …

Healing Right Way: Study Protocol For A Stepped Wedge Cluster Randomised Controlled Trial To Enhance Rehabilitation Services And Improve Quality Of Life In Aboriginal Australians After Brain Injury, Elizabeth Armstrong, Juli Coffin, Deborah J. Hersh, Judith M. Katzenellenbogen, Sandra Thompson, Leon Flicker, Meaghan Mcallister, Dominique A. Cadilhac, Tapan Rai, Erin Godecke, Colleen Hayward, Graeme J. Hankey, Neil M. Drew, Ivan Lin, Deborah Woods, Natalie Ciccone

Research outputs 2014 to 2021

Introduction: Despite higher incidence of brain injury among Aboriginal compared with non-Aboriginal Australians, suboptimal engagement exists between rehabilitation services and Aboriginal brain injury survivors. Aboriginal patients often feel culturally insecure in hospital and navigation of services post discharge is complex. Health professionals report feeling ill-equipped working with Aboriginal patients. This study will test the impact of a research-informed culturally secure intervention model for Aboriginal people with brain injury.

Methods and Analysis: Design: Stepped wedge cluster randomised control trial design; intervention sequentially introduced at four pairs of healthcare sites across Western Australia at 26-week intervals.

Recruitment: Aboriginal participants aged ≥18 years …

Polygenic Score Modifies Risk For Alzheimer's Disease In Ε4 Homozygotes At Phenotypic Extremes, Aamira J. Huq, Brian Fulton-Howard, Moeen Riaz, Simon Laws, Robert Sebra, Joanne Ryan, Alzheimer’S Disease Genetics Consortium, Alan E. Renton, Alison M. Goate, Colin L. Masters, Elsdon Storey, Raj C. Shah, Anne Murray, John Mcneil, Ingrid Winship, Paul A. Jones

Research outputs 2014 to 2021

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms. Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2; = .003). The difference in the same PRS …

The Development Of Aboriginal Brain Injury Coordinator Positions: A Culturally Secure Rehabilitation Service Initiative As Part Of A Clinical Trial, Elizabeth Armstrong, Kathy Mccoy, Rebecca Clinch, Maureen Merritt, Renee Speedy, Meaghan Mcallister, Kym Heine, Natalie Ciccone, Melanie Robinson, Julie Coffin

Research outputs 2014 to 2021

Brain injury, resulting from stroke and traumatic brain injury, is a common occurrence in Australia, with Aboriginal people affected at a significant rate and impact felt by individuals, families and communities. Access to brain injury rehabilitation services for Aboriginal people is reported to be often limited, with very little support outside the hospital environment. Our research involving Aboriginal brain injury survivors and their families to date has revealed that people often manage ‘on their own’ following such events. Following recommendations from survivors and their families, the Healing Right Way clinical trial, currently underway in Western Australia, has created the role …

High-Intensity Physical Activity Is Not Associated With Better Cognition In The Elder: Evidence From The China Health And Retirement Longitudinal Study, Zhiyuan Wu, Haiping Zhang, Xinlei Miao, Haibin Li, Huiying Pan, Di Zhou, Yue Liu, Zhiwei Li, Jinqi Wang, Xiangtong Liu, Deqiang Zheng, Xia Li, Wei Wang, Xiuhua Guo, Lixin Tao

Research outputs 2014 to 2021

Background: To evaluate the association of physical activity (PA) intensity with cognitive performance at baseline and during follow-up. Methods: A total of 4039 participants aged 45 years or above from the China Health and Retirement Longitudinal Study were enrolled in visit 1 (2011–2012) and followed for cognitive function in visit 2 (2013–2014), visit 3 (2015–2016), and visit 4 (2017–2018). We analyzed the association of PA intensity with global cognition, episodic memory, and mental intactness at baseline using adjusted regression methods and evaluated the long-term effect of PA intensity using multiple measures of cognition scores by mixed effect model. Results: In …

Transcranial Random Noise Stimulation Modulates Neural Processing Of Sensory And Motor Circuits – From Potential Cellular Mechanisms To Behaviour: A Scoping Review, Weronika Potok, Onno Van Der Groen, Marc Bächinger, Dylan Edwards, Nicole Wenderoth

Research outputs 2014 to 2021

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurological patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioural levels, and discuss how this emerging method might be harnessed to …

Cerebellar Coordination Of Neuronal Communication In Cerebral Cortex, Samuel S Mcafee, Yu Liu, Roy V Sillitoe, Detlef H Heck

Duncan NRI Faculty and Staff Publications

Cognitive processes involve precisely coordinated neuronal communications between multiple cerebral cortical structures in a task specific manner. Rich new evidence now implicates the cerebellum in cognitive functions. There is general agreement that cerebellar cognitive function involves interactions between the cerebellum and cerebral cortical association areas. Traditional views assume reciprocal interactions between one cerebellar and one cerebral cortical site, via closed-loop connections. We offer evidence supporting a new perspective that assigns the cerebellum the role of a coordinator of communication. We propose that the cerebellum participates in cognitive function by modulating the coherence of neuronal oscillations to optimize communications between multiple …

A Preliminary Dti Tractography Study Of Developmental Neuroplasticity 5–15 Years After Early Childhood Traumatic Brain Injury, James M Mchenry, Stephen R Mccauley, Jill V Hunter, Linda Ewing-Cobbs, Mary E Aitken, Marianne Macleod, Zili D Chu, Linda J Noble-Haeusslein, Harvey S Levin

Faculty, Staff and Student Publications

Plasticity is often implicated as a reparative mechanism when addressing structural and functional brain development in young children following traumatic brain injury (TBI); however, conventional imaging methods may not capture the complexities of post-trauma development. The present study examined the cingulum bundles and perforant pathways using diffusion tensor imaging (DTI) in 21 children and adolescents (ages 10-18 years) 5-15 years after sustaining early childhood TBI in comparison with 19 demographically-matched typically-developing children. Verbal memory and executive functioning were also evaluated and analyzed in relation to DTI metrics. Beyond the expected direction of quantitative DTI metrics in the TBI group, we …

Indications For Inpatient Magnetoencephalography In Children - An Institution's Experience, Manish N Shah, David I Sandberg, Jeremy Lankford, Stephen Thompson, John Mosher, Gretchen Von Allmen

Faculty, Staff and Student Publications

Magnetoencephalography (MEG) is recognized as a valuable non-invasive clinical method for localization of the epileptogenic zone and critical functional areas, as part of a pre-surgical evaluation for patients with pharmaco-resistant epilepsy. MEG is also useful in localizing functional areas as part of pre-surgical planning for tumor resection. MEG is usually performed in an outpatient setting, as one part of an evaluation that can include a variety of other testing modalities including 3-Tesla MRI and inpatient video-electroencephalography monitoring. In some clinical circumstances, however, completion of the MEG as an inpatient can provide crucial ictal or interictal localization data during an ongoing …