Neurosciences Commons^™

Longitudinal Alzheimer's Degeneration Reflects The Spatial Topography Of Cholinergic Basal Forebrain Projections, Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc Andre Bedard, R. Nathan Spreng

Brain and Mind Institute Researchers' Publications

© 2018 The Author(s) The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To …

Pet And Mri Measurements Of Neuroinflammation And Brain Plasticity After A Stroke, Brainscan , Western University, Jonathan Thiessen, Shawn Whitehead, Justin Hicks, Matthew Fox

Project Summaries

We are going to assess brain structure and function using magnetic resonance imaging (MRI) and positron emission tomography (PET) to study white matter inflammation and the density of synapses over time, alongside a behavioural assessment of motor and executive function. This kind of comprehensive assessment, especially using PET to measure synaptic density, has not been done before.

Assessing Listening With Engaging, Real-World Auditory Signals, Brainscan , Western University, Björn Herrmann, Ingrid Johnsrude 6612111

Project Summaries

Our project will develop and evaluate a novel way (using functional imaging, fMRI, and electrophysiology, EEG) to assess this cognitive impact of hearing loss with engaging, real‐world auditory stimuli. We will try to assess listening effort in more realistic listening situations among healthy listeners, comparing detected effort in degraded and clear acoustic conditions.

Using EEG, we will then develop measures that are sensitive to the cognitive demands imposed by degraded speech, using these features to assess hearing function with engaging narratives in natural listening conditions.

The Effect Of Musical Training On Speech And Sound Perception, Brainscan, Western University, Ingrid Johnsrude, Vanessa Irsik, Stephen Van Hedger

Project Summaries

We are going to carry out such a study, in conjunction with research labs at five other institutions. With six universities involved, we will be able to recruit a sufficiently large number of people in the study and decrease the likelihood of any regional bias influencing the outcomes. We will be trying to validate the following claims:

• that musicians have an improved ability to understand speech in noisy environments
• that the responses of a musician's brainstem to speech sounds is enhanced, and
• that older musicians have reduced symptoms from age-related hearing loss.

Attention Bias Modification Training As A Potential Preventative Tool, Brainscan, Western University, Elizabeth Hayden, Marc Joanisse, Pan Liu, Koraly Perez-Edgar, Thomas Olino

Project Summaries

We will use eye-tracking techniques to understand more about attentional bias and how it changes through ABM training.

Through neuroimaging, we will look at 'resting state functional connectivity', which is the activity and communication in the brain when a person is not engaging in any activity themselves. There are resting-state patterns of brain activity that have been identified in the brains of youth with depression, anxiety and related disorders, but we do not know if these brain patterns can be used to identify those at risk for these disorders. We also don't know if preventative approaches to depression and anxiety, …

Validating Methods For Using Noninvasive Brain Stimulation To Influence Auditory Perception, Brainscan, Western University, Jessica Grahn, Molly Henry, Blake Butler, Marc Joanisse, Stefan Everling

Project Summaries

We will be exploring the influence of a weak alternating current on neural activity at different frequencies to build a more complete picture of tACS. We will also incorporate EEG measurements to help us predict how the synchronization varies across individuals, to determine when to provide stimulation for each individual. Finally, we will vary the tACS stimulation and use participant behaviour as the measure to understand what stimulation timing produces the largest behavioural changes.

Uncovering The Neural Basis Of Cognitive Impairment Following Hearing Loss: An All-Optical Electrophysiology Approach, Brainscan, Western University, Brian Allman, Wataru Inoue

Project Summaries

We have access to state-of-the-art equipment that will enable us to visualize specific neuron types in animal models. This is a new approach that combines several recent advances in the field of 'optogenetics', a technique that uses light to control neurons. This approach will allow us to explore how hearing loss induced by loud noise exposure leads to abnormal neural activity in areas of the brain that control learning, memory and higher cognitive function.

Aging Is Associated With An Over-Sensitivity Of Brain Responses To Sounds, Brainscan, Western University, Björn Herrmann, Burkhard Maess, Ingrid S. Johnsrude

Research Summaries

Aging and hearing loss leads to increased neural responses to sounds in the auditory cortex compared to younger people. Enhanced neural activity to sound may be a physiological mechanism underlying the difficulty that older adults have with ignoring irrelevant sound information.

Astaxanthin Attenuates Mptp Induced Neurotoxicity And Modulates Cognitive Function In Aged Mice, Beth Grimmig

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease is the second common neurodegenerative disease and is most frequently diagnosed in individuals over 60. There are no available medications that can prevent or restore the loss of neurons that correspond to motor impairments in patients. Identifying novel therapeutic compounds that are capable of slowing and reversing the extensive neurodegeneration that occurs in PD remains an important goal of the field. While basic research has identified potential therapeutic agents, studies often use young model organisms to demonstrate efficacy of the target compound. This approach ignores the impact of the aged CNS on the disease process, and likely contributes …

Endothelial Function Is Associated With White Matter Microstructure And Executive Function In Older Adults, Nathan F. Johnson, Brian T. Gold, Christopher A. Brown, Emily F. Anggelis, Alison L. Bailey, Jody L. Clasey, David K. Powell

Physical Therapy Faculty Publications

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers

USF Tampa Graduate Theses and Dissertations

The last century has seen a steady increase in the extension of the average lifespan. This has concomitantly produced higher incidences of age-related chronic degenerative diseases like Alzheimer’s and Parkinson’s diseases. Age is the single greatest risk factor for the development of not just these degenerative conditions but cancer as well. The aged niche undergoes a number of maladaptive changes that allow underlying conditions to present and progress. Exactly which changes, contribute to the progression of which disease is currently an area of intense study. However, these answers often present therapeutic targets for disease prevention. Age is characterized by a …

Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette

Brain and Mind Institute Researchers' Publications

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. …

Change In Processing Speed And Its Associations With Cerebral White Matter Microstructure, Muzamil Arshad

Wayne State University Dissertations

The decline of cognition with age is one of the most feared aspects of aging, while the slowing of responses, or reduced processing speed, is one of the most reliable aspects of aging. Slowing of processing has been hypothesized to affect other domains of cognition as well. Despite the well-known slowing-age relationship and central position processing speed plays in theories of cognitive aging the neurobiological mechanisms which underpin slowing is unclear. If we could identify the biology associated with processing speed we could then attempt to develop interventions to mitigate the effects of age on those variables. In turn we …

Insulin Actions On Hippocampal Neurons, Shaniya Maimaiti

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aging is the main risk factor for cognitive decline. The hippocampus, a brain region critical for learning and memory formation, is especially vulnerable to normal and pathological age-related cognitive decline. Dysregulation of both insulin and intracellular Ca2+ signaling appear to coexist and their compromised actions may synergistically contribute to neuronal dysfunction with aging. This dissertation focused on the interaction between insulin, Ca2+ dysregulation, and cognition in hippocampal neurons by examining the contributions of insulin to Ca2+ signaling events that influence memory formation. I tested the hypothesis that insulin would increase cognition in aged animals by altering Ca2+-dependent physiological mechanisms involved …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Development, Validation And Application Of A New Fornix Template For Studies Of Aging And Preclinical Alzheimer's Disease, Christopher A. Brown, Nathan F. Johnson, Amelia J. Anderson-Mooney, Gregory A. Jicha, Leslie M. Shaw, John Q. Trojanowski, Linda J. Van Eldik, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Physical Therapy Faculty Publications

We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimer's disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in …

Category Learning In Older Adulthood: A Study Of The Shepard, Hovland, And Jenkins (1961) Tasks., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Shepard, Hovland, and Jenkins (1961) examined the categorization abilities of younger adults using tasks involving single-dimensional rule learning, disjunctive rule learning, and family resemblance learning. The current study examined category learning in older adults using this well-known category set. Older adults, like younger adults, found category tasks with a single relevant dimension the easiest to learn. In contrast to younger adults, older adults found complex disjunctive rule-based categories harder to learn than family resemblance based categories. Disjunctive rule-based category learning appeared to be the most difficult for older adults to learn because this category set placed the heaviest demands on …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Fusion Analysis Of Functional Mri Data For Classification Of Individuals Based On Patterns Of Activation., Mahdi Ramezani, Purang Abolmaesumi, Kris Marble, Heather Trang, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Classification of individuals based on patterns of brain activity observed in functional MRI contrasts may be helpful for diagnosis of neurological disorders. Prior work for classification based on these patterns have primarily focused on using a single contrast, which does not take advantage of complementary information that may be available in multiple contrasts. Where multiple contrasts are used, the objective has been only to identify the joint, distinct brain activity patterns that differ between groups of subjects; not to use the information to classify individuals. Here, we use joint Independent Component Analysis (jICA) within a Support Vector Machine (SVM) classification …

Age Related Decline In Memory: Examining The Mediation Effect Of Processing, Executive Functioning And Intelligence In Normal Adults, Jada J. Stewart

Theses and Dissertations

Multiple mediation analyses that collectively examine the prominent theories of cognitive aging (i.e., Common Cause, Processing, and Executive Decline Hypotheses) along with other cognitive domains that are sensitive to aging are rare. Moreover, having identified that cognition begins to decline as early as 30 years old, few studies have examined the mechanisms that underlie memory change among younger aging individuals. As a result, it is unclear whether relevant mediating variables have been excluded from early research on age-related memory decline, or to what extent rehabilitative strategies are applicable as early interventions for maintaining cognitive functioning into late life.

The present …

Deficits In Audiovisual Speech Perception In Normal Aging Emerge At The Level Of Whole-Word Recognition., Ryan A Stevenson, Caitlin E Nelms, Sarah H Baum, Lilia Zurkovsky, Morgan D Barense, Paul A Newhouse, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Over the next 2 decades, a dramatic shift in the demographics of society will take place, with a rapid growth in the population of older adults. One of the most common complaints with healthy aging is a decreased ability to successfully perceive speech, particularly in noisy environments. In such noisy environments, the presence of visual speech cues (i.e., lip movements) provide striking benefits for speech perception and comprehension, but previous research suggests that older adults gain less from such audiovisual integration than their younger peers. To determine at what processing level these behavioral differences arise in healthy-aging populations, we administered …

Stability Of Self-Referent Encoding Task Performance And Associations With Change In Depressive Symptoms From Early To Middle Childhood., Brandon L Goldstein, Elizabeth P Hayden, Daniel N Klein

Brain and Mind Institute Researchers' Publications

Depressed individuals exhibit memory biases on the self-referent encoding task (SRET), such that those with depression exhibit poorer recall of positive, and enhanced recall of negative, trait adjectives (referred to as positive and negative processing biases). However, it is unclear when SRET biases emerge, whether they are stable, and if biases predict, or are predicted by, depressive symptoms. To address this, a community sample of 434 children completed the SRET and a depressive symptoms measure at ages 6 and 9. Negative and positive processing exhibited low, but significant, stability. At ages 6 and 9, depressive symptoms correlated with higher negative, …

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 …

A Study Of Small Rnas From Cerebral Neocortex Of Pathology-Verified Alzheimer's Disease, Dementia With Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, And Non-Demented Human Controls, Sébastien S. Hébert, Wang-Xia Wang, Qi Zhu, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual diseases such as Alzheimer's disease (AD), making disease-to-disease comparisons impossible. Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent …

The Influence Of Gender And Aging On The Neural Circuitry Supporing Facial Emotion Processing In Adults With Major Depressive Disorder, Emily Briceno

Wayne State University Dissertations

Major Depressive Disorder (MDD) is associated with decrements in facial emotion processing (FEP). Previous studies investigating the neural substrates of these decrements have often reported hyperactivity of emotion processing circuitry. Neural circuitry supporting FEP has been shown to be different between healthy men and women, and between young and elder adults. However, no prior studies have investigated how gender and aging affect emotion processing circuitry in individuals with MDD. The present study aimed to investigate the influence of gender and aging on emotion processing circuitry in MDD. One hundred-ten adults, grouped into subgroups according to MDD status, gender, and age …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Protocol For A Randomized Controlled Trial Evaluating The Effect Of Physical Activity On Delaying The Progression Of White Matter Changes On Mri In Older Adults With Memory Complaints And Mild Cognitive Impairment: The Aibl Active Trial, E V Cyarto, N T Lautenschlager, P M Desmond, D Ames, C Szoeke, O Salvado, Matthew Sharman, Kathryn A Ellis, P M Phal, C L Masters, C C Rowe, Ralph Martins, Kay L Cox

Research outputs 2012

Background: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. …