Medicine and Health Sciences Commons^™

Protein Misfolding Toxicity And Inclusion Formation In Cellular Models Of Neurodegeneration, Sonja E. Di Gregorio

Electronic Thesis and Dissertation Repository

Protein misfolding characterizes most neurodegenerative diseases. Protein misfolding is the conversion of specific proteins from their normal, often soluble, and native three-dimensional conformation into an aberrant, often insoluble, non-functional conformation. Protein inclusions and aggregates are among the major pathological hallmarks of protein misfolding associated with many neurodegenerative diseases. Yet, the role of aggregates and inclusions is not clearly defined and heavily debated. This study utilizes powerful genetic approaches in yeast and verification in mammalian neuronal cell lines to address the misfolding and toxicity of three proteins, the Rho Guanine Nucleotide Exchange Factor (RGNEF), Matrin3, which are involved in amyotrophic lateral …

Thirty-Five Years Of Computerized Cognitive Assessment Of Aging — Where Are We Now?, Avital Sternin, Alistair Burns, Adrian M. Owen

Brain and Mind Institute Researchers' Publications

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of …

Moderating Effect Of Cortical Thickness On Bold Signal Variability Age-Related Changes, Daiana R. Pur, Roy A. Eagleson, Anik De Ribaupierre, Nathalie Mella, Sandrine De Ribaupierre

Brain and Mind Institute Researchers' Publications

© Copyright © 2019 Pur, Eagleson, de Ribaupierre, Mella and de Ribaupierre. The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or “BOLDSD,” is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that …

Can Self-Efficacy Training Improve Memory And Functional Activation In Older Adults With Mild Cognitive Impairment? A Proof-Of-Concept Intervention Study, Brainscan, Western University, Lindsay Nagamatsu, Derek Mitchell, Paul Minda, Amer Burhan, Becky Horst

Project Summaries

The goal of this study is to examine the changes in brain activity after a memory self-efficacy training program to better understand the mechanisms of memory self-efficacy. We will conduct a proof-of-concept six-week memory self-efficacy intervention in older adults with MCI, in order to demonstrate that self-efficacy impacts brain function. This will allow us to determine whether self-efficacy interventions may be a potential strategy for combating AD in the future.

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 …

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.

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.

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.

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.

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, …

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.

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.

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. …

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 …

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 …

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, …

Anosognosia In Mild Cognitive Impairment: Relationship To Activation Of Cortical Midline Structures Involved In Self-Appraisal, Michele L. Ries, Britta M. Jabbar, Taylor W. Schmitz, Mehul A. Trivedi, Carey E. Gleason, Cynthia M. Carlsson, Howard A. Rowley, Sanjay Asthana, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI …