Medicine and Health Sciences Commons^™

Exploring The Structural And Functional Effects Of Pediatric Hydrocephalus On The Hippocampus, Lili Meng

Undergraduate Student Research Internships Conference

Hydrocephalus is one of the most common pediatric neurological problems that requires brain surgery in children. Pediatric hydrocephalus is characterized as an abnormal cerebrospinal fluid (CSF) buildup in the brain’s ventricles due to ineffective CSF reabsorption. When this fluid builds up in these cavities, it increases intracranial pressure and has a direct mass effect on the surrounding brain tissue and structures. Ultimately, various functions are affected including—but not limited to—vision, learning, memory, motor control, and hearing. Despite current literature suggesting that hydrocephalus may be associated with reduced hippocampal volume among rats and human adults, findings remain limited in the human …

Sustained Neural Activity Correlates With Rapid Perceptual Learning Of Auditory Patterns, Björn Herrmann, Kurdo Araz, Ingrid S. Johnsrude

Brain and Mind Institute Researchers' Publications

Repeating structures forming regular patterns are common in sounds. Learning such patterns may enable accurate perceptual organization. In five experiments, we investigated the behavioral and neural signatures of rapid perceptual learning of regular sound patterns. We show that recurring (compared to novel) patterns are detected more quickly and increase sensitivity to pattern deviations and to the temporal order of pattern onset relative to a visual stimulus. Sustained neural activity reflected perceptual learning in two ways. Firstly, sustained activity increased earlier for recurring than novel patterns when participants attended to sounds, but not when they ignored them; this earlier increase mirrored …

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 …

Understanding Perirhinal Contributions To Perception And Memory: Evidence Through The Lens Of Selective Perirhinal Damage, Marika C. Inhoff, Andrew C. Heusser, Arielle Tambini, Chris B. Martin, Edward B. O'Neil, Stefan Köhler, Michael R. Meager, Karen Blackmon, Blanca Vazquez, Orrin Devinsky, Lila Davachi

Brain and Mind Institute Researchers' Publications

© 2019 Elsevier Ltd Although a memory systems view of the medial temporal lobe (MTL) has been widely influential in understanding how memory processes are implemented, a large body of work across humans and animals has converged on the idea that the MTL can support various other decisions, beyond those involving memory. Specifically, recent work suggests that perception of and memory for visual representations may interact in order to support ongoing cognition. However, given considerations involving lesion profiles in neuropsychological investigations and the correlational nature of fMRI, the precise nature of representations supported by the MTL are not well understood …

Developing And Validating Tools To Assess Higher Level Cognition In Children And Adolescents, Brainscan, Western University, Bobby Stojanoski, Marc Joanisse, Ryan Stevenson, Cambridge Brain Sciences Inc.

Project Summaries

Collaborating with CBS, we will create a unique platform for understanding, detecting and predicting delays in cognition during the formative period from childhood to adolescence. The aim of this project is to develop and validate a battery of tests specifically for children and adolescents between the ages of 7 and 15 to measure various aspects of higher-level cognitive abilities. These include short-term and episodic memory, planning, reasoning, verbal abilities and executive functioning (those processes necessary to control behaviour, such as controlling attention and inhibition, working memory, reasoning and problem solving).

Impaired Object-Location Learning And Recognition Memory But Enhanced Sustained Attention In M2 Muscarinic Receptor-Deficient Mice, Carola Romberg, Susan Bartko, Jürgen Wess, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous …

Genetic Manipulation Of Lactate Metabolism To Regulate Memory And Alzheimer's Disease Pathogenesis, Brainscan , Western University, Robert Cumming, Robert Bartha, Tim Scholl

Project Summaries

Our project will attempt to determine the relative importance of astrocyte or neuronal directed lactate generation on memory by modifying mouse models to either suppress or overexpress the lactate producing enzyme in either cell type. Using these newly created transgenic mouse models, we aim to understand the processes of production and utilization of lactate and its effect on memory and cognition in health and in AD across the lifespan. The outcome of our study may lead to entirely new clinical approaches to treating cognitive and neurodegenerative disorders via drugs which alter lactate metabolism.

The Role Of Astrocytes In Memory: Focus On Pattern Separation, Brainscan , Western University, Timothy Bussey, Vania Prado, Ceci Kramar, Marco Prado, Lisa Saksida

Project Summaries

It has recently been shown that astrocytes play a leading role in a particular aspect of memory known as 'pattern separation' - differentiating between similar experiences or episodes in memory (say, recalling where you parked your car today compared to where you parked it yesterday). Pattern separation is disrupted in a wide variety of diseases of the brain so it is of considerable interest to memory researchers.

We have already shown in a small pilot study that we can improve pattern separation with selective manipulation of astrocytes in a specific brain region. In this project, we will attempt to demonstrate …

Role Of Microglia Signaling In Brain Circuit Development And Cognition, Brainscan, Western University, Vania Prado, Marco Prado, Wataru Inoue

Project Summaries

We have generated two mouse models in which we can control the Gq and Gisignalling in microglia during specific periods of brain development so we can explore the mechanisms behind abnormal microglial function.

Using our mouse models, we can stimulate these signalling pathways during the critical period of postnatal brain development to understand whether they impact adult cognition by influencing normal synaptic pruning. Mouse models of autism show issues with social memory, attention, sociability and hyperactivity. We will therefore assess those behaviors in our mouse models to determine if any autism-like behaviours are present.

Integrating Behavioural, Imaging And Transcriptional Profiling To Discover The Impact Of Midlife Stress In Alzheimer's Disease, Brainscan , Western University, Tim Bussey, Flavio Beraldo, Chakravarty Maller, Rosemary Bagot, Sylvain Williams, Claudia Kleinman

Project Summaries

We will be integrating this cognitive assessment with imaging of brain structure and function to understand the mechanisms by which a risk factor, in this case modifiable life stress, influences Alzheimer's disease-related decline. The resultant data will be integrated and disseminated using a new open-access neuroinformatics platform developed at Western (MouseBytes.ca), which will become a unique resource for open science investigations and set the standard for sharing of behavioural data across the world.

Developing Optogenetics/Electrophysiology Applications For Studying Cognitive Impairment During Stress, Brainscan, Western University, Wataru Inoue, Brian Allman, Julio Martinez-Trujillo

Project Summaries

We will develop cutting-edge techniques to:

• precisely measure and artificially manipulate the activity of CRH neurons in the PFC, and
• measure small and local releases of CRH by these neurons.

The success of our project will open the door to understand the neural mechanisms for how stress impairs cognitive functions and how it may contribute to mental disorders.

Sleep-Based Memory Processing Facilitates Grammatical Generalization: Evidence From Targeted Memory Reactivation., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

Generalization-the ability to abstract regularities from specific examples and apply them to novel instances-is an essential component of language acquisition. Generalization not only depends on exposure to input during wake, but may also improve offline during sleep. Here we examined whether targeted memory reactivation during sleep can influence grammatical generalization. Participants gradually acquired the grammatical rules of an artificial language through an interactive learning procedure. Then, phrases from the language (experimental group) or stimuli from an unrelated task (control group) were covertly presented during an afternoon nap. Compared to control participants, participants re-exposed to the language during sleep showed larger …

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 …

The Representational-Hierarchical View Of Pattern Separation: Not Just Hippocampus, Not Just Space, Not Just Memory?, B. A. Kent, M. Hvoslef-Eide, L. M. Saksida, T. J. Bussey

Brain and Mind Institute Researchers' Publications

Pattern separation (PS) has been defined as a process of reducing overlap between similar input patterns to minimize interference amongst stored representations. The present article describes this putative PS process from the "representational-hierarchical" perspective (R-H), which uses a hierarchical continuum instead of a cognitive modular processing framework to describe the organization of the ventral visual perirhinal-hippocampal processing stream. Instead of trying to map psychological constructs onto anatomical modules in the brain, the R-H model suggests that the function of brain regions depends upon what representations they contain. We begin by discussing a main principle of the R-H framework, the resolution …

Neurogenesis-Mediated Forgetting Minimizes Proactive Interference., Jonathan R Epp, Rudy Silva Mera, Stefan Köhler, Sheena A Josselyn, Paul W Frankland

Brain and Mind Institute Researchers' Publications

Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens existing memories and, in doing so, facilitates the encoding of new, conflicting (but not non-conflicting) information in mice. Conversely, decreasing neurogenesis stabilizes existing memories, and impedes the encoding of new, conflicting information. These results suggest that reduced proactive interference is an adaptive benefit of neurogenesis-induced forgetting.

Phase Of Spontaneous Slow Oscillations During Sleep Influences Memory-Related Processing Of Auditory Cues., Laura J Batterink, Jessica D Creery, Ken A Paller

Brain and Mind Institute Researchers' Publications

UNLABELLED: Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned …

Context-Dependent Egr1 Expression In The Avian Hippocampus., Stephanie L Grella, Mélanie F Guigueno, David J White, David F Sherry, Diano F Marrone

Brain and Mind Institute Researchers' Publications

In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts.

Finding The Engram., Sheena A Josselyn, Stefan Köhler, Paul W Frankland

Brain and Mind Institute Researchers' Publications

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram.

Sharp Emergence Of Feature-Selective Sustained Activity Along The Dorsal Visual Pathway., Diego Mendoza-Halliday, Santiago Torres, Julio C Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-selective neurons in early visual area middle temporal (MT). However, it is robustly present immediately downstream, in multimodal association area medial superior temporal (MST), as well as and in the lateral prefrontal cortex (LPFC). This sharp emergence of sustained activity along the dorsal visual pathway suggests a functional boundary between early visual areas, which encode sensory inputs, …

Bilateral Saccadic Deficits Following Large And Reversible Inactivation Of Unilateral Frontal Eye Field., Tyler R Peel, Kevin Johnston, Stephen G Lomber, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Inactivation permits direct assessment of the functional contribution of a given brain area to behavior. Previous inactivation studies of the frontal eye field (FEF) have either used large permanent ablations or reversible pharmacological techniques that only inactivate a small volume of tissue. Here we evaluated the impact of large, yet reversible, FEF inactivation on visually guided, delayed, and memory-guided saccades, using cryoloops implanted in the arcuate sulcus. While FEF inactivation produced the expected triad of contralateral saccadic deficits (increased reaction time, decreased accuracy and peak velocity) and performance errors (neglect or misdirected saccades), we also found consistent increases in reaction …

Rule-Based Category Learning In Children: The Role Of Age And Executive Functioning., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Rule-based category learning was examined in 4-11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working …

Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Successful memory involves not only remembering information over time, but also keeping memories distinct and less confusable. The computational process for making representations for similar input patterns more distinct from each other has been referred to as "pattern separation." In this work, we developed a set of behavioral conditions that allowed us to manipulate the load for pattern separation at different stages of memory. Thus, we provide experimental evidence that a brain-derived neurotrophic factor (BDNF)-dependent pattern separation process occurs during the encoding/storage/consolidation, but not the retrieval stage of memory processing. We also found that a spontaneous increase in BDNF in …

The Touchscreen Operant Platform For Testing Working Memory And Pattern Separation In Rats And Mice., Charlotte A Oomen, Martha Hvoslef-Eide, Christopher J Heath, Adam C Mar, Alexa E Horner, Timothy J Bussey, Lisa M Saksida

Brain and Mind Institute Researchers' Publications

The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess memory for location. During these tasks, animals are trained to a predefined criterion during ∼20-40 daily sessions. In LD sessions, touching the same location on the screen is rewarded on consecutive trials, followed by a reversal of location-reward contingencies. TUNL, a working memory task, requires animals to 'nonmatch' to a sample location after a delay. In both the LD and …

The Touchscreen Operant Platform For Testing Learning And Memory In Rats And Mice., Alexa E Horner, Christopher J Heath, Martha Hvoslef-Eide, Brianne A Kent, Chi Hun Kim, Simon R O Nilsson, Johan Alsiö, Charlotte A Oomen, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, …

Shared Neural Substrates Of Emotionally Enhanced Perceptual And Mnemonic Vividness, Rebecca M. Todd, Taylor W. Schmitz, Josh Susskind, Adam K. Anderson

Brain and Mind Institute Researchers' Publications

It is well known that emotionally salient events are remembered more vividly than mundane ones. Our recent research has demonstrated that such memory vividness is due in part to the subjective experience of emotional events as more perceptually vivid, an effect we call emotion-enhanced vividness, or EEV. The present study built on previously reported research in which fMRI data were collected while participants rated relative levels of visual noise overlaid on emotionally salient and neutral images. Ratings of greater EEV were associated with greater activation in the amygdala, visual cortex, and posterior insula. In the present study, we measured BOLD …

Differential Effects Of Parkinson's Disease And Dopamine Replacement On Memory Encoding And Retrieval., Alex A Macdonald, Ken N Seergobin, Adrian M Owen, Ruzbeh Tamjeedi, Oury Monchi, Hooman Ganjavi, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

Increasingly memory deficits are recognized in Parkinson's disease (PD). In PD, the dopamine-producing cells of the substantia nigra (SN) are significantly degenerated whereas those in the ventral tegmental area (VTA) are relatively spared. Dopamine-replacement medication improves cognitive processes that implicate the SN-innervated dorsal striatum but is thought to impair those that depend upon the VTA-supplied ventral striatum, limbic and prefrontal cortices. Our aim was to examine memory encoding and retrieval in PD and how they are affected by dopamine replacement. Twenty-nine PD patients performed the Rey Auditory Verbal Learning Test (RAVLT) and a non-verbal analogue, the Aggie Figures Learning Test …

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory., Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this …

Activation Of Brain Regions Vulnerable To Alzheimer's Disease: The Effect Of Mild Cognitive Impairment, S. C. Johnson, T. W. Schmitz, C. H. Moritz, M. E. Meyerand, H. A. Rowley, A. L. Alexander, K. W. Hansen, C. E. Gleason, C. M. Carlsson, M. L. Ries, S. Asthana, K. Chen, E. M. Reiman, G. E. Alexander

Brain and Mind Institute Researchers' Publications

This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, …

Transient Inactivation Of Perirhinal Cortex Disrupts Encoding, Retrieval, And Consolidation Of Object Recognition Memory., Boyer D Winters, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Damage to perirhinal cortex (PRh) impairs object recognition memory in humans, monkeys, and rats when tested in tasks such as delayed nonmatching to sample, visual paired comparison, and its rodent analog, the spontaneous object recognition task. In the present study, we have capitalized on the discrete one-trial nature of the spontaneous object recognition task to investigate the role of PRh in several distinct stages of object recognition memory. In a series of experiments, transient inactivation of PRh was accomplished with bilateral infusions of lidocaine directly into PRh immediately before the sample phase (encoding), immediately before the choice phase (retrieval), or …

Gaze-Centered Updating Of Visual Space In Human Parietal Cortex., W Pieter Medendorp, Herbert C Goltz, Tutis Vilis, J Douglas Crawford

Brain and Mind Institute Researchers' Publications

Single-unit recordings have identified a region in the posterior parietal cortex (PPC) of the monkey that represents and updates visual space in a gaze-centered frame. Here, using event-related functional magnetic resonance imaging, we identified an analogous bilateral region in the human PPC that shows contralateral topography for memory-guided eye movements and arm movements. Furthermore, when eye movements reversed the remembered horizontal target location relative to the gaze fixation point, this PPC region exchanged activity across the two cortical lobules. This shows that the human PPC dynamically updates the spatial goals for action in a gaze-centered frame.