Neurosciences Commons^™

Obtaining And Maintaining Cortical Hand Representation As Evidenced From Acquired And Congenital Handlessness, Daan B. Wesselink, Fiona Mz Van Den Heiligenberg, Naveed Ejaz, Harriet Dempsey-Jones, Lucilla Cardinali, Aurelie Tarall-Jozwiak, Jörn Diedrichsen, Tamar R. Makin

Brain and Mind Institute Researchers' Publications

© Lukinova et al. A key question in neuroscience is how cortical organisation relates to experience. Previously we showed that amputees experiencing highly vivid phantom sensations maintain cortical representation of their missing hand (Kikkert et al., 2016). Here, we examined the role of sensory hand experience on persistent hand representation by studying individuals with acquired and congenital hand loss. We used representational similarity analysis in primary somatosensory and motor cortex during missing and intact hand movements. We found that key aspects of acquired amputees’ missing hand representation persisted, despite varying vividness of phantom sensations. In contrast, missing hand representation of …

Unmet Need For Mental Health Services Among People Screened But Not Admitted To An Early Psychosis Intervention Program, Jordan Edwards, Ross Norman, Paul Kurdyak, Arlene G. Macdougall, Lena Palaniyappan, Cindy Lau, Kelly K. Anderson

Brain and Mind Institute Researchers' Publications

Information is lacking on people screened for early psychosis intervention (EPI) but not admitted to the program. Using health administrative data, we constructed a retrospective cohort of incident cases of psychosis in the catchment of an EPI program. Use of mental health services was compared between people screened and not admitted with an EPI-admitted group. The non-admitted group had higher rates of subsequent emergency department visits, psychiatric hospitalizations, and involuntary admissions. These patterns are indicative of unmet need, and people screened but not admitted to EPI may benefit from protocols to improve transitions of care with other service providers.

Dorsal Striatum Does Not Mediate Feedback-Based, Stimulus-Response Learning: An Event-Related Fmri Study In Patients With Parkinson's Disease Tested On And Off Dopaminergic Therapy, Nole M. Hiebert, Adrian M. Owen, Hooman Ganjavi, Daniel Mendonça, Mary E. Jenkins, Ken N. Seergobin, Penny A. Macdonald

Brain and Mind Institute Researchers' Publications

© 2018 Learning associations between stimuli and responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-response learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-response learning methodology generally confounds learning and response selection processes. In 19 patients with Parkinson's disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-response learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these …

Investigating The Visual Number Form Area: A Replication Study, Rebecca Merkley, Benjamin Conrad, Gavin Price, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors. Published by the Royal Society The influential triple-code model of number representation proposed that there are three distinct brain regions for three different numerical representations: verbal words, visual digits and abstract magnitudes. It was hypothesized that the region for visual digits, known as the number form area, would be in ventral occipitotemporal cortex (vOTC), near other visual category-specific regions, such as the visual word form area. However, neuroimaging investigations searching for a region that responds in a category-specific manner to the visual presentation of number symbols have yielded inconsistent results. Price & Ansari (Price, Ansari 2011 …

A Touchscreen Motivation Assessment Evaluated In Huntington's Disease Patients And R6/1 Model Mice, Christopher J. Heath, Claire O'Callaghan, Sarah L. Mason, Benjamin U. Phillips, Lisa M. Saksida, Trevor W. Robbins, Roger A. Barker, Timothy J. Bussey, Barbara J. Sahakian

Brain and Mind Institute Researchers' Publications

Copyright © 2019 Heath, O'Callaghan, Mason, Phillips, Saksida, Robbins, Barker, Bussey and Sahakian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Apathy is pervasive across many neuropsychiatric disorders but is poorly characterized mechanistically, so targeted therapeutic interventions remain elusive. A key …

Translational Tests Involving Non-Reward: Methodological Considerations, Benjamin U. Phillips, Laura Lopez-Cruz, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). This review is concerned with methods for assessing the processing of unrewarded responses in experimental animals and the mechanisms underlying performance of these tasks. A number of clinical populations, including Parkinson’s disease, depression, compulsive disorders, and schizophrenia demonstrate either abnormal processing or learning from non-rewarded responses in laboratory-based reinforcement learning tasks. These effects are hypothesized to result from disturbances in modulatory neurotransmitter systems, including dopamine and serotonin. Parallel work in experimental animals has revealed consistent behavioral patterns associated with non-reward and, consistent with the human literature, modulatory roles for specific neurotransmitters. Classical tests involving an important …

White Matter Injury Predicts Disrupted Functional Connectivity And Microstructure In Very Preterm Born Neonates, Emma G. Duerden, Sheliza Halani, Karin Ng, Ting Guo, Justin Foong, Torin J.A. Glass, Vann Chau, Helen M. Branson, John G. Sled, Hilary E. Whyte, Edmond N. Kelly, Steven P. Miller

Brain and Mind Institute Researchers' Publications

© 2018 The Authors Objective: To determine whether the spatial extent and location of early-identified punctate white matter injury (WMI) is associated with regionally-specific disruptions in thalamocortical-connectivity in very-preterm born neonates. Methods: 37 very-preterm born neonates (median gestational age: 28.1 weeks; interquartile range [IQR]: 27–30) underwent early MRI (median age 32.9 weeks; IQR: 32–35), and WMI was identified in 13 (35%) neonates. Structural T1-weighted, resting-state functional Magnetic Resonance Imaging (rs-fMRI, n = 34) and Diffusion Tensor Imaging (DTI, n = 31) sequences were acquired using 3 T-MRI. A probabilistic map of WMI was developed for the 13 neonates demonstrating brain …

Girls' Internalizing Symptoms And White Matter Tracts In Cortico-Limbic Circuitry, Ola Mohamed Ali, Matthew R.J. Vandermeer, Haroon I. Sheikh, Marc F. Joanisse, Elizabeth P. Hayden

Brain and Mind Institute Researchers' Publications

© 2019 The Authors Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders (i.e., depressive and anxious disorders), but less is known about whether structural variations precede frank disorder and thus potentially mark risk. We therefore examined associations between white matter (WM) tract microstructure in cortico-limbic circuitry at age 7 and concurrent and longitudinal patterns of internalizing symptoms in 42 typically developing girls using Diffusion Tensor Imaging (DTI). Girls' internalizing symptoms were concurrently associated with reduced fractional anisotropy (FA) in segments of the cingulum bundle (CB) and the uncinate fasciculus (UF), bilaterally. Moreover, latent profile analysis showed that girls with …

The Benefit To Speech Intelligibility Of Hearing A Familiar Voice, Ysabel Domingo, Emma Holmes, Ingrid S. Johnsrude

Brain and Mind Institute Researchers' Publications

© 2019 American Psychological Association. Previous experience with a voice can help listeners understand speech when a competing talker is present. Using the coordinate-response measure task (Bolia, Nelson, Ericson, & Simpson, 2000), Johnsrude et al. (2013) demonstrated that speech is more intelligible when either the target or competing (masking) talker is a long-term spouse than when both talkers are unfamiliar (termed familiar-target and familiar-masker benefits, respectively). To better understand how familiarity improves intelligibility, we measured the familiar-target and familiar-masker benefits in older and younger spouses using a more challenging matrix task, and compared the benefits listeners gain from spouses' and …

Biomarkers Of Parkinson's Disease: Striatal Sub-Regional Structural Morphometry And Diffusion Mri, Ali R. Khan, Nole M. Hiebert, Andrew Vo, Brian T. Wang, Adrian M. Owen, Ken N. Seergobin, Penny A. Macdonald

Brain and Mind Institute Researchers' Publications

© 2018 The Authors Parkinson's disease (PD) is a progressive neurological disorder that has no reliable biomarkers. The aim of this study was to explore the potential of semi-automated sub-regional analysis of the striatum with magnetic resonance imaging (MRI) to distinguish PD patients from controls (i.e., as a diagnostic biomarker) and to compare PD patients at different stages of disease. With 3 Tesla MRI, diffusion- and T1-weighted scans were obtained on two occasions in 24 PD patients and 18 age-matched, healthy controls. PD patients completed one session on and the other session off dopaminergic medication. The striatum was parcellated into …

Linked Mri Signatures Of The Brain's Acute And Persistent Response To Concussion In Female Varsity Rugby Players, Kathryn Y. Manning, Alberto Llera, Gregory A. Dekaban, Robert Bartha, Christy Barreira, Arthur Brown, Lisa Fischer, Tatiana Jevremovic, Kevin Blackney, Timothy J. Doherty, Douglas D. Fraser, Jeff Holmes, Christian F. Beckmann, Ravi S. Menon

Brain and Mind Institute Researchers' Publications

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of …

Brain Activation Time-Locked To Sleep Spindles Associated With Human Cognitive Abilities, Zhuo Fang, Laura B. Ray, Adrian M. Owen, Stuart M. Fogel

Brain and Mind Institute Researchers' Publications

Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with "Reasoning" abilities (i.e., "fluid intelligence"; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain …

Alive Inside, Andrew Peterson, Adrian M. Owen, Jason Karlawish

Brain and Mind Institute Researchers' Publications

This article provides an ethical analysis of the U.S. practice guideline update on disorders of consciousness. Our analysis focuses on the guideline’s recommendations regarding the use of investigational neuroimaging methods to assess brain-injured patients. Complex and multifaceted ethical issues have emerged because these methods alter the clinical understanding of consciousness. We address issues of false hope, patient suffering, and cost. We argue that, in spite of these concerns, there is significant benefit to using neuroimaging to assess brain-injured patients in most cases.

The Neural Basis Of External Responsiveness In Prolonged Disorders Of Consciousness, Clara A. Stafford, Adrian M. Owen, Davinia Fernández-Espejo

Brain and Mind Institute Researchers' Publications

Objective: To investigate the structural integrity of fibre tracts underlying overt motor behaviour in PDOC. Methods: This cross-sectional study examined 15 PDOC patients and 22 healthy participants. Eight PDOC patients met the criteria for the vegetative state, 5 met the criteria for the minimally conscious state and 2 met the criteria for emerging from the minimally conscious state. We used fibre tractography to reconstruct the white matter fibres known to be involved in voluntary motor execution (i.e., those connecting thalamus with M1, M1 with cerebellum, and cerebellum with thalamus) and used fractional anisotropy (FA) as a measure of their integrity. …

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).

Multi-Area Organization Of Saccade-Evoked Traveling Waves, Brainscan, Western University, Julio Martinez-Trujillo, Lyle Muller, Adam Williamson

Project Summaries

In this project, we will employ new, large-scale electrophysiological recording techniques to sample widely across the visual system. It will allow us to test our hypothesis that neural traveling waves coordinated across multiple areas contribute to perceptual stability during eye movements. Using our newly developed signal processing technique to track traveling waves moment-by-moment in noisy multichannel data, we will detect and quantify them across multiple visual areas.

Detecting Fine-Grained Population Codes In Human Prefrontal Cortex, Brainscan, Western University, Marieke Mur, Julio Martinez-Trujillo, Ravi Menon, Joe Gati

Project Summaries

In this project, we will develop techniques for improving our measurement resolution so that we can gain access to prefrontal population codes. We will combine high-field fMRI with pattern analysis techniques to unlock population coding in the prefrontal cortex. This is essential for understanding how the brain supports higher-order cognition, and ultimately, for treating dysfunctions of cognitive flexibility in the clinic.

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.

Developing A Mechanistic Understanding Of Crossmodal Reorganization Following Sensory Loss, Brainscan, Western University, Blake E. Butler, Brian Allman, Ravi Menon

Project Summaries

Our long-term goal is to understand how plasticity reshapes circuits in the brain in response to atypical early experiences. This will allow us to better understand how the Deaf brain processes the world around us, and will make clear the challenges that must be overcome to optimize the function of cochlear implants and prostheses designed to restore sensory functions more broadly.

The Risk Of New-Onset Epilepsy And Refractory Epilepsy In Older Adult Stroke Survivors, Jorge G. Burneo, Tresah C. Antaya, Britney N. Allen, Andrea Belisle, Salimah Z. Shariff, Gustavo Saposnik

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• Stroke is a common cause of epilepsy in older adults, but little is known about stroke-related epilepsy or its outcomes in this population.
• 1.1% of older adult stroke survivors developed epilepsy in this study, of whom 12.9% developed refractory epilepsy, indicating that this population is particularly responsive to treatment.
• Over 85% of deaths in this population are not due to stroke or epilepsy.

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 …

The Psychological Science Accelerator: Advancing Psychology Through A Distributed Collaborative Network, Hannah Moshontz, Lorne Campbell, Charles R. Ebersole, Hans Ijzerman, Heather L. Urry, Patrick S. Forscher, Jon E. Grahe, Randy J. Mccarthy, Erica D. Musser, Jan Antfolk, Christopher M. Castille, Thomas Rhys Evans, Susann Fiedler, Jessica Kay Flake, Diego A. Forero, Steve M. Janssen, Justin Robert Keene, John Protzko, Balazs Aczel, Sara Álvarez Solas, Daniel Ansari, Dana Awlia, Ernest Baskin, Carlota Batres, Martha Lucia Borras-Guevara, Cameron Brick, Priyanka Chandel, Armand Chatard, William J. Chopik, David Clarance, Nicholas A. Coles, Katherine S. Corker

Brain and Mind Institute Researchers' Publications

Concerns have been growing about the veracity of psychological research. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions, or attempt to replicate prior …

Validation And Optimisation Of A Touchscreen Progressive Ratio Test Of Motivation In Male Rats, Jonathan M. Hailwood, Christopher J. Heath, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Across species, effort-related motivation can be assessed by testing behaviour under a progressive ratio (PR) schedule of reinforcement. However, to date, PR tasks for rodents have been available using traditional operant response systems only. Objectives: Touchscreen operant response systems allow the assessment of behaviour in laboratory rodents, using tasks that share high face validity with the computerised assessments used in humans. Here, we sought to optimise a rat touchscreen variant of PR and validate it by assessing the effects of a number of manipulations known to affect PR performance in non-touchscreen paradigms. Methods: Separate groups …

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 …

Abstract Concepts And Pictures Of Real-World Situations Activate One Another., Ken Mcrae, Daniel Nedjadrasul, Raymond Pau, Bethany Pui-Hei Lo, Lisa King

Brain and Mind Institute Researchers' Publications

concepts typically are defined in terms of lacking physical or perceptual referents. We argue instead that they are not devoid of perceptual information because knowledge of real-world situations is an important component of learning and using many abstract concepts. Although the relationship between perceptual information and abstract concepts is less straightforward than for concrete concepts, situation-based perceptual knowledge is part of many abstract concepts. In Experiment 1, participants made lexical decisions to abstract words that were preceded by related and unrelated pictures of situations. For example, share was preceded by a picture of two girls sharing a cob of corn. …

Selective Effects Of 5-Ht2c Receptor Modulation On Performance Of A Novel Valence-Probe Visual Discrimination Task And Probabilistic Reversal Learning In Mice, Benjamin U. Phillips, Sigma Dewan, Simon R.O. Nilsson, Trevor W. Robbins, Christopher J. Heath, Lisa M. Saksida, Timothy J. Bussey, Johan Alsiö

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Dysregulation of the serotonin (5-HT) system is a pathophysiological component in major depressive disorder (MDD), a condition closely associated with abnormal emotional responsivity to positive and negative feedback. However, the precise mechanism through which 5-HT tone biases feedback responsivity remains unclear. 5-HT2C receptors (5-HT2CRs) are closely linked with aspects of depressive symptomatology, including abnormalities in reinforcement processes and response to stress. Thus, we aimed to determine the impact of 5-HT2CR function on response to feedback in biased reinforcement learning. Methods: We used two touchscreen assays designed to assess the impact of positive and negative feedback …

The Effects Of Habits On Motor Skill Learning, Nicola J. Popp, Atsushi Yokoi, Paul L. Gribble, Jörn Diedrichsen

BrainsCAN Publications

Skill learning involves the formation of stable motor patterns. In musical and athletic 3 training, however, these stable patterns can also impede the attainment of higher levels 4 of performance, and hence constitute a motor habit. We developed an experimental 5 paradigm to induce a specific motor pattern in a sequence production task and 6 investigated how it affected subsequent optimization over a 3-week training period. 7 Participants initially practiced small segments of 2 to 3 finger movements, which were 8 then combined to form longer sequences. This initial training induced a persistent 9 chunking behavior, with shorter inter-press-intervals within …

Disorganized Gyrification Network Properties During The Transition To Psychosis, Tushar Das, Stefan Borgwardt, Daniel J. Hauke, Fabienne Harrisberger, Undine E. Lang, Anita Riecher-Rössler, Lena Palaniyappan, André Schmidt

Brain and Mind Institute Researchers' Publications

IMPORTANCE There is urgent need to improve the limited prognostic accuracy of clinical instruments to predict psychosis onset in individuals at clinical high risk (CHR) for psychosis. As yet, no reliable biological marker has been established to delineate CHR individuals who will develop psychosis from those who will not. OBJECTIVES To investigate abnormalities in a graph-based gyrification connectome in the early stages of psychosis and to test the accuracy of this systems-based approach to predict a transition to psychosis among CHR individuals. DESIGN, SETTING, AND PARTICIPANTS This investigation was a cross-sectional magnetic resonance imaging (MRI) study with follow-up assessment to …

Modified Origins Of Cortical Projections To The Superior Colliculus In The Deaf: Dispersion Of Auditory Efferents., Blake E Butler, Julia K Sunstrum, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (

Seeing The Forest And The Trees: Default Local Processing In Individuals With High Autistic Traits Does Not Come At The Expense Of Global Attention., Ryan A Stevenson, Sol Z Sun, Naomi Hazlett, Jonathan S Cant, Morgan D Barense, Susanne Ferber

Brain and Mind Institute Researchers' Publications

Atypical sensory perception is one of the most ubiquitous symptoms of autism, including a tendency towards a local-processing bias. We investigated whether local-processing biases were associated with global-processing impairments on a global/local attentional-scope paradigm in conjunction with a composite-face task. Behavioural results were related to individuals' levels of autistic traits, specifically the Attention to Detail subscale of the Autism Quotient, and the Sensory Profile Questionnaire. Individuals showing high rates of Attention to Detail were more susceptible to global attentional-scope manipulations, suggesting that local-processing biases associated with Attention to Detail do not come at the cost of a global-processing deficit, but …