Medicine and Health Sciences Commons^™

Striatum In Stimulus-Response Learning Via Feedback And In Decision Making., Nole M Hiebert, Andrew Vo, Adam Hampshire, Adrian M Owen, Ken N Seergobin, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

Cognitive deficits are recognized in Parkinson's disease. Understanding cognitive functions mediated by the striatum can clarify some of these impairments and inform treatment strategies. The dorsal striatum, a region impaired in Parkinson's disease, has been implicated in stimulus-response learning. However, most investigations combine acquisition of associations between stimuli, responses, or outcomes (i.e., learning) and expression of learning through response selection and decision enactment, confounding these separate processes. Using neuroimaging, we provide evidence that dorsal striatum does not mediate stimulus-response learning from feedback but rather underlies decision making once associations between stimuli and responses are learned. In the experiment, 11 males …

Burning Pain Secondary To Clozapine Use: A Case Report., Bradley Linton, Rachel Fu, Penny A Macdonald, Hooman Ganjavi

Brain and Mind Institute Researchers' Publications

BACKGROUND: The first of the atypical antipsychotics introduced in the 1970s, clozapine remains the most efficacious neuroleptic to this day. However, serious and potentially fatal side effects have necessitated careful regular monitoring among prescribing clinicians. Some adverse effects (e.g. ischaemic bowel) remain under recognized, while newly identified adverse effects continue to be described in the literature.

CASE PRESENTATION: In this report, we describe a healthy 43-year old Caucasian male who experienced onset of a full body deep burning pain several months after the onset of treatment with clozapine. The pain worsened over time, ceased with cessation of treatment, and returned …

Mirror Reversal And Visual Rotation Are Learned And Consolidated Via Separate Mechanisms: Recalibrating Or Learning De Novo?, Sebastian Telgen, Darius Parvin, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Motor learning tasks are often classified into adaptation tasks, which involve the recalibration of an existing control policy (the mapping that determines both feedforward and feedback commands), and skill-learning tasks, requiring the acquisition of new control policies. We show here that this distinction also applies to two different visuomotor transformations during reaching in humans: Mirror-reversal (left-right reversal over a mid-sagittal axis) of visual feedback versus rotation of visual feedback around the movement origin. During mirror-reversal learning, correct movement initiation (feedforward commands) and online corrections (feedback responses) were only generated at longer latencies. The earliest responses were directed into a nonmirrored …

Human Premotor Areas Parse Sequences Into Their Spatial And Temporal Features., Katja Kornysheva, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Skilled performance is characterized by precise and flexible control of movement sequences in space and time. Recent theories suggest that integrated spatio-temporal trajectories are generated by intrinsic dynamics of motor and premotor networks. This contrasts with behavioural advantages that emerge when a trained spatial or temporal feature of sequences is transferred to a new spatio-temporal combination arguing for independent neural representations of these sequence features. We used a new fMRI pattern classification approach to identify brain regions with independent vs integrated representations. A distinct regional dissociation within motor areas was revealed: whereas only the contralateral primary motor cortex exhibited unique …

Effector-Independent Motor Sequence Representations Exist In Extrinsic And Intrinsic Reference Frames., Tobias Wiestler, Sheena Waters-Metenier, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences …

What Are Ventilation Defects In Asthma?, Sarah Svenningsen, Miranda Kirby, Danielle Starr, Harvey O Coxson, Nigel A M Paterson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

BACKGROUND: Hyperpolarised (3)He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood.

OBJECTIVE: To better understand the determinants of ventilation defects in asthma, we evaluated well-established clinical as well as (3)He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma.

METHODS: Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation …

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 …

Observing Object Lifting Errors Modulates Cortico-Spinal Excitability And Improves Object Lifting Performance., Gavin Buckingham, Jeremy D Wong, Minnie Tang, Paul L Gribble, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

Observing the actions of others has been shown to modulate cortico-spinal excitability and affect behaviour. However, the sensorimotor consequences of observing errors are not well understood. Here, participants watched actors lift identically weighted large and small cubes which typically elicit expectation-based fingertip force errors. One group of participants observed the standard overestimation and underestimation-style errors that characterise early lifts with these cubes (Error video--EV). Another group watched the same actors performing the well-adapted error-free lifts that characterise later, well-practiced lifts with these cubes (No error video--NEV). We then examined actual object lifting performance in the subjects who watched the EV …

Dynamic And Opposing Adjustment Of Movement Cancellation And Generation In An Oculomotor Countermanding Task., Brian D Corneil, Joshua C Cheng, Samanthi C Goonetilleke

Brain and Mind Institute Researchers' Publications

Adaptive adjustments of strategies help optimize behavior in a dynamic and uncertain world. Previous studies in the countermanding (or stop-signal) paradigm have detailed how reaction times (RTs) change with trial sequence, demonstrating adaptive control of movement generation. Comparatively little is known about the adaptive control of movement cancellation in the countermanding task, mainly because movement cancellation implies the absence of an outcome and estimates of movement cancellation require hundreds of trials. Here, we exploit a within-trial proxy of movement cancellation based on recordings of neck muscle activity while human subjects attempted to cancel large eye-head gaze shifts. On a subset …

Two Distinct Ipsilateral Cortical Representations For Individuated Finger Movements., Jörn Diedrichsen, Tobias Wiestler, John W Krakauer

Brain and Mind Institute Researchers' Publications

Movements of the upper limb are controlled mostly through the contralateral hemisphere. Although overall activity changes in the ipsilateral motor cortex have been reported, their functional significance remains unclear. Using human functional imaging, we analyzed neural finger representations by studying differences in fine-grained activation patterns for single isometric finger presses. We demonstrate that cortical motor areas encode ipsilateral movements in 2 fundamentally different ways. During unimanual ipsilateral finger presses, primary sensory and motor cortices show, underneath global suppression, finger-specific activity patterns that are nearly identical to those elicited by contralateral mirror-symmetric action. This component vanishes when both motor cortices are …

Decoding The Neural Mechanisms Of Human Tool Use., Jason P Gallivan, D Adam Mclean, Kenneth F Valyear, Jody C Culham

Brain and Mind Institute Researchers' Publications

Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas …

The Human Brain Processes Syntax In The Absence Of Conscious Awareness., Laura Batterink, Helen J Neville

Brain and Mind Institute Researchers' Publications

Syntax is the core computational component of language. A longstanding idea about syntactic processing is that it is generally not available to conscious access, operating autonomously and automatically. However, there is little direct neurocognitive evidence on this issue. By measuring event-related potentials while human observers performed a novel cross-modal distraction task, we demonstrated that syntactic violations that were not consciously detected nonetheless produced a characteristic early neural response pattern, and also significantly delayed reaction times to a concurrent task. This early neural response was distinct from later neural activity that was observed only to syntactic violations that were consciously detected. …

Acute Alcohol Consumption Impairs Controlled But Not Automatic Processes In A Psychophysical Pointing Paradigm., Kevin Johnston, Brian Timney, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

Numerous studies have investigated the effects of alcohol consumption on controlled and automatic cognitive processes. Such studies have shown that alcohol impairs performance on tasks requiring conscious, intentional control, while leaving automatic performance relatively intact. Here, we sought to extend these findings to aspects of visuomotor control by investigating the effects of alcohol in a visuomotor pointing paradigm that allowed us to separate the influence of controlled and automatic processes. Six male participants were assigned to an experimental "correction" condition in which they were instructed to point at a visual target as quickly and accurately as possible. On a small …

Determinants Of Negative Pathways To Care And Their Impact On Service Disengagement In First-Episode Psychosis., Kelly K. Anderson, Rebecca Fuhrer, Norbert Schmitz, Ashok K Malla

Epidemiology and Biostatistics Publications

PURPOSE: Although there have been numerous studies on pathways to care in first-episode psychosis (FEP), few have examined the determinants of the pathway to care and its impact on subsequent engagement with mental health services.

METHODS: Using a sample of 324 FEP patients from a catchment area-based early intervention (EI) program in Montréal, we estimated the association of several socio-demographic, clinical, and service-level factors with negative pathways to care and treatment delay. We also assessed the impact of the pathway to care on time to disengagement from EI services.

RESULTS: Few socio-demographic or clinical factors were predictive of negative pathways …

The Bodily Experience Of Cerebral Palsy: A Journey To Self-Awareness., Laura K Brunton, Doreen J Bartlett

Physical Therapy Publications

PURPOSE: The aim of the study was to describe the lived bodily experience of cerebral palsy (CP).

METHOD: This was a descriptive phenomenological inquiry. Ten participants were interviewed about their bodily experiences of living with CP. Interviews were semi-structured around pain and fatigue. Inductive thematic analysis was used to identify themes.

RESULTS: The bodily experience of CP centered on issues of fatigue and pain as a feeling of muscle soreness. An overwhelming amount of the discussion on fatigue emphasized the fatigue that occurs with walking and prolonged activity. Self-awareness of the individuals' own bodies and adapting activity to continue to …

Screening For Adult Adhd In Ontario: A Cross-Sectional Study Examining Sex Differences, Mental Health Correlates And Substance Use, Deanne Daigle

Electronic Thesis and Dissertation Repository

The vast majority of studies on attention-deficit/hyperactivity disorder (ADHD) are based on samples with inherent age, sex, and referral biases. Therefore, the current study used population-based data to 1) estimate the prevalence of adult ADHD (as well as previous diagnosis and medication use using an ADHD screener) and co-occurring psychiatric distress and substance use in Ontario 2) examine the sex differences in ADHD screening status and co-occurring psychiatric distress and substance use and 3) model ADHD screening status as a risk factor for psychiatric distress using the 2011 cycle of the Centre for Addiction and Mental Health Monitor. A positive …

Male Gender Promotes An Increased Inflammatory Response To Lipopolysaccharide In Umbilical Vein Blood., Shunaha Kim-Fine, Timothy Regnault, James S Lee, Sarah A Gimbel, Jill A Greenspoon, Jonathan Fairbairn, Kelly Summers, Barbra De Vrijer

Paediatrics Publications

OBJECTIVES: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

METHODS: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population. Lipopolysaccharide (LPS)-stimulated cytokine response was measured in a second study.

RESULTS: There were no significant gender differences in either maternal or fetal unstimulated plasma cytokine concentrations, but concentrations of the proinflammatory cytokines IL-1β and …

Expanding The Basic Science Debate: The Role Of Physics Knowledge In Interpreting Clinical Findings., Mark Goldszmidt, John Paul Minda, Sarah L Devantier, Aimee L Skye, Nicole N Woods

Brain and Mind Institute Researchers' Publications

Current research suggests a role for biomedical knowledge in learning and retaining concepts related to medical diagnosis. However, learning may be influenced by other, non-biomedical knowledge. We explored this idea using an experimental design and examined the effects of causal knowledge on the learning, retention, and interpretation of medical information. Participants studied a handout about several respiratory disorders and how to interpret respiratory exam findings. The control group received the information in standard "textbook" format and the experimental group was presented with the same information as well as a causal explanation about how sound travels through lungs in both the …

Behavioral And Fmri Evidence That Cognitive Ability Modulates The Effect Of Semantic Context On Speech Intelligibility, Adriana A Zekveld, Mary Rudner, Ingrid Johnsrude, Dirk J Heslenfeld, Jerker Rönnberg

Brain and Mind Institute Researchers' Publications

Text cues facilitate the perception of spoken sentences to which they are semantically related (Zekveld, Rudner, et al., 2011). In this study, semantically related and unrelated cues preceding sentences evoked more activation in middle temporal gyrus (MTG) and inferior frontal gyrus (IFG) than nonword cues, regardless of acoustic quality (speech in noise or speech in quiet). Larger verbal working memory (WM) capacity (reading span) was associated with greater intelligibility benefit obtained from related cues, with less speech-related activation in the left superior temporal gyrus and left anterior IFG, and with more activation in right medial frontal cortex for related versus …

Greater Benefits Of Multisensory Integration During Complex Sensorimotor Transformations., Verena N Buchholz, Samanthi C Goonetilleke, W Pieter Medendorp, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Multisensory integration enables rapid and accurate behavior. To orient in space, sensory information registered initially in different reference frames has to be integrated with the current postural information to produce an appropriate motor response. In some postures, multisensory integration requires convergence of sensory evidence across hemispheres, which would presumably lessen or hinder integration. Here, we examined orienting gaze shifts in humans to visual, tactile, or visuotactile stimuli when the hands were either in a default uncrossed posture or a crossed posture requiring convergence across hemispheres. Surprisingly, we observed the greatest benefits of multisensory integration in the crossed posture, as indexed …

Encoding Of Sensory Prediction Errors In The Human Cerebellum., John Schlerf, Richard B Ivry, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two types of errors. Participants made fast out-and-back reaching movements, aiming either for an object that delivered a force pulse if intersected or for a gap between two objects, either of which …

Rapid Perceptual Learning Of Noise-Vocoded Speech Requires Attention, Julia Jones Huyck, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Humans are able to adapt to unfamiliar forms of speech (such as accented, time-compressed, or noise-vocoded speech) quite rapidly. Can such perceptual learning occur when attention is directed away from the speech signal? Here, participants were simultaneously exposed to noise-vocoded sentences, auditory distractors, and visual distractors. One group attended to the speech, listening to each sentence and reporting what they heard. Two other groups attended to either the auditory or visual distractors, performing a target-detection task. Only the attend-speech group benefited from the exposure when subsequently reporting noise-vocoded sentences. Thus, attention to noise-vocoded speech appears necessary for learning.

Vitamin D And Brain Imaging In The Elderly: Should We Expect Some Lesions Specifically Related To Hypovitaminosis D?, Cédric Annweiler, Manuel Montero-Odasso, Susan W Muir, Olivier Beauchet

Physical Therapy Publications

Hypovitaminosis D is associated with cognitive decline in the elderly, but the issue of causality remains unresolved. Definitive evidence would include the visualization of brain lesions resulting from hypovitaminosis D. The aim of the present article is to determine, through a literature review, the location and nature of possible brain disorders in hypovitaminosis D. We found limited brain-imaging data, which reported ischemic infarcts and white matter hyperintensities in hypovitaminosis D, though did not provide their specific location or report any focal atrophy. Based on the finding of executive dysfunctions (i.e., mental shifting and information updating impairments) in the presence of …

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

Discriminating Famous From Fictional Names Based On Lifetime Experience: Evidence In Support Of A Signal-Detection Model Based On Finite Mixture Distributions., Ben Bowles, Iain M Harlow, Melissa M Meeking, Stefan Köhler

Brain and Mind Institute Researchers' Publications

It is widely accepted that signal-detection mechanisms contribute to item-recognition memory decisions that involve discriminations between targets and lures based on a controlled laboratory study episode. Here, the authors employed mathematical modeling of receiver operating characteristics (ROC) to determine whether and how a signal-detection mechanism contributes to discriminations between moderately famous and fictional names based on lifetime experience. Unique to fame judgments is a lack of control over participants' previous exposure to the stimuli deemed "targets" by the experimenter; specifically, if they pertain to moderately famous individuals, participants may have had no prior exposure to a substantial proportion of the …

Multiple Mechanisms Of Consciousness: The Neural Correlates Of Emotional Awareness., Jayna M Amting, Steven G Greening, Derek G V Mitchell

Brain and Mind Institute Researchers' Publications

Emotional stimuli, including facial expressions, are thought to gain rapid and privileged access to processing resources in the brain. Despite this access, we are conscious of only a fraction of the myriad of emotion-related cues we face everyday. It remains unclear, therefore, what the relationship is between activity in neural regions associated with emotional representation and the phenomenological experience of emotional awareness. We used functional magnetic resonance imaging and binocular rivalry to delineate the neural correlates of awareness of conflicting emotional expressions in humans. Behaviorally, fearful faces were significantly more likely to be perceived than disgusted or neutral faces. Functionally, …

In-Theater Peritoneal Dialysis For Combat-Related Renal Failure, Joseph S. Pina, Soraya Moghadam, Howard M. Cushner, Greg J. Beilman, Vivian C. Mcalister

Surgery Publications

BACKGROUND: Complications of renal failure may prevent timely evacuation of injured soldiers. Conventional renal replacement therapy is not available in forward surgical units. METHODS: Records of in-theater improvised peritoneal dialysis (IPD) in level III hospitals or forward surgical units in Iraq or Afghanistan were reviewed to determine the following: cause of renal failure and associated injuries; type of dialysate, peritoneal access, and exchange technique; and patient outcome. These data were used to propose method for IPD using commonly available materials. RESULTS: IPD is described in four patients. Abdominal or chest drains were used with either improvised dextrose-electrolyte solution or commercial …

Resting State Default-Mode Network Connectivity In Early Depression Using A Seed Region-Of-Interest Analysis: Decreased Connectivity With Caudate Nucleus., Robyn Bluhm, Peter Williamson, Ruth Lanius, Jean Theberge, Maria Densmore, Robert Bartha, Richard Neufeld, Elizabeth Osuch

Department of Medicine Publications

AIM: Reports on resting brain activity in healthy controls have described a default-mode network (DMN) and important differences in DMN connectivity have emerged for several psychiatric conditions. No study to date, however, has investigated resting-state DMN in relatively early depression before years of medication treatment. The objective of the present study was, therefore, to investigate the DMN in patients seeking help from specialized mental health services for the first time for symptoms of depression.

METHODS: Fourteen depressed subjects and 15 matched controls were scanned using 4-T functional magnetic resonance imaging while resting with eyes closed. All but one subject was …

Adapting To Dynamic Stimulus-Response Values: Differential Contributions Of Inferior Frontal, Dorsomedial, And Dorsolateral Regions Of Prefrontal Cortex To Decision Making., Derek G V Mitchell, Qian Luo, Shelley B Avny, Tomasz Kasprzycki, Karanvir Gupta, Gang Chen, Elizabeth C Finger, R James R Blair

Brain and Mind Institute Researchers' Publications

Dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), and inferior frontal gyrus (IFG) have all been implicated in resolving decision conflict whether this conflict is generated by having to select between responses of similar value or by making selections following a reversal in reinforcement contingencies. However, work distinguishing their individual functional contributions remains preliminary. We used functional magnetic resonance imaging to delineate the functional role of these systems with regard to both forms of decision conflict. Within dmPFC and dlPFC, blood oxygen level-dependent responses increased in response to decision conflict regardless of whether the conflict occurred in the context of …

Perirhinal Cortex Contributes To Accuracy In Recognition Memory And Perceptual Discriminations., Edward B O'Neil, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

The prevailing view of the medial temporal lobe (MTL) holds that its structures are dedicated to long-term declarative memory. Recent evidence challenges this position, suggesting that perirhinal cortex (PRc) in the MTL may also play a role in perceptual discriminations of stimuli with substantial visual feature overlap. Relevant neuropsychological findings in humans have been inconclusive, likely because studies have relied on patients with large and variable MTL lesions. Here, we conducted a functional magnetic resonance imaging study in healthy individuals to determine whether PRc shows a performance-related involvement in perceptual oddball judgments that is comparable to its established role in …