Browsing by Author "Goodyear, Bradley"
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Item Open Access A Preliminary Study of the Influence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder(2014-03-06) Jaworska, Natalia; MacMaster, Frank P.; Gaxiola, Ismael; Cortese, Filomeno; Goodyear, Bradley; Ramasubbu, RajamannarBackground. Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Methods. Adults with MDD () and controls (HC; ) underwent magnetic resonance imaging. Twenty patients had MDD onset 24 years of age (pediatric onset) and 16 had onset 25 years of age (adult onset). The MDD group was also subdivided into those with () and without () physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Results. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. Conclusions. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.Item Open Access Advancing Concussion Assessment in Pediatrics (A-CAP): a prospective, concurrent cohort, longitudinal study of mild traumatic brain injury in children: protocol study(BMJ, 2017-07-01) Yeates, Keith O.; Beauchamp, Miriam; Craig, William; Doan, Quynh; Zemek, Roger; Bjornson, Bruce H.; Gravel, Jocelyn; Mikrogianakis, Angelo; Goodyear, Bradley; Abdeen, Nishard; Beaulieu, Christian; Dehaes, Mathieu; Deschenes, Sylvain; Harris, Ashley D.; Lebel, Catherine; Lamont, Ryan; Williamson, Tyler; Barlow, Karen M.; Bernier, Francois; Brooks, Brian L.; Emery, Carolyn; Freedman, Stephen B.; Kowalski, Kristina; Mrklas, Kelly; Tomfohr-Madsen, Lianne; Schneider, Kathryn J.Introduction Paediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI. Methods and analysis A-CAP is a prospective, longitudinal cohort study of children aged 8.00-16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses. Ethics and dissemination The ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals.Item Open Access Brain Magnetic Resonance Spectroscopy: Advances and Applications to Chronic Pain in Knee Osteoarthritis(2024-06-24) Leech, Samantha; Manske, Sarah; Harris, Ashley; Dunn, Jeffrey; Ng, Richard; Goodyear, Bradley; Dydak, UlrikeThis dissertation investigates advancements in brain proton magnetic resonance spectroscopy (1H-MRS) measures and their application to chronic pain in knee osteoarthritis. 1H-MRS measures proton signals, which can be converted into absolute concentrations using the properties of water, brain tissue, and neurochemicals. These concentrations serve as markers of brain health or dysfunction. Current methods to quantify absolute neurochemical concentrations assume an equal distribution of neurochemicals between white matter (WM) and gray matter (GM), an assumption not thoroughly examined. To address this, I determined the distribution of six neurochemicals between WM and GM to establish correction factors to replace assumptions with calculated values. After validation using an independent dataset, I created an open-source tool to implement the calculated correction factors, improving 1H-MRS accuracy by 30-55%. I used quantitative synthetic imaging to measure water properties — relaxation rates (T1 and T2) and proton density (PD) — in different brain tissues of healthy adults. I assessed the impact of inter-individual differences in T1, T2, and PD on neurochemical concentration measures by comparing concentrations calculated using literature-based constants (as is typically performed) to concentrations calculated using individual measures from quantitative maps. In a young, healthy population, individual measures contributed to subtle yet significant variations in calculated neurochemical concentrations, suggesting that using uniform literature values may not be accurate for every individual. Sensitivity analyses indicated that these inaccuracies are likely greater across a wider age range or in individuals with clinical disorders. Applying 1H-MRS, I identified potential neurochemicals and brain regions associated with chronic pain in knee osteoarthritis to understand the brain’s role in this condition. Knee osteoarthritis is a leading cause of chronic pain, with limited research on the specific neurochemicals and brain regions involved. I compared neurochemical levels and their association with pain measures in four brain regions between patients with knee osteoarthritis and healthy controls as well as longitudinally in patients three months after total knee replacement surgery. I found opposing relationships in brain regions associated with pain's sensory and affective dimensions. This dissertation enhances the accuracy of neurochemical concentration quantification and refines the understanding of the brain's contribution to knee osteoarthritis pain.Item Open Access Brain Mechanisms of Associative Memory Deficits in Mild Cognitive Impairment, With or Without Parkinson’s Disease(2021-06-14) Alrazi, Tazrina; Monchi, Oury; Goodyear, Bradley; Smith, Eric; Dunn, JeffreyMild cognitive impairment (MCI) is a condition of minor cognitive difficulties compared to age-matched healthy individuals. Independent activities of daily living are unaffected in MCI. MCI is a major risk factor for the development of dementia, including in patients with Parkinson’s Disease (PD). Individuals with and without PD with MCI might eventually develop dementia. MCI might give an opportunity to initiate interventional strategies to prevent dementia or prolong the duration to get dementia. A deficit in associative memory, the recollection of an association between two or more items, is a marker of early cognitive impairment in MCI. We hypothesized that the neural origins of associative memory deficits differ between MCI with and without PD, which is very important for understanding the MCI process. In this thesis, functional magnetic resonance imaging (fMRI) was used to investigate brain mechanisms of associative memory deficits in MCI with or without PD and compared with age-matched healthy controls. Study participants performed a face-scene associative memory task inside the MRI scanner. The results of this thesis demonstrate different mechanisms of associative memory deficits in MCI with and without PD. PD with MCI (PD-MCI) shows reduced activations in fronto-parietal, fronto-striatal and temporal regions compared to healthy and MCI without PD (non-PD-MCI) during the associative memory task. Non-PD-MCI shows increased activations in fronto-parietal, and temporal regions compared to healthy and both PD groups during the task. PD without MCI (PD-non-MCI) shows increased activations in fusiform gyrus compared to healthy and increased activations in fronto-striatal regions compared to PD-MCI. Both PD groups demonstrate reduced fronto-parietal activations compared to healthy. PD-non-MCI shows similar associative memory performance as healthy while MCI with or without PD groups show poorer performance on the task compared to healthy. Together, these results indicate that increased activations of specific brain regions in PD-non-MCI might be potentially compensatory, whereas increased aberrant activations in non-PD-MCI do not compensate for their underlying cognitive deficiency. Longitudinal follow-up of our subjects could indicate contribution of these brain regions in MCI and potential dementia. Our findings contribute to the understanding of brain functionality in MCI in the elderly with or without PD.Item Open Access Corticospinal Tract Diffusion Tensor Imaging and Motor Function in Children following Perinatal Stroke(2013-01-08) Hodge, Jacquelyn; Kirton, Adam; Goodyear, BradleyPerinatal stroke causes most hemiplegic cerebral palsy. Understanding developmental motor plasticity after perinatal injury is key to developing new therapies. Diffusion tensor imaging (DTI) facilitates this by interrogating functional white matter tracts (e.g. corticospinal tract, CST) but is not well studied in perinatal stroke. Our aim was to quantify CST integrity following perinatal stroke with DTI, evaluating different methodologies and correlations to motor outcome. Twenty-six children (Alberta Perinatal Stroke Project) underwent standardized DTI. Fiber tracking across different CST sections and ROI analysis compared CST diffusion variable (FA/AD/RD/MD) ratios (lesioned/non-lesioned). Correlations with validated motor outcome measures (AHA, MA, PSOM) were sought. DTI quantified differences in all CST diffusion parameters. Decreased FA and increased RD in the lesioned CST demonstrated the most robust correlations with motor outcomes. Analysis of defined CST subtracts may offer advantages over traditional DTI techniques. CST DTI carries both clinical and research utility in perinatal stroke.Item Open Access Cue-Induced Brain Activity in Pathological Gamblers(Elsevier, 2005-11) Crockford, David N.; Goodyear, Bradley; Edwards, Jodi; Quickfall, Jeremy; el-Guebaly, NadyPrevious studies using functional Magnetic Resonance Imaging (fMRI) have identified differential brain activity in healthy subjects performing gambling tasks and pathological gambling (PG) subjects with motivational and emotional predecessors for gambling and during tasks requiring response inhibition. The goal of the present study was to determine if PG subjects exhibit differential brain activity when exposed to visual gambling cues. Methods: 10 male DSM-IV-TR PG subjects and 10 matched healthy controls underwent fMRI during visual presentations of gambling-related video alternating with video of nature scenes. Results: PG subjects and controls exhibited overlap in areas of brain activity in response to the visual gambling cues; however, compared to control subjects, PG subjects exhibited significantly greater activity in the right dorsolateral prefrontal cortex (DLPFC), including the inferior and medial frontal gyri, the right parahippocampal gyrus, and left occipital cortex, including the fusiform gyrus. PG subjects also reported a significant increase in mean craving for gambling after the study. Post-hoc analyses revealed a dissociation in visual processing stream (dorsal vs. ventral) activation by subject group and cue type. Conclusions: These findings may represent a component of cue-induced craving for gambling or conditioned behavior that could underlie pathological gambling.Item Open Access Decreasing Brain Functional Network Segregation with Healthy Aging(2023-03-20) Singh Sidhu, Abhijot; Frayne, Richard; Goodyear, Bradley; Bray, Signe; McCreary, CherylThe functional architecture of the human brain consists of distinct sensory and associative functional networks that interact as needed. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown that functional connections (connectivity) between networks strengthen with age, suggesting that networks reconfigure in healthy aging by becoming less segregated. Few studies, however, have replicated these findings or investigated sex differences in network organization, and no studies have thoroughly investigated if age-related differences involve certain networks more than others. It is crucial to better understand healthy age-related brain changes as it provides a foundation to better address and investigate age-related diseases like dementia or Alzheimer’s disease. In this thesis, cross-sectional functional and structural MR data from 231 presumed healthy adult participants (~59% self-reported as female, aged 18-91 y) from the Calgary Normative Study were examined to investigate the hypotheses that (1) whole-brain and network segregation decreases with age due to decreasing within-network and increasing between-network connectivity, and (2) age-associated increases in between-network functional connectivity occur in associative network connections. Structural and functional MR data were parcellated into seven known functional networks, and average within- and between-network connectivity were computed as the z-transformed Pearson cross-correlation coefficients (zw and zb, respectively). Whole-brain and network segregation were then computed using the segregation index, SI = (|zw|-|zb|)/(|zw|). All networks exhibited decreasing segregation with age, because of increasing between-network connectivity; however, within-network connectivity did not change with age. Further, between-network connectivity increased with age in sensory-to-associative and associative-to-associative network connections, as hypothesized. Increased connectivity between associative networks was also observed in males, regardless of age. This thesis demonstrates that functional networks reconfigure with age because of increased connectivity in sensory-to-associative and associative-to-associative network connections. This may constitute compensatory and/or de-differentiation processes as humans age. The findings of this thesis also provide a foundation for better interpretation of changes in brain function that occur in age-related diseases.Item Open Access Diffusion tensor and functional magnetic resonance imaging as indicators of disease severity in multiple sclerosis: reproducibility and correlational studies(2006) Lau, Raymond Wai-Meng; Goodyear, BradleyItem Embargo Examining Chronic Post-Stroke Aphasia Recovery Using Non-Invasive Brain Stimulation and Neuroimaging(2024-06-24) Low, Trevor A; Dukelow, Sean; Goodyear, Bradley; Kirton, AdamAphasia, an impairment in language processing, affects approximately one-third of stroke survivors immediately after stroke and up to 50% will have long-term impairments. Rehabilitation of aphasia at the chronic phase is possible, though outcomes are variable and often minimal. Novel therapeutic approaches and an increased understanding of the neurobiology supporting recovery are needed. Chapter Two assessed the safety and feasibility of combining repetitive transcranial magnetic stimulation (rTMS) with high-intensity Multi-Modality Aphasia Therapy (M-MAT) in chronic post-stroke aphasia (n=20). This novel combination therapy was determined to be feasible and safe in chronic post-stroke aphasia. On the basis of all participants benefiting from M-MAT regardless of rTMS allocation, we used resting-state fMRI (Chapter Three) and diffusion-weighted MRI (Chapter Four) to examine functional and structural connectivity associated with changes in speech production. In individuals that made positive, significant changes in naming, pre-treatment functional and structural connectivity of left hemisphere temporal and parietal language regions were associated with greater treatment-related improvement in naming. Additionally, naming improvements were associated with decreases in functional connectivity of bilateral posterior temporoparietal regions with frontoparietal, sensorimotor and visual networks at post-treatment. In Chapter Five, we conducted a randomized controlled trial investigating the efficacy of rTMS plus M-MAT on aphasia severity in a larger cohort of chronic stroke participants (n=43). Delivery of rTMS combined with M-MAT resulted in significant supplemental improvements in aphasia severity compared to sham plus M-MAT at follow-up. This demonstrates that rTMS is a promising adjuvant therapy for M-MAT in chronic stroke. Chapter Six investigated the neural basis of adjuvant rTMS effects using overt naming fMRI. Participants who received rTMS with M-MAT demonstrated dynamic functional reorganization over time, resulting in increased recruitment of left hemisphere perisylvian and temporoparietal regions at 15 weeks compared to sham. These data demonstrate potential mechanisms for the behavioural improvements observed following rTMS plus M-MAT. This thesis provides evidence to support the efficacy of rTMS plus M-MAT for improving chronic post-stroke aphasia. In addition, this thesis advances our understanding of the structural and functional brain architecture that supports aphasia recovery. These behavioural and neuroimaging results are important for the advancement of post-stroke aphasia rehabilitation.Item Open Access fMRI techniques to investigate the functional recovery of individual patients following ischemic stroke(2005) Douglas, Erin Ashley; Goodyear, BradleyRecently, functional magnetic resonance imaging (fMRI) has been used to investigate recovery of function post-stroke; however, it has not been implemented clinically due to the variability of measurements taken from individuals across imaging sessions. In this project, it was demonstrated that brain activity measurements based on a laterality index (LI) exhibits less variability than counting fMRI map pixels in a region of interest. It was also demonstrated that combining data from three to four runs of a specific task was required to detect <10% changes in LI across imaging sessions in individuals. Finally, T 2 * within ischemic tissue was elevated and more homogenous than in normal tissue, suggesting the need for an alternative to conventional fMRI. Overall, the results of this project provide the foundation for a clinically useful tool to investigate functional recovery of an individual patient, with the potential to impact on clinical care to help reduce long-term disability.Item Open Access Fronto-striatal Network Dysfunction in Children with Developmental Coordination Disorder and Attention-Deficit/Hyperactivity Disorder(2015-04-06) McLeod, Kevin; Goodyear, Bradley; Dewey, DeborahDevelopmental coordination disorder (DCD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders that significantly impact a child’s physical and mental health. Importantly, DCD and ADHD frequently co-occur. Behavioral, genetic and neuroimaging research have identified commonalities between children with these disorders. This thesis used resting-state functional magnetic resonance imaging (rs-fMRI) to determine the functional connections of the motor network of children with DCD, ADHD, and combined DCD and ADHD, in comparison to healthy children. In the first study, common and distinct alterations in the functional connections with the left motor cortex were identified in children with these disorders, including regions involved in sensorimotor processing and motor control. In the second study, differences in the hemispherical asymmetry of functional connections within the motor networks were also identified. These findings suggest that common brain functional networks are involved in DCD and ADHD, and that rs-fMRI is a valuable tool for furthering our understanding of the neurological underpinnings of these disorders.Item Open Access Functional mri-of motor planning and execution in Parkinson's disease and the effect of medication(2012) D'Andrea, Jolyn; Goodyear, BradleyItem Open Access Functional neuroimaging of monetary reward and pathological gambling(2009) Power, Yuri; Goodyear, Bradley; Crockford, David N.Item Open Access Imaging Biomarkers for Head and Neck Cancers(2013-04-30) Dang, Mong; Goodyear, Bradley; Mitchell, RossIn recent years, biomarker classification using medical imaging informatics has generated significant research interest. Imaging biomarkers may provide a non-invasive method to assess important genetic characteristics of lesions and the impact of treatment. However, assessment of new imaging biomarkers in terms of measurement time, precision and accuracy, is critical for clinical acceptance. This research characterized two new imaging biomarkers in head and neck cancers: a rapid, parallel level-set for volume measurement of meningioma brain tumors; and, an image texture biomarker of an important gene in squamous cell carcinoma (SCC). Results suggest that the new volume measurement tool possesses better measurement time, precision and accuracy than an algorithm in current widespread clinical use. The image texture biomarker achieved good accuracy in predicting genetic status in SCC. These findings demonstrate the potential clinical utility of these new imaging biomarkers.Item Open Access Improved Classification of Optic Neuritis Patients Using Brain Visual Network Transfer Functions(2017-12-22) Shahrabi Farahani, Ehsan; Smith, Michael; Goodyear, Bradley; Sesay, Abu; Fapojuwo, AbrahamOne method to investigate how information propagates throughout brain networks is the transfer function (TF), which determines the amplification or attenuation of frequency components of signals from one brain region to another. Previous functional magnetic resonance imaging (fMRI) studies have demonstrated a disrupted cortical visual network (CVN) in the presence of optic neuritis (ON), which is often associated with the development of multiple sclerosis (MS). In this thesis, new approaches were developed to optimize TF metrics for resting state fMRI data for the purpose of distinguishing between the CVNs of healthy volunteers and ON patients. TF metrics were validated using receiver operating characteristics. Further development permitted the ability to distinguish CVNs between patients experiencing ON as a clinically isolated syndrome and ON patients with relapsing-remitting multiple sclerosis. Such a distinction has implications for the understanding of MS development and progression. Artificial neural networks were also explored as a potential tool to combine several TF metrics to further increase accuracy.Item Open Access Investigations of recovery following optic neuritis using functional and structural imaging(2010) Zayed, Nourhan Mohamed Hassan; Goodyear, Bradley; Smith, Michael RichardItem Open Access Neuroimaging and Robotic Assessment of Proprioceptive Impairments Post-Stroke(2017) Kenzie, Jeffrey; Dukelow, Sean; Goodyear, Bradley; Hill, MichaelBackground: Proprioception is the sense of position (position sense) and movement (kinesthesia) of our limbs and body. It is important for performing coordinated volitional movements, and is often affected after stroke, leading to worse functional recovery. Proprioception is difficult to reliably assess with current clinical measures. This thesis performed proprioceptive assessments in subjects with recent stroke using a robotic exoskeleton called a KINARM. Chapter Two identified specific lesion locations in a sample of subjects with recent stroke (n=142) that were associated with impairments in different aspects of kinesthesia (e.g. speed, direction, and amplitude of movement perception). Lesions to frontal, parietal and temporal cortices, and the insula were associated with impairments in kinesthesia. Chapter Three incorporated multiple measures from position sense and kinesthesia robotic tasks into a single composite score of proprioception. Proprioceptive impairments were common (over 60%, n=285) after stroke, and were correlated with clinical measures of functional independence. This composite score will have utility in monitoring proprioceptive impairments in future rehabilitation clinical trials. Next, Chapters Four and Five utilized functional MRI (fMRI) to identify disruptions in brain activity related to proprioceptive impairments. Chapter Four used a position-matching device and task during fMRI to identify brain areas associated with impaired proprioception. The ipsilesional supramarginal and superior temporal gyri as well as bilateral supplementary motor and ipsilesional premotor cortices were associated with impaired proprioception in subjects with recent stroke (n=16). Chapter Five measured resting-state functional connectivity in subjects with stroke (n=17) using fMRI. Changes in functional connectivity were computed in relation to impaired proprioception (measured using the KINARM). Impaired proprioception was associated with decreased functional connectivity between 1) contralesional opercular area 1 (seed) and ipsilesional temporal and parietal areas, and 2) supplementary motor/premotor areas (seed) and ipsilesional SI and supramarginal gyrus. Conclusions: We have developed an objective and reproducible robotic-based outcome measure of upper limb proprioception. Proprioception in the human brain appears to involve primary sensorimotor structures (e.g. SI, MI) and higher-level association areas such as superior and inferior parietal cortices, supplementary motor and premotor cortices.Item Open Access New approaches for the analysis of the brain's resting state(2011) Golestani, Ali-Mohammad; Goodyear, BradleyResting-state functional magnetic resonance imaging (fMRI) has increasingly gained attention since its introduction fifteen years ago. Its simple data collection procedure makes it a potentially useful clinical tool to investigate reorganization or adaptation of the brain's functional connections in the presence of neurological disease. Methods of data analysis, however, are not well established, and there are several pitfalls in resting-state data processing. In this thesis, specific problems associated with region-of-interest (ROI)based analysis methods are addressed, and new methods to overcome these problems are developed and introduced. Specifically, an algorithm for ROI selection based on its internal connectivity is proposed as a means to objectively select regions for connectivity analysis without the need for a task-based fMRI localizer. Next, a connectivity calculation is introduced that is less sensitive to image noise and artifacts; this calculation is based on a procedure that normalizes connectivity in a given brain region to that of the connectivity of the seed with the seed itself. Furthermore, a time-frequency approach based on the Stockwell transform is introduced to measure similarity between seed and target region signals, without assuming signals are stationary. This method is less sensitive to inadvertent and unwanted brain activation occurring at unpredictable times and over unpredictable frequency ranges. Finally, the proposed methods are used in a preliminary clinical application to determine resting-state connectivity in the motor network of stroke patients with a motor deficit during the acute phase and after recovery. The studies in this thesis answer some problems associated with ROI-based resting-state analysis techniques, and will help establish a framework for ROI-based analysis with higher consistency and reliability.Item Open Access Novel Transfer Function Based Approaches for Analysis of Resting-State Connectivity in Patients with Optic Neuritis(2014-01-28) Choudhury, Samiul Hayder; Smith, Michael Richard; Goodyear, BradleyGenerating reliable imaging markers to study connectivity changes of brain regions associated with optic neuritis (ON) allows ON to be used as a system model for advanced treatment and pathology of multiple sclerosis (MS). Markers that can differentiate ON subject groups are obtained using new transfer function based approaches to characterize the connectivity paths of visual signal propagation. We suggest three thresholding methods to alleviate the effect of possible noisy peaks in the transfer function spectrum. Artificial neural networks (ANN) are used to provide an improved classifier via the integration of the proposed metrics. We propose a new simulated annealing approach to improve the sensitivity of ANN trained with small datasets such as obtained from ON data. We evaluate the ability of the metrics to differentiate between normal subjects and ON patients, with and without MS, using two-way and three-way receiver operator characteristics.Item Open Access On the Malleability of Human Cognition: Working Memory Training and Transfer(2017) Clark, Cameron; Goghari, Vina; Campbell, Tavis; Longman, Richard Stewart; Goodyear, Bradley; Ramasubbu, Rajamannar; Yang, LixiaTraining working memory (WM) to increase WM capacity and fluid intelligence (Gf) has received much experimental attention in recent years, though its efficacy remains highly controversial. The current study investigated the effect of a randomized six-week online WM intervention on cognitive abilities and patterns of neural activation in a community-recruited sample of healthy young adults, in relation to both a processing speed training active control condition, as well as a no-contact control condition. Results of this randomized trial are discussed in three parts: Chapter 2 examines group-level fMRI activation patterns for tasks of WM and Gf before the training intervention. Consistent with previous research, results indicate large areas of fronto-parietal activation in response to increasing task demands for our WM task, which largely subsume more circumscribed regions of activation for our Gf task. These results are discussed in terms of a task-general central network which may underlie performance of WM, Gf, and perhaps even goal-directed behaviour more generally. Chapter 3 investigates potential differences in a wide range of cognitive test scores before and after WM training, processing speed training, or no-contact. Results revealed support for the null hypothesis across all cognitive tests administered. Because these results are consistent with experimental trials of equal or greater methodological rigor, we suggest that future research re-focus on promising interventions known to increase memory performance in healthy young adults; and/or examine alternative populations in which WM training may be efficacious. Chapter 4 examines potential differences in pre- and post-training patterns of neural activation for WM and Gf tasks in our WM training, and processing speed training groups. Results indicated significant post-training reductions in activation for the WM trained group in relation to the processing speed group for the WM task, but not the Gf task. These results suggest that WM training does not affect patterns of neural activation for Gf tasks. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired; and/or WM training interventions in populations that have returned more promising results compared to those with healthy young adults.