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Precision Of Metabolite-Selective Mrs Measurements Of Glutamate, Gaba And Glutathione: A Review Of Human Brain Studies., Kesavi Kanagasabai, Lena Palaniyappan, Jean Theberge

Department of Medicine Publications

Single-voxel proton magnetic resonance spectroscopy (SV 1 H-MRS) is an in vivo noninvasive imaging technique used to detect neurotransmitters and metabolites. It enables repeated measurements in living participants to build explanatory neurochemical models of psychiatric symptoms and testing of therapeutic approaches. Given the tight link among glutamate, gamma-amino butyric acid (GABA), glutathione and glutamine within the cellular machinery, MRS investigations of neurocognitive and psychiatric disorders must quantify a network of metabolites simultaneously to capture the pathophysiological states of interest. Metabolite-selective sequences typically provide improved metabolite isolation and spectral modelling simplification for a single metabolite at a time. Non-metabolite-selective sequences provide …

Cognitive Decline In Thrombotic Thrombocytopenic Purpura Survivors: The Role Of White Matter Health As Assessed By Mri., F Hannan, J Hamilton, C J Patriquin, K Pavenski, M T Jurkiewicz, L Tristao, A M Owen, P K Kosalka, S C L Deoni, J Théberge, J Mandzia, S H S Huang, J D Thiessen

Department of Medicine Publications

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.

Identifying Canonical And Replicable Multi-Scale Intrinsic Connectivity Networks In 100k+ Resting-State Fmri Datasets., A Iraji, Z Fu, A Faghiri, M Duda, J Chen, S Rachakonda, T Deramus, P Kochunov, B M Adhikari, A Belger, J M Ford, D H Mathalon, G D Pearlson, S G Potkin, A Preda, J A Turner, T G M Van Erp, J R Bustillo, K Yang, K Ishizuka, A Faria, A Sawa, K Hutchison, E A Osuch, Jean Theberge, C Abbott, B A Mueller, D Zhi, C Zhuo, S Liu, Y Xu, M Salman, J Liu, Y Du, J Sui, T Adali, V D Calhoun

Department of Medicine Publications

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, …

A Tale Of Two Targets: Examining The Differential Effects Of Posterior Cingulate Cortex- And Amygdala-Targeted Fmri-Neurofeedback In A Ptsd Pilot Study, Jonathan M. Lieberman, Daniela Rabellino, Maria Densmore, Paul Frewen, David Steyrl, Frank Scharnowski, Jean Theberge, Niki Hosseini-Kamkar, Richard W.J. Neufeld, Rakesh Jetly, Benicio N. Frey, Tomas Ros, Ruth A. Lanius, Andrew A. Nicholson

Department of Medicine Publications

Introduction: Real-time fMRI-based neurofeedback (rt-fMRI-NFB) is a non-invasive technology that enables individuals to self-regulate brain activity linked to neuropsychiatric symptoms, including those associated with post-traumatic stress disorder (PTSD). Selecting the target brain region for neurofeedback-mediated regulation is primarily informed by the neurobiological characteristics of the participant population. There is a strong link between PTSD symptoms and multiple functional disruptions in the brain, including hyperactivity within both the amygdala and posterior cingulate cortex (PCC) during trauma-related processing. As such, previous rt-fMRI-NFB studies have focused on these two target regions when training individuals with PTSD to regulate neural activity. However, the differential …

Social Capital Associates With Better Cognitive Health, Oral Health And Epigenetic Age Deceleration: Findings From The Canadian Longitudinal Study On Aging., Aileen Liang, Noha Gomaa

Department of Medicine Publications

Background: Social exposures are linked to an array of health outcomes, especially around aging. In this study, we examined the association of social capital, defined as social relationships and networks, with clinical and biological outcomes including cognitive health, oral inflammation, and epigenetic aging. Methods: We used data from the Canadian Longitudinal Study on Aging (CLSA) (n =1,479; aged 45–85 years), categorizing social capital as structural and cognitive capital. Oral inflammation was determined as the presence of gum bleeding. Epigenetic aging was computed as the difference between chronological age and DNA methylation age. We constructed multivariable regression models adjusted for covariates …

Large-Scale Functional Hyperconnectivity Patterns In Trauma-Related Dissociation: An Rs-Fmri Study Of Ptsd And Its Dissociative Subtype, Saurabh B. Shaw, Braeden A. Terpou, Maria Densmore, Jean Theberge, Pau Frewen, Margaret C. Mckinnon, Ruth A. Lanius

Department of Medicine Publications

The dissociative subtype of post-traumatic stress disorder (PTSD) is a distinct PTSD phenotype characterized by trauma-related dissociation, alongside unique patterns of functional connectivity. However, disparate findings across multiple scales of investigation have highlighted the need for a cohesive understanding of dissociative neurobiology. We took a step towards this goal by conducting one of the broadest region of interest (ROI)-to-ROI analyses performed on a PTSD population to date. In this retrospective study, we investigated resting-state functional MRI data collected from a total of 192 participants, 134 of whom were diagnosed with PTSD. Small functional connectivity differences (maximum effect size 0.27) were …

Variability And Magnitude Of Brain Glutamate Levels In Schizophrenia: A Meta And Mega-Analysis., Kate Merritt, Robert A Mccutcheon, André Aleman, Sarah Ashley, Katherine Beck, Wolfgang Block, Oswald J N Bloemen, Faith Borgan, Christiana Boules, Juan R Bustillo, Aristides A Capizzano, Jennifer M Coughlin, Anthony David, Camilo De La Fuente-Sandoval, Arsime Demjaha, Kara Dempster, Kim Q Do, Fei Du, Peter Falkai, Beata Galińska-Skok, Jürgen Gallinat, Charles Gasparovic, Cedric E Ginestet, Naoki Goto, Ariel Graff-Guerrero, Beng-Choon Ho, Oliver Howes, Sameer Jauhar, Peter Jeon, Tadafumi Kato, Charles A Kaufmann, Lawrence S Kegeles, Matcheri S Keshavan, Sang-Young Kim, Bridget King, Hiroshi Kunugi, J Lauriello, Pablo León-Ortiz, Edith Liemburg, Meghan E Mcilwain, Gemma Modinos, Elias Mouchlianitis, Jun Nakamura, Igor Nenadic, Dost Öngür, Miho Ota, Lena Palaniyappan, Christos Pantelis, Tulsi Patel, Eric Plitman, Sotirios Posporelis, Scot E Purdon, Jürgen R Reichenbach, Perry F Renshaw, Francisco Reyes-Madrigal, Bruce R Russell, Akira Sawa, Martin Schaefer, Dikoma C Shungu, Stefan Smesny, Jeffrey A Stanley, James Stone, Agata Szulc, Reggie Taylor, Katharine N Thakkar, Jean Theberge, Philip G Tibbo, Thérèse Van Amelsvoort, Jerzy Walecki, Peter C Williamson, Stephen J Wood, Lijing Xin, Hidenori Yamasue, Philip Mcguire, Alice Egerton

Department of Medicine Publications

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on …

2022 Canadian Cardiovascular Society Guideline For Use Of Glp-1 Receptor Agonists And Sglt2 Inhibitors For Cardiorenal Risk Reduction In Adults, G.B. John Mancini, Eileen O'Meara, Shelley Zieroth, Mathieu Bernier, Alice Y.Y. Cheng, David Z.I. Cherney, Kim A. Connelly, Justin Ezekowitz, Ronald M. Goldenberg, Lawrence A. Leiter, Gihad Nesrallah, Breay W. Paty, Marie-Eve Piche, Peter Senior, Abhinav Sharma, Subodh Verma, Vincent Woo, Pol Darras, Jonathan Y. Gabor, Jean Gregoire, Eva Lonn, James A. Stone, Jean-Francois Yale, Colin Yeung, Deborah Zimmerman

Department of Medicine Publications

This guideline synthesizes clinical trial data supporting the role of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for treatment of heart failure (HF), chronic kidney disease, and for optimizing prevention of cardiorenal morbidity and mortality in patients with type 2 diabetes. It is on the basis of a companion systematic review and meta-analysis guided by a focused set of population, intervention, control, and outcomes (PICO) questions that address priority cardiorenal end points. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system and a modified Delphi process were used. We encourage comprehensive assessment of cardiovascular (CV) patients …

Shame On The Brain: Neural Correlates Of Moral Injury Event Recall In Posttraumatic Stress Disorder, Chantelle S. Lloyd, Andrew A. Nicholson, Maria Densmore, Jean Théberge, Richard W. J. Neufeld, Rakesh Jetly, Margaret C. Mckinnon, Ruth A. Lanius

Department of Medicine Publications

Background: Moral injury (MI) is consistently associated with adverse mental healthoutcomes, including the development of posttraumatic stress disorder (PTSD) andsuicidality. Methods: We investigated neural activation patterns associated with MI eventrecall using functional magnetic resonance imaging in participants with military andpublic safety‐related PTSD, relative to civilian MI‐exposed controls. Results: MI recall in the PTSD as compared to control group was associatedwith increased neural activation among salience network nodes involved inviscerosensory processing and hyperarousal (right posterior insula, dorsalanterior cingulate cortex; dACC), regions involved in defensive responding(left postcentral gyrus), and areas responsible for top‐down cognitive controlof emotions (left dorsolateral prefrontal cortex; dlPFC). Within …

Acute Conceptual Disorganization In Untreated First-Episode Psychosis: A Combined Magnetic Resonance Spectroscopy And Diffusion Imaging Study Of The Cingulum, Yunzhi Pan, Kara Dempster, Peter Jeon, Jean Théberge, Ali R. Khan, Lena Palaniyappan

Department of Medicine Publications

Background: Disorganized thinking is a core feature of acute psychotic episodes that is linked to social and vocational functioning. Several lines of evidence implicate disrupted cognitive control, excitatory overdrive and oxidative stress relating to the anterior cingulate cortex as mechanisms of conceptual disorganization (CD). We examined 3 candidate mechanistic markers related to CD in firstepisode psychosis: glutamate excess, cortical antioxidant (glutathione) status and the integrity of the cingulum bundle that connects regions implicated in cognitive control. Methods: We used fractional anisotropy maps from 7 T diffusion-weighted imaging to investigate the bilateral cingulum based on a probabilistic white matter atlas. We …

Improved Pet/Mri Accuracy By Use Of Static Transmission Source In Empirically Derived Hardware Attenuation Correction, Adam Farag, R. Terry Thompson, Jonathan D. Thiessen, Frank S. Prato, Jean Théberge

Department of Medicine Publications

Background

Accurate quantification of radioactivity, measured by an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system, is still a challenge. One aspect of such a challenge is to correct for the hardware attenuation, such as the patient table and radio frequency (RF) resonators. For PET/MRI systems, computed tomography (CT) is commonly used to produce hardware attenuation correction (AC) maps, by converting Hounsfield units (HU) to a linear attenuation coefficients (LAC) map at the PET energy level 511 keV, using a bilinear model. The model does not address beam hardening, nor higher density materials, which can lead to …

A Randomized, Controlled Trial Of Alpha-Rhythm Eeg Neurofeedback In Posttraumatic Stress Disorder: A Preliminary Investigation Showing Evidence Of Decreased Ptsd Symptoms And Restored Default Mode And Salience Network Connectivity Using Fmri., Andrew A Nicholson, Tomas Ros, Maria Densmore, Paul A Frewen, Richard W J Neufeld, Jean Theberge, Rakesh Jetly, Ruth A Lanius

Department of Medicine Publications

OBJECTIVE: The default-mode network (DMN) and salience network (SN) have been shown to display altered connectivity in posttraumatic stress disorder (PTSD). Restoring aberrant connectivity within these networks with electroencephalogram neurofeedback (EEG-NFB) has been shown previously to be associated with acute decreases in symptoms. Here, we conducted a double-blind, sham-controlled randomized trial of alpha-rhythm EEG-NFB in participants with PTSD (n = 36) over 20-weeks. Our aim was to provide mechanistic evidence underlying clinical improvements by examining changes in network connectivity via fMRI.

METHODS: We randomly assigned participants with a primary diagnosis of PTSD to either the experimental group (n = 18) …

Perioperative Venous Thromboembolism Prophylaxis In Prostate Cancer Surgery, Zachary Klaasson, Christopher J.D. Wallis, Luke T. Lavallee, Philippe D. Violette

Department of Medicine Publications

Purpose

To describe a patient and procedure specific approach to selecting Venous thromboembolism (VTE) prophylaxis for men who undergo radical prostatectomy.

Methods

We performed a literature search and narrative review of VTE after radical prostatectomy. We describe the current paradigm of perioperative thromboprophylaxis and underlying rationale. Relevant findings from the European Association of Urology thromboprophylaxis guidelines are interpreted and summarized.

Results

The use of extended post-operative thromboprophylaxis for patients who undergo radical prostatectomy is appropriate when the risk of symptomatic VTE outweighs the risk of major bleeding. Patient and procedure factors impact VTE risk. Patient risk can be stratified as …

Assessment Of A Novel 32-Channel Phased Array For Cardiovascular Hybrid Pet/Mri Imaging: Mri Performance., Adam Farag, R Terry Thompson, Jonathan D Thiessen, John Butler, Frank S Prato, Jean Theberge

Department of Medicine Publications

BACKGROUND: Cardiovascular imaging using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) requires a radio frequency phased array resonator capable of high acceleration factors in order to achieve the shortest breath-holds while maintaining optimal MRI signal-to-noise ratio (SNR) and minimum PET photon attenuation. To our knowledge, the only two arrays used today for hybrid PET/MRI cardiovascular imaging are either incapable of achieving high acceleration or affect the PET photon count greatly.

PURPOSE: This study is focused on the evaluation of the MRI performance of a novel third-party prototype 32-channel phased array designed for simultaneous PET/MRI cardiovascular imaging. The …

Overlapping Frontoparietal Networks In Response To Oculomotion And Traumatic Autobiographical Memory Retrieval: Implications For Eye Movement Desensitization And Reprocessing., Sherain Harricharan, Margaret C Mckinnon, Mischa Tursich, Maria Densmore, Paul Frewen, Jean Theberge, Bessel Van Der Kolk, Ruth A Lanius

Department of Medicine Publications

Background: Oculomotor movements have been shown to aid in the retrieval of episodic memories, serving as sensory cues that engage frontoparietal brain regions to reconstruct visuospatial details of a memory. Frontoparietal brain regions not only are involved in oculomotion, but also mediate, in part, the retrieval of autobiographical episodic memories and assist in emotion regulation. Objective: We sought to investigate how oculomotion influences retrieval of traumatic memories by examining patterns of frontoparietal brain activation during autobiographical memory retrieval in post-traumatic stress disorder (PTSD) and in healthy controls. Method: Thirty-nine participants (controls, n = 19; PTSD, n = 20) recollected both …

Swahn Southwestern Academic Health Network Conference 2017 : The Patient Voice & Experience In Southwestern Ontario, Schulich School Of Medicine & Dentistry

Department of Medicine Publications

The conference, held at Western University in London, Ontario, was a full-day event that included presentations based on its theme: The Patient Voice and Experience in Southwestern Ontario. The day began with a two-part presentation featuring Health Quality Ontario’s patient partnership framework, delivered by Jennifer Schipper, Health Quality Ontario’s Chief of Communication and Patient Engagement. Dr. Gillian Kernaghan, President and CEO of St. Joseph’s Health Care London (and Co-Chair of SWAHN) then shared her organization’s care partnership that has involved the contributions of patients, residents, families, and caregivers.

Other presentations included a personal story shared by Mr. Wayne Kristoff who …

Aberrant Functional Connectivity Of The Amygdala Complexes In Ptsd During Conscious And Subconscious Processing Of Trauma-Related Stimuli, Daniela Rabellino, Maria Densmore, Paul A Frewen, Jean Theberge, Margaret C Mckinnon, Ruth A Lanius

Department of Medicine Publications

Post-traumatic stress disorder (PTSD) is characterized by altered functional connectivity of the amygdala complexes at rest. However, amygdala complex connectivity during conscious and subconscious threat processing remains to be elucidated. Here, we investigate specific connectivity of the centromedial amygdala (CMA) and basolateral amygdala (BLA) during conscious and subconscious processing of trauma-related words among individuals with PTSD (n = 26) as compared to non-trauma-exposed controls (n = 20). Psycho-physiological interaction analyses were performed using the right and left amygdala complexes as regions of interest during conscious and subconscious trauma word processing. These analyses revealed a differential, context-dependent responses by each amygdala …

Acc Neuro-Over-Connectivity Is Associated With Mathematically Modeled Additional Encoding Operations Of Schizophrenia Stroop-Task Performance, Reggie Taylor, Jean Theberge, Peter C Williamson, Maria Densmore, Richard W J Neufeld

Department of Medicine Publications

Functional magnetic resonance imaging at 7.0 Tesla was undertaken among Schizophrenia participants (Sz), and clinical (major mood disorder; MDD) and healthy controls (HC), during performance of the Stoop task. Stroop conditions included congruent and incongruent word color items, color-only items, and word-only items. Previous modeling results extended to this most widely used selective-attention task. All groups executed item-encoding operations (subprocesses of the item encoding process) at the same rate (performance accuracy being similarly high throughout), thus displaying like processing capacity; Sz participants, however, employed more subprocesses for item completions than did the MDD participants, who in turn used more subprocesses …

Istent As A Solo Procedure For Glaucoma Patients: A Systematic Review And Meta-Analysis, Monali S. Malvankar-Mehta, Yufeng Nancy Chen, Yiannis Iordanous, Wan Wendy Wang, John Costella, Cindy M. L. Hutnik

Department of Medicine Publications

BACKGROUND: Glaucoma is a leading cause of irreversible blindness. It is firmly entrenched in the traditional treatment paradigm to start with pharmacotherapy. However, pharmacotherapy is not benign and has been well documented to have a number of significant challenges. Minimally invasive glaucoma surgery (MIGS) that targets the outflow pathway with minimal to no scleral dissection has resulted in the need to reconsider the glaucoma treatment paradigm.

PURPOSE: To perform a systematic review and meta-analysis to evaluate and quantify the effect on post-operative intraocular pressure (IOP) and number of topical glaucoma medications, in patients receiving the iStent MIGS device as the …

Practice Patterns And Trends In The Use Of Medical Therapy In Patients Undergoing Percutaneous Coronary Intervention In Ontario, Pallav Garg, Harindra C. Wijeysundera, Lingsong Yun, Warren J. Cantor, Dennis T. Ko

Department of Medicine Publications

Background

Clinical guidelines emphasize medical therapy as the initial approach to the management of patients with stable coronary artery disease (CAD). However, the extent to which medical therapy is applied before and after percutaneous coronary intervention (PCI) in contemporary clinical practice is uncertain. We evaluated medication use for patients with stable CAD undergoing PCI, and assessed whether the COURAGE study altered medication use in the Canadian healthcare system.

Methods and Results

A population‐based cohort of 23 680 older patients >65 years old) with stable CAD undergoing PCI in Ontario between 2003 and 2010 was assembled. Optimal medical therapy (OMT) was …

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 …