Digital Commons Network^™

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 …

Roadmap Consensus On Carotid Artery Plaque Imaging And Impact On Therapy Strategies And Guidelines: An International, Multispecialty, Expert Review And Position Statement, L. Saba, W. Brinjikji, J. D. Spence, M. Wintermark, M. Castillo, G. J.D. Borst, Q. Yang, C. Yuan, A. Buckler, M. Edjlali, T. Saam, D. Saloner, B. K. Lal, D. Capodanno, J. Sun, N. Balu, R. Naylor, A. V.D. Lugt, B. A. Wasserman, M. E. Kooi, J. Wardlaw, J. Gillard, G. Lanzino, U. Hedin, D. Mikulis, A. Gupta, J. K. Demarco, C. Hess, J. V. Goethem

Department of Medicine Publications

Current guidelines for primary and secondary prevention of stroke in patients with carotid atherosclerosis are based on the quantification of the degree of stenosis and symptom status. Recent publications have demonstrated that plaque morphology and composition, independent of the degree of stenosis, are important in the risk stratification of carotid atherosclerotic disease. This finding raises the question as to whether current guidelines are adequate or if they should be updated with new evidence, including imaging for plaque phenotyping, risk stratification, and clinical decision-making in addition to the degree of stenosis. To further this discussion, this roadmap consensus article defines the …

The Intriguing Association Between Patent Foramen Ovale And Atrial Fibrillation, J. David Spence, Luciano A. Sposato

Department of Medicine Publications

No abstract provided.

Conned In Pregnancy, Spoorthy Kulkarni, Anna F. Dominiczak, Rhian M. Touyz, J. David Spence, Daniel Batlle, Mohammed Barigou, Morris Brown, Robert M. Carey, Fernando Elijovich, Sandra Taler, Ian B. Wilkinson

Department of Medicine Publications

No abstract provided.

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 …

Egg Consumption Associated With All-Cause Mortality In Rural China: A 14-Year Follow-Up Study, Lishun Liu, Xiao Huang, Binyan Wang, Yun Song, Tengfei Lin, Ziyi Zhou, Huiyuan Guo, Ping Chen, Yan Yang, Wenhua Ling, Xianhui Qin, Genfu Tang, Chengzhang Liu, Jianping Li, Yan Zhang, J. David Spence, Yong Huo, Hao Zhang, Xiping Xu

Department of Medicine Publications

Background: Dietary recommendations regarding egg intake remain controversial topic for public health. We hypothesized that there was a positive association between egg consumption and all-cause mortality. Methods: To test this hypothesis, we enrolled 9885 adults from a community-based cohort in Anhui Province, China during 2003-05. Egg consumption was assessed by food questionnaire. Stratified analyses were performed for age, sex, body mass index (BMI), blood pressure, smoking, drinking and laboratory tests. Results: After an average follow-up of 14.1 years, 9444 participants were included for analysis. A total of 814 deaths were recorded. Participants' BMI and lipid profile had no significantly difference …

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 …

Five-Year Outcomes Of Pfo Closure Or Antiplatelet Therapy For Cryptogenic Stroke, Scott E. Kasner, John F. Rhodes, Grethe Andersen, Helle K. Iversen, Jens E. Nielsen-Kudsk, Magnus Settergren, Christina Sjöstrand, Risto O. Roine, David Hildick-Smith, J. David Spence, Lars Søndergaard

Department of Medicine Publications

No abstract provided.

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 …

Increased Sympathetic Activity And Excess Aldosterone Secretion In Masked Hypertension, J. David Spence

Department of Medicine Publications

No abstract provided.

Emotion Regulation In Emerging Adults With Major Depressive Disorder And Frequent Cannabis Use, Emily S. Nichols, Jacob Penner, Kristen A. Ford, Michael Wammes, Richard W. J. Neufeld, Derek G. V. Mitchell, Steven G. Greening, Jean Théberge, Peter C. Williamson, Elizabeth A. Osuch

Department of Medicine Publications

In people with mental health issues, approximately 20% have co-occurring substance use, often involving cannabis. Although emotion regulation can be affected both by major depressive disorder (MDD) and by cannabis use, the relationship among all three factors is unknown. In this study, we used fMRI to evaluate the effect that cannabis use and MDD have on brain activation during an emotion regulation task. Differences were assessed in 74 emerging adults aged 16–23 with and without MDD who either used or did not use cannabis. Severity of depressive symptoms, emotion regulation style, and age of cannabis use onset were also measured. …

Cardiovascular Harm From Egg Yolk And Meat: More Than Just Cholesterol And Saturated Fat, J. David Spence, Korbua Kristie Srichaikul, David J.A. Jenkins

Department of Medicine Publications

No abstract provided.

Intracerebral Hemorrhage In Sparcl: What Was The Relationship To Ldl-C?, J. David Spence

Department of Medicine Publications

No abstract provided.

Uses Of Ultrasound In Stroke Prevention, J. David Spence

Department of Medicine Publications

Ultrasound methods are useful in stroke prevention in several ways. Measurement of carotid plaque burden, as either total plaque area (TPA) or total plaque volume (TPV) are strong predictors of cardiovascular risk: much stronger than intima-media thickness, which does not represent true atherosclerosis, but a biologically and genetically distinct phenotype. Measurement of plaque burden is also useful for the study of genetics, and of new risk factors such as toxic products of the intestinal microbiome. Carotid plaque burden is highly correlated with and as predictive of risk as coronary calcium scores, but is less costly and does not require radiation. …

Impaired Renal Function And Cerebrovascular Disease, J. David Spence

Department of Medicine Publications

No abstract provided.

Stroke Prevention: A Lifetime Of Lessons, J. David Spence

Department of Medicine Publications

In 44 years of practicing stroke prevention, I have learned many lessons; in this article, I hope to impart some of them. Three areas of my research are discussed. Controlling resistant hypertension is markedly improved by physiologically individualized therapy based on renin/aldosterone phenotyping; this is particularly important in black patients. Measurement of carotid plaque burden strongly predicts cardiovascular risk and is useful for genetic research and for a process called treating arteries instead of risk factors. Doing so in high-risk patients with asymptomatic carotid stenosis was associated with a >80% reduction in the 2-year risk of stroke and myocardial infarction. …

Triglyceride Lowering Drugs: Not Just Icosapent Ethyl, J. David Spence

Department of Medicine Publications

No abstract provided.

Adding Insight To Injury!, A. R. Naylor, J. D. Spence

Department of Medicine Publications

No abstract provided.

Traffic-Related Air Pollution And Carotid Plaque Burden In A Canadian City With Low-Level Ambient Pollution, Markey Johnson, Jeffrey R. Brook, Robert D. Brook, Tor H. Oiamo, Isaac Luginaah, Paul A. Peters, J. David Spence

Department of Medicine Publications

BACKGROUND: The association between fine particulate matter and cardiovascular disease has been convincingly demonstrated. The role of traffic-related air pollutants is less clear. To better understand the role of traffic-related air pollutants in cardiovascular disease development, we examined associations between NO2, carotid atherosclerotic plaque, and cardiometabolic disorders associated with cardiovascular disease. METHODS AND RESULTS: Cross-sectional analyses were conducted among 2227 patients (62.9±13.8 years; 49.5% women) from the Stroke Prevention and Atherosclerosis Research Centre (SPARC) in London, Ontario, Canada. Total carotid plaque area measured by ultrasound, cardiometabolic disorders, and residential locations were provided by SPARC medical records. Long-term outdoor residential NO2 …

Asymptomatic Carotid Stenosis: High Risk With Suboptimal Treatment: Re: Five Year Outcomes In Men Screened For Carotid Artery Stenosis At 65 Years Of Age: A Population Based Cohort Study, J. David Spence

Department of Medicine Publications

No abstract provided.

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) …

Chili Pepper Consumption And Cardiovascular Mortality, J. David Spence

Department of Medicine Publications

No abstract provided.

Trimethylamine N-Oxide: Not Just Red Meat - Egg Yolk And Renal Function Are Also Important, J. David Spence

Department of Medicine Publications

No abstract provided.