Medicine and Health Sciences Commons^™

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, …

Neuroimaging-Based Classification Of Ptsd Using Data-Driven Computational Approaches: A Multisite Big Data Study From The Enigma-Pgc Ptsd Consortium., Xi Zhu, Yoojean Kim, Orren Ravid, Xiaofu He, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Seonjoo Lee, Chadi G Abdallah, Michael Angstadt, Christopher L Averill, C Lexi Baird, Lee A Baugh, Jennifer U Blackford, Jessica Bomyea, Steven E Bruce, Richard A Bryant, Zhihong Cao, Kyle Choi, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Michael D Debellis, Emily L Dennis, Maria Densmore, Terri Deroon-Cassini, Seth G Disner, Wissam El Hage, Amit Etkin, Negar Fani, Kelene A Fercho, Jacklynn Fitzgerald, Gina L Forster, Jessie L Frijling, Elbert Geuze, Atilla Gonenc, Evan M Gordon, Staci Gruber, Daniel W Grupe, Jeffrey P Guenette, Courtney C Haswell, Ryan J Herringa, Julia Herzog, David Bernd Hofmann, Bobak Hosseini, Anna R Hudson, Ashley A Huggins, Jonathan C Ipser, Neda Jahanshad, Meilin Jia-Richards, Tanja Jovanovic, Milissa L Kaufman, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B J Koch, Inga K Koerte, Sheri M Koopowitz, Mayuresh S Korgaonkar, John H Krystal, Ruth Lanius, Christine L Larson, Lauren A M Lebois, Gen Li, Israel Liberzon, Guang Ming Lu, Yifeng Luo, Vincent A Magnotta, Antje Manthey, Adi Maron-Katz, Geoffery May, Katie Mclaughlin, Sven C Mueller, Laura Nawijn, Steven M Nelson, Richard W J Neufeld, Jack B Nitschke, Erin M O'Leary, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, K Luan Phan, Rongfeng Qi, Yann Quidé, Ivan Rektor, Kerry Ressler, Pavel Riha, Marisa Ross, Isabelle M Rosso, Lauren E Salminen, Kelly Sambrook, Christian Schmahl, Martha E Shenton, Margaret Sheridan, Chiahao Shih, Maurizio Sicorello, Anika Sierk, Alan N Simmons, Raluca M Simons, Jeffrey S Simons, Scott R Sponheim, Murray B Stein, Dan J Stein, Jennifer S Stevens, Thomas Straube, Delin Sun, Jean Theberge, Paul M Thompson, Sophia I Thomopoulos, Nic J A Van Der Wee, Steven J A Van Der Werff, Theo G M Van Erp, Sanne J H Van Rooij, Mirjam Van Zuiden, Tim Varkevisser, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Li Wang, Xin Wang, Carissa Weis, Sherry Winternitz, Hong Xie, Ye Zhu, Melanie Wall, Yuval Neria, Rajendra A Morey

Department of Medicine Publications

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.

METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls …

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 …

Can The Power Of Sport Help Men With Overweight/Obesity Improve Their Health Through A Tailored Healthy Lifestyle Program?, Robert Petrella, Melissa Majoni, Marisa Kfrerer, Narton Boa Sorte Silva, Brendan Riggin, Wendy Blunt, Dawn P. Gill, Brooke Bliss, Guangyong Zou, Paul Aspinall, Jennifer Irwin

Department of Medicine Publications

Abstract

Context: In Canada and the U.S., a greater proportion of men (vs. women) have overweight or obesity. Despite this, men are underrepresented in weight loss research and fewer are recruited into weight loss services.

Objective: To determine whether participants who received an innovative gender-sensitized healthy lifestyle program (Hockey Fans in Training: Hockey FIT) would have greater weight loss and reduced waist circumference (WC), after 3 and 12 months, compared with a wait-list control group.

Study Design and Analysis: Cluster randomized controlled trial whereby 42 sites were randomly assigned to either the intervention (i.e., Hockey FIT) or a wait-list control …

Hockey Fans In Training Graduate Program (Hfit Grad): Process Evaluation Of An Add-On Fitness Program For Hfit Participants, Robert Petrella, Marisa Kfrerer, Olivia Crozier, Brendan Riggin, Wendy Blunt, Dawn P. Gill, Brooke Bliss

Department of Medicine Publications

Context: Approximately 1 in 4 Canadian adults are living with obesity, indicating a need to provide accessible, sustainable, and locally tailored programs to manage the disease long-term. HFIT Grad was a 6-week exercise and physical activity pilot program offered to previous participants who completed Hockey FIT (a 12-week healthy lifestyle program for male hockey fans who were overweight or had obesity) within the last 12 months. Objective: Evaluate the acceptability of HFIT Grad for promoting maintenance of health behaviours developed in Hockey FIT. Study Design and Analysis: Participants who completed HFIT Grad (n=27) were invited to participate in a virtual …

Hockey Fit For Women (Hfit For Women): Evaluating Reach And Implementation Of A Gender-Sensitized Healthy Lifestyle Program, Robert Petrella, Melissa Majoni, Marisa Kfrerer, Brendan Riggin, Wendy Blunt, Dawn P. Gill, Brooke Bliss, Olivia Crozier, Paul Aspinall

Department of Medicine Publications

Context: 57% of Canadian women have obesity or are overweight, indicating a need for novel mitigation strategies. Research suggests health promotion programs tailored to at-risk groups are more likely to be effective in improving health and sustaining implementation and outcomes long-term. Hockey FIT for Women (HFIT for Women) was adapted from Hockey Fans In Training (HFIT), a 12-week gendersensitized healthy lifestyle program for men who were hockey fans with obesity/overweight. Process evaluation findings from both a HFIT pilot and large-scale trial indicated a need to adapt to women. Objective: Evaluate reach and implementation of the HFIT for Women program from …

Recruitment And Characteristics Of Men With Overweight/Obesity From A Trial Of A Gender-Sensitized Healthy Lifestyle Program, Robert Petrella, Melissa Majoni, Marisa Kferer, Narlon Boa Sorte Silva, Precious Adekoya, Brendan Riggin, Wendy Blunt, Dawn P. Gill, Brooke Bliss, Matthew Dinunzio, Paul Aspinall, Jennifer Irwin

Department of Medicine Publications

Context: Engaging men in chronic disease prevention is critical as rates of obesity in men continue to increase, coupled with men being less likely to proactively seek preventative health care services.

Objective: To report on the recruitment and baseline characteristics of a healthy lifestyle program using the power of sport (hockey) to engage men.

Study Design and Analysis: Cluster randomized controlled trial where 42 sites were randomly assigned to either the intervention or wait-list control group. The intervention group received the Hockey Fans in Training (Hockey FIT) program (3-month active phase; 9-month minimally-supported phase) while the control group continued with …

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 …

Increased Top-Down Control Of Emotions During Symptom Provocation Working Memory Tasks Following A Rct Of Alpha-Down Neurofeedback In Ptsd., Saurabh Bhaskar Shaw, Andrew A Nicholson, Tomas Ros, Sherain Harricharan, Braeden Terpou, Maria Densmore, Jean Theberge, Paul Frewen, Ruth A Lanius

Department of Medicine Publications

BACKGROUND: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task.

METHODS: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected …

Homeostatic Normalization Of Alpha Brain Rhythms Within The Default-Mode Network And Reduced Symptoms In Post-Traumatic Stress Disorder Following A Randomized Controlled Trial Of Electroencephalogram Neurofeedback., Andrew A Nicholson, Maria Densmore, Paul A Frewen, Richard W J Neufeld, Jean Theberge, Rakesh Jetly, Ruth A Lanius, Tomas Ros

Department of Medicine Publications

Collective research has identified a key electroencephalogram signature in patients with post-traumatic stress disorder, consisting of abnormally reduced alpha (8-12 Hz) rhythms. We conducted a 20-session, double-blind, randomized controlled trial of alpha desynchronizing neurofeedback in patients with post-traumatic stress disorder over 20 weeks. Our objective was to provide mechanistic evidence underlying potential clinical improvements by examining changes in aberrant post-traumatic stress disorder brain rhythms (namely, alpha oscillations) as a function of neurofeedback treatment. We randomly assigned participants with a primary diagnosis of post-traumatic stress disorder (

How The Body Remembers: Examining The Default Mode And Sensorimotor Networks During Moral Injury Autobiographical Memory Retrieval In Ptsd., Breanne E Kearney, Braeden A Terpou, Maria Densmore, Saurabh B Shaw, Jean Theberge, Rakesh Jetly, Margaret C Mckinnon, Ruth A Lanius

Department of Medicine Publications

Neural representations of sensory percepts and motor responses constitute key elements of autobiographical memory. However, these representations may remain as unintegrated sensory and motor fragments in traumatic memory, thus contributing toward re-experiencing and reliving symptoms in trauma-related conditions such as post-traumatic stress disorder (PTSD). Here, we investigated the sensorimotor network (SMN) and posterior default mode network (pDMN) using a group independent component analysis (ICA) by examining their functional connectivity during a script-driven memory retrieval paradigm of (potentially) morally injurious events in individuals with PTSD and healthy controls. Moral injury (MI), where an individual acts or fails to act in a …

Association Of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth And Neurodevelopmental Outcomes Among Children Born Very Preterm With A Neonatal Infection., Noha Gomaa, Chaini Konwar, Nicole Gladish, Stephanie H Au-Young, Ting Guo, Min Sheng, Sarah M Merrill, Edmond Kelly, Vann Chau, Helen M Branson, Linh G Ly, Emma G Duerden, Ruth E Grunau, Michael S Kobor, Steven P Miller

Department of Medicine Publications

IMPORTANCE: Very preterm neonates (24-32 weeks' gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.

OBJECTIVES: To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.

DESIGN, SETTING, AND …

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 …

The Trajectory Of Putative Astroglial Dysfunction In First Episode Schizophrenia: A Longitudinal 7-Tesla Mrs Study, Peter Jeon, Michael Mackinley, Jean Théberge, Lena Palaniyappan

Department of Medicine Publications

Myo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same …

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 …

Progressive Changes In Glutamate Concentration In Early Stages Of Schizophrenia: A Longitudinal 7-Tesla Mrs Study, Peter Jeon, Roberto Limongi, Sabrina D. Ford, Michael Mackinley, Kara Dempster, Jean Théberge, Lena Palaniyappan

Department of Medicine Publications

Progressive reduction in glutamatergic transmission has been proposed as an important component of the illness trajectory of schizophrenia. Despite its popularity, to date, this notion has not been convincingly tested in patients in early stages of schizophrenia. In a longitudinal 7T magnetic resonance spectroscopy (1H-MRS), we quantified glutamate at the dorsal anterior cingulate cortex in 21 participants with a median lifetime antipsychotic exposure of less than 3 days and followed them up after 6 months of treatment. Ten healthy controls were also scanned at 2 time points. While patients had significantly lower overall glutamate levels than healthy controls (F(1,27) = …

Classifying Heterogeneous Presentations Of Ptsd Via The Default Mode, Central Executive, And Salience Networks With Machine Learning., Andrew A Nicholson, Sherain Harricharan, Maria Densmore, Richard W J Neufeld, Tomas Ros, Margaret C Mckinnon, Paul A Frewen, Jean Theberge, Rakesh Jetly, David Pedlar, Ruth A Lanius

Department of Medicine Publications

Intrinsic connectivity networks (ICNs), including the default mode network (DMN), the central executive network (CEN), and the salience network (SN) have been shown to be aberrant in patients with posttraumatic stress disorder (PTSD). The purpose of the current study was to a) compare ICN functional connectivity between PTSD, dissociative subtype PTSD (PTSD+DS) and healthy individuals; and b) to examine the use of multivariate machine learning algorithms in classifying PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our neuroimaging dataset consisted of resting-state fMRI scans from 186 participants [PTSD (n = 81); PTSD + DS (n = 49); and …

The Hijacked Self: Disrupted Functional Connectivity Between The Periaqueductal Gray And The Default Mode Network In Posttraumatic Stress Disorder Using Dynamic Causal Modeling., Braeden A Terpou, Maria Densmore, Jean Theberge, Paul Frewen, Margaret C Mckinnon, Andrew A Nicholson, Ruth A Lanius

Department of Medicine Publications

Self-related processes define assorted self-relevant or social-cognitive functions that allow us to gather insight and to draw inferences related to our own mental conditions. Self-related processes are mediated by the default mode network (DMN), which, critically, shows altered functionality in individuals with posttraumatic stress disorder (PTSD). In PTSD, the midbrain periaqueductal gray (PAG) demonstrates stronger functional connectivity with the DMN [i.e., precuneus (PCN), medial prefrontal cortex (mPFC)] as compared to healthy individuals during subliminal, trauma-related stimulus processing. Here, we analyzed the directed functional connectivity between the PAG and the PCN, as well as between the PAG and the mPFC 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 …

The Threatful Self: Midbrain Functional Connectivity To Cortical Midline And Parietal Regions During Subliminal Trauma-Related Processing In Ptsd., Braeden A Terpou, Maria Densmore, Jean Theberge, Janine Thome, Paul Frewen, Margaret C Mckinnon, Ruth A Lanius

Department of Medicine Publications

BACKGROUND: The innate alarm system consists of a subcortical network of interconnected midbrain, lower brainstem, and thalamic nuclei, which together mediate the detection of evolutionarily-relevant stimuli. The periaqueductal gray is a midbrain structure innervated by the innate alarm system that coordinates the expression of defensive states following threat detection. In participants with post-traumatic stress disorder, the periaqueductal gray displays overactivation during the subliminal presentation of trauma-related stimuli as well as altered resting-state functional connectivity. Aberrant functional connectivity is also reported in post-traumatic stress disorder for the default-mode network, a large-scale brain network recruited during self-referential processing and autobiographical memory. Here, …

Back To The Basics: Resting State Functional Connectivity Of The Reticular Activation System In Ptsd And Its Dissociative Subtype., Janine Thome, Maria Densmore, Georgia Koppe, Braeden Terpou, Jean Theberge, Margaret C Mckinnon, Ruth A Lanius

Department of Medicine Publications

BACKGROUND: Brainstem and midbrain neuronal circuits that control innate, reflexive responses and arousal are increasingly recognized as central to the neurobiological framework of post-traumatic stress disorder (PTSD). The reticular activation system represents a fundamental neuronal circuit that plays a critical role not only in generating arousal but also in coordinating innate, reflexive responding. Accordingly, the present investigation aims to characterize the resting state functional connectivity of the reticular activation system in PTSD and its dissociative subtype.

METHODS: We investigated patterns of resting state functional connectivity of a central node of the reticular activation system, namely, the pedunculopontine nuclei, among individuals …

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 …