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 …

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 …

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 …

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 …

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 …

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) …

Desynchronization Of Autonomic Response And Central Autonomic Network Connectivity In Posttraumatic Stress Disorder, Janine Thome, Maria Densmore, Paul A Frewen, Margaret C Mckinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius

Department of Medicine Publications

OBJECTIVES: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest.

METHODS: PTSD patients (N = 57) and healthy controls (N = 41) underwent resting-state fMRI. Connectivity patterns of key regions within the central autonomic network …

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 …

Spontaneous Low-Frequency Fluctuations In The Bold Signal In Schizophrenic Patients: Anomalies In The Default Network, Robyn L Bluhm, Jodi Miller, Ruth A Lanius, Elizabeth A Osuch, Kristine Boksman, R W J Neufeld, Jean Theberge, Betsy Schaefer, Peter Williamson

Department of Medicine Publications

Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable …