Altered functional connectivity between sub-regions in the thalamus and cortex in schizophrenia patients measured by resting state BOLD fMRI at 7T

Abstract

Contributors Jun Hua conducted data collection, data analysis and interpretation, drafting of the article, revision of the article, and final approval. Nicholas I.S. Blair conducted the functional MRI data analysis. Adrian Paez contributed to data analysis and revision of the article. Ann Choe contributed to data interpretation and revision of the article. Anita D. Barber contributed to data interpretation and revision of the article. Allison Brandt contributed to the collection and analysis of the clinical data, and revision of the article. Issel Anne L. Lim contributed to data collection. Feng Xu contributed to data interpretation and revision of the article. Vidyulata Kamath contributed to data interpretation and revision of the article. James J. Pekar contributed to study design, data interpretation and revision of the article. Peter C.M. van Zijl contributed to study design, data interpretation, and revision of the article. Christopher A. Ross contributed to study design, data interpretation, and revision of the article. Russell L. Margolis contributed to study design, data analysis and interpretation, drafting of the article, revision of the article, and final approval. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of interest Equipment used in the study was manufactured by Philips. Peter C.M. van Zijl receives grant support from Philips, is a paid lecturer for Philips, and is the inventor of technology that is licensed to Philips. This arrangement has been approved by Johns Hopkins in accordance with its conflict of interest policies.

Altered Temporal Variability of Local and Large-Scale Resting-State Brain Functional Connectivity Patterns in Schizophrenia and Bipolar Disorder

“…Fourth, although it has been proven to be reliable for analyzing the intra-and inter-network dynamic FC (39), the AAL atlas only provides a relatively coarse parcellation. However, some key brain structures such as the thalamus could be subdivided into more precise subregions with different FC patterns (47,68). Thus, future studies to investigate the temporal variability of dynamic FC with finer parcellation schemes would further improve our understanding of its important role in differentiating schizophrenia and bipolar disorder.…”

Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents

“…Thalamocortical gating alone cannot explain SSA (Lundstrom et al, 2010;Nelken, 2014), and ERP studies in general in SZ, including the ''P50 gating'' ERP, often cannot disentangle true deficits in ERP adaptation from simply reduced baseline ERPs (i.e., reduced cortical response to the initial stimulus vs. the repeated one (Clementz et al, 1998;Hamm et al, 2014). Still, the evidence linking SZ to altered thalamocortical connectivity extends beyond MMN and P50 paradigms and this disconnect is thought to underlie several aspects of symptomology (Sodhi et al, 2011;Klingner et al, 2014;Chen et al, 2019;Hua et al, 2019;Huang et al, 2019;Tu et al, 2019). It is noteworthy that some genetic SZ animal models possess altered thalamocortical networks (Chun et al, 2014;Kröcher et al, 2015), and administering ketamine, which blocks NMDARs to produce SZ-like phenotypes in healthy patients and animals alike, alters thalamocortical connectivity (Höflich et al, 2015;Becker et al, 2016;Furth et al, 2017).…”

Temporal-thalamic and cingulo-opercular connectivity in people with schizophrenia

“…Broadly, rsFC analyses in SZ have revealed two main findings, with respect to the thalamus: 1) hypo -connectivity between sub regions of the thalamus and frontal, cingulate, and thalamic regions in people with SZ compared to healthy controls (HCs) ( Anticevic et al, 2014 , Anticevic et al, 2015a , Bernard et al, 2017 , Cheng et al, 2015 , Ferri et al, 2018 , Hua et al, 2019 , Lencer et al, 2019 , Lui et al, 2009 , Martino et al, 2018 , Penner et al, 2018 , Ramsay, 2019 , Tu et al, 2019 , Wang et al, 2015 , Welsh et al, 2010 , Woodward and Heckers, 2016 , Yamamoto et al, 2018 , Zhu et al, 2015 ); 2) hyper -connectivity between sub regions of the thalamus and motor, somatosensory, temporal, occipital, and insular cortices including the superior temporal gyrus ( Anticevic et al, 2014 , Anticevic et al, 2015a , Bernard et al, 2017 , Ferri et al, 2018 , Hua et al, 2019 , Iwabuchi and Palaniyappan, 2017 , Lencer et al, 2019 , Lui et al, 2009 , Martino et al, 2018 , Penner et al, 2018 , Tu et al, 2019 , Wang et al, 2015 , Woodward and Heckers, 2016 , Yamamoto et al, 2018 ). Both of these findings have been documented in a recent meta-analysis ( Ramsay, 2019 ).…”

“…While previous reports establishing aberrant thalamic and cingulo-opercular connectivity in people with SZ have been informative, most have utilized seed-based metrics ( Anticevic et al, 2014 , Anticevic et al, 2015a , Bernard et al, 2017 , Ferri et al, 2018 , Hua et al, 2019 , Iwabuchi and Palaniyappan, 2017 , Lencer et al, 2019 , Lui et al, 2009 , Martino et al, 2018 , Penner et al, 2018 , Tu et al, 2019 , Wang et al, 2015 , Woodward and Heckers, 2016 , Yamamoto et al, 2018 ) or conducted network-based statistics on predetermined brain regions ( Sheffield et al, 2017 ). Seed-based approaches require researchers to define a single a priori brain region, which is then used to create a rsFC map across the entire brain.…”