Decreased Interhemispheric Functional Connectivity and Its Associations with Clinical Correlates following Traumatic Brain Injury

Abstract

Objective. To explore the interhemispheric functional coordination following traumatic brain injury (TBI) and its association with posttraumatic anxiety and depressive symptoms. Methods. This was a combination of a retrospective cohort study and a cross-sectional observational study. We investigated the functional coordination between hemispheres by voxel-mirrored homotopic connectivity (VMHC). Grey matter volumes were examined by voxel-based morphometry (VBM), and microstructural integrity of the corpus callosum (CC) was assessed by diffusion tension imaging (DTI). The anxiety and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale. Results. The VMHC values of the bilateral middle temporal gyrus (MTG) and orbital middle frontal gyrus (MFG) were significantly decreased in TBI patients versus the healthy controls. Weakened homotopic functional connectivity (FC) in the bilateral orbital MFG is moderate positively correlated with anxiety and depressive symptoms. The white matter integrity in the CC was extensively reduced in TBI patients. In the receiver operating characteristic analysis, the VMHC value of the orbital MFG could distinguish TBI from HC with an area under the curve of 0.939 (sensitivity of 1 and specificity of 0.867). Conclusion. TBI disrupts the interhemispheric functional and structural connection, which is correlated with posttraumatic mood disorders. These findings may serve as a clinical indicator for diagnosis.

Reduced homotopic interhemispheric connectivity in psychiatric disorders: evidence for both transdiagnostic and disorder specific features

“…Strong homotopic rsFC has also been found in the middle occipital gyrus (MOG), inferior parietal lobule (IPL), precentral gyrus (preCG), middle frontal gyrus (MFG), inferior temporal gyrus (ITG), superior temporal gyrus (STG), and anterior insula (aINS) across different tasks (Toro et al ., 2008 ). Homotopic interhemispheric rsFC can be extensively reduced by traumatic brain injury (Li et al ., 2017a ; Mäki-Marttunen et al ., 2013 ; Ovadia-Caro et al ., 2012 ; Raizman et al ., 2022 ; Song et al ., 2022 ) and predict the degree of consciousness or coma severity in disorders of consciousness (Mäki-Marttunen et al ., 2013 ; Ovadia-Caro et al ., 2012 ). Both animal model (Bukhari et al ., 2018 ) and human (Nir et al ., 2022 ) studies have also reported that loss of consciousness produced by general anesthesia reduces the strength of homotopic interhemispheric rsFC and correspondingly increases hemispheric lateralization.…”

Treatment effects of N-acetyl cysteine on resting-state functional MRI and cognitive performance in patients with chronic mild traumatic brain injury: a longitudinal study

“…Recent neuropsychological and neuroimaging literature suggested the vulnerability of the MTG in various aspects of working memory and emotional cognitive perception ( 56 ). Specially, frontotemporal network and brain activity dysfunction in this area has been known to be a target of mTBI which is mainly responsible for cognitive impairment in these patients ( 57 , 58 ). A prior study showed increased functional connectivity between subnetwork nodes in the DMN including the temporal cortex areas in patients with chronic mTBI after 1 year post-injury that was linked with working memory and cognitive dysfunction in those patients ( 59 ).…”

Identification of chronic mild traumatic brain injury using resting state functional MRI and machine learning techniques

“…Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used in neuroscience for detecting intrinsic brain functional architecture as well as interactions between and within neural networks as the biomarkers of cognitive and neurological disorders ( Jeter et al, 2013 ; Sours et al, 2015 ). Various approaches have been proposed for analyzing rs-fMRI data in mTBI cohorts including independent component analysis (ICA) ( Bittencourt-Villalpando et al, 2021 ), graph theory ( van der Horn et al, 2017 ), seed-based FC ( Madhavan et al, 2019 ; Lemme et al, 2021 ; Philippi et al, 2021 ), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) ( Zhan et al, 2015 ; Vedaei et al, 2021 ), degree centrality (DC) ( Li et al, 2019 ), voxel-mirrored homotopic connectivity (VMHC) ( Puig et al, 2020 ; Song et al, 2022 ). The growing body of studies of functional neuroimaging of the resting brain has shown that mTBI is accompanied by alterations of resting-state functional connectivity between and within intrinsic brain networks including the default mode network (DMN), fronto-parietal, motor, dorsal attention, and visual networks ( Shumskaya et al, 2012 ; Stevens et al, 2012 ; Zhou et al, 2012 , 2014 ; Dall’Acqua et al, 2017 ; Palacios et al, 2017 ; Liu et al, 2018 ; Li et al, 2019 ; Madhavan et al, 2019 ; Meier et al, 2020 ; Song et al, 2022 ).…”

“…Various approaches have been proposed for analyzing rs-fMRI data in mTBI cohorts including independent component analysis (ICA) ( Bittencourt-Villalpando et al, 2021 ), graph theory ( van der Horn et al, 2017 ), seed-based FC ( Madhavan et al, 2019 ; Lemme et al, 2021 ; Philippi et al, 2021 ), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) ( Zhan et al, 2015 ; Vedaei et al, 2021 ), degree centrality (DC) ( Li et al, 2019 ), voxel-mirrored homotopic connectivity (VMHC) ( Puig et al, 2020 ; Song et al, 2022 ). The growing body of studies of functional neuroimaging of the resting brain has shown that mTBI is accompanied by alterations of resting-state functional connectivity between and within intrinsic brain networks including the default mode network (DMN), fronto-parietal, motor, dorsal attention, and visual networks ( Shumskaya et al, 2012 ; Stevens et al, 2012 ; Zhou et al, 2012 , 2014 ; Dall’Acqua et al, 2017 ; Palacios et al, 2017 ; Liu et al, 2018 ; Li et al, 2019 ; Madhavan et al, 2019 ; Meier et al, 2020 ; Song et al, 2022 ). However, most of the studies were performed at the group level analysis which makes it challenging to generalize the findings to the identification of mTBI findings in individuals.…”