Whole-brain Resting-state Functional Connectivity Research Articles

Connectome-based prediction of cognitive performance in patients with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) patients often exhibit varying degrees of cognitive impairments. This study aims to predict cognitive performance in TLE patients by applying a connectome-based predictive model (CPM) to whole-brain resting-state functional connectivity (RSFC) data. A CPM was established and leave-one-out cross-validation was employed to decode the cognitive performance of patients with TLE based on the whole-brain RSFC. Our findings indicate that cognitive performance in TLE can be predicted through the internal and network connections of the parietal lobe, limbic lobe, and cerebellum systems. These systems play crucial roles in cognitive control, emotion processing, and social perception and communication, respectively. In the subgroup analysis, CPM successfully predicted TLE patients with and without focal to bilateral tonic-clonic seizures (FBCTS). Additionally, significant differences were noted between the two TLE patient groups and the normal control group. This data-driven approach provides evidence for the potential of predicting brain features based on the inherent resting-state brain network organization. Our study offers an initial step towards an individualized prediction of cognitive performance in TLE patients, which may be beneficial for diagnosis, prognosis, and treatment planning.

Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury.

Several recent works using resting-state fMRI suggest possible alterations of resting-state functional connectivity after mild traumatic brain injury. However, the literature is plagued by various analysis approaches and small study cohorts, resulting in an inconsistent array of reported findings. In this study, we aimed to investigate differences in whole-brain resting-state functional connectivity between adult patients with mild traumatic brain injury within 1 month of injury and healthy control subjects using several comprehensive resting-state functional connectivity measurement methods and analyses. A total of 123 subjects (72 patients with mild traumatic brain injury and 51 healthy controls) were included. A standard fMRI preprocessing pipeline was used. ROI/seed-based analyses were conducted using 4 standard brain parcellation methods, and the independent component analysis method was applied to measure resting-state functional connectivity. The fractional amplitude of low-frequency fluctuations was also measured. Group comparisons were performed on all measurements with appropriate whole-brain multilevel statistical analysis and correction. There were no significant differences in age, sex, education, and hand preference between groups as well as no significant correlation between all measurements and these potential confounders. We found that each resting-state functional connectivity measurement revealed various regions or connections that were different between groups. However, after we corrected for multiple comparisons, the results showed no statistically significant differences between groups in terms of resting-state functional connectivity across methods and analyses. Although previous studies point to multiple regions and networks as possible mild traumatic brain injury biomarkers, this study shows that the effect of mild injury on brain resting-state functional connectivity has not survived after rigorous statistical correction. A further study using subject-level connectivity analyses may be necessary due to both subtle and variable effects of mild traumatic brain injury on brain functional connectivity across individuals.

Whole-brain correlates of post-traumatic stress disorder in military-related mild traumatic brain injury: A voxel-wise meta-analysis

Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used in studying mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) among military service personnel (MSP). The risk for PTSD is greater after mTBI than after non-mTBI trauma, and PTSD is associated with worse biological, psychological, and social (biopsychosocial) outcomes after mTBI. Studying the neural correlates of mTBI-related PTSD in this population may provide insights into the pathophysiology of both conditions and help identify MSPs most at risk of developing persistent symptoms. This voxel-wise meta-analysis aimed to examine the current literature on rs-fMRI in mTBI-related PTSD, collect neuroimaging data, and perform a voxel-wise meta-analysis to identify significant nodes of functional connectivity across studies. We searched the literature using PubMed, EMBASE, and ScienceDirect. The database query yielded 1455 articles, narrowed with specified eligibility criteria to a final cohort of 33 studies, with 1521 experiment group participants and 1369 controls. Article quality was assessed using the QUADAS-2 instrument. Our meta-analysis revealed a robust correlation between PTSD-mTBI and increased whole-brain resting-state functional connectivity (rsFC) in the amygdala. Our meta-analysis also showed strong correlations between PTSD-mTBI and decreased whole-brain rsFC across regions implicated in speech and language processing. Our meta-regression highlighted robust correlations between less time after a recent mTBI and increased whole-brain rsFC in posterior regions of the default mode network. Our meta-regression also showed strong correlations between increased PTSD symptom severity, increased connectivity in the amygdala, and decreased connectivity in Broca's area.

Predicting conversational satisfaction of face-to-face conversation through interpersonal similarity in resting-state functional connectivity

When conversing with an unacquainted person, if it goes well, we can obtain much satisfaction (referred to as conversational satisfaction). Can we predict how satisfied dyads will be with face-to-face conversation? To this end, we employed interpersonal similarity in whole-brain resting-state functional connectivity (RSFC), measured using functional magnetic resonance imaging before dyadic conversation. We investigated whether conversational satisfaction could be predicted from interpersonal similarity in RSFC using multivariate pattern analysis. Consequently, prediction was successful, suggesting that interpersonal similarity in RSFC is an effective neural biomarker predicting how much face-to-face conversation goes well. Furthermore, regression coefficients from predictive models suggest that both interpersonal similarity and dissimilarity contribute to good interpersonal relationships in terms of brain activity. The present study provides the potential of an interpersonal similarity approach using RSFC for understanding the foundations of human relationships and new neuroscientific insight into whether success in human interactions is predetermined.

In the face of ambiguity: intrinsic brain organization in development predicts one's bias toward positivity or negativity.

Exacerbated negativity bias, including in responses to ambiguity, represents a common phenotype of internalizing disorders. Individuals differ in their propensity toward positive or negative appraisals of ambiguity. This variability constitutes one's valence bias, a stable construct linked to mental health. Evidence suggests an initial negativity in response to ambiguity that updates via regulatory processes to support a more positive bias. Previous work implicates the amygdala and prefrontal cortex, and regions of the cingulo-opercular system, in this regulatory process. Nonetheless, the neurodevelopmental origins of valence bias remain unclear. The current study tests whether intrinsic brain organization predicts valence bias among 119 children and adolescents (6 to 17years). Using whole-brain resting-state functional connectivity, a machine-learning model predicted valence bias (r = 0.20, P = 0.03), as did a model restricted to amygdala and cingulo-opercular system features (r = 0.19, P = 0.04). Disrupting connectivity revealed additional intra-system (e.g. fronto-parietal) and inter-system (e.g. amygdala to cingulo-opercular) connectivity important for prediction. The results highlight top-down control systems and bottom-up perceptual processes that influence valence bias in development. Thus, intrinsic brain organization informs the neurodevelopmental origins of valence bias, and directs future work aimed at explicating related internalizing symptomology.

Connectome-based predictive modeling of Internet addiction symptomatology.

Internet addiction symptomatology (IAS) is characterized by persistent and involuntary patterns of compulsive Internet use, leading to significant impairments in both physical and mental well-being. Here, a connectome-based predictive modeling approach was applied to decode IAS from whole-brain resting-state functional connectivity in healthy population. The findings showed that IAS could be predicted by the functional connectivity between prefrontal cortex with the cerebellum and limbic lobe and connections of the occipital lobe with the limbic lobe and insula lobe. The identified edges associated with IAS exhibit generalizability in predicting IAS within an independent sample. Furthermore, we found that the unique contributing network, which predicted IAS in contrast to the prediction networks of alcohol use disorder symptomatology (the range of symptoms and behaviors associated with alcohol use disorder), prominently comprised connections involving the occipital lobe and other lobes. The current data-driven approach provides the first evidence of the predictive brain features of IAS based on the organization of intrinsic brain networks, thus advancing our understanding of the neurobiological basis of Internet addiction disorder (IAD) susceptibility, and may have implications for the timely intervention of people potentially at risk of IAD.

Discovering individual fingerprints in resting-state functional connectivity using deep neural networks.

Non-negligible idiosyncrasy due to interindividual differences is an ongoing issue in resting-state functional MRI (rfMRI) analysis. We show that a deep neural network (DNN) can be employed for individual identification by learning important features from the time-varying functional connectivity (FC) of rfMRI in the Human Connectome Project. We employed the trained DNN to identify individuals from an independent dataset acquired at our institution. The results revealed that the DNN could successfully identify 300 individuals with an error rate of 2.9% using 15 s time-window and 870 individuals with an error rate of 6.7%. A trained DNN with nonlinear hidden layers led to the proposal of the "fingerprint of FC" (fpFC) as representative edges of individual FC. The fpFCs for individuals exhibited commonly important and individual-specific edges across time-window lengths (from 5 min to 15 s). Furthermore, the utility of our model for another group of subjects was validated, supporting the feasibility of our technique in the context of transfer learning. In conclusion, our study offers an insight into the discovery of the intrinsic mode of the human brain using whole-brain resting-state FC and DNNs.

Bidirectional connectivity alterations in schizophrenia: a multivariate, machine-learning approach.

It is well known that altered functional connectivity is a robust neuroimaging marker of schizophrenia. However, there is inconsistency in the direction of alterations, i.e., increased or decreased connectivity. In this study, we aimed to determine the direction of the connectivity alteration associated with schizophrenia using a multivariate, data-driven approach. Resting-state functional magnetic resonance imaging data were acquired from 109 individuals with schizophrenia and 120 controls across two openly available datasets. A whole-brain resting-state functional connectivity (rsFC) matrix was computed for each individual. A modified connectome-based predictive model (CPM) with a support vector machine (SVM) was used to classify patients and controls. We conducted a series of multivariate classification analyses using three different feature sets, increased, decreased, and both increased and decreased rsFC. For both datasets, combining information from both increased and decreased rsFC substantially improved prediction accuracy (Dataset 1: accuracy = 70.2%, permutation p = 0.001; Dataset 2: accuracy = 64.4%, permutation p = 0.003). When tested across datasets, the prediction model using decreased rsFC performed best. The identified predictive features of decreased rsFC were distributed mostly in the motor network for both datasets. These findings suggest that bidirectional alterations in rsFC are distributed in schizophrenia patients, with the pattern of decreased rsFC being more similar across different populations.

Connectome-based predictive modeling of empathy in adolescents with and without the low-prosocial emotion specifier

Empathy impairments are an important part of a broader affective impairments defining the youth antisocial phenotype callous-unemotional (CU) traits and the DSM-5 low prosocial emotion (LPE) specifier. While functional connectivity underlying empathy and CU traits have been well studied, less is known about what functional connections underly differences in empathy amongst adolescents qualifying for the LPE specifier. Such information can provide mechanistic distinctions for this clinically relevant specifier. The present study uses connectome-based predictive modeling that uses whole-brain resting-state functional connectivity data to predict cognitive and affective empathy for those meeting the LPE specifier (n = 29) and those that do not (n = 57). Additionally, we tested if models of empathy generalized between groups as well as density differences for each model of empathy between groups. Results indicate the LPE group had lower cognitive and affective empathy as well as higher CU traits and conduct problems. Negative and positive models were identified for affective empathy for both groups, but only the negative model for the LPE and positive model for the normative group reliably predicted cognitive empathy. Models predicting empathy did not generalize between groups. Density differences within the default mode, salience, executive control, limbic, and cerebellar networks were found as well as between the executive control, salience, and default mode networks. And, importantly, connections between the executive control and default mode networks characterized empathy differences the LPE group such that more positive connections characterized cognitive differences and less negative connections characterized affective differences. These findings indicate neural differences in empathy for those meeting LPE criteria that may explain decrements in empathy amongst these youth. These findings support theoretical accounts of empathy decrements in the LPE clinical specifier and extend them to identify specific circuits accounting for variation in empathy impairments. The identified negative models help understand what connections inhibit empathy whereas the positive models reveal what brain patterns are being used to support empathy in those with the LPE specifier. LPE differences from the normative group and could be an appropriate biomarker for predicting CU trait severity. Replication and validation using other large datasets are important next steps.

Connectome-based prediction of the severity of autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by social and behavioural deficits. Current diagnosis relies on behavioural criteria, but machine learning, particularly connectome-based predictive modelling (CPM), offers the potential to uncover neural biomarkers for ASD. This study aims to predict the severity of ASD traits using CPM and explores differences among ASD subtypes, seeking to enhance diagnosis and understanding of ASD. Resting-state functional magnetic resonance imaging data from 151 ASD patients were used in the model. CPM with leave-one-out cross-validation was conducted to identify intrinsic neural networks that predict Autism Diagnostic Observation Schedule (ADOS) scores. After the model was constructed, it was applied to independent samples to test its replicability (172 ASD patients) and specificity (36 healthy control participants). Furthermore, we examined the predictive model across different aspects of ASD and in subtypes of ASD to understand the potential mechanisms underlying the results. The CPM successfully identified negative networks that significantly predicted ADOS total scores [r (df=150) = 0.19, P=0.008 in all patients; r (df=104) = 0.20, P=0.040 in classic autism] and communication scores [r (df=150) = 0.22, P=0.010 in all patients; r (df=104) = 0.21, P=0.020 in classic autism]. These results were reproducible across independent databases. The networks were characterized by enhanced inter- and intranetwork connectivity associated with the occipital network (OCC), and the sensorimotor network (SMN) also played important roles. A CPM based on whole-brain resting-state functional connectivity can predicted the severity of ASD. Large-scale networks, including the OCC and SMN, played important roles in the predictive model. These findings may provide new directions for the diagnosis and intervention of ASD, and maybe could be the targets in novel interventions.

Neural correlates of schizotypal traits: Findings from connectome-based predictive modelling

Schizotypal traits can be conceptualized as a phenotype for schizophrenia spectrum disorders. As such, a better understanding of schizotypal traits could potentially improve early identification and treatment of schizophrenia. We used connectome-based predictive modelling (CPM) based on whole-brain resting-state functional connectivity to predict schizotypal traits in 82 healthy participants. Results showed that only the negative network could reliably predict an individual's schizotypal traits (r=0.29). The 10 nodes with the highest edges in the negative network were those known to play a key role in sensation and perception, cognitive control as well as motor control. Our findings suggest that CPM might be a promising approach to improve early identification and prevention of schizophrenia from a spectrum perspective.

Impact of childhood trauma on the abnormal functional connectivity of brain regions in the fear network model of panic disorder

BackgroundPeople who have suffered childhood trauma may be more susceptible to panic disorder (PD). Existing evidence indicates that childhood trauma can significantly impact brain function. Meanwhile, the brain regions involved in the fear network model (FNM) of PD highly overlap with the brain regions affected by childhood trauma. However, it remains unclear whether functional connections between brain regions associated with the FNM in patients with PD are affected by childhood trauma. This study aimed to investigate the effects of childhood trauma on the functional connectivity (FC) of brain regions associated with the FNM in patients with PD. MethodThis study recruited 62 patients with PD, including 21 with a high level of childhood trauma (PD_HCT), 41 with a low level of childhood trauma (PD_LCT), and 40 healthy controls (HCs). The patients underwent magnetic resonance imaging resting-state scanning. The amygdala, anterior cingulate, thalamus, and hippocampus were chosen as regions of interest (ROIs) to examine group differences in ROIs and whole-brain resting-state FC (rsFC). ResultsCompared with PD_HCT patients, PD_LCT patients exhibited significantly increased rsFC in the right thalamus, right temporo-occipital middle temporal gyrus, left thalamus, and right temporo-occipital middle temporal gyrus. Compared with HCs, PD_LCT patients had increased rsFC between the right thalamus and the right temporo-occipital middle temporal gyrus. ConclusionPatients with PD who had suffered high and low levels of childhood trauma were found to exhibit different pathological rsFC alterations in the FNM, suggesting that childhood trauma may be an important risk factor for the development of PD symptoms.

Multimodal brain connectome-based prediction of suicide risk in people with late-life depression

Suicidal ideation, plans and behavior are particularly serious health issues among the older population, resulting in a higher likelihood of deaths than in any other age group. The increasing prevalence of depression in late life reflects the urgent need for efficient screening of suicide risk in people with late-life depression. Employing a cross-sectional design, we performed connectome-based predictive modelling using whole-brain resting-state functional connectivity and white matter structural connectivity data to predict suicide risk in late-life depression patients (N = 37 non-suicidal patients, N = 24 patients with suicidal ideation/plan, N = 30 patients who attempted suicide). Suicide risk was measured using three standardized questionnaires. Brain connectivity profiles were used to classify three groups in our dataset and two independent datasets using machine learning. We found that brain patterns could predict suicide risk in the late-life depression population, with the explained variance up to 30.34%. The functional and structural connectivity profiles improved the classification-prediction accuracy compared with using questionnaire scores alone and could be applied to identify depressed patients who had higher suicide risk in two independent datasets. Our findings suggest that multimodal brain connectivity could capture individual differences in suicide risk among late-life depression patients. Our predictive models might be further tested to help clinicians identify patients who need detailed assessments and interventions. The trial registration number for this study is ChiCTR2200066356.

Connectome-based predictive modeling of trait forgiveness.

Forgiveness is a positive, prosocial manner of reacting to transgressions and is strongly associated with mental health and well-being. Despite recent studies exploring the neural mechanisms underlying forgiveness, a model capable of predicting trait forgiveness at the individual level has not been developed. Herein, we applied a machine-learning approach, connectome-based predictive modeling (CPM), with whole-brain resting-state functional connectivity (rsFC) to predict individual differences in trait forgiveness in a training set (dataset 1, N = 100, 35 men, 17-24 years). As a result, CPM successfully predicted individual trait forgiveness based on whole-brain rsFC, especially via the functional connectivity of the limbic, prefrontal and temporal areas, which are key contributors to the prediction model comprising regions previously implicated in forgiveness. These regions include the retrosplenial cortex, temporal pole, dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, precuneus and dorsal posterior cingulate cortex. Importantly, this predictive model could be successfully generalized to an independent sample (dataset 2, N = 71, 17 men, 16-25 years). These findings highlight the important roles of the limbic system, PFC and temporal region in trait forgiveness prediction and represent the initial steps toward establishing an individualized prediction model of forgiveness.

Connectome-based predictive modeling predicts paranoid ideation in young men with paranoid personality disorder: a resting-state functional magnetic resonance imaging study.

Paranoid personality disorder (PPD), a mental disorder that affects interpersonal relationships and work, is frequently neglected during diagnosis and evaluation at the individual-level. This preliminary study aimed to investigate whether connectome-based predictive modeling (CPM) can predict paranoia scores of young men with PPD using whole-brain resting-state functional connectivity (rs-FC). College students with paranoid tendencies were screened using paranoia scores ≥60 derived from the Minnesota Multiphasic Personality Inventory; 18 participants were ultimately diagnosed with PPD according to the Diagnostic and Statistical Manual of Mental Disorders and subsequently underwent resting-state functional magnetic resonance imaging. Whole-brain rs-FC was constructed, and the ability of this rs-FC to predict paranoia scores was evaluated using CPM. The significance of the models was assessed using permutation tests. The model constructed based on the negative prediction network involving the limbic system-temporal lobe was observed to have significant predictive ability for paranoia scores, whereas the model constructed using the positive and combined prediction network had no significant predictive ability. In conclusion, using CPM, whole-brain rs-FC predicted the paranoia score of patients with PPD. The limbic system-temporal lobe FC pattern is expected to become an important neurological marker for evaluating paranoid ideation.

Right amygdala-right precuneus connectivity is associated with childhood trauma in major depression patients and healthy controls.

The present study investigated the effect of childhood trauma (CT) on amygdala and hippocampus functional connectivity (FC) and the association with clinical presentations of major depressive disorder (MDD). Participants included 73 MDD patients (42 with moderate-to-severe CT and 31 with no or low CT) and 64 healthy controls (HC; 30 with moderate-to-severe CT and 34 with no or low CT). Seed-based whole-brain resting-state FC analyses were performed with seeds located in amygdala and hippocampus. Individuals with moderate-to-severe CT, irrespective of MDD diagnosis, had decreased right amygdala-right precuneus connectivity compared to those with no or low CT. Right amygdala-right precuneus connectivity was significantly correlated with physical and social trait anhedonia in MDD. Mediation effects of this FC on relationship between CT (specifically neglect but not abuse) and trait anhedonia in MDD were significant. MDD patients demonstrated increased right amygdala-left middle frontal gyrus FC, decreased right amygdala-right medial superior frontal gyrus (mSFG) FC and decreased right hippocampus-bilateral mSFG FC relative to HC. Findings highlight the effect of CT on right amygdala-right precuneus FC irrespective of MDD diagnosis. FC of right amygdala-right precuneus may be involved in the mechanism linking CT and depression through its association with trait anhedonia.

Altered whole-brain resting-state functional connectivity and brain network topology in typhoon-related post-traumatic stress disorder.

Altered resting-state functional connectivity has been found in patients with post-traumatic stress disorder (PTSD). However, the alteration of resting-state functional connectivity at whole-brain level in typhoon-traumatized individuals with PTSD remains largely unknown. To investigate changes in whole-brain resting-state functional connectivity and brain network topology in typhoon-traumatized subjects with and without PTSD. Cross-sectional study. Twenty-seven patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC) underwent resting-state functional MRI scanning. The whole brain resting-state functional connectivity network was constructed based on the automated anatomical labeling atlas. The graph theory method was used to analyze the topological properties of the large-scale resting-state functional connectivity network. Whole-brain resting-state functional connectivity and the topological network property were compared by analyzing the variance. There was no significant difference in the area under the curve of γ, λ, σ, global efficiency, and local efficiency among the three groups. The PTSD group showed increased dorsal cingulate cortex (dACC) resting-state functional connectivity with the postcentral gyrus (PoCG) and paracentral lobe and increased nodal betweenness centrality in the precuneus relative to both control groups. Compared with the PTSD and HC groups, the TEC group showed increased resting-state functional connectivity between the hippocampus and PoCG and increased connectivity strength in the putamen. In addition, compared with the HC group, both the PTSD and TEC groups showed increased connectivity strength and nodal efficiency in the insula. Aberrant resting-state functional connectivity and topology were found in all trauma-exposed individuals. These findings broaden our knowledge of the neuropathological mechanisms of PTSD.

Altered Resting-State functional connectivity in the anterior and posterior hippocampus in Post-traumatic stress disorder: The central role of the anterior hippocampus

BackgroundPost-traumatic stress disorder can be viewed as a memory disorder, with trauma-related flashbacks being a core symptom. Given the central role of the hippocampus in autobiographical memory, surprisingly, there is mixed evidence concerning altered hippocampal functional connectivity in PTSD. We shed light on this discrepancy by considering the distinct roles of the anterior versus posterior hippocampus and examine how this distinction may map onto whole-brain resting-state functional connectivity patterns among those with and without PTSD. MethodsWe first assessed whole-brain between-group differences in the functional connectivity profiles of the anterior and posterior hippocampus within a publicly available data set of resting-state fMRI data from 31 male Vietnam war veterans diagnosed with PTSD (mean age = 67.6 years, sd = 2.3) and 29 age-matched combat-exposed male controls (age = 69.1 years, sd = 3.5). Next, the connectivity patterns of each subject within the PTSD group were correlated with their PTSD symptom scores. Finally, the between-group differences in whole-brain functional connectivity profiles discovered for the anterior and posterior hippocampal seeds were used to prescribe post-hoc ROIs, which were then used to perform ROI-to-ROI functional connectivity and graph-theoretic analyses. ResultsThe PTSD group showed increased functional connectivity of the anterior hippocampus with affective brain regions (anterior/posterior insula, orbitofrontal cortex, temporal pole) and decreased functional connectivity of the anterior/posterior hippocampus with regions involved in processing bodily self-consciousness (supramarginal gyrus). Notably, decreased anterior hippocampus connectivity with the posterior cingulate cortex/precuneus was associated with increased PTSD symptom severity. The left anterior hippocampus also emerged as a central locus of abnormal functional connectivity, with graph-theoretic measures suggestive of a more central hub-like role for this region in those with PTSD compared to trauma-exposed controls. ConclusionsOur results highlight that the anterior hippocampus plays a critical role in the neurocircuitry underlying PTSD and underscore the importance of the differential roles of hippocampal sub-regions in serving as biomarkers of PTSD. Future studies should investigate whether the differential patterns of functional connectivity stemming from hippocampal sub-regions is observed in PTSD populations other than older war veterans.

Different functional alteration in attention-deficit/hyperactivity disorder across developmental age groups: A meta-analysis and an independent validation of resting-state functional connectivity studies.

Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered. In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset. As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset. Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD.