Most recent paper
Constraint Induced Movement Therapy Confers only a Transient Behavioral Benefit but Enduring Functional Circuit-Level Changes after Experimental TBI
bioRxiv [Preprint]. 2024 Aug 6:2024.08.02.606449. doi: 10.1101/2024.08.02.606449.
ABSTRACT
Although the behavioral outcome of Constraint-Induced Movement Therapy (CIMT) is well known, and that a combination of CIMT and arm use training potentiates the effect, there has been limited study of the brain circuits involved that respond to therapy. An understanding of CIMT from a brain network level would be useful for guiding the duration of effective therapy, the type of training regime to potentiate the outcome, as well as brain regional targets that might be amenable for direct neuromodulation. Here we investigated the effect of CIMT therapy alone unconfounded by additional rehabilitation training in order to determine the impact of intervention at the circuit level. Adult rats were injured by controlled cortical impact injury and studied before and then after 2wks of CIMT or noCIMT at 1-3wks post-injury using a combination of forelimb behavioral tasks and task-based and resting state functional magnetic resonance imaging at 3 and 7wks post-injury and compared to sham rats. There was no difference in behavior or functional imaging between CIMT and noCIMT after injury before intervention so that data are unlikely to be confounded by differences in injury severity. CIMT produced only a transient reduction in limb deficits compared to noCIMT immediately after the intervention, but no difference thereafter. However, CIMT resulted in a persistent reduction in contralesional limb-evoked activation and a corresponding ipsilesional cortical plasticity compared to noCIMT that endured 4wks after intervention. This was associated with a significant amelioration of intra and inter-hemispheric connectivity present in the noCIMT group at 7wks post-injury.
PMID:39149371 | PMC:PMC11326145 | DOI:10.1101/2024.08.02.606449
A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults
J Affect Disord. 2024 Aug 14:S0165-0327(24)01256-4. doi: 10.1016/j.jad.2024.08.042. Online ahead of print.
ABSTRACT
Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions.
PMID:39151757 | DOI:10.1016/j.jad.2024.08.042
Neurocognitive effects of 3 mA prefrontal electrical stimulation in schizophrenia: A randomized sham-controlled tDCS-fMRI study protocol
PLoS One. 2024 Aug 16;19(8):e0306422. doi: 10.1371/journal.pone.0306422. eCollection 2024.
ABSTRACT
BACKGROUND: Schizophrenia (SCZ) is characterized by cognitive deficits that are linked to prefrontal cortex dysfunction. While transcranial direct current stimulation (tDCS) shows promise for improving cognition, the effects of intensified 3mA tDCS protocols on brain physiology are unknown. This project aims to elucidate the neurophysiological and cognitive effects of an intensified prefrontal tDCS protocol in SCZ.
METHODS: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, trial. Forty-eight participants with SCZ and cognitive impairment (measured via a set of executive functions tests) will be randomly allocated to receive either a single session of active (n = 24) or sham (n = 24) tDCS (20-min, 3-mA). The anodal and cathodal electrodes are positioned over the left and right DLPFC respectively. The stimulation occurs concurrently with the working memory task, which is initiated precisely 5 minutes after the onset of tDCS. Structural and resting-state (rs-fMRI) scans are conducted immediately before and after both active and sham tDCS using a 3 Tesla scanner (Siemens Prisma model) equipped with a 64-channel head coil. The primary outcome will be changes in brain activation (measures vis BOLD response) and working memory performance (accuracy, reaction time).
DISCUSSION: The results of this study are helpful in optimizing tDCS protocols in SCZ and inform us of neurocognitive mechanisms underlying 3 mA stimulation. This study will additionally provide initial safety and efficacy data on a 3 mA tDCS protocol to support larger clinical trials. Positive results could lead to rapid and broader testing of a promising tool for debilitating symptoms that affect the majority of patients with SCZ. The results will be made available through publications in peer-reviewed journals and presentations at national and international conferences.
PMID:39150917 | PMC:PMC11329159 | DOI:10.1371/journal.pone.0306422
Blink-induced changes in pupil dynamics are consistent and heritable
Res Sq [Preprint]. 2024 Aug 6:rs.3.rs-4718613. doi: 10.21203/rs.3.rs-4718613/v1.
ABSTRACT
Pupil size and blink rates are heritable but the extent to which they interact with one another has not been properly investigated. Though changes in pupil size due to eye blinks have been reported, they are considered a pupillary artifact. In this study we used the HCP 7T fMRI dataset with resting state eye-tracking data obtained in monozygous and dizygous twins to assess their heritability and their interactions. For this purpose, we characterized the pupil dilation (positive peak) and constriction (negative peak) that followed blink events, which we describe as blink-induced pupillary response (BIPR). We show that the BIPR is highly consistent with a positive dilatory peak (D-peak) around 500ms and a negative constricting peak (C-peak) around 1s. These patterns were reproducible within- and between-subjects across two time points and differed by vigilance state (vigilant versus drowsy). By comparing BIPR between monozygous and dizygous twins we show that BIPR have a heritable component with significant additive genetic (A) and environmental (E) factors dominating the structural equation models, particularly in the time-domain for both D- and C-peaks and amplitude domain for the C-peak. (a 2 between 42-49%). Blink duration, pupil size and blink rate were also found to be highly heritable (a 2 up to 62% for pupil size). Our study documents an association between BIPR and wakefulness and indicates that BIPR should not be treated as a coincidental artefact, but part of a larger oculomotor system that we label here as Oculomotor Adaptive System, OAS, that is genetically determined.
PMID:39149500 | PMC:PMC11326410 | DOI:10.21203/rs.3.rs-4718613/v1
Individual patterns of functional connectivity in neonates as revealed by surface-based Bayesian modeling
bioRxiv [Preprint]. 2024 Aug 8:2023.07.24.550218. doi: 10.1101/2023.07.24.550218.
ABSTRACT
Resting-state functional connectivity is a widely used approach to study the functional brain network organization during early brain development. However, the estimation of functional connectivity networks in individual infants has been rather elusive due to the unique challenges involved with functional magnetic resonance imaging (fMRI) data from young populations. Here, we use fMRI data from the developing Human Connectome Project (dHCP) database to characterize individual variability in a large cohort of term-born infants (N = 289) using a novel data-driven Bayesian framework. To enhance alignment across individuals, the analysis was conducted exclusively on the cortical surface, employing surface-based registration guided by age-matched neonatal atlases. Using 10 minutes of resting-state fMRI data, we successfully estimated subject-level maps for fourteen brain networks/subnetworks along with individual functional parcellation maps that revealed differences between subjects. We also found a significant relationship between age and mean connectivity strength in all brain regions, including previously unreported findings in higher-order networks. These results illustrate the advantages of surface-based methods and Bayesian statistical approaches in uncovering individual variability within very young populations.
PMID:39149306 | PMC:PMC11326129 | DOI:10.1101/2023.07.24.550218
Amygdala fMRI-A Critical Appraisal of the Extant Literature
Neurosci Insights. 2024 Aug 13;19:26331055241270591. doi: 10.1177/26331055241270591. eCollection 2024.
ABSTRACT
Even before the advent of fMRI, the amygdala occupied a central space in the affective neurosciences. Yet this amygdala-centred view on emotion processing gained even wider acceptance after the inception of fMRI in the early 1990s, a landmark that triggered a goldrush of fMRI studies targeting the amygdala in vivo. Initially, this amygdala fMRI research was mostly confined to task-activation studies measuring the magnitude of the amygdala's response to emotional stimuli. Later, interest began to shift more towards the study of the amygdala's resting-state functional connectivity and task-based psychophysiological interactions. Later still, the test-retest reliability of amygdala fMRI came under closer scrutiny, while at the same time, amygdala-based real-time fMRI neurofeedback gained widespread popularity. Each of these major subdomains of amygdala fMRI research has left its marks on the field of affective neuroscience at large. The purpose of this review is to provide a critical assessment of this literature. By integrating the insights garnered by these research branches, we aim to answer the question: What part (if any) can amygdala fMRI still play within the current landscape of affective neuroscience? Our findings show that serious questions can be raised with regard to both the reliability and validity of amygdala fMRI. These conclusions force us to cast doubt on the continued viability of amygdala fMRI as a core pilar of the affective neurosciences.
PMID:39148643 | PMC:PMC11325331 | DOI:10.1177/26331055241270591
Evaluation of potential alterations related to ADHD in the effective connectivity between the default mode network and cerebellum, hippocampus, thalamus, and primary visual cortex
Cereb Cortex. 2024 Aug 1;34(8):bhae335. doi: 10.1093/cercor/bhae335.
ABSTRACT
Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11 years disappeared after 14 years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.
PMID:39147392 | DOI:10.1093/cercor/bhae335
Static and dynamic interactions within the triple-network model in stroke patients with multidomain cognitive impairments
Neuroimage Clin. 2024 Aug 10;43:103655. doi: 10.1016/j.nicl.2024.103655. Online ahead of print.
ABSTRACT
BACKGROUND: Internal capsule strokes often result in multidomain cognitive impairments across memory, attention, and executive function, typically due to disruptions in brain network connectivity. Our study examines these impairments by analyzing interactions within the triple-network model, focusing on both static and dynamic aspects.
METHODS: We collected resting-state fMRI data from 62 left (CI_L) and 56 right (CI_R) internal capsule stroke patients, along with 57 healthy controls (HC). Using independent component analysis to extract the default mode (DMN), executive control (ECN), and salience networks (SAN), we conducted static and dynamic functional network connectivity analyses (DFNC) to identify differences between stroke patients and controls. For DFNC, we used k-means clustering to focus on temporal properties and multilayer network analysis to examine integration and modularity Q, where integration represents dynamic interactions between networks, and modularity Q measures how well the network is divided into distinct modules. We then calculated the correlations between SFNC/DFNC properties with significant inter-group differences and cognitive scales.
RESULTS: Compared to HC, both CI_L and CI_R patients showed increased static FCs between SAN and DMN and decreased dynamic interactions between ECN and other networks. CI_R patients also had heightened static FCs between SAN and ECN and maintained a state with strongly positive FNCs across all networks in the triple-network model. Additionally, CI_R patients displayed decreased modularity Q.
CONCLUSION: These findings highlight that stroke can result in the disruption of static and dynamic interactions in the triple network model, aiding our understanding of the neuropathological basis for multidomain cognitive deficits after internal capsule stroke.
PMID:39146837 | DOI:10.1016/j.nicl.2024.103655
Chronic hypercortisolism disrupts the principal functional gradient in Cushing's disease: A multi-scale connectomics and transcriptomics study
Neuroimage Clin. 2024 Aug 10;43:103652. doi: 10.1016/j.nicl.2024.103652. Online ahead of print.
ABSTRACT
Cushing's disease (CD) represents a state of cortisol excess, serving as a model to investigate the effects of prolonged hypercortisolism on functional brain. Potential alterations in the functional connectome of the brain may explain frequently reported cognitive deficits and affective disorders in CD patients. This study aims to elucidate the effects of chronic hypercortisolism on the principal functional gradient, which represents a hierarchical architecture with gradual transitions across cognitive processes, by integrating connectomics and transcriptomics approaches. Utilizing resting-state functional magnetic resonance imaging data from 140 participants (86 CD patients, 54 healthy controls) recruited at a single center, we explored the alterations in the principal gradient in CD patients. Further, we thoroughly explored the underlying associative mechanisms of the observed characteristic alterations with cognitive function domains, biological attributes, and neuropsychiatric representations, as well as gene expression profiles. Compared to healthy controls, CD patients demonstrated changes in connectome patterns in both primary and higher-order networks, exhibiting an overall converged trend along the principal gradient axis. The gradient values in CD patients' right prefrontal cortex and bilateral sensorimotor cortices exhibited a significant correlation with cortisol levels. Moreover, the cortical regions showing gradient alterations were principally associated with sensory information processing and higher-cognitive functions, as well as correlated with the gene expression patterns which involved synaptic components and function. The findings suggest that converged alterations in the principal gradient in CD patients may mediate the relationship between hypercortisolism and cognitive impairments, potentially involving genes regulating synaptic components and function.
PMID:39146836 | DOI:10.1016/j.nicl.2024.103652
Functional magnetic resonance imaging studies in bipolar disorder in resting state: A coordinates-based meta-analysis
Psychiatry Res Neuroimaging. 2024 Aug 10;344:111869. doi: 10.1016/j.pscychresns.2024.111869. Online ahead of print.
ABSTRACT
Exploring changes in the intrinsic activity of the brain in people with bipolar disorder (BD) is necessary. However, the findings have not yet led to consistent conclusions. In this regard, this paper aims to extract more obvious differential brain areas and neuroimaging markers, for the purpose of providing assistance for early clinical diagnosis and subsequent treatment. We conducted a meta-analysis of whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) studies using seed-based d-mapping software that examined differences in amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) between patients with BD and healthy controls (HCs). Seed-based d-Mapping (formerly Signed Differential Mapping) with Permutation of Subject Images, or SDM-PSI, is a statistical technique for meta-analyzing studies of differences in brain activity or structure. A total of 16 articles involving 1112 individuals were included in this study for meta-analysis. This paper confidently analyzes the correlation between the clinical scales HAMD, HAMA, and YMRS, and the area of difference. We found significant changes that increased activation in the anterior connective and left lens nucleus, the nucleus of the shell, and BA 48 in BD patients compared with HC (P < 0.05, uncorrected), as well as a significant correlation between HAMD and the left superior frontal gyrus (after FWE correction P < 0.05). Therefore, basal ganglia and frontal cortex may have important significance in the pathogenesis and pathological basis of BD, making it an important issue to be attached importance to.
PMID:39146823 | DOI:10.1016/j.pscychresns.2024.111869
The abnormalities of brain function in females with primary insomnia: a resting-state functional magnetic resonance imaging study
Front Neurosci. 2024 Jul 31;18:1414154. doi: 10.3389/fnins.2024.1414154. eCollection 2024.
ABSTRACT
BACKGROUND: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC).
MATERIALS AND METHODS: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function.
RESULTS: ALFF values were increased in the Cerebelum_4_5_L, as well as decreased ALFF in the bilateral Frontal_Sup_Medial (SFGmed), Angular_L (ANG.L), Parietal_Inf_R (IPL.R), SupraMarginal_R (SMG.R), and Postcentral_R (PoCG.R). ReHo values were increased in the Temporal_Pole_Mid_R (TPOsup.R), as well as decreased ReHo in the Insula_R (INS.R), Frontal_Inf_Oper_R (ORBinf.R), Putamen_R (PUT.R), Rolandic_Oper_R (ROL.R), bilateral Cingulum_Post (PCG), bilateral Frontal_Sup_Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular_R and Frontal_Sup_Medial_L.
CONCLUSION: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability.
PMID:39145301 | PMC:PMC11322055 | DOI:10.3389/fnins.2024.1414154
Dynamic functional connectivity and gene expression correlates in temporal lobe epilepsy: insights from hidden markov models
J Transl Med. 2024 Aug 14;22(1):763. doi: 10.1186/s12967-024-05580-2.
ABSTRACT
BACKGROUD: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE.
METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database.
RESULTS: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function.
CONCLUSIONS: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE.
PMID:39143498 | DOI:10.1186/s12967-024-05580-2
The amplitude of low-frequency fluctuations is correlated with birth trauma in patients with postpartum post-traumatic stress disorder
Transl Psychiatry. 2024 Aug 14;14(1):332. doi: 10.1038/s41398-024-03018-3.
ABSTRACT
Postpartum post-traumatic stress disorder (PP-PTSD) is a severe mental disorder worldwide. In recent years, some studies have reported that PP-PTSD stems from birth trauma. The present study was dedicated in finding ways to predict the occurrence of emergency caesarean section (ECS), trying to analyze the methods to reduce incidence of PP-PTSD on this basis, further exploring the neuroimaging changes in PP-PTSD. A total of 245 primiparas with intention of vaginal delivery were recruited. The internal tocodynamometry measurement was performed during labor for all mothers, and respectively taken at 3-5 cm, 5-8 cm, and 8-10 cm of cervical dilation. The receiver operating characteristic (ROC) curve and Binary logistic regression analyses were also performed to identify fetal head descending thrust that might help in the prediction of ECS. Resting-state magnetic resonance imaging (MRI) was performed on 26 patients diagnosed with PP-PTSD of 245 mothers, the amplitude of low-frequency fluctuations (ALFF) technology was used to observe the spontaneous neural activity of all PP-PTSD patients and correlation analyses were performed. We found that the natural delivery rate of mothers with fetal head descending thrust <16.29 N (5-8 cm), 26.36 N (8-10 cm) were respectively lower than other mothers with fetal head descending thrust ≥16.29 N (5-8 cm), 26.36 N (8-10 cm) (P < 0.05). The ROC curve analysis showed that the area under the receiver operating characteristic curve (AUC) value of thrust (5-8 cm) was 0.896 (95% CI: 0.854-0.938, p < 0.001), AUC of thrust(8-10 cm) was 0.786 (95% CI: 0.714-0.858, p < 0.001), which showed strong potential for predicting ECS. In addition, the Binary logistic regression analysis showed thrust (5-8 cm) and thrust (8-10 cm) were independent correlates of ECS. The resting-state functional magnetic resonance imaging (rs-fMRI) results indicated that PP-PTSD group showed decreased ALFF in the bilateral insula cortex (IC), right anterior cingulate cortex (ACC), and left midcingulate cortex (MCC) compared with healthy postpartum women (HPW) (false discovery rate (FDR) correction q-value < 0.05). The ALFF value of the right ACC was positively correlated with the Perinatal Post-traumatic stress disorder Questionnaire (PPQ) score (r = 0.4046 p = 0.0403) and Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) score (r = 0.3909 p = 0.0483). The internal tocodynamometry measurement can serve as a predictive tool for ECS, on this basis, the implementation of effective emotional support may help to reduce the incidence of PP-PTSD. Besides, this study has verified the presence of altered ALFF in the brain regions of PP-PTSD patients, mainly involving the bilateral IC, right ACC, and left MCC, that might be associated with emotion, cognition, and memory disorders functions in PP-PTSD patients.
PMID:39143051 | DOI:10.1038/s41398-024-03018-3
Cortical-striatal network functional connectivity markers in poststroke fatigue: a single-centre fMRI case-control study protocol
BMJ Open. 2024 Aug 13;14(8):e081800. doi: 10.1136/bmjopen-2023-081800.
ABSTRACT
INTRODUCTION: Structural and functional abnormalities in the cortical-striatal network (CSN) are hypothesised to play a key role in the pathogenesis of neurological disease-associated fatigue. Some small-scale functional MRI (fMRI) studies have suggested that poststroke fatigue (PSF) is related to focal functional connectivity (FC) changes. To date, there has been no published large-scale fMRI study on PSF. This planned study will examine the role of the CSN FC on PSF.
METHODS AND ANALYSIS: The planned study will be a prospective cohort study conducted at the Neurology Unit of the Prince of Wales Hospital. We will recruit 738 participants. The project duration will be 36 months. A psychiatrist will administer the Fatigue Severity Scale (FSS) at 3 months (P1) following the index stroke. PSF is defined as an FSS Score≥4.0. PSF severity will be defined by the FSS total score at P1. Participants with PSF at P1 will undergo two follow-up assessments at 9 (P2) and 15 (P3) months post stroke. PSF remission at P2 or P3 will be defined as a 50% reduction in FSS. Participants will undergo MRI examinations within 2 weeks of the 3-month poststroke assessment. Structural MRI, resting-state fMRI and diffusion tensor imaging will be performed. FC, structural connectivity, infarcts, cerebral microbleeds and white matter hyperintensities will be analysed. For the primary analysis, the effect of PSF on the FC, structural connectivity and diffusion metrics of CSN of stroke survivors, voxel-wise two-sample t-tests will be performed with FDR correction for multiple comparison and significance level set at p<0.05.
ETHICS AND DISSEMINATION: Ethical approval was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster clinical research ethics committee. The study findings will be shared through peer-reviewed journal publications, national and international conferences and social media platforms.
PMID:39142668 | DOI:10.1136/bmjopen-2023-081800
Exploring the mediating role of the ventral attention network and somatosensory motor network in the association between childhood trauma and depressive symptoms in major depressive disorders
J Affect Disord. 2024 Aug 12:S0165-0327(24)01240-0. doi: 10.1016/j.jad.2024.08.024. Online ahead of print.
ABSTRACT
BACKGROUND: Childhood trauma is closely tied to adult depression, but the neurobiological mechanisms remain unclear. Previous studies suggested associations between depression and large-scale brain networks such as the Ventral Attention Network (VAN) and Somatosensory Motor Network (SMN). This study hypothesized that functional connectivity (FC) within and between these networks mediates the link between childhood trauma and adult depression.
METHODS: The Childhood Trauma Questionnaire (CTQ) assessed developmental experiences, and the Hamilton Rating Scale for Depression (HAMD-17) gauged depressive symptoms. Resting-state functional magnetic resonance imaging (fMRI) analyzed FC within and between the VAN and SMN.
RESULTS: Depression group exhibited significantly higher HAMD and CTQ scores, as well as elevated FC within the VAN and between the VAN and SMN (P < 0.05). Positive correlations were found between HAMD total score and FC within the VAN (P < 0.05, r = 0.35) and between the VAN and SMN (P < 0.05, r = 0.34), as well as with CTQ total score (P < 0.05, r = 0.27). Positive correlations were also observed between CTQ total score and FC within the VAN (P < 0.05, r = 0.31) and between the VAN and SMN (P < 0.05, r = 0.29). In the mediation model, FC within and between the VAN and SMN significantly mediated childhood trauma and depression.
LIMITATIONS: The cross-sectional design limits causal inference. The sample size for different trauma types is relatively small, urging caution in generalizing findings.
CONCLUSIONS: The study underscores the association between depression severity, VAN dysfunction, abnormal VAN-SMN FC, and childhood trauma. These findings contribute to understanding the neurobiological mechanisms underlying childhood trauma and depression.
PMID:39142581 | DOI:10.1016/j.jad.2024.08.024
Resting-state functional magnetic resonance imaging alterations in first-degree relatives of individuals with bipolar disorder: A systematic review
J Affect Disord. 2024 Aug 12:S0165-0327(24)01254-0. doi: 10.1016/j.jad.2024.08.040. Online ahead of print.
ABSTRACT
BACKGROUND: Relatives of individuals with bipolar disorder (BD) are at higher risk of developing the disorder. Identifying brain alterations associated with familial vulnerability in BD can help discover endophenotypes, which are quantifiable biological traits more prevalent in unaffected relatives of BD (BD-RELs) than the general population. This review aimed at expanding our knowledge on endophenotypes of BD by providing an overview of resting-state functional magnetic resonance imaging (rs-fMRI) alterations in BD-RELs.
METHODS: A systematic search of PubMed, Scopus, and Web of Science was performed to identify all available rs-fMRI studies conducted in BD-RELs up to January 2024. A total of 18 studies were selected. Six included BD-RELs with no history of psychiatric disorders and 10 included BD-RELs that presented psychiatric disorders. Two investigations examined rs-fMRI alterations in BD-RELs with and without subthreshold symptoms for BD.
RESULTS: BD-RELs presented rs-fMRI alterations in the cortico-limbic network, fronto-thalamic-striatal circuit, fronto-occipital network, and, to a lesser extent, in the DMN. This was true both for BD-RELs with no history of psychopathology and for BD-RELs that presented psychiatric disorders. The direct comparison of rs-fMRI alterations in BD-RELs with and without psychiatric symptoms displayed largely non-overlapping patterns of rs-fMRI abnormalities.
LIMITATIONS: Small sample sizes and the clinical heterogeneity of BD-RELs limit the generalizability of our findings.
CONCLUSIONS: The current literature suggests that first-degree BD-RELs exhibit rs-fMRI alterations in brain circuits involved in emotion regulation, cognition, reward processing, and psychosis susceptibility. Future studies are needed to validate these findings and to explore their potential as biomarkers for early detection and intervention.
PMID:39142577 | DOI:10.1016/j.jad.2024.08.040
Investigating the impact of lumping heterogenous conduct problems: aggression and rule-breaking rely on distinct spontaneous brain activity
Eur Child Adolesc Psychiatry. 2024 Aug 14. doi: 10.1007/s00787-024-02557-w. Online ahead of print.
ABSTRACT
Accumulating evidence suggests that aggression and rule-breaking may have distinct origins. However, grouping these heterogeneous behaviors into a single dimension labelled Conduct Problems (CP) has become the norm rather than the exception. Yet, the neurobiological features that differentiate aggression and rule-breaking remain largely unexplored. Using a large sample of children and adolescents (n = 1360, 6-18 years old), we examined the common and specific brain activity between CP, aggression, and rule-breaking behaviors. Analyses were conducted using fMRI resting-state data from a 10-minute session to explore the correlations between low frequency fluctuations and both broad and fine-grained CP dimensions. The broad CP dimension was associated with deficits in the precentral gyrus, superior temporal gyrus, and tempo-parietal junction. However, only the superior temporal gyrus was shared between aggression and rule-breaking. Activity of the precentral gyrus was mainly associated with rule-breaking, and the temporo-parietal cortex with aggression. More importantly, voxel-wise analyses on fine-grained dimensions revealed additional specific effects that were initially obscured when using a broad CP dimension. Finally, we showed that the findings specific to aggression and rule-breaking may be related to distinct brain networks and mental functions, especially ventral attention/sensorimotor processes and default mode network/social cognitions, respectively. The current study highlights that aggression and rule-breaking may be related to distinct local and distributed neurobiological markers. Overall, using fine-grained dimensions may provide a clearer picture of the role of neurobiological correlates in CP and their invariance across measurement levels. We advocate for adopting a more thorough examination of the lumping/splitting effect across neuroimaging studies on CP.
PMID:39143190 | DOI:10.1007/s00787-024-02557-w
Association study of brain structure-function coupling and glymphatic system function in patients with mild cognitive impairment due to Alzheimer's disease
Front Neurosci. 2024 Jul 29;18:1417986. doi: 10.3389/fnins.2024.1417986. eCollection 2024.
ABSTRACT
BACKGROUND: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer's disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition.
METHOD: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed.
RESULT: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN.
CONCLUSION: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.
PMID:39139498 | PMC:PMC11320604 | DOI:10.3389/fnins.2024.1417986
Brain neuroplasticity in multiple sclerosis patients in functional magnetic resonance imaging studies. Part 2: Effect of aerobic training
Pol J Radiol. 2024 Jul 12;89:e328-e335. doi: 10.5114/pjr/189251. eCollection 2024.
ABSTRACT
PURPOSE: The aim of this study was to evaluate the effects of aerobic training on motor cortical areas in multiple sclerosis (MS) patients, based on task-based functional magnetic resonance imaging (t-fMRI) as well as on brain activity at rest, according to resting state functional MRI (rs-fMRI) studies.
MATERIAL AND METHODS: Multiple sclerosis patients were divided into 2 groups consisting of 14 participants each: the MS study group and the MS control group. All MS patients underwent clinical assessment and MRI examination, twice: in the MS study group at the time of inclusion in the study and after a 4-week period of aerobic training, whereas in the MS control group it happened at the time of inclusion and after a period of one month without exercise rehabilitation. The MRI study protocol included rs-fMRI and t-fMRI sequences, which were the grounds for an analysis of resting state networks (RSN) as well as peak level and cluster level parameters within motor cortex areas - the primary motor cortex, premotor area, and supplementary motor area, respectively.
RESULTS: In the MS study group, aerobic training improved the clinical condition and decreased the functional correlation between the sensorimotor network and the salience network. Also, significant decreases of the mean cluster level (72.42 vs. 38.35) and peak level values (10.89 vs. 7.64) were observed in the contralateral primary motor cortex in this group of patients between examinations.
CONCLUSIONS: Aerobic training not only improves physical performance but also contributes to changes in brain activity - both within RSN and motor cortex areas in MS patients.
PMID:39139257 | PMC:PMC11321027 | DOI:10.5114/pjr/189251
Spatio-temporal learning and explaining for dynamic functional connectivity analysis: Application to depression
J Affect Disord. 2024 Aug 11:S0165-0327(24)01228-X. doi: 10.1016/j.jad.2024.08.014. Online ahead of print.
ABSTRACT
Background Functional connectivity has been shown to fluctuate over time. The present study aimed to identifying major depressive disorders (MDD) with dynamic functional connectivity (dFC) from resting-state fMRI data, which would be helpful to produce tools of early depression diagnosis and enhance our understanding of depressive etiology. Methods The resting-state fMRI data of 178 subjects were collected, including 89 MDD and 89 healthy controls. We propose a spatio-temporal learning and explaining framework for dFC analysis. A yet effective spatio-temporal model is developed to classifying MDD from healthy controls with dFCs. The model is a stacking neural network model, which learns network structure information by a multi-layer perceptron based spatial encoder, and learns time-varying patterns by a Transformer based temporal encoder. We propose to explain the spatio-temporal model with a two-stage explanation method of importance feature extracting and disorder-relevant pattern exploring. The layer-wise relevance propagation (LRP) method is introduced to extract the most relevant input features in the model, and the attention mechanism with LRP is applied to extract the important time steps of dFCs. The disorder-relevant functional connections, brain regions, and brain states in the model are further explored and identified. Results We achieved the best classification performance in identifying MDD from healthy controls with dFC data. The top important functional connectivity, brain regions, and dynamic states closely related to MDD have been identified. Limitations The data preprocessing may affect the classification performance of the model, and this study needs further validation in a larger patient population. Conclusions The experimental results demonstrate that the proposed spatio-temporal model could effectively classify MDD, and uncover structural and temporal patterns of dFCs in depression.
PMID:39137835 | DOI:10.1016/j.jad.2024.08.014