Resting-state Functional Connectivity Research Articles

Developmental changes in brain structure and function following exposure to oral LSD during adolescence

LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90–120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90–120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.

Ventral striatal-cingulate resting-state functional connectivity in healthy adolescents relates to later depression symptoms in adulthood

BackgroundDepression is a significant public health concern. Identifying biopsychosocial risk factors for depression is important for developing targeted prevention. Studies have demonstrated that blunted striatal activation during reward processing is a risk factor for depression; however, few have prospectively examined whether adolescent reward-related resting-state functional connectivity (rsFC) predicts depression symptoms in adulthood and how this relates to known risk factors (e.g., childhood trauma). MethodsAt baseline, 66 adolescents (mean age = 14.7, SD = 1.4, 68 % female) underwent rsFC magnetic resonance imaging and completed the Children's Depression Inventory (CDI). At follow-up (mean time between adolescent scan and adult follow-up = 10.1 years, SD = 1.6, mean adult age = 24.8 years, SD = 1.7), participants completed the Childhood Trauma Questionnaire (CTQ) and Beck Depression Inventory– Second Edition (BDI-2). Average rsFC was calculated between nodes in mesocorticolimbic reward circuitry: ventral striatum (VS), rostral anterior cingulate cortex (rACC), medial orbitofrontal cortex, and ventral tegmental area. Linear regressions assessed associations between rsFC, BDI-2, and CTQ, controlling for adolescent CDI, sex assigned at birth, and scan age (Bonferroni corrected). ResultsGreater childhood trauma was associated with higher adulthood depression symptoms. Stronger VS-rACC rsFC during adolescence was associated with greater depression symptoms in adulthood and greater childhood trauma. LimitationsThe small sample size, limited depression severity, and seed-based approach are limitations. ConclusionsThe associations between adolescent striatal-cingulate rsFC and childhood trauma and adult depression symptoms suggest this connectivity may be an early neurobiological risk factor for depression and that early life experience plays an important role. Increased VS-rACC connectivity may represent an over-regulatory response on the striatum, commonly reported in depression, and warrants further investigation.

Distinct homotopic functional connectivity patterns of the amygdalar sub-regions as biomarkers in major depressive disorder

BackgroundMajor depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs). MethodSixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment. ResultsPatients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = −0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases. LimitationsThe current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined. ConclusionsUsing a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.

Individual suicide risk factors with resting-state brain functional connectivity patterns in bipolar disorder patients based on latent Dirichlet allocation model

BackgroundThe widespread problem of suicide and its severe burden in bipolar disorder (BD) necessitate the development of objective risk markers, aiming to enhance individual suicide risk prediction in BD. MethodsThis study recruited 123 BD patients (61 patients with prior suicide attempted history (PSAs), 62 without (NSAs)) and 68 healthy controls (HEs). The Latent Dirichlet Allocation (LDA) model was used to decompose the resting state functional connectivity (RSFC) into multiple hyper/hypo-RSFC patterns. Thereafter, according to the quantitative results of individual heterogeneity over latent factor dimensions, the correlations were analyzed to test prediction ability. ResultsModel constructed without introducing suicide-related labels yielded three latent factors with dissociable hyper/hypo-RSFC patterns. In the subsequent analysis, significant differences in the factor distributions of PSAs and NSAs showed biases on the default-mode network (DMN) hyper-RSFC factor (factor 3) and the salience network (SN) and central executive network (CEN) hyper-RSFC factor (factor 1), indicating predictive value. Correlation analysis of the individuals' expressions with their Nurses' Global Assessment of Suicide Risk (NGASR) revealed factor 3 positively correlated (r = 0.4180, p < 0.0001) and factor 1 negatively correlated (r = − 0.2492, p = 0.0055) with suicide risk. Therefore, it could be speculated that patterns more associated with suicide reflected hyper-connectivity in DMN and hypo-connectivity in SN, CEN. ConclusionsThis study provided individual suicide-associated risk factors that could reflect the abnormal RSFC patterns, and explored the suicide related brain mechanisms, which is expected to provide supports for clinical decision-making and timely screening and intervention for individuals at high risks of suicide.

Individual patterns of functional connectivity in neonates as revealed by surface-based Bayesian modeling.

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.

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study

BackgroundStudies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. MethodsA double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. ResultsThe subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. ConclusionsAfter 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.

Altered functional connectivity of parietal opercular 2 in patients with vestibular migraine: a resting-state fMRI study

Objective: To investigate the differences in resting-state functional connectivity (FC) between patients with vestibular migraine (VM) and migraine without aura (MwoA) in order to infer the possible neuroimaging mechanisms of VM. Methods: Thirty VM patients admitted to the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from December 2019 to December 2022 were selected as the experimental group (EG) (6 males and 24 females, with mean age of 38.3 years) and 26 MwoA patients as the control group (7 males and 19 females, mean age 35.5 years). General demographic and clinical data such as gender, age, year of education, course of disease and frequency of attacks were collected for all the patients, as well as data of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), headache Visual Arialogue Scale (VAS), Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment Questionnaire (MIDAS). VM patients were also assessed by Dizziness Handicap Inventory (DHI), dizziness VAS and Vestibular Disorders Activities of Daily Living (VADL) scales. All patients underwent resting-sate functional Magnetic Resonance Imaging (fMRI) scans. Bilateral parietal opercular cortex 2 (OP2) and primary visual cortex (V1) were used as regions of interests (ROIs). Differences in FC between ROIs and other brain regions were calculated between the two groups. In view of the brain regions with significant differences, z-values of FC were extracted for each subject in the EG, and Pearson partial correlation analysis was conducted between z-values of FC and clinical characteristics of patients, P<0.05 was considered to have significant correlation. SPSS 22.0 was used for statistical analysis. Results: There was no significant difference in gender, age, years of education, course of disease, frequency of attack and scores of MoCA, HAMA and HAMD between the two groups (P>0.05). Headache VAS, HIT-6 and MIDAS scores in VM patients were significantly lower than those in MwoA patients (P<0.05). Compared with MwoA patients, the FC between left OP2 and bilateral precuneus and left thalamus was significantly increased in VM patients, and the FC between right OP2 and left thalamus and right anterior cingulate gyrus were significantly increased (P<0.05, False Discovery Rate correction). Correlation analysis showed that the FC between left OP2 and left precuneus was positively correlated with DHI score in VM patients (P=0.007, r=0.480), and the FC between right OP2 and left thalamus was positively correlated with the disease course in VM patients (P=0.015, r=0.439). Conclusions: The pathogenesis of VM may be related to the altered FC of vestibular, pain and visual-motor networks, abnormalities of these neural pathways may be important imaging biomarkers of VM pathogenesis.

Translation of monosynaptic circuits underlying amygdala fMRI neurofeedback training.

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in each ROI (SN: anterior cingulate, ventrolateral, and insular cortices; DMN: temporal pole, middle frontal gyrus, angular gyrus, precuneus, posterior cingulate cortex, parahippocampal gyrus, hippocampus, and thalamus). We also performed additional injections in specific ROIs to validate the results following amygdala injections and delineate potential disynaptic pathways. Finally, we used high-resolution diffusion MRI data from four post-mortem macaque brains and one in vivo human brain to translate our findings to the neuroimaging domain. Different amygdala nuclei had significant monosynaptic connections with all the SN and DMN ipsilateral ROIs. Amygdala connections with the DMN contralateral ROIs are disynaptic through the hippocampus and parahippocampal gyrus. Diffusion MRI in both species benefitted from using the ground-truth tracer data to validate its findings, as we identified false-negative ipsilateral and false-positive contralateral connectivity results. This study provides the foundation for future causal investigations of amygdala neurofeedback modulation of the SN and DMN through these anatomic connections.

Brain modulation after exergaming training in advanced forms of Parkinson’s disease: a randomized controlled study

BackgroundPhysical activity combined with virtual reality and exergaming has emerged as a new technique to improve engagement and provide clinical benefit for gait and balance disorders in people with Parkinson’s disease (PD).ObjectiveTo investigate the effects of a training protocol using a home-based exergaming system on brain volume and resting-state functional connectivity (rs-FC) in persons with PD.MethodsA single blind randomized controlled trial was conducted in people with PD with gait and/or balance disorders. The experimental (active) group performed 18 training sessions at home by playing a custom-designed exergame with full body movements, standing in front of a RGB-D Kinect® motion sensor, while the control group played using the computer keyboard. Both groups received the same training program. Clinical scales, gait recordings, and brain MRI were performed before and after training. We assessed the effects of both training on both the grey matter volumes (GVM) and rs-FC, within and between groups.ResultsTwenty-three patients were enrolled and randomly assigned to either the active (n = 11) or control (n = 12) training groups. Comparing pre- to post-training, the active group showed significant improvements in gait and balance disorders, with decreased rs-FC between the sensorimotor, attentional and basal ganglia networks, but with an increase between the cerebellar and basal ganglia networks. In contrast, the control group showed no significant changes, and rs-FC significantly decreased in the mesolimbic and visuospatial cerebellar and basal ganglia networks. Post-training, the rs-FC was greater in the active relative to the control group between the basal ganglia, motor cortical and cerebellar areas, and bilaterally between the insula and the inferior temporal lobe. Conversely, rs FC was lower in the active relative to the control group between the pedunculopontine nucleus and cerebellar areas, between the temporal inferior lobes and the right thalamus, between the left putamen and dorsolateral prefrontal cortex, and within the default mode network.ConclusionsFull-body movement training using a customized exergame induced brain rs-FC changes within the sensorimotor, attentional and cerebellar networks in people with PD. Further research is needed to comprehensively understand the neurophysiological effects of such training approaches.Trial registration ClinicalTrials.gov NCT03560089.

The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study.

N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates (i) alcohol cue-elicited activation, and (ii) intrinsic functional connectivity compared to placebo in patients with AUD. In this preliminary study, twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400mg/day, n = 9), or a placebo (n = 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 377 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by-time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC-treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. However, the absence of cue reactivity findings may result from low power, rather than the absence of cue reactivity findings associated with NAC. These results provide preliminary evidence that NAC treatment may modulate intrinsic functional connectivity brain activation in patients with alcohol use disorder, but replication in larger studies are required to determine the strength of this effect and any associations with clinical outcomes. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT03879759.

Individualized prediction of online shopping addiction from whole-brain functional connectivity

Online shopping addiction (OSA) is defined as a behavioral addiction where an individual exhibits an unhealthy and excessive attachment to shopping on the Internet. Since the OSA shown its adverse impacts on individuals' daily life and social functions, it is important to examine the neurobiological underpinnings of OSA that could be used in clinical practice to identify individuals with OSA. The present study addressed this question by employing a connectome-based prediction model approach to predict the OSA tendency of healthy subjects from whole-brain resting-state functional connectivity. The OSA connectome - a set of connections across multiple brain networks that contributed to predict individuals' OSA tendency was identified, including the functional connectivity between the frontal-parietal network (FPN) and cingulo-opercular network (CON) (i.e., positive network), as well as the functional connectivity within default mode network (DMN) and that between FPN and DMN (i.e., negative network). Key nodes that contributed to the prediction model included the middle frontal gyrus, inferior frontal gyrus, anterior cingulate cortex, and inferior temporal gyrus, which have been associated with impulsivity and emotional processing. Notably, this connectome has shown its specific role in predicting OSA by controlling for the influence of general Internet addiction. Moreover, the strength of the negative network mediated the relationship between OSA and impulsivity, highlighting that the negative network underlies the impulsivity characteristic of OSA. Together, these findings advanced our understanding of the neural correlates of OSA and provided a promising framework for diagnosing OSA.

Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?

BackgroundInflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. MethodsWe used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. ResultsWe found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. ConclusionsThus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression.

Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Abnormal resting-state hyperconnectivity in schizophrenia: A whole-head near-infrared spectroscopy study

Near-infrared spectroscopy (NIRS) is a noninvasive functional neuroimaging modality that can detect changes in blood oxygenation levels by tracking cortical neural activity. We recorded the resting-state brain activity of 24 individuals with schizophrenia and 90 healthy controls for 8 min using a whole-head NIRS arrangement and then used partial correlation analysis to estimate the resting-state functional connectivity (RSFC) between 17 cortical regions. We found that the RSFC between the bilateral orbitofrontal cortices (OFCs) and between the right temporal and parietal lobes was significantly higher in patients with schizophrenia than in healthy controls. The RSFC between the bilateral OFCs was positively correlated with negative symptom severity, whereas the RSFC between the right temporal and parietal lobes was positively correlated with the chlorpromazine equivalent for antipsychotics prescribed to patients with schizophrenia. This finding was consistent with that for the RSFC calculated using the anterior 52-channel signals. Our results suggest that NIRS-based RSFC measurements have potential clinical applications.

From convergence insufficiency to functional reorganization: Alongitudinal randomized controlled trial of treatment-induced connectivity plasticity.

Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting-state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office-based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task-related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms. A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one-hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting-state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t-tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group-level analysis for correlations with clinical measures. Paired t-test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)-SEF-Right (R)-V1, L-SEF-CV, R-SEF-R-PEF, R-SEF-L-V1, R-SEF-R-V1, R-SEF-CV, R-PEF-CV, L-V1-CV, R-V1-CV, and L-V1-R-V1. Significant correlations were observed between the RSFC strength of the R-SEF-R-PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05). OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants.

Exploration of resting-state brain functional connectivity as preclinical markers for arousal prediction in prolonged disorders of consciousness: A pilot study based on functional near-infrared spectroscopy.

There is no diagnostic assessment procedure with moderate or strong evidence of use, and evidence for current means of treating prolonged disorders of consciousness (pDOC) is sparse. This may be related to the fact that the mechanisms of pDOC have not been studied deeply enough and are not clear enough. Therefore, the aim of this study was to explore the mechanism of pDOC using functional near-infrared spectroscopy (fNIRS) to provide a basis for the treatment of pDOC, as well as to explore preclinical markers for determining the arousal of pDOC patients. Five minutes resting-state data were collected from 10 pDOC patients and 13healthy adults using fNIRS. Based on the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the time series, the resting-state cortical brain functional connectivity strengths of the two groups were calculated, and the functional connectivity strengths of homologous and heterologous brain networks were compared at the sensorimotor network (SEN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), and visual network (VIS) levels. Univariate binary logistic regression analyses were performed on brain networks with statistically significant differences to identify brain networks associated with arousal in pDOC patients. The receiver operating characteristic (ROC) curves were further analyzed to determine the cut-off value of the relevant brain networks to provide clinical biomarkers for the prediction of arousal in pDOC patients. The results showed that the functional connectivity strengths of oxyhemoglobin (HbO)-based SEN∼SEN, VIS∼VIS, DAN∼DAN, DMN∼DMN, SEN∼VIS, SEN∼FPN, SEN∼DAN, SEN∼DMN, VIS∼FPN, VIS∼DAN, VIS∼DMN, HbR-based SEN∼SEN, and SEN∼DAN were significantly reduced in the pDOC group and were factors that could reflect the participants' state of consciousness. The cut-off value of resting-state functional connectivity strength calculated by ROC curve analysis can be used as a potential preclinical marker for predicting the arousal state of subjects. Resting-state functional connectivity strength of cortical networks is significantly reduced in pDOC patients. The cut-off values of resting-state functional connectivity strength are potential preclinical markers for predicting arousal in pDOC patients.

Leveraging Distributed Brain Signal at Rest to Predict Internalizing Symptoms in Youth: Deriving a Polyneuro Risk Score From the ABCD Study Cohort

BackgroundThe prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear. MethodsYouths from the Adolescent Brain Cognitive Development (ABCD) Study (ages 9–10 years at baseline) with a resting-state functional magnetic resonance imaging scan and mental health data were eligible for inclusion. Internalizing subscale scores from the Brief Problem Monitor-Youth Form were combined across 2 years of follow-up to generate a cumulative measure of internalizing symptoms. The total sample (N = 6521) was split into a large discovery dataset and a smaller validation dataset. Brain-behavior associations of resting-state functional connectivity with internalizing symptoms were estimated in the discovery dataset. The weighted contributions of each functional connection were aggregated using multivariate statistics to generate a polyneuro risk score (PNRS). The predictive power of the PNRS was evaluated in the validation dataset. ResultsThe PNRS explained 10.73% of the observed variance in internalizing symptom scores in the validation dataset. Model performance peaked when the top 2% functional connections identified in the discovery dataset (ranked by absolute β weight) were retained. The resting-state functional connectivity networks that were implicated most prominently were the default mode, dorsal attention, and cingulo-parietal networks. These findings were significant (p < 1 × 10−6) as accounted for by permutation testing (n = 7000). ConclusionsThese results suggest that the neural phenotype associated with internalizing symptoms during adolescence is functionally distributed. The PNRS approach is a novel method for capturing relationships between resting-state functional connectivity and behavior.

Resting-state functional connectivity of the occipital cortex in different subtypes of Parkinson's disease.

To examine whether functional connectivity (FC) of the occipital gyrus differs between patients with Parkinson's disease (PD) motor subtypes and healthy controls (HCs). We enrolled 30 PD patients exhibiting tremor dominance (TD), 43 PD patients with postural instability and gait disturbance (PIGD), and 42 HCs. The occipital gyrus was partitioned into six areas of interest, as seed points, via the Anatomical Automatic Labeling template to compare the FC of the three groups and analyze the relationship of FC with clinical scales. Compared with the PIGD group, the TD group showed increased FC between the left superior occipital gyrus (SOG.L) and right median cingulate and paracingulate gyri (DCG.R)/right paracentral lobule/bilateral inferior parietal, but supramarginal and angular gyri; the left middle occipital gyrus (MOG.L) and left posterior cingulate gyrus (PCG.L); the MOG.R and SOG.L/right calcarine fissure and surrounding cortex/DCG.R/PCG.L/right cuneus; the left inferior occipital gyrus (IOG.L) and right caudate nucleus; and the IOG.R and PCG.L. Differentiated FC between the occipital gyrus and other brain areas within the PD motor subtypes, which may serve as neural markers to distinguish between patients with TD and PIGD PD.

Oxytocin pathway gene variation and corticostriatal resting-state functional connectivity

Genetic variations in single nucleotide polymorphisms (SNPs) within oxytocin pathway genes have been linked to social behavior and neurodevelopmental conditions. However, the neurobiological mechanisms underlying these associations remain elusive. In this study, we investigated the relationship between variations of 10 SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components using a large sample from the UK Biobank (N ≈ 30,000). Our findings revealed that individuals with the GG genotype at rs4813627 within the oxytocin structural gene (OXT) exhibited weaker resting-state functional connectivity in the corticostriatal circuit compared to those with the GA/AA genotypes. Empirical evidence has linked the GG genotype at OXT rs4813627 with a behavioral tendency of insensitivity to others. These results inform the neural mechanisms by which oxytocin-related genetic factors can influence social behavior.

Abnormal resting-state functional connectivity in subregions of amygdala in adults and adolescents with major depressive disorder

BackgroundThe different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups.MethodsIn the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion.ResultsA significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG).ConclusionsThe rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.