Negative Functional Connectivity Research Articles

The functional connectivity of the right superior temporal gyrus is associated with psychological risk and resilience factors for suicidality

IntroductionSuicide attempters show increased activation in the right superior temporal gyrus (rSTG). Here, we investigated the rSTG functional connectivity (FC) to identify a functional network involved in suicidality and its associations with psychological suicidality risk and resilience factors. MethodsThe resting state functional magnetic resonance imaging data of 151 healthy individuals from the Human Connectome Project Young Adult database were used to explore the FC of the rSTG with itself and with the rest of the brain. The correlation between the rSTG FC and loneliness and purpose in life scores was assessed with the NIH Toolbox. The effect of sex was also investigated. ResultsThe rSTG had a positive FC with bilateral cortical and subcortical regions, including frontal, temporal, parietal, occipital, limbic, and cerebellar regions, and a negative FC with the medulla oblongata. The FC of the rSTG with itself and with the left central operculum were associated with loneliness scores. The within rSTG FC was also negatively correlated with purpose in life scores, although at a trend level. We did not find any effect of sex on FC and its associations with psychological factors. LimitationsThe cross-sectional design, the limited age range, and the lack of measures of suicidality limit the generalizability of our findings. ConclusionsThe rSTG functional network is associated with loneliness and purpose in life. Together with the existing literature on suicide, this supports the idea that the neural activity of rSTG may contribute to suicidality by modulating risk and resilience factors associated with suicidality.

Dynamic graph transformer network via dual-view connectivity for autism spectrum disorder identification

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that requires objective and accurate identification methods for effective early intervention. Previous population-based methods via functional connectivity (FC) analysis ignore the differences between positive and negative FCs, which provide the potential information complementarity. And they also require additional information to construct a pre-defined graph. Meanwhile, two challenging demand attentions are the imbalance of performance caused by the class distribution and the inherent heterogeneity of multi-site data. In this paper, we propose a novel dynamic graph Transformer network based on dual-view connectivity for ASD Identification. It is based on the Autoencoders, which regard the input feature as individual feature and without any inductive bias. First, a dual-view feature extractor is designed to extract individual and complementary information from positive and negative connectivity. Then Graph Transformer network is innovated with a hot plugging K-Nearest Neighbor (KNN) algorithm module which constructs a dynamic population graph without any additional information. Additionally, we introduce the PolyLoss function and the Vrex method to address the class imbalance and improve the model's generalizability. The evaluation experiment on 1102 subjects from the ABIDE I dataset demonstrates our method can achieve superior performance over several state-of-the-art methods and satisfying generalizability for ASD identification.

Perceiving humanness across ages: neural correlates and behavioral patterns.

Humanness perception, which attributes fundamental and unique human characteristics to other objects or people, has significant consequences for people's interactions. Notably, the failure to perceive humanness in older adults can lead to prejudice. This study investigates the effect of a target's age on humanness perception in terms of two dimensions: agency (the ability to act and do) and experience (the ability to feel and sense). We also examined brain activity using a magnetic resonance imaging (MRI) scanner in order to understand the underlying neural mechanisms. Healthy university students viewed the facial images of older and younger individuals and judged the humanness of each individual in terms of agency and experience while inside the MRI scanner. The results indicated that older adults were rated higher on experience, and no difference was found in ratings for agency between younger and older face images. Analysis of brain imaging data indicated that positive functional connectivity between the ventral and dorsal regions of the medial prefrontal cortex (mPFC) was greater when judging the humanness of younger faces than older faces. We also found that the negative functional connectivity between the left inferior frontal gyrus and postcentral gyrus was greater when judging the humanness of older faces as compared to that of younger faces. Although the current study did not show distinct brain activities related to humanness perception, it suggests the possibility that different brain connectivities are related to humanness perception regarding targets belonging to different age groups.

Lower cerebrovascular reactivity in prefrontal cortex and weaker negative functional connectivity between prefrontal cortex and insula contribute to white matter hyperintensity-related anxiety or depression

BackgroundWhite matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms. MethodsParticipants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The CVR and FC maps were constructed from resting-state functional MRI. Two-way analysis of covariance with fixed factors A/D and WMH was performed to identify regional CVR abnormalities. Seed-based FC analyses were then conducted on regions with WMH × A/D interaction effects on CVR. Logistic regression models were constructed to examine the utility of these measurements for identifying WMH-related A/D. ResultsParticipants with WMH related A/D exhibited significantly greater CVR in left insula and lower CVR in right superior frontal gyrus (SFG.R), and HAMA scores were negatively correlated with CVR in SFG.R (r = −0.156, P = 0.016). Insula–SFG.R negative FC was significantly weaker in WMH patients with suspected or definite A/D. A model including CVR plus FC changes identified WMH-associated A/D with highest sensitivity and specificity. In contrast, NCs with A/D exhibited greater CVR in prefrontal cortex and stronger FC within the default mode network (DMN) and between the DMN and executive control network. LimitationsThis cross-sectional study requires validation by longitudinal and laboratory studies. ConclusionsImpaired CVR in SFG.R and weaker negative FC between prefrontal cortex and insula may contribute to WMH-related A/D, providing potential diagnostic imaging markers and therapeutic targets.

Differential functional organization of amygdala-medial prefrontal cortex networks in macaque and human

Over the course of evolution, the amygdala (AMG) and medial frontal cortex (mPFC) network, involved in behavioral adaptation, underwent structural changes in the old-world monkey and human lineages. Yet, whether and how the functional organization of this network differs remains poorly understood. Using resting-state functional magnetic resonance imagery, we show that the functional connectivity (FC) between AMG nuclei and mPFC regions differs between humans and awake macaques. In humans, the AMG-mPFC FC displays U-shaped pattern along the corpus callosum: a positive FC with the ventromedial prefrontal (vmPFC) and anterior cingulate cortex (ACC), a negative FC with the anterior mid-cingulate cortex (MCC), and a positive FC with the posterior MCC. Conversely, in macaques, the negative FC shifted more ventrally at the junction between the vmPFC and the ACC. The functional organization divergence of AMG-mPFC network between humans and macaques might help understanding behavioral adaptation abilities differences in their respective socio-ecological niches.

Left superior parietal lobe mediates the link between spontaneous mind-wandering tendency and task-switching performance

While increasing studies have documented the link between mind wandering and task switching, less is known about which brain regions mediate this relationship. Using the MPI-Leipzig Mind-Brain-Body dataset (N = 173), we investigated the association between trait-level tendencies of mind wandering, task-switching performance, structural connectivity, and resting-state functional connectivity. At the behavioral level, we found that higher spontaneous mind-wandering trait scores were associated with shorter reaction times on both repeat and switch trials. The whole brain cortical thickness analysis revealed a strong mediating role of the left superior parietal lobe, which is part of the dorsal attention network, in the link between spontaneous mind-wandering tendency and task-switching performance. The resting-state functional connectivity analysis further demonstrated that this association was partly mediated by the negative dorsal attention network-default mode network functional connectivity. No significant mediating effects were found for deliberate mind-wandering tendency. Overall, the findings highlight the pivotal role of the left superior parietal lobe in activating new mental set during mind-wandering and task-switching processes, providing another evidence in favor of a role for switching in mind wandering.

Cognitive impairment after sleep deprivation: The role of precuneus related connectivity on the intra-individual variability changes

ObjectiveIntra-individual variability (IIV) in cognitive performance is thought to reflect the efficiency with which attentional resources are allocated in different circumstances requiring cognitive control. IIV in cognitive performance is associated with the strength of the negative correlation between task-positive network and default mode network (DMN) activity. In this study, we investigated the impact of sleep deprivation (SD) on functional connectivity (FC) between the DMN and psychomotor vigilance task-related network (PVT-RN), and its relationship with IIV in cognitive performance. MethodsTwo analyses, network-level independent component analysis (NL-ICA) and region-level (RL)-ICA, were employed to compare the coefficient of variation (CV) of the PVT between normal sleep and SD conditions across 67 healthy participants. ResultsAfter SD, in NL-ICA, the FC between the PVT-RN and DMN was positively correlated with the CV of the PVT, as well as the changes therein, compared with normal sleep. Using a mask derived from the DMN and PVT-RN, the RL-ICA revealed that 12 edges/connections between DMN and PVT independent components were associated with the CV of the PVT, with nine of these connections involving the precuneus. ConclusionsThese findings suggest that the precuneus may play a crucial role in the interactions of various brain functions during the PVT, with the connections between the precuneus and frontoparietal and somatosensory networks being significantly altered after SD. Moreover, following SD, weakened negative FC between the precuneus and bilateral inferior parietal lobule may disrupt the balance between cognitive and executive control functions, leading to a decline in cognitive performance.

Resting-state functional connectivity of the cerebellum-cerebrum in older women with depressive symptoms

BackgroundAlthough there has been much neurobiological research on major depressive disorder, research on the neurological function of depressive symptoms (DS) or subclinical depression is still scarce, especially in older women with DS.ObjectivesResting-state functional magnetic resonance imaging (rs-fMRI) was used to compare functional connectivity (FC) between the cerebellum and cerebral in older women with DS and normal controls (NC), to explore unique changes in cerebellar FC in older women with DS.MethodsIn all, 16 older women with DS and 17 NC were recruited. All subjects completed rs-fMRI. The 26 sub-regions of the cerebellum divided by the AAL3 map were used as regions of interest (ROI) to analyze the difference in FC strength of cerebellar seeds from other cerebral regions between the two groups. Finally, partial correlation analysis between abnormal FC strength and Geriatric Depression Scale (GDS) score and Reminiscence Functions Scale (RFS) score in the DS group.ResultsCompared with NC group, the DS group showed significantly reduced FC between Crus I, II and the left frontoparietal region, and reduced FC between Crus I and the left temporal gyrus. Reduced FC between right insula (INS), right rolandic operculum (ROL), right precentral gyrus (PreCG) and the Lobule IX, X. Moreover, the negative FC between Crus I, II, Lobule IX and visual regions was reduced in the DS group. The DS group correlation analysis showed a positive correlation between the left Crus I and the right cuneus (CUN) FC and GDS. In addition, the abnormal FC strength correlated with the scores in different dimensions of the RFS, such as the negative FC between the Crus I and the left middle temporal gyrus (MTG) was positively associated with intimacy maintenance, and so on.ConclusionOlder women with DS have anomalous FC between the cerebellum and several regions of the cerebrum, which may be related to the neuropathophysiological mechanism of DS in the DS group.

Application of functional connectivity neurofeedback in patients with treatment-resistant depression: A preliminary report

Functional connectivity neurofeedback (FCNef) is a technique that modulates synchronous neural activity through training and is being investigated as a potential novel treatment for patients suffering from treatment-resistant depression (TRD). An FCNef protocol, based on the analysis of resting-state functional imaging data from a large cohort of depressed individuals, has been proposed to promote negative functional connectivity between the dorsolateral prefrontal cortex and the posterior cingulate cortex (DLPFC-PCC FC). This study aimed to assess the therapeutic efficacy and practicality of the protocol in a small sample of TRD patients. Of the six patients recruited, five completed the FCNef sessions. Depression and rumination scores significantly improved post-treatment, however, there were no significant changes in DLPFC-PCC FC. The study demonstrated efficacy of FCNef in ameliorating depressive symptoms, yet, it also indicated that the training itself may be burdensome for depressed patients, as evidenced by participants reporting fatigue (one of whom dropped out). Thus, a more efficient and less burdensome protocol is needed for future investigations and applications.

Urinary incontinence-related effects on functional connectivity circuits in persons with Parkinson's disease.

Urinary incontinence (UI) is a common and disruptive symptom of Parkinson's disease (PD). This study aimed to identify neural correlates associated with UI among PD patients with UI (UI-PD) compared to those PD patients without UI (nonUI-PD) with the expectation of demonstrating increased functional connectivity (FC) between areas in the striatum and limbic system and decreased FC in executive areas. rsfMRI and T1w data (n = 119) were retrieved from the Parkinson's Progression Markers Initiative (PPMI). Resting-state FC analyses assessed temporal covariance with anterior cingulate gyrus, precuneus, and putamen seed regions. The UI-PD group (n = 32, 16 females) showed significantly greater positive FC between the bilateral putamen seed and the right caudate and right thalamus (p < 0.01), relative to individuals with PD but who did not have UI (n = 87, 18 females). The UI-PD group showed greater negative FC between the anterior cingulate seed and right angular gyrus (p < 0.01) relative to nonUI-PD. Individuals with PD and UI display stronger FC within neural circuits likely affected by PD such as between the putamen and caudate, as well as within those associated with brain bladder control, compared to persons with PD and without UI. Clinical application based on this study's results can provide greater discernment of treatment strategies for UI-PD patients.

The Impact of Sleep Deprivation on Brain Networks in Response to Social Evaluation Tasks.

Sleep loss may lead to negative bias during social interaction. In the current study, we conducted a revised social evaluation task experiment to investigate how sleep deprivation influences the self-referential and cognitive processes of social feedback. The experiment consisted of a first impression task and a social feedback task. Seventy-eight participants completed the first impression task and were divided into normal and poor sleep groups. The results of an independent samples t-test showed that participants who slept worse were less likely to socialize with others but did not evaluate others as less attractive. Afterward, 22 of the participants from the first impression task were recruited to complete the social feedback task during functional magnetic resonance imaging (fMRI) on the mornings following two different sleep conditions at night: one night of normal sleep and one night of sleep deprivation. The results of this within-subject design study showed that participants who experienced the latter condition showed increased activation within the default mode network (i.e. superior parietal lobule, precuneus, inferior parietal lobule, inferior temporal gyrus, and medial frontal gyrus) and anterior cingulate cortex (ACC) and stronger negative insula functional connectivity (FC) with the precuneus to negative feedback than positive feedback. The altered activation and behavioral pattern may indicate a negative bias for social cues. However, stronger negative coupling may indicate stronger cognitive control, which may protect against potential damage to self-concept. Our study suggested that sleep impairs most social functions, but may protect against impairment of important ones, such as self-concept.

Brain Activation and Functional Connectivity of Reappraisal and Acceptance for Anxious Events.

Despite the significant health consequences of anxiety, the neural basis of regulation for personal anxious events is not well understood. We examined brain activity and functional connectivity during cognitive emotion regulation strategies (reappraisal and acceptance) for personal anxious events. Functional MRI (fMRI) data were obtained while 35 college students were thinking about (the control condition), reappraising, or accepting their own anxiety-provoking situations. Although reappraisal and acceptance decreased anxiety, no statistically significant differences were observed in the brain activation levels between cognitive emotion regulation strategies and the control condition. However, acceptance decreased activation in the posterior cingulate cortex and precuneus more than reappraisal. Moreover, functional connectivity with the amygdala and ventral anterior insula distinguished the emotion regulation strategies for anxiety. Reappraisal showed stronger negative functional connectivity with the amygdala and cognitive control regions than other strategies. In addition, reappraisal had negative functional coupling between the ventral anterior insula and temporal pole compared with acceptance. In contrast, acceptance showed stronger positive functional coupling between the ventral anterior insula and precentral and postcentral gyrus compared with the control condition. Our findings contribute to the understanding of emotion regulation processes by revealing the brain activity and functional connectivity patterns in reappraisal and acceptance for personal anxious events.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

Alterations in Dynamic Functional Connectivity in Patients with Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people’s health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks that represents a powerful tool for gaining novel insight into neurological diseases. To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function. We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI (rs-fMRI) with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the functional connectivity (FC) strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance. A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse FC both inter-network and intra-networks. Additionally, the CSVD group had a reduced number of windows and shorter mean dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state 2 and state 3 and between state 3 and state 4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a significant difference in the FC strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance. Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC alterations could help us to better understand the progressive dysfunction of networks in CSVD patients.

Connectivity Profile of Middle Inferior Parietal Cortex Confirms the Hypothesis About Modulating Cortical Areas

According to the correlated transmitter-receptor based structure of the inferior parietal cortex (IPC), this brain area is divided into three clusters, namely, the caudal, the middle and the rostral. Nevertheless, in associating different cognitive functions to the IPC, previous studies considered this part of the cortex as a whole and thus inconsistent results have been reported. Using multiband echo planar imaging (EPI), we investigated the connectivity profile of the middle IPC while forty-five participants performed a task requiring cognitive control. The middle IPC demonstrated functional associations which do not have similarities to a contributing part in the frontoparietal network, in processing cognitive control. At the same time, this cortical area showed negative functional connectivity with both the precuneus cortex, which is resting- state related, and brain areas related to general cognitive functions. That is, the functions of the middle IPC are not accommodated by the traditional categorization of different brain areas i.e. resting state-related or task-related networks and this advanced our hypothesis about modulating cortical areas. Such brain areas are characterized by their negative functional connectivity with parts of the cortex involved in task performance, proportional to the difficulty of the task; yet, their functional associations are inconsistent with the resting state-related cortical areas.

Hitting the Target of Image-Guided Psychiatry?

Hitting the Target of Image-Guided Psychiatry?

Ketamine-induced hippocampal functional connectivity alterations associated with clinical remission in major depression

ObjectiveHippocampal functional connectivity (FC) alterations, which may happen following ketamine treatment, play a key role in major depression remission. This study aims to investigate the resting-state FC changes of the hippocampus associated with clinical remission after repeated ketamine infusions. MethodsForty-four major depressive patients received six intravenous ketamine (0.5 mg/kg) infusions in 12 days. The FC change of the hippocampus subregions following ketamine treatment was compared between remitters (MADRS score ≤ 10 post-treatment) and nonremitters. We also investigated whether baseline hippocampus FC predicted the antidepressant efficiency of ketamine using Receiver Operating Characteristic Curve analyses. ResultsThirty-nine patients were included in the analysis. There were significant differences in change of left rostral hippocampus FC with the right angular gyrus (the key node of the default mode network, DMN), left inferior parietal cortex and the right superior parietal cortex (parts of the dorsal attention network, dAN) between remitters and nonremitters following ketamine treatment. Specifically, while the remitters showed significantly less negative hippocampus FC than the nonremitters at baseline, the FC significantly decreased in remitters but increased in nonremitters after ketamine injections. Moreover, baseline hippocampus FC with the above three regions predicted the antidepressant effect of ketamine, with the highest predictive strength identified in the hippocampus-right angular gyrus FC (Area-Under-Curve = 0.8179, p < 0.05). ConclusionKetamine treat depression by modulating the left rostral hippocampus resting-state FC with the DMN and dAN. The FC between the hippocampus and parts of the DMN and dAN may show promising potential in predicting remission after ketamine treatment in MDD.

Functional Connectivity Pattern Using Resting-state fMRI as an Assessment Tool for Spatial Neglect during the Recovery Stage of Stroke: A Pilot Study.

To determine if functional connectivity measured with resting-state functional MRI could be used as a tool to assess unilateral spatial neglect during stroke recovery. Resting-state functional MRI was performed on 13 stroke patients with lesions in the right cerebral hemisphere and 31 healthy subjects. The functional connectivity score was defined as a correlation of a target region with the right inferior parietal lobule. Spatial neglect was measured with a behavioral inattention test. First, the functional connectivity scores between the right inferior parietal lobule and right inferior frontal gyrus, including the opercular and triangular parts, were significantly decreased in stroke patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Second, the functional connectivity scores between the bilateral inferior parietal lobules were also significantly decreased in patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Third, negative functional connectivity scores between the right inferior parietal lobule and bilateral medial orbitofrontal cortexes, which are related to the default mode network, were detected in patients without unilateral spatial neglect in contrast to a reduction of this negative tendency in patients with unilateral spatial neglect. The functional connectivity scores between these regions were significantly different between patients with and without unilateral spatial neglect and were negatively correlated with the behavioral inattention test score. Though still in the pilot research stage and using a small number of cases, our findings are consistent with the hypothesis that functional connectivity maps generated with resting-state functional MRI may be used as a tool to evaluate unilateral spatial neglect during stroke recovery.

Dissociation of categorical and coordinate spatial relations on dynamic network organization states.

Humans can flexibly represent both categorical and coordinate spatial relations. Previous research has mainly focused on hemisphere lateralization in representing these two types of spatial relations, but little is known about how distinct network organization states support representations of the two. Here we used dynamic resting-state functional connectivity (FC) to explore this question. To do this, we separated a meta-identified navigation network into a ventral and two other subnetworks. We revealed a Weak State and a Strong State within the ventral subnetwork and a Negative State and a Positive State between the ventral and other subnetworks. Further, we found the Weak State (i.e., weak but positive FC) within the ventral subnetwork was related to the ability of categorical relation recognition, suggesting that the representation of categorical spatial relations was related to weak integration among focal regions in the navigation network. In contrast, the Negative State (i.e., negative FC) between the ventral and other subnetworks was associated with the ability of coordinate relation processing, suggesting that the representation of coordinate spatial relations may require competitive interactions among widely distributed regions. In sum, our study provides the first empirical evidence revealing different focal and distributed organizations of the navigation network in representing different types of spatial information.

Effects of maternal childhood trauma on child emotional health: maternal mental health and frontoamygdala pathways.

Experiences of early life adversity pose significant psychological and physical health risks to exposed individuals. Emerging evidence suggests that these health risks can be transmitted across generations; however, the mechanisms underlying the intergenerational impacts of maternal early-life trauma on child health remain unknown. The current study used a prospective longitudinal design to determine the unique and joint contributions of maternal childhood trauma (neglect and abuse) and maternal prenatal and postnatal mental health (anxiety and depressive symptoms) (N= 541) to children's resting frontoamygdala functional connectivity at 6 years (N= 89) and emotional health at 7-8 years, as indexed by parent-reported internalizing problems and child self-reported anxiety and depressive symptoms (N= 268-418). Greater maternal childhood neglect was indirectly associated with greater internalizing problems serially through a pathway of worse maternal prenatal and postnatal mental health (greater maternal anxiety and depressive symptoms). Worse maternal postnatal mental health was also uniquely associated with more negative child frontoamygdala resting-state functional connectivity, over and above maternal childhood trauma (both neglect and abuse) and prenatal mental health. More negative frontoamygdala functional connectivity was, in turn, associated with poorer child emotional health outcomes. Findings from the current study provide support for the existence of intergenerational influences of parental exposure to childhood trauma on childhood risk for psychopathology in the next generation and point to the importance of maternal factors proximal to the second generation (maternal prenatal and postnatal mental health) in determining the intergenerational impact of maternal early experiences.