Networks of worry—towards a connectivity-based signature of late-life worry using higher criticism
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ABSTRACT:
SUBMITTER: Gerlach A
PROVIDER: S-EPMC8553743 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe worry includes a complex blend of maladaptive affective and cognitive processes. Contrary to other forms of anxiety, there is no consensus in the field regarding the neural basis of worry. To date, no study has looked at neural patterns associated specifically with in-scanner induction and reappraisal of worry. In this study, we attempt to describe distinct components of the 'neural phenomenology' of worry: induction, maintenance, severity and reappraisal, by using a personalized, in-scanner worry script. Twenty older, non-anxious participants and twenty late-life generalized anxiety disorder (GAD) participants were included. Whole-brain axial pseudo-continuous arterial spin-labeling scans were collected. We used a voxel-wise two-way ANOVA to test the group-by-block interaction. Worry induction was associated with greater cerebral blood flow (CBF) in the visual cortex, thalamus, caudate and medial frontal cortex compared with the rest. Reappraisal was associated with greater CBF in similar regions, whereas the orbital frontal gyrus showed lower CBF relative to rest. Relative to non-anxious participants, GAD had greater CBF in multiple regions during worry induction (visual and parietal cortex, middle and superior frontal) and lower CBF during reappraisal in the supplemental motor area, middle cingulate gyrus, insula and putamen. Except for the thalamus, there was no change in CBF throughout the five blocks of worry induction and reappraisal. Severe worry is distinctly associated with increased CBF in several neocortical regulatory regions. We present new data supporting the view of worry as a complex process, engaging multiple regions in the initiation, maintenance and reappraisal of worry.
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Project description:Molecular interactions are studied as independent networks in systems biology. However, molecular networks do not exist independently of each other. In a network of networks approach (called multiplex), we study the joint organization of transcriptional regulatory network (TRN) and protein-protein interaction (PPI) network. We find that TRN and PPI are non-randomly coupled across five different eukaryotic species. Gene degrees in TRN (number of downstream genes) are positively correlated with protein degrees in PPI (number of interacting protein partners). Gene-gene and protein-protein interactions in TRN and PPI, respectively, also non-randomly overlap. These design principles are conserved across the five eukaryotic species. Robustness of the TRN-PPI multiplex is dependent on this coupling. Functionally important genes and proteins, such as essential, disease-related and those interacting with pathogen proteins, are preferentially situated in important parts of the human multiplex with highly overlapping interactions. We unveil the multiplex architecture of TRN and PPI. Multiplex architecture may thus define a general framework for studying molecular networks. This approach may uncover the building blocks of the hierarchical organization of molecular interactions.
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Project description:Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.
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Project description:Background: Frequent exposure to criticism is a known risk factor for various adult psychiatric disorders. Adolescents may be even more vulnerable to (parental) criticism, as their imbalanced brain maturation makes them prone to stronger mood changes and less effective emotional regulation. Identifying which adolescent subgroups are more vulnerable than others could be of great clinical relevance. Perceived criticism (PC) and self-criticism (SC), two related but distinct traits, could well be crucial vulnerability factors. Hypotheses: After exposure to criticism during fMRI scanning, rapid changes in amygdalar functional connectivity (FC) with other brain areas involved in emotion regulation and social cognitive processing will occur. These changes will depend on trait moderators, such as the adolescents' proneness to (a) perceive others as critical of them (PC) or (b) perceive themselves positively or negatively (SC). Methods: Sixty-four healthy 14-17-year-olds were exposed to a series of auditory comments. Changes in mood states were assessed based on the Profile of Mood States (POMS) prior to and after exposure to these segments. Pre- and post-experiment FC of the left and right amygdalae with other brain areas were also measured. Correlates between FC changes and psychometric measures-including the perceived criticism measure (PCM) and self-perception profile for adolescents (SPPA)-were assessed. Results: First, after being criticized, FC increases of the left amygdala seed region with brain areas related to sustained emotional processing were found, but no right amygdalar FC changes. Second, there was a significant positive partial correlation between individual PCM scores and FC changes between the left amygdala seed region and the left precuneus and left superior parietal cortex, both part of the default mode network. Conclusion: Exposure to criticism resulted in a rapid negative mood change accompanied by an increase in FC between the left amygdala and regions known to be involved in sustained emotional processing, but no right amygdalar FC changes. Furthermore, higher PC but not SC was correlated with stronger left amygdalar FC increases with these regions, suggesting an elevated vulnerability for disturbed emotional processing, as observed in mood disorders, in healthy adolescents with higher PCM scores.
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Project description:Human higher cognition arises from the main tertiary association cortices including the frontal, temporal and parietal lobes. Many studies have suggested that cortical functions must be shaped or emerge from the pattern of underlying physical (white matter) connectivity. Despite the importance of this hypothesis, there has not been a large-scale analysis of the white-matter connectivity within and between these associative cortices. Thus, we explored the pattern of intra- and inter-lobe white matter connectivity between multiple areas defined in each lobe. We defined 43 regions of interest on the lateral associative cortex cytoarchitectonically (6 regions of interest - ROIs in the frontal lobe and 17 ROIs in the parietal lobe) and anatomically (20 ROIs in the temporal lobe) on individuals' native space. The results demonstrated that intra-region connectivity for all 3 lobes was dense and graded generally. In contrary, the inter-lobe connectivity was relatively discrete and regionally specific such that only small sub-regions exhibited long-range connections to another lobe. The long-range connectivity was mediated by 6 major associative white matter tracts, consistent with the notion that these higher cognitive functions arises from brain-wide distributed connectivity. Using graph-theory network analysis we revealed five physically-connected sub-networks, which correspond directly to five known functional networks. This study provides strong and direct evidence that core functional brain networks mirror the brain's structural connectivity.
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Project description:Neuroticism is a robust personality trait that constitutes a risk factor for psychopathology, especially anxiety disorders and depression. High neurotic individuals tend to be more self-critical and are overly sensitive to criticism by others. Hence, we used a novel resting-state paradigm to investigate the effect of criticism on functional brain connectivity and associations with neuroticism. Forty-eight participants completed the NEO Personality Inventory Revised (NEO-PI-R) to assess neuroticism. Next, we recorded resting state functional magnetic resonance imaging (rsfMRI) during two sessions. We manipulated the second session before scanning by presenting three standardized critical remarks through headphones, in which the subject was urged to please lie still in the scanner. A seed-based functional connectivity method and subsequent clustering were used to analyse the resting state data. Based on the reviewed literature related to criticism, we selected brain regions associated with self-reflective processing and stress-regulation as regions of interest. The findings showed enhanced functional connectivity between the clustered seed regions and brain areas involved in emotion processing and social cognition during the processing of criticism. Concurrently, functional connectivity was reduced between these clusters and brain structures related to the default mode network and higher-order cognitive control. Furthermore, individuals scoring higher on neuroticism showed altered functional connectivity between the clustered seed regions and brain areas involved in the appraisal, expression and regulation of negative emotions. These results may suggest that the criticized person is attempting to understand the beliefs, perceptions and feelings of the critic in order to facilitate flexible and adaptive social behavior. Furthermore, multiple aspects of emotion processing were found to be affected in individuals scoring higher on neuroticism during the processing of criticism, which may increase their sensitivity to negative social-evaluation.
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Project description:To use novel methods to examine age associations across an integrated brain network in healthy older adults (HOA) and individuals with late-life depression (LLD). Graph theory metrics describe the organizational configuration of both the global network and specified brain regions.Cross-sectional data were acquired. Graph theory was used to explore diffusion tensor imaging-derived white matter networks. Forty-eight HOA and 28 adults with LLD were recruited from the community. Global and local metrics in prefrontal, cingulate, and temporal regions were calculated. Group differences and associations with age were explored.Group differences were noted in local metrics of the right prefrontal and temporal regions, but no significant differences were observed on global metrics. Local (not global) metrics were associated with age differently across groups. For HOA, local metrics across all regions correlated with age, whereas in adults with LLD, correlations were only observed within temporal regions. In keeping with hypothesized regions impacted by LLD, stronger hubs in right temporal regions were observed among HOA, whereas LLD individuals were characterized by robust hubs in frontal regions.We demonstrate widespread age-related changes in local network properties among HOA with different and more restricted local changes in LLD. Although a preliminary analysis, different patterns of correlations in local networks coupled with equivalent global metrics may reflect altered local structural brain networks in patients with LLD.
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Project description:It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online.
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