Graph theoretical measures of the uncinate fasciculus subnetwork as predictors and correlates of treatment response in a transdiagnostic psychiatric cohort.
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ABSTRACT:
SUBMITTER: Thomas PJ
PROVIDER: S-EPMC7183891 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Emotion regulation refers to strategies through which individuals influence their experience and expression of emotions. Two typical strategies are reappraisal, a cognitive strategy for reframing the context of an emotional experience, and suppression, a behavioral strategy for inhibiting emotional responses. Functional neuroimaging studies have revealed that regions of the prefrontal cortex modulate amygdala reactivity during both strategies, but relatively greater downregulation of the amygdala occurs during reappraisal. Moreover, these studies demonstrated that engagement of this modulatory circuitry varies as a function of gender. The uncinate fasciculus is a major structural pathway connecting regions of the anterior temporal lobe, including the amygdala to inferior frontal regions, especially the orbitofrontal cortex. The objective of the current study was to map variability in the structural integrity of the uncinate fasciculus onto individual differences in self-reported typical use of reappraisal and suppression. Diffusion tensor imaging was used in 194 young adults to derive regional fractional anisotropy values for the right and left uncinate fasciculus. All participants also completed the Emotion Regulation Questionnaire. In women but not men, self-reported typical reappraisal use was positively correlated with fractional anisotropy values in a region of the left uncinate fasciculus within the orbitofrontal cortex. In contrast, typical use of suppression was not significantly correlated with fractional anisotropy in any region of the uncinate fasciculus in either men or women. Our data suggest that in women typical reappraisal use is specifically related to the integrity of white matter pathways linking the amygdala and prefrontal cortex.
| S-EPMC4094171 | biostudies-literature
Project description:BACKGROUND:Recent initiatives in psychiatry emphasize the utility of characterizing psychiatric symptoms in a multidimensional manner. However, strategies for applying standard self-report scales for multiaxial assessment have not been well-studied, particularly where the aim is to support both categorical and dimensional phenotypes. METHODS:We propose a method for applying natural language processing to derive dimensional measures of psychiatric symptoms from questionnaire data. We utilized nine self-report symptom measures drawn from a large cellular biobanking study that enrolled individuals with mood and psychotic disorders, as well as healthy controls. To summarize questionnaire results we used word embeddings, a technique to represent words as numeric vectors preserving semantic and syntactic meaning. A low-dimensional approximation to the embedding space was used to derive the proposed succinct summary of symptom profiles. To validate our embedding-based disease profiles, these were compared to presence or absence of axis I diagnoses derived from structured clinical interview, and to objective neurocognitive testing. RESULTS:Unsupervised and supervised classification to distinguish presence/absence of axis I disorders using survey-level embeddings remained discriminative, with area under the receiver operating characteristic curve up to 0.85, 95% confidence interval (CI) (0.74,0.91) using Gaussian mixture modeling, and cross-validated area under the receiver operating characteristic curve 0.91, 95% CI (0.88,0.94) using logistic regression. Derived symptom measures and estimated Research Domain Criteria scores also associated significantly with performance on neurocognitive tests. CONCLUSIONS:Our results support the potential utility of deriving dimensional phenotypic measures in psychiatric illness through the use of word embeddings, while illustrating the challenges in identifying truly orthogonal dimensions.
| S-EPMC7122719 | biostudies-literature
Project description:BACKGROUND: Recent investigations of white matter (WM) connectivity suggest an important role of the uncinate fasciculus (UF), connecting anterior temporal areas including the amygdala with prefrontal-/orbitofrontal cortices, for anxiety-related processes. Volume of the UF, however, has rarely been investigated, but may be an important measure of structural connectivity underlying limbic neuronal circuits associated with anxiety. Since UF volumetric measures are newly applied measures, it is necessary to cross-validate them using further neural and behavioral indicators of anxiety. RESULTS: In a group of 32 subjects not reporting any history of psychiatric disorders, we identified a negative correlation between left UF volume and trait anxiety, a finding that is in line with previous results. On the other hand, volume of the left amygdala, which is strongly connected with the UF, was positively correlated with trait anxiety. In addition, volumes of the left UF and left amygdala were inversely associated. CONCLUSIONS: The present study emphasizes the role of the left UF as candidate WM fiber bundle associated with anxiety-related processes and suggests that fiber bundle volume is a WM measure of particular interest. Moreover, these results substantiate the structural relatedness of UF and amygdala by a non-invasive imaging method. The UF-amygdala complex may be pivotal for the control of trait anxiety.
| S-EPMC3398321 | biostudies-literature
Project description:In the last decades, neuroimaging studies have attempted to unveil the neurobiological markers underlying pediatric psychiatric disorders. Yet, the vast majority of neuroimaging studies still focus on a single nosological category, which limit our understanding of the shared/specific neural correlates between these disorders. Therefore, we aimed to investigate the transdiagnostic neural correlates through a novel and data-driven meta-analytical method. A data-driven meta-analysis was carried out which grouped similar experiments' topographic map together, irrespectively of nosological categories and task-characteristics. Then, activation likelihood estimation meta-analysis was performed on each group of experiments to extract spatially convergent brain regions. One hundred forty-seven experiments were retrieved (3124 cases compared to 3100 controls): 79 attention-deficit/hyperactivity disorder, 32 conduct/oppositional defiant disorder, 14 anxiety disorders, 22 major depressive disorders. Four significant groups of experiments were observed. Functional characterization suggested that these groups of aberrant brain regions may be implicated internally/externally directed processes, attentional control of affect, somato-motor and visual processes. Furthermore, despite that some differences in rates of studies involving major depressive disorders were noticed, nosological categories were evenly distributed between these four sets of regions. Our results may reflect transdiagnostic neural correlates of pediatric psychiatric disorders, but also underscore the importance of studying pediatric psychiatric disorders simultaneously rather than independently to examine differences between disorders.
| S-EPMC8941086 | biostudies-literature
Project description:BackgroundThis cohort study utilized diffusion tensor imaging tractography to compare the uncinate fasciculus and inferior longitudinal fasciculus in children with Phelan-McDermid syndrome with age-matched controls and investigated trends between autism spectrum diagnosis and the integrity of the uncinate fasciculus and inferior longitudinal fasciculus white matter tracts.MethodsThis research was conducted under a longitudinal study that aims to map the genotype, phenotype, and natural history of Phelan-McDermid syndrome and identify biomarkers using neuroimaging (ClinicalTrial NCT02461420). Patients were aged three to 21 years and underwent longitudinal neuropsychologic assessment over 24 months. MRI processing and analyses were completed using previously validated image analysis software distributed as the Computational Radiology Kit (http://crl.med.harvard.edu/). Whole-brain connectivity was generated for each subject using a stochastic streamline tractography algorithm, and automatically defined regions of interest were used to map the uncinate fasciculus and inferior longitudinal fasciculus.ResultsThere were 10 participants (50% male; mean age 11.17 years) with Phelan-McDermid syndrome (n = 8 with autism). Age-matched controls, enrolled in a separate longitudinal study (NIH R01 NS079788), underwent the same neuroimaging protocol. There was a statistically significant decrease in the uncinate fasciculus fractional anisotropy measure and a statistically significant increase in uncinate fasciculus mean diffusivity measure, in the patient group versus controls in both right and left tracts (P ≤ 0.024).ConclusionBecause the uncinate fasciculus plays a critical role in social and emotional interaction, this tract may underlie some deficits seen in the Phelan-McDermid syndrome population. These findings need to be replicated in a larger cohort.
| S-EPMC7190002 | biostudies-literature
Project description:BackgroundNeighborhood- or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology.MethodsIn 200 adolescents (ages 13-20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations.ResultsGreater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (β = -0.24, false discovery rate [FDR]-corrected p = .035) and right uncinate fasciculus (β = -0.32, FDR-corrected p = .002) above and beyond the effects of family-level socioeconomic status. Depressive symptoms significantly moderated the association between left arcuate fasciculus FA and both neighborhood (β = 0.17, FDR-corrected p = .026) and unemployment (β = 0.22, FDR-corrected p = .004) disadvantage such that these associations were only significant in adolescents who reported less severe depression. Sex did not moderate the association between socioeconomic disadvantage and FA in these tracts.ConclusionsGreater neighborhood socioeconomic disadvantage, particularly poverty and educational attainment levels, was associated with lower FA in the arcuate fasciculus and uncinate fasciculus above and beyond the effects of family-level measures of socioeconomic status. These patterns were only observed in adolescents with low levels of depression, suggesting that we must be cautious about generalizing these findings to youths who struggle with mental health difficulties.
| S-EPMC10709004 | biostudies-literature
Project description:Verbal short-term memory (STM) deficits are associated with language processing impairments in people with aphasia. Importantly, the integrity of STM can predict word learning ability and anomia therapy gains in aphasia. While the recruitment of perilesional and contralesional homologous brain regions has been proposed as a possible mechanism for aphasia recovery, little is known about the white-matter pathways that support verbal STM in post-stroke aphasia. Here, we investigated the relationships between the language-related white matter tracts and verbal STM ability in aphasia. Nineteen participants with post-stroke chronic aphasia completed a subset of verbal STM subtests of the TALSA battery including nonword repetition (phonological STM), pointing span (lexical-semantic STM without language output) and repetition span tasks (lexical-semantic STM with language output). Using a manual deterministic tractography approach, we investigated the micro- and macrostructural properties of the structural language network. Next, we assessed the relationships between individually extracted tract values and verbal STM scores. We found significant correlations between volume measures of the right Uncinate Fasciculus and all three verbal STM scores, with the association between the right UF volume and nonword repetition being the strongest one. These findings suggest that the integrity of the right UF is associated with phonological and lexical-semantic verbal STM ability in aphasia and highlight the potential compensatory role of right-sided ventral white matter language tracts in supporting verbal STM after aphasia-inducing left hemisphere insult.
| S-EPMC10147778 | biostudies-literature
Project description:Conduct disorder (CD) is one of the most common behavior disorders in adolescents, such as impulsivity, aggression, and running from school. Males are more likely to develop CD than females, and two previous diffusion tensor imaging (DTI) studies have demonstrated abnormal microstructural integrity in the uncinate fasciculus (UF) in boys with CD compared to a healthy control group. However, little is known about changes in the UF in females with CD. In this study, the UF was illustrated by tractography; then, the fractional anisotropy (FA), axial diffusivity, mean diffusion, radial diffusivity (RD), and the length and number of the UF fiber bundles were compared between male and female patients with CD and between female patients with CD and female healthy controls, as well as between males with CD and healthy males. We found that males with CD showed significantly higher FA of the bilateral UF and significantly lower RD of the left UF when comparing with females with CD. Meanwhile, significantly higher FA and lower RD of the bilateral UF were also found in boys with CD relative to the male healthy controls. Our results replicated previous reports that the microstructural integrity of the UF was abnormal in boys with CD. Additionally, our results demonstrated significant gender effects on the UF of patients with CD, which may indicate why boys have higher rates of conduct problems than girls.
| S-EPMC4009134 | biostudies-literature
Project description:OBJECTIVE:Anxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions. Because of the early onset of anxiety disorders and the increased incidence in anxiety disorders in females during their reproductive years, it is important to understand whether the reduction in uncinate fasciculus FA exists in children with anxiety disorders and the extent to which this alteration is sex related. To address these issues, the authors assessed FA in the uncinate fasciculus in unmedicated boys and girls with anxiety disorders. METHODS:FA measures were derived from diffusion tensor images that were acquired from 98 unmedicated children (ages 8-12); 52 met criteria for generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, or anxiety disorder not otherwise specified, and 46 were matched control subjects. RESULTS:Tract-based results demonstrated that children with anxiety disorders have significant reductions in uncinate fasciculus FA. A significant sex-by-group interaction and post hoc testing revealed that this effect was evident only in boys. No other main effects or sex-by-group interactions were found for other white matter tracts. CONCLUSIONS:These findings provide evidence of uncinate fasciculus white matter alterations in boys with anxiety disorders. The data demonstrate that anxiety disorder-related alterations in prefrontal-limbic structural connectivity are present early in life, are not related to psychotropic medication exposure, and are sex specific. Building on these findings, future research has the potential to provide insights into the genesis and sexual dimorphism of the pathophysiology that leads to anxiety disorders, as well as to identify sex-specific early-life treatment targets.
| S-EPMC6661168 | biostudies-literature
Project description:Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969).
| S-EPMC4908122 | biostudies-literature