Preliminary examination of the effects of an early parenting intervention on amygdala-orbitofrontal cortex resting-state functional connectivity among high-risk children: A randomized clinical trial.

We examined the long-term causal effects of an evidence-based parenting program delivered in infancy on children's emotion regulation and resting-state functional connectivity (rs-fc) during middle childhood. Families were referred to the study by Child Protective Services (CPS) as part of a diversion from a foster care program. A low-risk group of families was also recruited. CPS-involved families were randomly assigned to receive the target (Attachment and Biobehavioral Catch-up, ABC) or a control intervention (Developmental Education for Families, DEF) before infants turned 2. Both interventions were home-based, manualized, and 10-sessions long. During middle childhood, children underwent a 6-min resting-state functional MRI scan. Amygdala seed-based rs-fc analysis was completed with intervention group as the group-level predictor of interest. Fifty-seven children (NABC = 21; NDEF = 17; NCOMP = 19; Mage = 10.02 years, range = 8.08-12.14) were scanned successfully. The DEF group evidenced negative left amygdala↔OFC connectivity, whereas connectivity was near zero in the ABC and comparison groups (ABCvsDEF: Cohen's d = 1.17). ABC may enhance high-risk children's regulatory neurobiology outcomes ∼8 years after the intervention was completed.

Assessing the utility of a novel cortical marker of delay discounting (C-DD) in two independent samples of early adolescents: Links with externalizing pathology.

Delay discounting is a well-established risk factor for risky behaviors and the development of externalizing spectrum disorders. Building upon recent work that developed a novel cortical marker of delay discounting (C-DD) in adult samples, the objective of this study was to test whether the C-DD relates to delay discounting and subsequently externalizing pathology in adolescent samples. The current study used two samples: 9992 early adolescents participating in the ABCD study (Mage = 9.93 years old, 48.7% female), and 56 early adolescents recruited from the community (Mage = 12.27 years old, 55.4% female). Cortical thickness was estimated using the FreeSurfer standard pipeline, and the cortical marker of delay discounting (C-DD) was calculated based on procedures outlined by the initial validation study. All data are cross-sectional in nature. As expected, C-DD was positively related to delay discounting in the ABCD sample, even after accounting for age, biological sex, collection site and data quality indicators. Moreover, results showed that C-DD was discriminately associated with externalizing, but not internalizing, symptoms in both samples of young adolescents. Findings replicate those found in adult samples, suggestive that C-DD may be a useful neuroanatomical marker of youth delay discounting. Replication of findings in other samples will be needed to determine whether C-DD has translational relevance to understanding externalizing psychopathology in adolescent samples.

Negative emotion differentiation and white matter microstructure.

BACKGROUND: Deficits in the differentiation of negative emotions - the ability to specifically identify one's negative emotions - are associated with poorer mental health outcomes. However, the processes that lead to individual differences in negative emotion differentiation are not well understood, hampering our understanding of why this process is related to poor mental health outcomes. Given that disruptions in some affective processes are associated with white matter microstructure, identifying the circuitry associated with different affective processes can inform our understanding of how disturbances in these networks may lead to psychopathology. Thus, examination of how white matter microstructure relates to individual differences in negative emotion differentiation (NED) may provide insights into (i) its component processes and (ii) its relationship to brain structure. METHOD: The relationship between white matter microstructure and NED was examined. RESULTS: NED was related to white matter microstructure in right anterior thalamic radiation and inferior fronto-occipital fasciculus and left peri-genual cingulum. LIMITATIONS: Although participants self-reported psychiatric diagnoses and previous psychological treatment, psychopathology was not directly targeted, and thus, the extent to which microstructure related to NED could be examined in relation to maladaptive outcomes is limited. CONCLUSIONS: Results indicate that NED is related to white matter microstructure and suggest that pathways subserving processes that facilitate memory, semantics, and affective experience are important for NED. Our findings provide insights into the mechanisms by which individual differences in NED arise, suggesting intervention targets that may disrupt the relationship between poor differentiation and psychopathology.

Intolerance of uncertainty, anxiety sensitivity, and health anxiety during the COVID-19 pandemic: Exploring temporal relationships using cross-lag analysis.

Intolerance of uncertainty (IU) and anxiety sensitivity (AS) have been widely discussed and explored as factors that may contribute to health anxiety. We propose that IU and AS are salient issues for many during the COVID-19 pandemic, and may play a role in the development or exacerbation of health anxiety during the pandemic. Studies have examined links between IU and AS with health anxiety during the pandemic, but these relationships have not been tested together using a longitudinal study design. In the present study, measures of IU, AS, and health anxiety were collected from 301 adults at two time points 6 months apart during (early stages of) the COVID-19 pandemic using an online survey platform. Cross-lagged analysis was utilized to simultaneously estimate cross-sectional and longitudinal associations between these three variables. Robust cross-sectional associations were observed, and IU prospectively predicted changes in both health anxiety and AS. No other statistically significant prospective associations emerged. Present findings support the putative role of IU in health anxiety, suggesting that some observed links between AS and health anxiety could be driven by shared variance with IU. IU may be an important factor to monitor and target in health anxiety interventions during the pandemic.

Development of a cortical delay discounting assay: a potential biomarker of externalizing disorders.

BACKGROUND: People who tend to impulsively choose smaller, sooner rewards over larger, later rewards are at increased risk for addiction and psychiatric disorders. A neurobiological measure of the tendency to overvalue immediate gratification could facilitate the study of individuals who are susceptible to these mental disorders. The objective of this research was to develop a cortical assay of impulsive choice for immediate rewards. METHODS: A cortex-based assay of impulsive choice was developed using 1105 healthy adults from the Human Connectome Project, and then cross-validated in two independent samples of adults with elevated rates of psychiatric disorders. RESULTS: Study 1: Cortical delay discounting (C-DD) was developed using a multivariate additive model of gray matter thickness across both hemispheres. Higher C-DD corresponded to thinner cortex and greater impulsive choice for immediate rewards. It also predicted cannabis use beyond established risk factors for drug use, including familial substance use, childhood conduct problems, personality traits, and cognitive functioning. Study 2: C-DD replicated the association with delay discounting performance from study 1. Structural equation modeling showed C-DD covaried with symptoms of externalizing, but not internalizing disorders. Study 3: C-DD positively predicted future delay discounting behavior (6-34 months later). CONCLUSIONS: Across three studies, a cortical assay of impulsive choice evidenced consistent associations with drug use and delay discounting task performance. It was also uniquely associated with psychiatric disorders that share impulsivity as a core feature. Together, findings support the utility of C-DD as a neurobiological assay of impulsive decision-making and a possible biomarker of externalizing disorders.

Mapping brain mechanical property maturation from childhood to adulthood.

Magnetic resonance elastography (MRE) is a phase contrast MRI technique which uses external palpation to create maps of brain mechanical properties noninvasively and in vivo. These mechanical properties are sensitive to tissue microstructure and reflect tissue integrity. MRE has been used extensively to study aging and neurodegeneration, and to assess individual cognitive differences in adults, but little is known about mechanical properties of the pediatric brain. Here we use high-resolution MRE imaging in participants of ages ranging from childhood to adulthood to understand brain mechanical properties across brain maturation. We find that brain mechanical properties differ considerably between childhood and adulthood, and that neuroanatomical subregions have differing maturational trajectories. Overall, we observe lower brain stiffness and greater brain damping ratio with increasing age from 5 to 35 years. Gray and white matter change differently during maturation, with larger changes occurring in gray matter for both stiffness and damping ratio. We also found that subregions of cortical and subcortical gray matter change differently, with the caudate and thalamus changing the most with age in both stiffness and damping ratio, while cortical subregions have different relationships with age, even between neighboring regions. Understanding how brain mechanical properties mature using high-resolution MRE will allow for a deeper understanding of the neural substrates supporting brain function at this age and can inform future studies of atypical maturation.

Clarifying the synergistic effects of emotion dysregulation and inhibitory control on physical aggression.

Rising rates of violence underscore the need to better understand how systems that regulate distress and impulse control jointly modulate aggression risk. The goals of the current study were to investigate the unique and interactive effects of emotional dysregulation and inhibitory control on the perpetration of physical aggression. We recruited a high-risk community sample of 206 adults (M/SDage  = 33.55/10.89 years old; 47.1% female) who reported a range of physically aggressive behaviors. All participants completed a self-report measure (Difficulties in Emotion Regulation Scale), neuropsychological testing (Color Word Interference Test), and clinical interviewing (Lifetime History of Aggression Interview), and a subset of individuals (n = 134) underwent a neuroanatomical scan. As expected, the interplay of emotional and inhibitory control explained unique variance in physical aggression above and beyond their main effects. The positive association between emotion dysregulation and aggression strengthened as inhibitory control decreased. Cortical thickness in two right prefrontal clusters, one that peaked in the superior frontal gyrus and one that peaked in the caudal middle frontal gyrus, was also associated with the interactive effects of emotional dysregulation and inhibitory control. Notably, thickness in the superior frontal gyrus mediated the association between emotion dysregulation and physical aggression at low levels of inhibitory control. Using a multilevel and multimethod approach, the present study revealed neuroanatomical correlates of emotion-cognition interactions that have translational relevance to violence perpetration. These findings extend previous work primarily focused on functional-based neural assessments and point to the utility of examining neuroanatomical correlates of emotion-cognition interactions for understanding human aggression.

The structural brain network topology of episodic memory.

Episodic memory is supported by a distributed network of brain regions, and this complex network of regions does not operate in isolation. To date, neuroscience research in this area has typically focused on the activation levels in specific regions or pairwise connectivity between such regions. However, research has yet to investigate how the complex interactions of structural brain networks influence episodic memory abilities. We applied graph theory methods to diffusion-based anatomical networks in order to examine the structural architecture of the medial temporal lobe needed to support effective episodic memory functioning. We examined the relationship between performance on tests of verbal and non-verbal episodic memory with node strength, which indexes how well connected a brain region is in the network. Findings mapped onto the Posterior Medial memory system, subserved by the parahippocampal cortex and overlapped with findings of previous studies of episodic memory employing different methodologies. This expands our current understanding by providing independent evidence for the importance of identified regions and suggesting the particular manner in which these regions support episodic memory.

Longitudinal relationships between COVID-19 preventative behaviors and perceived vulnerability to disease.

Engagement in infection-preventing behaviors (e.g., mask wearing) has become crucial in the context of the COVID-19 pandemic, and health-related anxiety may be an important determinant of individual compliance with recommended guidelines. However, little is known about transactional associations between health anxiety and preventative behaviors, particularly with respect to COVID-19. The present study aimed to longitudinally examine the links between preventative behaviors and both emotion-driven (Germ Aversion) and belief-based (Perceived Infectability) aspects of health anxiety during the COVID-19 pandemic. We hypothesized that greater health anxiety at Time 1 (early in the pandemic) would predict future compliance with preventative behaviors six months later. Two hundred and ninety-six adults (M/SDage= 30.9/10.9 years, 42.2% female) completed two online assessments during the COVID-19 pandemic (Time 1 =June 2020; Time 2 =December 2020). Longitudinal cross-lagged analyses revealed that initial Germ Aversion predicted greater engagement in preventative behaviors at follow-up (ß = 0.16; p = <.001), over and above initial engagement in such behaviors. Similarly, initial engagement in preventative behaviors predicted increases in Germ Aversion at follow-up (ß = .23; p = <.001), over and above initial Germ Aversion. The present findings indicate that affect-driven aspects of health anxiety have a complex transactional relationship with engagement in behaviors aimed at curbing the spread of the COVID-19 pandemic. Clinical and public health implications are discussed.

Cortical thickness in parietal regions link perseverative thinking with suicidal ideation.

INTRODUCTION: Suicide represents a major public health concern, as the tenth leading cause of death in the United States. Links between perseverative thinking (PT) and suicidal ideation have previously been examined, while their biological underpinnings remain understudied. The present study had two aims: 1) investigate whether cortical thickness varied as a function of PT, and 2) examine whether variation in thickness partially explained associations between PT and lifetime history of ideation. We hypothesized that cortical thickness would vary as a function of PT and PT would be positively associated with lifetime history of ideation. METHODS: A community sample of 73 adults (ages 18-55; 42.5% female) completed self-report measures examining PT and ideation, as well as a neuroimaging protocol. Mean scores on the Perseverative Thinking Questionnaire were entered as the explanatory variable in the analysis of cortical thickness clusters related to PT. The indirect effect of PT on ideation through thickness was tested cross-sectionally. RESULTS: PT was positively associated with i) thickness in three clusters bilaterally in the parietal cortex and ii) suicidal ideation. Follow-up analyses revealed a significant indirect effect of PT on suicidal ideation through left superior parietal thickness. LIMITATIONS: Limitations of the study include the use of cross-sectional data and a modest sample size. CONCLUSIONS: PT is associated with variations in cortical thickness, and increased thickness in the left parietal region may partially explain the link between PT and suicidal ideation, identifying a novel neurobiological mechanism of ideation.

Differences in network properties of the structural connectome in bipolar and unipolar depression.

BACKGROUND: Differentiation between Bipolar Disorder Depression (BDD) and Unipolar Major Depressive Disorder (MDD) is critical to clinical practice. This study investigated machine learning classification of BDD and MDD using graph properties of Diffusion-weighted Imaging (DWI)-based structural connectome. METHODS: This study included a large number of medication-free (N =229) subjects: 60 BDD, 95 MDD, and 74 Healthy Control (HC) subjects. DWI probabilistic tractography was performed to create Fractional Anisotropy (FA) and Total Streamline (TS)-based structural connectivity matrices. Global and nodal graph properties were computed from these matrices and tested for group differences. Next, using identified graph properties, machine learning classification (MLC) between BDD, MDD, MDD with risk factors for developing BD (MDD+), and MDD without risk factors for developing BD (MDD-) was conducted. RESULTS: Communicability Efficiency of the left superior frontal gyrus (SFG) was significantly higher in BDD vs. MDD. In particular, Communicability Efficiency using TS-based connectivity in the left SFG as well as FA-based connectivity in the right middle anterior cingulate area was higher in the BDD vs. MDD- group. There were no significant differences in graph properties between BDD and MDD+. Direct comparison between MDD+ and MDD- showed differences in Eigenvector Centrality (TS-based connectivity) of the left middle frontal sulcus. Acceptable Area Under Curve (AUC) for classification were seen between the BDD and MDD- groups, and between the MDD+ and MDD- groups, using the differing graph properties. CONCLUSION: Graph properties of DWI-based connectivity can discriminate between BDD and MDD subjects without risk factors for BD.

Resting-state functional connectivity graph-properties correlate with bipolar disorder-risk in young medication-free depressed subjects: Bipolar-risk Resting State Functional Connectivity in Major Depression.

BACKGROUND: Major Depressive Disorder (MDD) is frequently associated with risk factors for the development of Bipolar Disorder (BD). Using graph theory, we investigated brain network properties associated with BD risk factors in young MDD subjects. METHODS: Resting-state fMRI was acquired from a large cohort (N= 104) of medication-free currently depressed participants (25 BD depression (BDD), 79 MDD). Lifetime mania symptom count (LMSC), current Young Mania Rating Scale (YMRS) score, and family history of mood disorders (FHMD) were examined as BD risk factors. Functional connectivity matrices from 280 regions of interests (ROIs) were first entered into the Network Based Statistic (NBS) toolbox to identify connections that varied with each risk factor. Next, within the correlated network for each risk factor, global and nodal graph properties for the top five linked nodes were calculated. Last, using identified graph properties, machine learning classification (MLC) between BDD, MDD with BD risk factors (MDD+), and without BD risk factors (MDD-) was conducted. RESULTS: LMSC positively correlated with left lateral orbitofrontal cortex (LOFC) Communication Efficiency and with left middle temporal Eigenvector Centrality. Current YMRS score positively correlated with right amygdala Communication Efficiency and Closeness Centrality. FHMD positively correlated with right insula Eigenvector Centrality. Acceptable MLC accuracy was seen between BDD and MDD- using middle temporal Eigenvector Centrality, whereas moderate accuracy was seen between MDD+ and MDD- using OFC Communication Efficiency. LIMITATION: Although participants were medication-free, they were not medication-naïve. CONCLUSION: Functional connectome graph properties may serve as BD vulnerability biomarkers in young individuals with MDD.

Affect Regulation-Related Emergent Brain Network Properties Differentiate Depressed Bipolar Disorder From Major Depression and Track Risk for Bipolar Disorder.

BACKGROUND: Individuals with or at risk for bipolar disorder (BD) often present initially for the treatment of depressive symptoms. Unfortunately, pharmacological treatments for major depressive disorder (MDD) can be iatrogenic, precipitating mania that may not have otherwise occurred. Current diagnostic procedures rely solely on self-reported/observable symptoms, and thus alternative data sources, such as brain network properties, are needed to supplement current self-report/observation-based indices of risk for mania. METHODS: Brain connectivity during affect maintenance/regulation was examined in a large (N = 249), medication-free sample of currently depressed patients with BD (n = 50) and MDD (n = 116) and healthy control subjects (n = 83). BD risk was categorized in a subset of patients with MDD. We used graph theory to identify emergent network properties that differentiated between patients with BD and MDD and between patients with MDD at high and low risk for BD. RESULTS: BD and MDD differed in the extent to which the rostral anterior cingulate cortex was embedded in the local network, amount of influence the hippocampus exerted over global network communication, and clarity of orbitofrontal cortex communication. Patients with MDD at high risk for BD showed a pattern of local network clustering around the right amygdala that was similar to the pattern observed in healthy control subjects, whereas patients with MDD at low risk for BD deviated from this pattern. CONCLUSIONS: BD and MDD differed in emergent network mechanisms subserving affect regulation, and amygdala properties tracked BD risk in patients with MDD. If replicated, our findings may be combined with other markers to assess the presence of BD and/or BD risk in individuals presenting with depressive symptoms to prevent the use of iatrogenic treatments.

Childhood trauma moderates morphometric associations between orbitofrontal cortex and amygdala: implications for pathological personality traits.

BACKGROUND: Research has demonstrated that chronic stress exposure early in development can lead to detrimental alterations in the orbitofrontal cortex (OFC)-amygdala circuit. However, the majority of this research uses functional neuroimaging methods, and thus the extent to which childhood trauma corresponds to morphometric alterations in this limbic-cortical network has not yet been investigated. This study had two primary objectives: (i) to test whether anatomical associations between OFC-amygdala differed between adults as a function of exposure to chronic childhood assaultive trauma and (ii) to test how these environment-by-neurobiological effects relate to pathological personality traits. METHODS: Participants were 137 ethnically diverse adults (48.1% female) recruited from the community who completed a clinical diagnostic interview, a self-report measure of pathological personality traits, and anatomical MRI scans. RESULTS: Findings revealed that childhood trauma moderated bilateral OFC-amygdala volumetric associations. Specifically, adults with childhood trauma exposure showed a positive association between medial OFC volume and amygdalar volume, whereas adults with no childhood exposure showed the negative OFC-amygdala structural association observed in prior research with healthy samples. Examination of the translational relevance of trauma-related alterations in OFC-amygdala volumetric associations for disordered personality traits revealed that trauma exposure moderated the association of OFC volume with antagonistic and disinhibited phenotypes, traits characteristic of Cluster B personality disorders. CONCLUSIONS: The OFC-amygdala circuit is a potential anatomical pathway through which early traumatic experiences perpetuate emotional dysregulation into adulthood and confer risk for personality pathology. Results provide novel evidence of divergent neuroanatomical pathways to similar personality phenotypes depending on early trauma exposure.

Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume.

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10-20), thalamus (p = 7.46 × 10-10), caudate (p = 1.97 × 10-18), putamen (p = 1.7 × 10-12), and nucleus accumbens (p = 1.99 × 10-7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = -0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p < 1 × 10-19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10-7) or PTSD (rs10861272; p = 1.78 × 10-6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.

Identifying brain regions supporting amygdalar functionality: Application of a novel graph theory technique.

Effective amygdalar functionality depends on the concerted activity of a complex network of regions. Thus, the role of the amygdala cannot be fully understood without identifying the set of brain structures that allow the processes performed by the amygdala to emerge. However, this identification has yet to occur, hampering our ability to understand both normative and pathological processes that rely on the amygdala. We developed and applied novel graph theory methods to diffusion-based anatomical networks in a large sample (n = 1,052, 54.28% female, mean age=28.75) to identify nodes that critically support amygdalar interactions with the larger brain network. We examined three graph properties, each indexing a different emergent aspect of amygdalar network communication: current-flow betweenness centrality (amygdalar influence on information flowing between other pairs of nodes), node communicability (clarity of communication between the amygdala and other nodes), and subgraph centrality (amygdalar influence over local network processing). Findings demonstrate that each of these aspects of amygdalar communication is associated with separable sets of regions and, in some cases, these sets map onto previously identified sub-circuits. For example, betweenness and communicability were each associated with different sub-circuits that have been identified in previous work as supporting distinct aspects of memory-guided behavior. Other regions identified span basic (e.g., visual cortex) to higher-order (e.g., insula) sensory processing and executive functions (e.g., dorsolateral prefrontal cortex). Present findings expand our current understanding of amygdalar function by showing that there is no single 'amygdala network', but rather multiple networks, each supporting different modes of amygdalar interaction with the larger brain network. Additionally, our novel method allowed for the identification of how such regions support the amygdala, which has not been previously explored.

A multilevel examination of lifetime aggression: integrating cortical thickness, personality pathology and trauma exposure.

Aggression represents a significant public health concern, causing serious physical and psychological harm. Although many studies have sought to characterize the etiology of aggression, research on the contributions of risk factors that span multiple levels of analysis for explaining aggressive behavior is lacking. To address this gap, we investigated the direct and unique contributions of cortical thickness (level 1), pathological personality traits (level 2) and trauma exposure (level 3) for explaining lifetime physical aggression in a high-risk sample of community adults (N = 129, 47.3% men). First, the frequency of lifetime aggression was inversely associated with cortical thickness in regions of prefrontal and temporal cortices that have been implicated in executive functioning, inhibitory mechanisms and socio-emotional processing. Further, aggression was positively associated with pathological personality traits (antagonism and disinhibition) and exposure to assaultive trauma. Notably, all three levels of analysis (cortical thickness, pathological personality traits and assaultive trauma exposure) explained non-overlapping variance in aggressive behavior when examined simultaneously in integrative models. Together, the findings provide a multilevel assessment of the biopsychosocial factors associated with the frequency of aggression. They also indicate that cortical thickness explains novel variance in these harmful behaviors not captured by well-established personality and environmental risk factors for aggression.

Differential spatial patterns of structural connectivity of amygdala nuclei with orbitofrontal cortex.

The orbitofrontal cortex (OFC)-amygdala circuit is critical to goal-directed behavior, learning, and valuation. However, our understanding of the OFC-amygdala connections that support these emergent processes is hampered by our reliance on the primate literature and insufficient knowledge regarding the connectivity patterns between regions of OFC and amygdala nuclei, each of which is differentially involved in these processes in humans. Thus, we examined structural connectivity between different OFC regions and four amygdala nuclei in healthy adults (n = 1,053) using diffusion-based anatomical networks and probabilistic tractography in four conceptually distinct ways. First, we identified the OFC regions that connect with each nucleus. Second, we identified the OFC regions that were more likely to connect with a given nucleus than the others. Finally, we developed probabilistic and rank-order maps of OFC (one for each nucleus) based upon the likelihood of each OFC voxel exhibiting preferential connectivity with each nucleus and the relative density of connectivity between each OFC voxel and each nucleus, respectively. The first analyses revealed that the connections of each nucleus spanned all of OFC, reflecting widespread overall amygdala linkage with OFC. Analysis of preferential connectivity and probabilistic and rank-order maps of OFC converged to reveal differential patterns of connectivity between OFC and each nucleus. Present findings illustrate the importance of accounting for spatial specificity when examining links between OFC and amygdala. This fine-grained examination of OFC-amygdala connectivity can be applied to understand how such connectivity patterns support a range of emergent functions including affective and motivational processes.

Neuroimaging correlates of emotional response-inhibition discriminate between young depressed adults with and without sub-threshold bipolar symptoms (Emotional Response-inhibition in Young Depressed Adults).

BACKGROUND: Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-). METHOD: This study included 118 medication-free young adults (15 - 30 yrs.): 20 BDD, 28 MDD+, 41 MDD- and 29 HC subjects. Participants underwent fMRI during emotional and non-emotional Go/No-go tasks during which they responded for Go stimuli and inhibited response for happy, fear, and non-emotional (gender) faces No-go stimuli. Univariate linear mixed-effects (LME) analysis for group effects and multivariate Gaussian Process Classifier (GPC) analyses were conducted. RESULTS: MDD- group compared to both the BDD and MDD+ groups, exhibited significantly lower activation in parietal, temporal and frontal regions (cluster-wise corrected p <0.05) for emotional inhibition conditions vs. non-emotional condition. GPC classification of emotional (happy + fear) vs. non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD- subjects (AUC: 0.70; balanced accuracy: 70% (corrected p = 0.018)) as well as between MDD+ and MDD- subjects (AUC: 0.72; balanced accuracy: 67% (corrected p = 0.045)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (corrected p = 0.273)). Notably, classification of the MDD- group was weighted for left amygdala activation pattern. LIMITATIONS: Results also need to be tested in a different independent dataset. CONCLUSION: Using an fMRI emotional Go-Nogo task, MDD- subjects can be discriminated from BDD and MDD+ subjects.

Effective connectivity between Broca's area and amygdala as a mechanism of top-down control in worry.

Individuals higher in trait worry exhibit increased activation in Broca's area during inhibitory processing tasks. To identify whether such activity represents an adaptive mechanism supporting top-down control, functional and effective connectivity of Broca's area were investigated during a task of inhibitory control. fMRI data obtained from 106 participants performing an emotion-word Stroop task were examined using psychophysiological interaction and Granger Causality (GC) analyses. Findings revealed greater directed connectivity from Broca's to amygdala in the presence of emotional distraction. Furthermore, a predictive relationship was observed between worry and the asymmetry in effective connectivity, with worriers exhibiting greater directed connectivity from Broca's to amygdala. When performing the task, worriers with greater GC directional asymmetry were more accurate than worriers with less asymmetry. Present findings indicate that individuals with elevated trait worry employ a mechanism of top-down control in which communication from Broca's to amygdala fosters successful compensation for interference effects.