Amygdala Functional and Structural Connectivity Predicts Individual Risk Tolerance.
ABSTRACT: Risk tolerance, the degree to which an individual is willing to tolerate risk in order to achieve a greater expected return, influences a variety of financial choices and health behaviors. Here we identify intrinsic neural markers for risk tolerance in a large (n = 108) multimodal imaging dataset of healthy young adults, which includes anatomical and resting-state functional MRI and diffusion tensor imaging. Using a data-driven approach, we found that higher risk tolerance was most strongly associated with greater global functional connectivity (node strength) of and greater gray matter volume in bilateral amygdala. Further, risk tolerance was positively associated with functional connectivity between amygdala and medial prefrontal cortex and negatively associated with structural connectivity between these regions. These findings show how the intrinsic functional and structural architecture of the amygdala, and amygdala-medial prefrontal pathways, which have previously been implicated in anxiety, are linked to individual differences in risk tolerance during economic decision making.
Project description:Generalized anxiety disorder (GAD) typically begins during adolescence and can persist into adulthood. The pathophysiological mechanisms underlying this disorder remain unclear. Recent evidence from resting state functional magnetic resonance imaging (R-fMRI) studies in adults suggests disruptions in amygdala-based circuitry; the present study examines this issue in adolescents with GAD.Resting state fMRI scans were obtained from 15 adolescents with GAD and 20 adolescents without anxiety who were group matched on age, sex, scanner, and intelligence. Functional connectivity of the centromedial, basolateral, and superficial amygdala subdivisions was compared between groups. We also assessed the relationship between amygdala network dysfunction and anxiety severity.Adolescents with GAD exhibited disruptions in amygdala-based intrinsic functional connectivity networks that included regions in medial prefrontal cortex, insula, and cerebellum. Positive correlations between anxiety severity scores and amygdala functional connectivity with insula and superior temporal gyrus were also observed within the GAD group. There was some evidence of greater overlap (less differentiation of connectivity patterns) of the right basolateral and centromedial amygdala networks in the adolescents with, relative to those without, GAD.These findings suggest that adolescents with GAD manifest alterations in amygdala circuits involved in emotion processing, similar to findings in adults. In addition, disruptions were observed in amygdala-based networks involved in fear processing and the coding of interoceptive states.
Project description:OBJECTIVE:Suicide is the second leading cause of death among adolescents; however, objective biomarkers of suicide risk are lacking. Aberrant self-face amygdala activity is associated with suicide ideation, and its connectivity with neural regions that enable self-processing (eg medial prefrontal cortex) may be a suicide risk factor. METHOD:Adolescents (aged 11-17 years; N = 120) were sorted into four groups: healthy controls (HC), depressed individuals with low suicide ideation (LS), depressed individuals with high suicide ideation (HS), and depressed suicide attempters (SA). Youth completed an emotional (Happy, Sad, Neutral) self-face recognition task in the scanner. Bilateral amygdala task-dependent functional connectivity was determined with psychophysiological interaction analysis. Connectivity was compared across groups and within Self versus Other faces across emotions and hemispheres. Voxelwise results were thresholded (p < .005, uncorrected) and corrected for multiple comparisons (p < .05, familywise error). RESULTS:Both HS and SA displayed greater amygdala connectivity with the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and precuneus, compared to LS, who, in turn, showed greater connectivity than HC. Greater left amygdala-rostral anterior cingulate cortex (rACC) connectivity was observed in SA compared to all other groups, whereas right amygdala-rACC connectivity was greater in HS versus LS and HC. CONCLUSION:Greater connectivity between amygdala and other regions implicated in self-face processing differentiated suicide ideation and suicide attempt groups. A dose-dependent response showed that greater rACC-left amygdala connectivity during self-face processing was associated with a recent suicide attempt, but that a greater rACC-right amygdala connectivity was associated with suicide ideation.
Project description:Early life trauma exposure represents a potent risk factor for the development of mental illnesses such as anxiety, depression and post-traumatic stress disorder. Moreover, deleterious consequences of trauma are exacerbated in youth living in impoverished, urban environments. A priori probability maps were used to examine resting-state functional connectivity (FC) of the amygdala in 21 trauma-exposed, and 21 age- and sex-matched urban children and adolescents (youth) without histories of trauma. Intrinsic FC analyses focused on amygdala-medial prefrontal circuitry, a key emotion regulatory pathway in the brain. We discovered reduced negative amygdala-subgenual cingulate connectivity in trauma-exposed youth. Differences between groups were also identified in anterior insula and dorsal anterior cingulate to amygdala connectivity. Overall, results suggest a model in which urban-dwelling trauma-exposed youth lack negative prefrontal to amygdala connectivity that may be critical for regulation of emotional responses. Functional changes in amygdala circuitry might reflect the biological embedding of stress reactivity in early life and mediate enhanced vulnerability to stress-related psychopathology.
Project description:Greater responsiveness of emotional arousal circuits in relation to delivered visceral pain has been implicated as underlying central pain amplification in irritable bowel syndrome (IBS), with female subjects showing greater responses than male subjects. Functional magnetic resonance imaging was used to measure neural responses to an emotion recognition paradigm, using faces expressing negative emotions (fear and anger). Sex and disease differences in the connectivity of affective and modulatory cortical circuits were studied in 47 IBS (27 premenopausal female subjects) and 67 healthy control subjects (HCs; 38 premenopausal female subjects). Male subjects (IBS+HC) showed greater overall brain responses to stimuli than female subjects in prefrontal cortex, insula, and amygdala. Effective connectivity analyses identified major sex- and disease-related differences in the functioning of brain networks related to prefrontal regions, cingulate, insula, and amygdala. Male subjects had stronger connectivity between anterior cingulate subregions, amygdala, and insula, whereas female subjects had stronger connectivity to and from the prefrontal modulatory regions (medial/dorsolateral cortex). Male IBS subjects demonstrate greater engagement of cortical and affect-related brain circuitry compared to male control subjects and female subjects, when viewing faces depicting emotions previously shown to elicit greater behavioral and brain responses in male subjects.
Project description:Generalized social anxiety disorder (gSAD) is characterized by exaggerated amygdala reactivity to social signals of threat, but if and how the amygdala interacts with functionally and anatomically connected prefrontal cortex (PFC) remains largely unknown. Recent evidence points to aberrant amygdala connectivity to medial PFC in gSAD at rest, but it is difficult to attribute functional relevance without the context of threat processing. Here, we address this by studying amygdala-frontal cortex connectivity during viewing of fearful faces and at rest in gSAD patients.Twenty patients with gSAD and 17 matched healthy controls (HCs) participated in functional magnetic resonance imaging of an emotional face matching task and a resting state task. Functional connectivity and psychophysiological interaction analysis were used to assess amygdala connectivity.Compared to HCs, gSAD patients exhibited less connectivity between amygdala and the rostral anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) while viewing fearful faces. gSAD patients also showed less connectivity between amygdala and rostral ACC at rest in the absence of fearful faces. DLPFC connectivity was negatively correlated with LSASFear (where LSAS is Liebowitz Social Anxiety Scale).Task and rest paradigms provide unique and important information about discrete and overlapping functional networks. In particular, amygdala coupling to DLPFC may be a phasic abnormality, emerging only in the presence of a social predictor of threat, whereas amygdala coupling to the rostral ACC may reflect both phasic and tonic abnormalities. These findings prompt further studies to better delineate intrinsic and externally evoked brain connectivity in anxiety and depression in relation to amygdala dysfunction.
Project description:Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S' allele carriers relative to L(A)L(A) individuals. Neuroticism was negatively correlated with functional connectivity between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left lOFC/vlPFC, such that S' carriers exhibited a more negative association relative to L(A)L(A) individuals. These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders.
Project description:BACKGROUND:Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry. METHODS:We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects. RESULTS:Traumatized youths showed altered amygdala-anterior midcingulate cortex (aMCC) and amygdala-ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala-aMCC and amygdala-vmPFC functional connectivity, and also mediated the observed group difference in amygdala-aMCC connectivity. CONCLUSIONS:Our findings suggest that traumatic stress may influence amygdala-prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness.
Project description:Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate through amygdala-ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.
Project description:The human brain undergoes protracted development, with dramatic changes in expression and regulation of emotion from childhood to adulthood. The amygdala is a brain structure that plays a pivotal role in emotion-related functions. Investigating developmental characteristics of the amygdala and associated functional circuits in children is important for understanding how emotion processing matures in the developing brain. The basolateral amygdala (BLA) and centromedial amygdala (CMA) are two major amygdalar nuclei that contribute to distinct functions via their unique pattern of interactions with cortical and subcortical regions. Almost nothing is currently known about the maturation of functional circuits associated with these amygdala nuclei in the developing brain. Using intrinsic connectivity analysis of functional magnetic resonance imaging data, we investigated developmental changes in functional connectivity of the BLA and CMA in twenty-four 7- to 9-y-old typically developing children compared with twenty-four 19- to 22-y-old healthy adults. Children showed significantly weaker intrinsic functional connectivity of the amygdala with subcortical, paralimbic, and limbic structures, polymodal association, and ventromedial prefrontal cortex. Importantly, target networks associated with the BLA and CMA exhibited greater overlap and weaker dissociation in children. In line with this finding, children showed greater intraamygdala connectivity between the BLA and CMA. Critically, these developmental differences were reproducibly identified in a second independent cohort of adults and children. Taken together, our findings point toward weak integration and segregation of amygdala circuits in young children. These immature patterns of amygdala connectivity have important implications for understanding typical and atypical development of emotion-related brain circuitry.
Project description:Locus of control (LOC) is an important personality trait. LOC over cognitive competency reflects an individual's perceived control of desired cognitive outcomes, which is critical for maintaining successful cognitive aging. It is important to understand the neural substrates of LOC over cognitive competency in older adults, especially for individuals at high risk of dementia. Here, we characterized a cohesive functional and structural connectivity profile underlying LOC among 55 older adults with amnestic mild cognitive impairment (aMCI), combining resting-state functional magnetic resonance imaging and diffusion tensor imaging. The results showed that both functional and structural connectivity between the medial prefrontal cortex and amygdala were significantly correlated with external LOC. The functional connectivity mediated the correlation between structural connectivity and external LOC. In addition, aging-associated neurodegeneration moderated the relationship between structural connectivity and external LOC, showing that the structural connectivity was positively correlated with external LOC in low, but not high neurodegeneration. Our results suggest a critical role of the functional amygdala-frontal network, which may serve as a bridge between its white matter tract and LOC over cognitive competency in groups at high risk for dementia.