Associations between Amygdala-Prefrontal Functional Connectivity and Age Depend on Neighborhood Socioeconomic Status.
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ABSTRACT:
SUBMITTER: Ramphal B
PROVIDER: S-EPMC7503474 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Bipolar disorder (BD) is a serious mental illness. Several studies have shown that brain structure and function changes and the development of BD are associated with age and sex differences. Therefore, we hypothesized that the functional and structural neural circuitry of BD patients would differ according to age. The amygdala and prefrontal cortex (PFC) are play a key role in the emotional and cognitive processing of patients with BD. In this study, we used magnetic resonance imaging (MRI) to examine the structural and functional connectivity within amygdala-PFC neural circuitry in women with BD at different ages. METHODS:Forty-nine female patients with BD who were aged 13-25 years and 60 age-matched healthy control (HC) individuals, as well as 43 female patients with BD who were aged 26-45 years and 60 age-matched HC individuals underwent resting-state functional MRI (rs-fMRI) and diffusion tensor imaging to examine the structural and functional connectivity within the amygdala-PFC neural circuitry. RESULTS:We found abnormalities in the amygdala-PFC functional connectivity in patients aged 13-25 years and significantly different fractional anisotropy (FA) values in patients aged 26-45 compared with the age-matched HCs. The significance of these findings was indicated by corrected p values of less than 0.05 (uncorrected p values less than 0.001). CONCLUSIONS:The findings in this cross-sectional study suggested that abnormalities in the functional connectivity of the amygdala-PFC neural circuitry are related to the pathophysiology of BD in women aged 13-25 years, while changes in the structural integrity of this neural circuitry are associated with the pathophysiology of BD in women aged 26-45 years. Therefore, functional and structural brain alterations may occur at different ages in female patients with BD.
| S-EPMC5989351 | biostudies-literature
Project description:ObjectiveIn this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation.MethodsParticipants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces.ResultsA history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces.ConclusionsOur results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders.
| S-EPMC4308069 | biostudies-literature
Project description:Recent evidence suggests that early life stress (ELS) changes stress reactivity via reduced resting state functional connectivity (rs-FC) between amygdala and the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and attenuates responses to psychosocial stress, but its effect appears to be moderated by ELS. Here we first investigate the effect of ELS on amygdala-prefrontal rs-FC, and examine whether ELS-associated changes of rs-FC in this neural circuit predict its response to psychosocial stress. Secondly, we explore the joint effect of OXT and ELS on the amygdala-prefrontal circuit. Eighteen healthy young males participated in a resting-state fMRI study of OXT effects using a double-blind, randomized, placebo-controlled, within-subject crossover design. We measured the rs-FC to bilateral amygdalae and subsequently assessed changes of state anxiety and prefrontal responses to psychosocial stress. Multiple linear regressions showed that ELS, specifically emotional abuse, predicted reduced rs-FC between the right amygdala and pregenual anterior cingulate cortex (pgACC), which in turn predicted elevated state anxiety after psychosocial stress. In subjects with lower ELS scores, stronger pgACC-amygdala rs-FC predicted stronger pgACC deactivation during the psychosocial stress task, and this rest-task interaction was attenuated by OXT. In subjects with higher ELS scores however, the rest-task interaction was altered and OXT showed no significant effect. These findings highlight that ELS reduces pgACC-amygdala rs-FC and alters how rs-FC of this circuit predicts its stress responsiveness. Such changes in pgACC-amygdala functional dynamics may underlie the altered sensitivity to the effects of OXT after ELS.
| S-EPMC6869775 | biostudies-literature
Project description:Many features of posttraumatic stress disorder (PTSD) can be linked to exaggerated and dysregulated emotional responses. Central to the neurocircuitry regulating emotion are functional interactions between the amygdala and the ventromedial prefrontal cortex (vmPFC). Findings from human and animal studies suggest that disruption of this circuit predicts individual differences in emotion regulation. However, only a few studies have examined amygdala-vmPFC connectivity in the context of emotional processing in PTSD. The aim of the present research was to investigate the hypothesis that PTSD is associated with disrupted functional connectivity of the amygdala and vmPFC in response to emotional stimuli, extending previous findings by demonstrating such links in an understudied, highly traumatized, civilian population. 40 African-American women with civilian trauma (20 with PTSD and 20 non-PTSD controls) were recruited from a large urban hospital. Participants viewed fearful and neutral face stimuli during functional magnetic resonance imaging (fMRI). Relative to controls, participants with PTSD showed an increased right amygdala response to fearful stimuli (p(corr) < .05). Right amygdala activation correlated positively with the severity of hyperarousal symptoms in the PTSD group. Participants with PTSD showed decreased functional connectivity between the right amygdala and left vmPFC (p(corr) < .05). The findings are consistent with previous findings showing PTSD is associated with an exaggerated response of amygdala-mediated emotional arousal systems. This is the first study to show that the amygdala response may be accompanied by disruption of an amygdala-vmPFC functional circuit that is hypothesized to be involved in prefrontal cortical regulation of amygdala responsivity.
| S-EPMC3743923 | biostudies-literature
Project description:BackgroundAnxiety produced by environmental threats can impair goal-directed processing and is associated with a range of psychiatric disorders, particularly when aversive events occur unpredictably. The prefrontal cortex (PFC) is thought to implement controls that minimize performance disruptions from threat-induced anxiety and goal distraction by modulating activity in regions involved in threat detection, such as the amygdala. The inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), and ventromedial PFC (vmPFC) have been linked to the regulation of anxiety during threat exposure. We developed a paradigm to determine if threat-induced anxiety would enhance functional connectivity between the amygdala and IFG, OFC, and vmPFC.MethodsHealthy adults performed a computer-gaming style task involving capturing prey and evading predators to optimize monetary rewards while exposed to the threat of unpredictable shock. Psychophysiological recording (n = 26) and functional magnetic resonance imaging scanning (n = 17) were collected during the task in separate cohorts. Task-specific changes in functional connectivity with the amygdala were examined using psychophysiological interaction analysis.ResultsThreat exposure resulted in greater arousal measured by increased skin conductance but did not influence performance (i.e., monetary losses or rewards). Greater functional connectivity between the right amygdala and bilateral IFG, OFC, vmPFC, anterior cingulate cortex, and frontopolar cortex was associated with threat exposure.ConclusionsExposure to unpredictable threat modulates amygdala-PFC functional connectivity that may help maintain performance when experiencing anxiety induced by threat. Our paradigm is well-suited to explore the neural underpinnings of the anxiety response to unpredictable threat in patients with various anxiety disorders.
| S-EPMC4349396 | biostudies-literature
Project description:Processing facial expressions of emotion draws on a distributed brain network. In particular, judging ambiguous facial emotions involves coordination between multiple brain areas. Here, we applied multimodal functional connectivity analysis to achieve network-level understanding of the neural mechanisms underlying perceptual ambiguity in facial expressions. We found directional effective connectivity between the amygdala, dorsomedial prefrontal cortex (dmPFC), and ventromedial PFC, supporting both bottom-up affective processes for ambiguity representation/perception and top-down cognitive processes for ambiguity resolution/decision. Direct recordings from the human neurosurgical patients showed that the responses of amygdala and dmPFC neurons were modulated by the level of emotion ambiguity, and amygdala neurons responded earlier than dmPFC neurons, reflecting the bottom-up process for ambiguity processing. We further found parietal-frontal coherence and delta-alpha cross-frequency coupling involved in encoding emotion ambiguity. We replicated the EEG coherence result using independent experiments and further showed modulation of the coherence. EEG source connectivity revealed that the dmPFC top-down regulated the activities in other brain regions. Lastly, we showed altered behavioral responses in neuropsychiatric patients who may have dysfunctions in amygdala-PFC functional connectivity. Together, using multimodal experimental and analytical approaches, we have delineated a neural network that underlies processing of emotion ambiguity.
| S-EPMC10613296 | biostudies-literature
Project description:BACKGROUND:Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development. METHODS:Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging. RESULTS:Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood. CONCLUSIONS:Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in the emergence of psychiatric disorders in adolescence.
| S-EPMC5522367 | biostudies-literature
Project description:Altered functional connectivity (FC) between the medial prefrontal cortex (mPFC) and amygdala is widely implicated as a neural mechanism explaining risk for psychopathology among those exposed to early life trauma. Nonetheless, contemporary neuroimaging research has shifted toward large-scale network models of brain function, and it is not clear how this common bi-nodal finding fits into larger-scale network models. Here, using dynamic functional connectivity (DFC) approaches combined with large-scale network analyses, the larger role of bi-nodal FC between mPFC and amygdala among a sample of adolescent girls is investigated. The sample was comprised of 30 healthy control girls and 26 girls exposed to either physical or sexual assault who underwent a resting-state scan during 3T MRI. DFC using a sliding window approach was used to create weighted, undirected, graphs from the resting-state data following parcellation with a 215 regions-of-interest (ROI) atlas. Using a priori ROI, the predicted finding of lessor FC between mPFC and amygdala as a function of early life trauma was replicated in this sample. By contrast, early life trauma was associated with greater large-scale network modularity. Using a dynamic FC approach, it is also demonstrated that within-subject variability in this bi-nodal FC closely tracks within-subject fluctuations in large-scale network patterns, including connectivity between a limbic and default mode network (in which the amygdala and mPFC nodes belong, respectively) as well as overall modular organization. These results suggest that bi-nodal FC, such as amygdala-mPFC FC, may generally reflect larger-scale network patterns. Future research is necessary to understand whether these associations between nodal FC and large-scale network organization better reflect top-down processes (larger-scale network organization drives bi-nodal FC) or bottom-up processes (bi-nodal FC drives larger-scale network organization) and the related impact of early life trauma.
| S-EPMC5425605 | biostudies-literature
Project description:BackgroundNeurobiological 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.MethodsWe 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.ResultsTraumatized 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.ConclusionsOur 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.
| S-EPMC6650776 | biostudies-literature
Project description:Slower epigenetic aging is associated with exposure to green space (greenness); however, the longitudinal relationship has not been well studied, particularly in minority groups. We investigated the association between 20-year exposure to greenness [Normalized Difference Vegetation Index (NDVI)] and epigenetic aging in a large, biracial (Black/white), U.S. urban cohort. Using generalized estimating equations adjusted for individual and neighborhood socioeconomic characteristics, greater greenness was associated with slower epigenetic aging. Black participants had less surrounding greenness and an attenuated association between greenness and epigenetic aging [βNDVI5km: -0.80, 95% confidence interval (CI): -4.75, 3.13 versus βNDVI5km: -3.03, 95% CI: -5.63, -0.43 in white participants]. Participants in disadvantaged neighborhoods showed a stronger association between greenness and epigenetic aging (βNDVI5km: -3.36, 95% CI: -6.65, -0.08 versus βNDVI5km: -1.57, 95% CI: -4.12, 0.96 in less disadvantaged). In conclusion, we found a relationship between greenness and slower epigenetic aging, and different associations by social determinants of health such as race and neighborhood socioeconomic status.
| S-EPMC10306284 | biostudies-literature