Connectivity characterization of the mouse basolateral amygdalar complex.
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ABSTRACT:
SUBMITTER: Hintiryan H
PROVIDER: S-EPMC8129205 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The amygdala has long been considered a vital region involved in acute and chronic stress responses. Extensive evidences from animal and human studies suggest that the functional connectivity of amygdalar subnuclei (basolateral amygdala (BLA), centromedial amygdala (CMA) and superficial amygdala (SFA)) undergo specific alterations in stress-related psychopathology. However, whether and how intrinsic functional connectivity within the amygdalar subcomponents is differently altered in the aftermath of an acute stressor remains unknown. In the present study, using a within-subject design, we examined the impact of acute psychological social stress on the functional connectivity of amygdalar subregions at rest. Results showed that stress mainly affected the connectivity pattern of CMA. In particular, in the stress condition compared with the control, the connectivity of CMA to left posterior cingulate cortex and right thalamus was decreased under stress, while the connectivity of CMA to left caudate connectivity was increased at rest post-stressor. The findings suggest that healthy individuals may adapt to threatening surroundings by reducing threatening information input, and shifting to well-learned procedural behaviors.
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Project description:BackgroundExternalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs.MethodsMulti-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined.ResultsNo significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results.ConclusionsThe current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations.
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Project description:ObjectiveEmotional reactivity is one of the most disabling symptoms associated with attention-deficit/hyperactivity disorder (ADHD). We aimed to identify neural substrates associated with emotional reactivity and to assess the effects of stimulants on those substrates.MethodWe used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (n = 15) and without (n = 15) ADHD while they performed a task involving the subliminal presentation of fearful faces. Using dynamic causal modeling, we also examined the effective connectivity of two regions associated with emotional reactivity, i.e., the amygdala and the lateral prefrontal cortex (LPFC). The participants with ADHD underwent scanning both on and off stimulant medication in a counterbalanced fashion.ResultsDuring the task, we found that activity in the right amygdala was greater in adolescents with ADHD than in control subjects. In addition, in adolescents with ADHD, greater connectivity was detected between the amygdala and LPFC. Stimulants had a normalizing effect on both the activity in the right amygdala and the connectivity between the amygdala and LPFC.ConclusionsOur findings demonstrate that in adolescents with ADHD, a neural substrate of fear processing is atypical, as is the connectivity between the amygdala and LPFC. These findings suggest possible neural substrates for the emotional reactivity that is often present in youths with ADHD, and provide putative neural targets for the development of novel therapeutic interventions for this condition.
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Project description:While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning. The kissing scenes were either accompanied by happy music, sad music or no music. Evidence from cross-modal studies motivated a predefined three-region network for multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this network were investigated using dynamic causal models of effective connectivity. This revealed bilinear modulations by happy and sad music with suppression effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal modeling showed a suppressive gating effect of aSTG on fusiform-amygdalar connectivity. In conclusion, fusiform to amygdala coupling strength is modulated via feedback through aSTG as region for multisensory integration of emotional material. This mechanism was emotion-specific and more pronounced for sad music. Therefore, soundtrack valences may modulate emotion elicitation in movies by differentially changing preprocessed visual information to the amygdala.
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Project description:The primary cilium plays a key role in the development of mammals and in the maintenance of health. Primary cilia are assembled and maintained by the process of intraflagellar transport (IFT). In this work, we characterize mouse IFT complex B by identifying all of the mammalian orthologues of complex B and B-associated proteins previously identified in Chlamydomonas and Caenorhabditis and also identify a new component (IFT25/Hspb11) of complex B by database analysis. We tagged each of these proteins with the FLAG epitope and show that all except IFT172 and IFT20 localize to cilia and the peri-basal body or centrosomal region at the base of cilia. All of the proteins except IFT172 immunoprecipitate IFT88 indicating that they are co-assembled into a complex. IFT20 is the only complex B protein that localizes to the Golgi apparatus. However, overexpression of IFT54/Traf3ip1, the mouse orthologue of Dyf-11/Elipsa, displaces IFT20 from the Golgi apparatus. IFT54 does not localize to the Golgi complex nor does it interact with GMAP210, which is the protein that anchors IFT20 to the Golgi apparatus. This suggests that IFT54s effect on IFT20 is a dominant negative phenotype caused by its overexpression. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.
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Project description:Recent findings indicate that alterations of the amygdalar resting-state fMRI connectivity play an important role in the etiology of depression. While both depression and resting-state brain activity are shaped by genes and environment, the relative contribution of genetic and environmental factors mediating the relationship between amygdalar resting-state connectivity and depression remain largely unexplored. Likewise, novel neuroimaging research indicates that different mathematical representations of resting-state fMRI activity patterns are able to embed distinct information relevant to brain health and disease. The present study analyzed the influence of genes and environment on amygdalar resting-state fMRI connectivity, in relation to depression risk. High-resolution resting-state fMRI scans were analyzed to estimate functional connectivity patterns in a sample of 48 twins (24 monozygotic pairs) informative for depressive psychopathology (6 concordant, 8 discordant and 10 healthy control pairs). A graph-theoretical framework was employed to construct brain networks using two methods: (i) the conventional approach of filtered BOLD fMRI time-series and (ii) analytic components of this fMRI activity. Results using both methods indicate that depression risk is increased by environmental factors altering amygdalar connectivity. When analyzing the analytic components of the BOLD fMRI time-series, genetic factors altering the amygdala neural activity at rest show an important contribution to depression risk. Overall, these findings show that both genes and environment modify different patterns the amygdala resting-state connectivity to increase depression risk. The genetic relationship between amygdalar connectivity and depression may be better elicited by examining analytic components of the brain resting-state BOLD fMRI signals.
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Project description:BackgroundThere is evidence of altered corticolimbic circuitry in adults with chronic pain, but relatively little is known of functional brain mechanisms in adolescents with neuropathic pain (NeuP). Pediatric NeuP is etiologically and phenotypically different from NeuP in adults, highlighting the need for pediatric-focused research. The amygdala is a key limbic region with important roles in the emotional-affective dimension of pain and in pain modulation.ObjectiveTo investigate amygdalar resting state functional connectivity (rsFC) in adolescents with NeuP.MethodsThis cross-sectional observational cohort study compared resting state functional MRI scans in adolescents aged 11-18 years with clinical features of chronic peripheral NeuP (n = 17), recruited from a tertiary clinic, relative to healthy adolescents (n = 17). We performed seed-to-voxel whole-brain rsFC analysis of the bilateral amygdalae. Next, we performed post hoc exploratory correlations with clinical variables to further explain rsFC differences.ResultsAdolescents with NeuP had stronger negative rsFC between right amygdala and right dorsolateral prefrontal cortex (dlPFC) and stronger positive rsFC between right amygdala and left angular gyrus (AG), compared to controls (P FDR <0.025). Furthermore, lower pain intensity correlated with stronger negative amygdala-dlPFC rsFC in males (r = 0.67, P = 0.034, n = 10), and with stronger positive amygdala-AG rsFC in females (r = -0.90, P = 0.006, n = 7). These amygdalar rsFC differences may thus be pain inhibitory.ConclusionsConsistent with the considerable affective and cognitive factors reported in a larger cohort, there are rsFC differences in limbic pain modulatory circuits in adolescents with NeuP. Findings also highlight the need for assessing sex-dependent brain mechanisms in future studies, where possible.
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Project description:Acute moderate exercise has been shown to induce prolonged changes in functional connectivity (FC) within affect and reward networks. The influence of different exercise intensities on FC has not yet been explored. Twenty-five male athletes underwent 30?min of "low"- (35% < lactate?threshold (LT)) and "high"- (20% > LT) intensity exercise bouts on a treadmill. Resting-state fMRI was acquired at 3 Tesla before and after exercise, together with the Positive and Negative Affect Scale (PANAS). Data of 22 subjects (3 dropouts) were analyzed using the FSL feat pipeline and a seed-to-network-based analysis with the bilateral amygdala as the seed region for determining associated FC changes in the "emotional brain." Data were analyzed using a repeated measures ANOVA. Comparisons between pre- and post-exercise were analyzed using a one-sample t-test, and a paired t-test was used for the comparison between "low" and "high" exercise conditions (nonparametric randomization approach, results reported at p < 0.05). Both exercise interventions induced significant increases in the PANAS positive affect scale. There was a significant interaction effect of amygdalar FC to the right anterior insula, and this amygdalar-insular FC correlated significantly with the PANAS positive affect scale (r = 0.47, p = 0.048) in the "high"-intensity exercise condition. Our findings suggest that mood changes after exercise are associated with prolonged alterations in amygdalar-insular FC and occur in an exercise intensity-dependent manner.
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Project description:Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although, the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum) connected with the bed nucleus of the stria terminalis (pallidum). This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homolog of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a framework for the regulation of the stress response, including the medial habenula and the subgenual cingulate cortex, in which dysfunction may explain the major symptoms of mood and anxiety disorders.
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Project description:Aging is associated with increased difficulty in facial emotion identification, possibly due to age-related network change. The neuropeptide oxytocin (OT) facilitates emotion identification, but this is understudied in aging. To determine the effects of OT on dynamic facial emotion identification across adulthood, 46 young and 48 older participants self-administered intranasal OT or a placebo in a randomized, double-blind procedure. Older participants were slower and less accurate in identifying emotions. Although there was no behavioral treatment effect, partial least squares analysis supported treatment effects on brain patterns during emotion identification that varied by age and emotion. For young participants, OT altered the processing of sadness and happiness, whereas for older participants, OT only affected the processing of sadness (15.3% covariance, p = 0.004). Furthermore, seed partial least squares analysis showed that older participants in the OT group recruited a large-scale amygdalar network that was positively correlated for anger, fear, and happiness, whereas older participants in the placebo group recruited a smaller, negatively correlated network (7% covariance, p = 0.002). Advancing the literature, these findings show that OT alters brain activity and amygdalar connectivity by age and emotion.
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