High-precision magnetoencephalography for reconstructing amygdalar and hippocampal oscillations during prediction of safety and threat.
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ABSTRACT:
SUBMITTER: Tzovara A
PROVIDER: S-EPMC6772181 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The medial prefrontal cortex and amygdala are involved in the regulation of social behavior and associated with psychiatric diseases but their detailed neurophysiological mechanisms at a network level remain unclear. We recorded local field potentials (LFPs) from the dorsal medial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) while male mice engaged on social behavior. We found that in wild-type mice, both the dmPFC and BLA increased 4-7 Hz oscillation power and decreased 30-60 Hz power when they needed to attend to another target mouse. In mouse models with reduced social interactions, dmPFC 4-7 Hz power further increased especially when they exhibited social avoidance behavior. In contrast, dmPFC and BLA decreased 4-7 Hz power when wild-type mice socially approached a target mouse. Frequency-specific optogenetic manipulations replicating social approach-related LFP patterns restored social interaction behavior in socially deficient mice. These results demonstrate a neurophysiological substrate of the prefrontal cortex and amygdala related to social behavior and provide a unified pathophysiological understanding of neuronal population dynamics underlying social behavioral deficits.
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Project description:Previous studies on the associations between trait anxiety and amygdalar responses to threat stimuli have resulted in mixed findings, possibly due to sample characteristics, specific tasks, and analytical methods. The present functional magnetic resonance imaging (fMRI) study aimed to investigate linear or non-linear associations between trait anxiety and amygdalar responses in a sample of participants with low, medium, and high trait anxiety scores. During scanning, participants were presented with threat-related or neutral pictures and had either to solve an emotional task or an emotional-unrelated distraction task. Results showed that only during the explicit task trait anxiety was associated with right amygdalar responses to threat-related pictures as compared to neutral pictures. The best model was a cubic model with increased amygdala responses for very low and medium trait anxiety values but decreased amygdala activation for very high trait anxiety values. The findings imply a non-linear relation between trait anxiety and amygdala activation depending on task conditions.
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Project description:Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution (18)F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.
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Project description:Both animal and human studies have identified a critical role of the hippocampus in contextual fear conditioning. In humans mainly functional magnetic resonance imaging has been used. To extend these findings to volumetric properties, 58 healthy participants underwent structural magnetic resonance imaging and participated in a differential fear conditioning paradigm with contextual stimuli. Ratings of emotional valence, arousal, and contingency as well as skin conductance responses (SCRs) were used as indicators of conditioning. Twenty-nine participants with the smallest hippocampal volumes were compared with 29 persons with the largest hippocampal volumes. Persons with larger hippocampal volume (especially on the right side) learned to discriminate between two conditioned contexts, whereas those with small hippocampal volumes did not, as indicated by SCRs. Further analyses showed that these results could not be explained by amygdalar volumes. In contrast, the participant answers on the self-report measures were not significantly influenced by hippocampal or amygdalar, but by total brain volume, suggesting a role of cortical structures in these more cognitive evaluation processes. Reanalysis of the self-report data using partial hippocampal volumes revealed a significant influence of the posterior but not anterior subvolumes, which is in accordance with theories and empirical findings on hippocampal functioning. This study shows the relevance of hippocampal volume for contextual fear conditioning in healthy volunteers and may have important implications for anxiety disorders.
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Project description:ObjectivesMorphological abnormalities have been reported for the hippocampi and amygdalae in young schizophrenia patients, but very little is known about the pattern of abnormalities in elderly schizophrenia patients. Here we investigated local structural differences in the hippocampi and amygdalae of elderly schizophrenia patients compared with healthy elderly subjects. We also related these differences to clinical symptom severity.Design20 schizophrenia patients (mean age: 67.4 ± 6.2 years; Mini-Mental State Exam: 22.8 ± 4.4) and 20 healthy elderly subjects (70.3 ± 7.5 years; 29.0 ± 1.1) underwent high resolution magnetic resonance imaging of the brain. The Radial Atrophy Mapping technique was used to reconstruct the 3D shape of the amygdala and the hippocampus. Local differences in tissue reductions were computed between groups and permutation tests were run to correct for multiple comparisons, in statistical maps thresholded at p = 0.05.ResultsSignificant tissue reduction was observed bilaterally in the amygdala and hippocampus of schizophrenia patients. The basolateral-ventral-medial amygdalar nucleus showed the greatest involvement, with over 30% local tissue reduction. The centro-medial, cortical, and lateral nuclei were also atrophic in patients. The hippocampus showed significant tissue loss in the medio-caudal and antero-lateral aspects of CA1, and in medial section of its left head (pre- and para-subiculum). In the left amygdala and hippocampus, local tissue volumes were significantly correlated with negative symptoms.ConclusionsTissue loss and altered morphology were found in elderly schizophrenia patients. Tissue loss mapped to amygdalo-hippocampal subregions known to have bidirectional and specific connections with frontal cortical and limbic structures and was related to clinical severity.
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