The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural ...networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST.
•The CeA and BNST have overlapping functional connections.•The CeA is more strongly connected to regions involved in sensory processing.•The BNST is more strongly connected to regions involved in motivational processing.
Dispositional anxiety is a well-established risk factor for the development of psychiatric disorders along the internalizing spectrum, including anxiety and depression. Importantly, many of the ...maladaptive behaviors characteristic of anxiety, such as anticipatory apprehension, occur when threat is absent. This raises the possibility that anxious individuals are less efficient at gating threat's access to working memory, a limited capacity workspace where information is actively retained, manipulated, and used to flexibly guide goal-directed behavior when it is no longer present in the external environment. Using a well-validated neurophysiological index of working memory storage, we demonstrate that threat-related distracters were difficult to filter on average and that this difficulty was exaggerated among anxious individuals. These results indicate that dispositionally anxious individuals allocate excessive working memory storage to threat, even when it is irrelevant to the task at hand. More broadly, these results provide a novel framework for understanding the maladaptive thoughts and actions characteristic of internalizing disorders.
When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently ...begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of childhood temperament and adult personality and a prominent risk factor for the development of pediatric and adult anxiety disorders. Converging lines of epidemiological, neurobiological, and mechanistic evidence suggest that dispositional negativity increases the likelihood of psychopathology via specific neurocognitive mechanisms, including attentional biases to threat and deficits in executive control. Collectively, these observations provide an integrative translational framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.
Pathological fear and anxiety are a leading cause of human misery and morbidity, afflicting millions of individuals worldwide. Yet existing treatments are inconsistently effective or associated with ...significant adverse effects, underscoring the urgency of developing a more complete understanding of the neural systems governing fear and anxiety in humans. This emphasis reflects the fact that fear and anxiety disorders are defined and diagnosed based on subjective symptoms, and human studies are essential for understanding the neural mechanisms that underlie the experience of fear and anxiety. Human studies are also crucial for identifying the features of animal models that are conserved and, hence, most relevant to human disease and treatment development ('forward translation'). Finally, human studies afford opportunities for developing objective biomarkers of disease or disease risk, accelerating the development of new diagnostic and treatment strategies, and generating novel hypotheses that can be mechanistically assessed in animal models ('reverse translation'). The present Special Issue—The Neurobiology of Human Fear and Anxiety—provides a concise survey of recent progress in this burgeoning area of research. Here we provide an Introduction to the Special Issue, highlighting some of the most significant and exciting advances.
Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to ...experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.
Social anxiety lies on a continuum, and young adults with elevated symptoms are at risk for developing a range of psychiatric disorders. Yet relatively little is known about the factors that govern ...the hour-by-hour experience and expression of social anxiety in the real world.
Here we used smartphone-based ecological momentary assessment (EMA) to intensively sample emotional experience across different social contexts in the daily lives of 228 young adults selectively recruited to represent a broad spectrum of social anxiety symptoms.
Leveraging data from over 11 000 real-world assessments, our results highlight the central role of close friends, family members, and romantic partners. The presence of such close companions was associated with enhanced mood, yet socially anxious individuals had fewer confidants and spent less time with the close companions that they do have. Although higher levels of social anxiety were associated with a general worsening of mood, socially anxious individuals appear to derive larger benefits - lower levels of negative affect, anxiety, and depression - from their close companions. In contrast, variation in social anxiety was unrelated to the amount of time spent with strangers, co-workers, and acquaintances; and we uncovered no evidence of emotional hypersensitivity to these less-familiar individuals.
These findings provide a framework for understanding the deleterious consequences of social anxiety in emerging adulthood and set the stage for developing improved intervention strategies.
According to the World Health Organization, anxiety and depressive disorders are a leading source of disability, affecting hundreds of millions of people. Children can inherit an extremely anxious ...temperament, which is a prominent risk factor for the later development of anxiety, depression, and comorbid substance abuse. This study uses high-resolution functional and structural imaging in our well-established developmental nonhuman primate model to identify the heritable neural substrate that underlies extreme childhood anxious temperament. Using a large multigenerational family pedigree, genetic correlation analyses revealed a tripartite neural circuit where metabolism likely shares a genetic substrate with early-life dispositional anxiety. Interestingly, we found that brain functionânot structureâis the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.
Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolismânot brain structureâthat is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.
The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a critical role in triggering fear and anxiety and is ...implicated in the development of a range of debilitating neuropsychiatric disorders. Although it is widely believed that these disorders reflect the coordinated activity of distributed neural circuits, the functional architecture of the EAc network and the degree to which the BST and the Ce show distinct patterns of functional connectivity is unclear. Here, we used a novel combination of imaging approaches to trace the connectivity of the BST and the Ce in 130 healthy, racially diverse, community‐dwelling adults. Multiband imaging, high‐precision registration techniques, and spatially unsmoothed data maximized anatomical specificity. Using newly developed seed regions, whole‐brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala, the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed stronger connectivity with the thalamus, striatum, periaqueductal gray, and several prefrontal territories. The only regions showing stronger functional connectivity with the Ce were neighboring regions of the dorsal amygdala, amygdalohippocampal area, and anterior hippocampus. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and showcase image registration techniques that are likely to be useful for researchers working with “deidentified” neuroimaging data.
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