Dispositional negativity—the propensity to experience and express more frequent, intense, or enduring negative affect—is a fundamental dimension of childhood temperament and adult personality. Elevated levels of dispositional negativity can have profound consequences for health, wealth, and happiness, drawing the attention of clinicians, researchers, and policy makers. Here, we highlight recent advances in our understanding of the psychological and neurobiological processes linking stable individual differences in dispositional negativity to momentary emotional states. Self-report data suggest that three key pathways—increased stressor reactivity, tonic increases in negative affect, and increased stressor exposure—explain most of the heightened negative affect that characterizes individuals with a more negative disposition. Of these three pathways, tonically elevated, indiscriminate negative affect appears to be most central to daily life and most relevant to the development of psychopathology. New behavioral and biological data provide insights into the neural systems underlying these three pathways and motivate the hypothesis that seemingly ‘tonic’ increases in negative affect may actually reflect increased reactivity to stressors that are remote, uncertain, or diffuse. Research focused on humans, monkeys, and rodents suggests that this indiscriminate negative affect reflects trait-like variation in the activity and connectivity of several key brain regions, including the central extended amygdala and parts of the prefrontal cortex. Collectively, these observations provide an integrative psychobiological framework for understanding the dynamic cascade of processes that bind emotional traits to emotional states and, ultimately, to emotional disorders and other kinds of adverse outcomes.

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. While it is widely believed that these disorders reflect the coordinated activity of widely 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 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 which may be useful for researchers working with ‘de-identified’ neuroimaging data.

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the neurocognitive mechanisms that confer increased risk have only recently begun to come into focus. Here we review recent work highlighting the importance of neural circuits centered on the amygdala. We begin by describing dispositional negativity, a core dimension of childhood temperament and adult personality and an important risk factor for the development of anxiety disorders and other kinds of stress-sensitive psychopathology. Converging lines of epidemiological, neurophysiological, and mechanistic evidence indicate that the amygdala supports stable individual differences in dispositional negativity across the lifespan and contributes to the etiology of anxiety disorders in adults and youth. Hyper-vigilance and attentional biases to threat are prominent features of the anxious phenotype and there is growing evidence that they contribute to the development of psychopathology. Anatomical studies show that the amygdala is a hub, poised to govern attention to threat via projections to sensory cortex and ascending neuromodulatory systems. Imaging and lesion studies demonstrate that the amygdala plays a key role in selecting and prioritizing the processing of threat-related cues. Collectively, these observations provide a neurobiologically-grounded framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.

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.

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.

The central extended amygdala (EAc)-including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)-plays a key role in orchestrating states of fear and anxiety and is implicated in the development and maintenance of anxiety disorders, depression, and substance abuse. Although it is widely thought that these disorders reflect the coordinated actions of large-scale functional circuits in the brain, the architecture of the EAc functional network, and the degree to which the BST and the Ce show distinct patterns of intrinsic functional connectivity, remains incompletely understood. Here, we leveraged a combination of approaches to trace the connectivity of the BST and the Ce in 130 psychiatrically healthy, racially diverse, community-dwelling adults with enhanced power and precision. Multiband imaging, high-precision data registration techniques, and spatially unsmoothed data were used to maximize 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 ('substantia innominata'), the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed significant coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed significantly stronger connectivity with prefrontal territories-including the vmPFC, anterior MCC and pregenual anterior cingulate cortex-as well as the thalamus, striatum, and the periaqueductal gray. The only regions showing stronger functional connectivity with the Ce were located in the anterior hippocampus and dorsal amygdala. 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 highlight the value of several new approaches to image registration which may be particularly useful for researchers working with 'de-identified' neuroimaging data.

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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.