Acute alcohol administration dampens central extended amygdala reactivity

Hur, Juyoen; Kaplan, Claire M.; Smith, Jason F.; Bradford, Daniel E.; Fox, Andrew S.; Curtin, John J.; Shackman, Alexander J.

doi:10.1038/s41598-018-34987-3

Cited by 25 publications

(26 citation statements)

References 92 publications

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“…Across a range of comparisons, the BST and dorsal amygdala evinced statistically equivalent responses during the anticipation of certain and uncertain threat, reinforcing the possibility that they make similar contributions to human anxiety. These observations provide a novel framework for conceptualizing fear and anxiety, and for guiding the development of mechanistic work in humans and animals aimed at developing more effective intervention strategies for extreme anxiety (12, 92, 93). A relatively large sample, well-controlled task, and advanced techniques for fMRI data acquisition and processing enhance confidence in the robustness and translational relevance of these results.…”

Section: Discussionmentioning

confidence: 99%

Anxiety and the neurobiology of temporally uncertain threat anticipation

Hur

Smith

DeYoung

et al. 2020

Preprint

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When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature of situations that elicit signs of anxiety across disorders, species, and assays. Despite the significance of anxiety for human health and wellbeing, the neurobiology of uncertain threat anticipation remains remarkably unsettled. Leveraging a paradigm adapted from animal research and optimized for functional MRI, we examined the neural circuits engaged during the anticipation of temporally uncertain and certain threat in 99 men and women. Results revealed that uncertain and certain threat are anatomically co-localized in fronto-cortical regions and the extended amygdala (EA). Comparison of the two threat conditions demonstrated that this core network can be fractionated, with fronto-cortical regions showing relatively stronger engagement during the anticipation of uncertain threat, and the EA showing the reverse pattern. Although there is widespread agreement that the bed nucleus of the stria terminalis and dorsal amygdala—the two major subdivisions of the EA—play a critical role in orchestrating adaptive responses to potential danger, their precise contributions to human anxiety have remained contentious. Follow-up analyses demonstrated that these regions show statistically indistinguishable responses to temporally uncertain and certain threat. These observations provide a framework for conceptualizing anxiety and fear, for understanding the functional neuroanatomy of threat anticipation in humans, and for guiding the development of more effective intervention strategies for extreme anxiety.SIGNIFICANCE STATEMENTAnxiety—an emotion prototypically associated with the anticipation of uncertain harm—has profound significance for public health and wellbeing, yet it is unclear how the human brain responds to uncertain threat. Leveraging a novel neuroimaging paradigm in a large sample, we identify a core network responsive to both uncertain and certain threat anticipation, and show that this network bifurcates into regions with a bias for one kind of threat over the other. The extended-amygdala occupies center-stage in neuroscientific models of anxiety, but its functional architecture has remained contentious. Here we demonstrate that its major subdivisions show statistically indistinguishable responses to temporally uncertain and certain threat. Collectively, these observations indicate the need to revise how we think about anxiety and fear.

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Section: Discussionmentioning

confidence: 99%

Anxiety and the neurobiology of temporally uncertain threat anticipation

Hur

Smith

DeYoung

et al. 2020

Preprint

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“…Is attenuated by clinically effective cognitive-behavioral and pharmacological (e.g., benzodiazepine) treatments for anxiety and depression in adults (Månsson et al, 2016; Shackman et al, 2016a). More recent work shows that amygdala reactivity is also dampened by low to moderate doses of ethyl alcohol (Hur et al, 2018), a well-established anxiolytic that, like the benzodiazepines, enhances inhibitory neurotransmission in the Ce (Bartholow, Henry, Lust, Saults, & Wood, 2012; Kaye, Bradford, Magruder, & Curtin, 2017; Sharko, Kaigler, Fadel, & Wilson, 2016). These observations suggest that the amygdala causally contributes to pathological anxiety in humans, consistent with the mechanistic work reviewed in the prior section.…”

Section: The Nature Consequences and Neurobiology Of Dispositional mentioning

confidence: 99%

“…Although investigators need to be cautious when assigning specific labels (e.g., Ce) to activation clusters in imaging studies, we encourage them to describe the relative position of activation peaks (e.g., dorsal-posterior amygdala) and interpret their results on the basis of the most likely sub-component of the amygdala (e.g., ‘in the region of the Ce’). The use of high-field MRI or specialized analytic approaches (e.g., spatially unsmoothed data) may also prove useful (Fox & Shackman, 2019; Hur et al, 2018; Tillman et al, 2018).…”

Section: Future Challengesmentioning

confidence: 99%

Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

Hur

Stockbridge

Fox

et al. 2019

Progress in Brain Research

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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.

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“…Anatomical Data Processing.-Methods are similar to those described in recent reports by our group (Hur, et al, 2018;Smith, Monterosso, Wakslak, Bechara, & Read, 2018;Tillman, et al, 2018) and others (Meyer, Padmala, & Pessoa, 2017;Najafi, Kinnison, & Pessoa, 2017) and are only briefly summarized here. T1-weighted images were inhomogeneity-corrected using N4 (Tustison, et al, 2014), brain-extracted, and spatially normalized to the 1-mm MNI152 template using the high-precision diffeomorphic approach implemented in ANTS (Avants, Epstein, Grossman, & Gee, 2008;Avants, et al, 2011;Avants, et al, 2010;Iglesias, Liu, Thompson, & Tu, 2011).…”

Section: Mri Data Processingmentioning

confidence: 99%

Striatal bases of temporal discounting in early adolescents

et al. 2020

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Steeper rates of temporal discounting-the degree to which smaller-sooner (SS) rewards are preferred over larger-later (LL) ones-have been associated with impulsive and ill-advised behaviors in adolescence. Yet, the underlying neural systems remain poorly understood. Here we used a well-established temporal discounting paradigm and functional MRI (fMRI) to examine engagement of the striatum-including the caudate, putamen, and ventral striatum (VS)-in early adolescence (13-15 years; N=27). Analyses provided evidence of enhanced activity in the caudate and VS during impulsive choice. Exploratory analyses revealed that trait impulsivity was associated with heightened putamen activity during impulsive choices. A more nuanced pattern was evident in the cortex, with the dorsolateral prefrontal cortex mirroring the putamen and posterior parietal cortex showing the reverse association. Taken together, these observations provide an important first glimpse at the distributed neural systems underlying economic choice and trait-like individual differences in impulsivity in the early years of adolescence, setting the stage for prospective-longitudinal and intervention research.

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Acute alcohol administration dampens central extended amygdala reactivity

Cited by 25 publications

References 92 publications

Anxiety and the neurobiology of temporally uncertain threat anticipation

Anxiety and the neurobiology of temporally uncertain threat anticipation

Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

Striatal bases of temporal discounting in early adolescents

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