| 1. |
- Walton, Esther, et al.
(författare)
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Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa : A Coordinated Analysis by the ENIGMA Eating Disorders Working Group
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 92:9, s. 730-738
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and de-pendencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data.METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251).RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of un-dernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients.CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.
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| 2. |
- Dunsmoor, Joseph E., et al.
(författare)
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Extinction in multiple virtual reality contexts diminishes fear reinstatement in humans
- 2014
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Ingår i: Neurobiology of Learning and Memory. - : Elsevier BV. - 1074-7427 .- 1095-9564. ; 113:0, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Although conditioned fear can be effectively extinguished by unreinforced exposure to a threat cue, fear responses tend to return when the cue is encountered some time after extinction (spontaneous recovery), in a novel environment (renewal), or following presentation of an aversive stimulus (reinstatement). As extinction represents a context-dependent form of new learning, one possible strategy to circumvent the return of fear is to conduct extinction across several environments. Here, we tested the effectiveness of multiple context extinction in a two-day fear conditioning experiment using 3-D virtual reality technology to create immersive, ecologically-valid context changes. Fear-potentiated startle served as the dependent measure. All three experimental groups initially acquired fear in a single context. A multiple extinction group then underwent extinction in three contexts, while a second group underwent extinction in the acquisition context and a third group underwent extinction in a single different context. All groups returned 24 h later to test for return of fear in the extinction context (spontaneous recovery) and a novel context (renewal and reinstatement/test). Extinction in multiple contexts attenuated reinstatement of fear but did not reduce spontaneous recovery. Results from fear renewal were tendential. Our findings suggest that multi-context extinction can reduce fear relapse following an aversive event – an event that often induces return of fear in real-world settings – and provides empirical support for conducting exposure-based clinical treatments across a variety of environments.
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| 3. |
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| 4. |
- Åhs, Fredrik, et al.
(författare)
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Medial prefrontal pathways for the contextual regulation of extinguished fear in humans
- 2015
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 122, s. 262-271
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Tidskriftsartikel (refereegranskat)abstract
- The maintenance of anxiety disorders is thought to depend, in part, on deficits in extinction memory, possibly due to reduced contextual control of extinction that leads to fear renewal. Animal studies suggest that the neural circuitry responsible fear renewal includes the hippocampus, amygdala, and dorsomedial (dmPFC) and ventromedial (vmPFC) prefrontal cortex. However, the neural mechanisms of context-dependent fear renewal in humans remain poorly understood. We used functional magnetic resonance imaging (fMRI), combined with psychophysiology and immersive virtual reality, to elucidate how the hippocampus, amygdala, and dmPFC and vmPFC interact to drive the context-dependent renewal of extinguished fear. Healthy human participants encountered dynamic fear-relevant conditioned stimuli (CSs) while navigating through 3-D virtual reality environments in the MRI scanner. Conditioning and extinction were performed in two different virtual contexts. Twenty-four hours later, participants were exposed to the CSs without reinforcement while navigating through both contexts in the MRI scanner. Participants showed enhanced skin conductance responses (SCRs) to the previously-reinforced CS + in the acquisition context on Day 2, consistent with fear renewal, and sustained responses in the dmPFC. In contrast, participants showed low SCRs to the CSs in the extinction context on Day 2, consistent with extinction recall, and enhanced vmPFC activation to the non-reinforced CS -. Structural equation modeling revealed that the dmPFC fully mediated the effect of the hippocampus on right amygdala activity during fear renewal, whereas the vmPFC partially mediated the effect of the hippocampus on right amygdala activity during extinction recall. These results indicate dissociable contextual influences of the hippocampus on prefrontal pathways, which, in turn, determine the level of reactivation of fear associations.
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| 5. |
- Åhs, Fredrik, et al.
(författare)
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Spatial proximity amplifies valence in emotional memory and defensive approach-avoidance
- 2015
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Ingår i: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 70, s. 476-85
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Tidskriftsartikel (refereegranskat)abstract
- In urban areas, people often have to stand or move in close proximity to others. The egocentric distance to stimuli is a powerful determinant of defensive behavior in animals. Yet, little is known about how spatial proximity to others alters defensive responses in humans. We hypothesized that the valence of social cues scales with egocentric distance, such that proximal social stimuli have more positive or negative valence than distal stimuli. This would predict enhanced defensive responses to proximal threat and reduced defensive responses to proximal reward. We tested this hypothesis across four experiments using 3-D virtual reality simulations. Results from Experiment 1 confirmed that proximal social stimuli facilitate defensive responses, as indexed by fear-potentiated startle, relative to distal stimuli. Experiment 2 revealed that interpersonal defensive boundaries flexibly increase with aversive learning. Experiment 3 examined whether spatial proximity enhances memory for aversive experiences. Fear memories for social threats encroaching on the body were more persistent than those acquired at greater interpersonal distances, as indexed by startle. Lastly, Experiment 4 examined how egocentric distance influenced startle responses to social threats during defensive approach and avoidance. Whereas fear-potentiated startle increased with proximity when participants actively avoided receiving shocks, startle decreased with proximity when participants tolerated shocks to receive monetary rewards, implicating opposing gradients of distance on threat versus reward. Thus, proximity in egocentric space amplifies the valence of social stimuli that, in turn, facilitates emotional memory and approach-avoidance responses. These findings have implications for understanding the consequences of increased urbanization on affective interpersonal behavior.
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