Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study

Ganella, Despina E.; Drummond, Katherine; Ganella, Eleni P.; Whittle, Sarah; Kim, Jee Hyun

doi:10.3389/fnhum.2017.00647

Cited by 57 publications

(42 citation statements)

References 60 publications

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“…The PCC, perhaps best known for being a hub of the default mode network,is highly connected to many subcortical and cortical regions involved in emotion processing and also part of the dorsal attention network. The PCC has numerous functions that may be implicated in social anxiety, including self‐referential processing (Northoff et al, ), cognitive control (Leech, Kamourieh, Beckmann, & Sharp, ), and fear extinction recall (Ganella, Drummond, Ganella, Whittle, & Kim, ); however, future studies will be necessary to dissect the role of BNST–PCC connectivity in social anxiety.…”

Section: Discussionmentioning

confidence: 99%

Social anxiety is associated with BNST response to unpredictability

et al. 2019

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Background: Anxiety disorders are highly prevalent and cause substantial suffering and impairment. Whereas the amygdala has well-established contributions to anxiety, evidence from rodent and nonhuman primate models suggests that the bed nucleus of the stria terminalis (BNST) may play a critical, and possibly distinct, role in human anxiety disorders. The BNST mediates hypervigilance and anticipatory anxiety in response to an unpredictable or ambiguous threat, core symptoms of social anxiety, yet little is known about the BNST's role in social anxiety.Methods: Functional magnetic resonance imaging was used to measure neural responses during a cued anticipation task with an unpredictable, predictable threat, and predictable neutral cues followed by threat or neutral images. Social anxiety was examined using a dimensional approach (N = 44 adults).Results: For unpredictable cues, higher social anxiety was associated with lower BNST-amygdala connectivity. For unpredictable images, higher social anxiety was associated with greater connectivity between the BNST and both the ventromedial prefrontal cortex and the posterior cingulate cortex and lower connectivity between the BNST and postcentral gyrus. Social anxiety moderated the BNST-amygdala dissociation for unpredictable images; higher social anxiety was associated with BNST > amygdala response to unpredictable threat relative to unpredictable neutral images.Conclusions: Social anxiety was associated with alterations in BNST responses to unpredictability, particularly in the BNST's interactions with other brain regions, including the amygdala and prefrontal cortex. To our knowledge, these findings provide the first evidence for the BNST's role in social anxiety, which may be a potential new target for prevention and intervention.

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Section: Discussionmentioning

confidence: 99%

Social anxiety is associated with BNST response to unpredictability

et al. 2019

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“…Several lines of evidence suggest that alterations in attention, memory, and learning contribute to the etiology and maintenance of PTSD symptoms (Liberzon and Abelson, 2016;Lissek and van Meurs, 2015). Interestingly, while fear learning emerges early in life, fear memories undergo dynamic changes during adolescence (Baker and Richardson, 2015;Ganella et al, 2017;King et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Developmental regulation of fear memories by an obesogenic high-saturated fat/high-sugar diet

Vega-Torres

Reyes-Rivera

Figueroa

2019

Preprint

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Background: Anxiety and stress-related disorders are strongly linked with obesity and the consumption of obesogenic diets. Paralleling clinical findings, we showed that the consumption of an obesogenic diet during adolescence disrupts the structural integrity of amygdalar and prefrontal cortex circuits underlying emotional responses to stress. These abnormalities were associated with a PTSD-like phenotype, including heightened stress reactivity to predator odor trauma, anxietylike behaviors, and profound learning deficits. The present follow-up study investigates how an obesogenic diet alters aversion-related associative memories across adolescence. Methods: Adolescent Lewis rats were fed for eight weeks with an experimentalWestern-like high-saturated fat/high-sugar diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). Acoustic fear-potentiated startle (FPS) responses were assessed longitudinally at weeks 1, 4, and 8 after commencing the diets to determine the effects of the WD on cued fear conditioning, fear extinction learning, and fear extinction retention. Results:We found that the rats that consumed the WD exhibited substantial attenuation of fear extinction and fear extinction retention when remote memory was tested. One-week WD consumption was sufficient to induce impairments in fear extinction learning. This phenotype was associated with reduced dopamine receptor 1 mRNA levels in the prefrontal cortex. Interestingly, our reconditioning paradigm revealed that early-acquired fear memories were resistant to the disruptive effects of chronic WD consumption on cued fear learning. Vega-Torres et. al., 3Conclusions: Our findings demonstrate that consumption of an obesogenic WD during adolescence heightens behavioral vulnerabilities associated with risk for anxiety and stress-related disorders. Given that fear extinction promotes resilience and that fear extinction principles are the foundation of psychological treatments for PTSD, understanding how obesity and obesogenic diets affect the acquisition and expression of fear extinction memories is of tremendous clinical relevance. HIGHLIGHTS• Acute WD consumption impairs cued fear extinction learning in a fearpotentiated startle paradigm.• WD consumption attenuates fear extinction memory retention • WD consumption during adolescence increases acoustic startle responsivity over time • Chronic WD consumption decreases dopamine receptor D1 mRNA levels in the prefrontal cortex.

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“…Chambers, Taylor, & Potenza, ; Flores, Morales‐Medina, & Diaz, ; Spear, ; Volkow & Morales, ). Although the biological bases for this vulnerability are uncertain, they could be related to the natural maturation of the brain during adolescence (Andersen, Thompson, Rutstein, Hostetter, & Teicher, ; Ganella, Drummond, Ganella, Whittle, & Kim, ; Gogtay et al, ; Kim, Perry, Ganella, & Madsen, ; Rakic, Bourgeois, Eckenhoff, Zecevic, & Goldman‐Rakic, ; Sowell, Thompson, & Toga, ).…”

Section: Introductionmentioning

confidence: 99%

Postnatal developmental trajectory of dopamine receptor 1 and 2 expression in cortical and striatal brain regions

Cullity

Madsen

Perry

et al. 2018

J of Comparative Neurology

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Healthy brain function requires a balance between the activity of dopamine receptor 1 (D1) and dopamine receptor 2 (D2). Alterations in this balance increase the risk for numerous developmental brain disorders. Indeed, D1 and D2 expression fluctuates throughout maturation, although there is conflicting evidence regarding the precise changes that occur. Here, we used stereology to investigate the developmental changes in the number of D1‐ or D2‐expressing neurons in the prelimbic cortex, infralimbic cortex (IL), insula cortex, dorsal striatum, and ventral striatum of female and male mice with green fluorescent protein‐tagged D1 or D2. Postnatal day 17, 25, 35, 49, and 70 were examined to cover juvenility to adulthood. In all regions, analysis of D1 density compared to D2 density within each sex seldom detected effects or interactions involving age. However, D1:D2 density ratio changed across age depending on sex. In the IL, D1:D2 density ratio increased in females from adolescence, whereas it was stable in males. In the insula cortex, D1:D2 ratio initially increased in males but decreased in females from juvenility to preadolescence. The ratio then increased in males and females from adolescence to adulthood, with males showing a more dramatic increase. In both the dorsal and ventral striatum, the ratio increased from adolescence. In all regions, females had a higher ratio compared to males throughout maturation except in the insula cortex at P25. These comprehensive observations are novel, and highlight how the maturational changes in the expression of these receptors may contribute to developmental disorders.

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Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study

Cited by 57 publications

References 60 publications

Social anxiety is associated with BNST response to unpredictability

Social anxiety is associated with BNST response to unpredictability

Developmental regulation of fear memories by an obesogenic high-saturated fat/high-sugar diet

Postnatal developmental trajectory of dopamine receptor 1 and 2 expression in cortical and striatal brain regions

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