- Email: [email protected]
125. Alterations in the Neurobehavioral Mechanisms of Fear Extinction and Extinction Recall in Specific Phobia
Biological Psychiatry
Thursday Abstracts
Results: All scents were perceived as negative in valance. The groups did not differ in LPP amplitude or behavioral ratings prior to treatment. In the veteran group, increased pre-treatment Clinician-Administered PTSD Scale (CAPS) Hyperarousal scores related to an increased early window LPP amplitude in response to the diesel fuel scent (β 5 .52, p 5 .004). Veterans with larger pre-treatment LPP amplitudes across scents showed larger pre- to posttreatment reduction in the CAPS Hyperarousal score, after covarying for pre-treatment CAPS Hyperarousal scores, r(20) 5 2.42, p 5 .05. Conclusions: There were no group-level relationships or treatment changes with behavioral ratings or LPP amplitudes. However, a larger amplitude LPP response to negatively-valanced scents prior to treatment was related to greater improvement in hyperarousal symptoms from the exposure-based treatment. It is possible that emotional responsivity to negative odors may serve as a treatment response moderator in combat veterans with PTSD, particularly for hyperarousal symptoms. Supported By: U.S. Army Military Operations Medical Research Program (08214003) Keywords: PTSD - Posttraumatic Stress Disorder, olfaction, Event-related Potentials, late positive potential, Hyperarousal
124. Functional Architecture of Central Extended Amygdala Networks Rachael Tillman1, Melissa Stockbridge1, Brendon Nacewicz2, Jason Smith1, and Alexander Shackman1 1
University of Maryland - College Park, Wisconsin-Madison
2
University of
Background: The central extended amygdala (EAc)—a circuit encompassing the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a critical 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 neural networks, the functional architecture of the extended amygdala network remains poorly understood. Methods: The use of higher-resolution (2-mm3; no spatial smoothing) ‘resting-state’ multiband fMRI acquired from a large sample of community-dwelling adults (n 5 185; n 5 130 usable; 18-40 years), cutting-edge spatial registration techniques (BBR, SyN/ANTS), and newly developed, anatomically precise seeds, allowed us to compute the intrinsic functional connectivity of the BST and Ce with an unparalleled combination of robustness and specificity. Results: Whole-brain analyses revealed that both poles of the EAc show robust functional connectivity with one another via the sublenticular extended amygdala (‘substantia innominata’), the gray matter region encompassing the amygdalofugal pathway (all ps,.0001, Šidák corrected). Both regions also showed significant vmPFC coupling. BST showed strong connectivity with cingulate territories involved in the adaptive control of anxiety-related behavior (MCC, pgACC), while Ce
S52
showed significant coupling with neighboring amygdala nuclei, anterior hippocampus, and regions of the ventral visual processing stream involved in social processing (e.g. STS). Conclusions: These observations provide a novel neurobiological framework for understanding a range of stresssensitive disorders and set the stage for mechanistic work aimed at developing more effective intervention strategies. Supported By: This was supported by the National Institutes of Health (DA040717, MH107444), University of Wisconsin, and University of Maryland Keywords: Addiction, Amygdala, fear and anxiety, fMRI, extended amygdala (CeA/BST)
125. Alterations in the Neurobehavioral Mechanisms of Fear Extinction and Extinction Recall in Specific Phobia Iris Lange, Liesbet Goossens, Stijn Michielse, Jindra Bakker, Therese van Amelsvoort, and Koen Schruers Maastricht University Background: Fear extinction is the decrease in conditioned fear responses occurring with repeated presentation of a conditioned threat stimulus without reinforcement. Exposurebased treatments are thought to rely on extinction learning mechanisms. Clinical anxiety is however associated with a failure in this process, which may result in the maintenance of conditioned fear responses, and a lower response to therapy. The current study provides novel unpublished data examining whether individuals with a specific phobia (model disorder for excessive fear) show alterations in the neurobehavioral mechanisms of fear extinction and extinction recall. Methods: Individuals aged 16-25 with a spider phobia (SP; n 5 37) and healthy controls (HC; n 5 37) were included. All individuals underwent a 3-day fMRI fear conditioning, extinction and extinction recall paradigm with geometrical shapes as conditioned threat (CS1) and safety (CS-) stimuli. Generalization stimuli (GS) were additionally shown during extinction recall. Fear, valence, shock expectancy and blood-oxygen-level-dependent responses were measured. Results: Results show a trend for a smaller increase in valence for the CS1 from pre-to-post extinction in SP compared to HC (p 5 .08), suggesting impaired extinction learning in SP. Further, a smaller decrease in valence from end of extinction to recall for the CS1 was found for SP, reflecting better extinction retention (p 5 .04). At extinction recall, SP tended to reported higher shock expectancy for GS than HC (p 5 .08). Neuroimaging data show results in the fear extinction network, including the vmPFC, hippocampus, and amygdala. Conclusions: The results point towards impaired extinction learning and reduced safety processing during extinction recall in specific phobia. Supported By: Stichting De Weijerhorst Keywords: Extinction Learning and Recall, Phobia, fMRI
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
Biological Psychiatry
Thursday Abstracts
126. Irritability and Amygdala-Ventral Prefrontal Cortex Connectivity in Children with High Functioning Autism Spectrum Disorder Cynthia Kiefer1, Maria Kryza-Lacombe2, Katrina Cole1, Catherine Lord3, Christopher Monk3, and Jillian Lee Wiggins4 1
Department of Psychology, San Diego State University, SDSU/UCSD Joint Doctoral Program in Clinical Psychology, 3University of Michigan, Department of Psychology, 4 SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego State University 2
Background: Irritability is a common, highly impairing symptom among youth with high functioning autism spectrum disorder (HF-ASD) and predicts long-term adverse outcomes. Impaired processing of emotional faces, found in both autism and irritability, may lead to inappropriate social responses. Indeed, amygdala hyperactivation elicited by emotional faces has been found in autism and irritability in other diagnoses (i.e., bipolar disorder, disruptive mood dysregulation disorder). Yet, little is known about the neural correlates of irritability in HF-ASD, nor how other brain regions within amygdala networks may relate to irritability within HF-ASD. To characterize neural correlates of irritability in HF-ASD, this study investigated amygdala functional connectivity. Methods: Children with HF-ASD (N 5 33, aged 8-19 years) performed an implicit face emotion processing task during fMRI acquisition, in which participants identified the gender of faces with happy, sad, fearful, and neutral expressions. Wholebrain amygdala functional connectivity across emotions was calculated for each individual and correlated with an irritabilitylike measure, the Aggressive Behavior subscale of the Child Behavior Checklist (CBCL), which includes items (e.g., “temper tantrums or hot temper”) shown to comprise an irritability factor conceptualized as low threshold for anger. Results: Whole-brain analyses revealed alterations in right amygdala to ventral prefrontal cortex functional connectivity, which correlated with the irritability-like subscale of the CBCL. Worse irritability-like symptoms related to greater amygdalaprefrontal cortex connectivity (xyz 5 34,62,-2, t(31) 5 3.12, p,.05, k 5 80). Conclusions: Results suggest that the neural substrates of irritability in HF-ASD include amygdala-prefrontal cortex dysfunction, providing evidence that faces may elicit emotion dysregulation in autism, which may lead to irritability. Supported By: Autism Speaks (C.S.M.) and the National Institutes of Health grants U19 HD035482 and MH066496 Keywords: High-functioning autism, Amygdala, fMRI, Functional connectivity, Irritability
Boys Town National Research Hospital, 2Creighton University; University of Nebraska Medical Center, 3Boys Town National Research Hospital; University of Nebraska Medical Center 1
Background: Youth displaying disruptive behavior show amygdala hypo-responsiveness to fearful expressions as a function of a callous-unemotional (CU) personality (i.e., reduced guilt and empathy). This has been related to increased levels of goal-directed antisocial behavior and instrumental aggression. However, some research suggests that trauma exposure may moderate this relationship. Specifically, work has identified two groups of disruptive youth with equivalent high levels of CU-traits, but differing levels of anxiety and trauma exposure. Methods: The objective of the first of two studies was to examine whether trauma exposure influenced the neurobiology underlying fear expression processing in 72 youth with varying levels of disruptive behavior and trauma exposure. Participants performed a gender discrimination task while viewing morphed expressions (0%, 50%, 100%, 150% fear). A linear regression analysis was performed on the BOLD data, using level of CU-traits and trauma exposure as covariates. The second study aimed at examining how the neurobiology underpinning fear expression processing predicted social behavior as a function of trauma exposure. Participants were invited back to complete a social goals task. Results: A significant CU-traits-by-trauma exposure interaction on fear intensity processing within right amygdala was found; CU-traits were negatively associated with fear intensity modulated amygdala responses, but only in low trauma participants. Our second study suggests that stronger fear responsivity in the amygdala predicts prosocial behavior in low trauma youth, whereas stronger fear responsivity predicts non-social behavior (revenge) in high trauma youth. Conclusions: The current data suggest that the pathophysiology associated with CU-personality may depend on trauma exposure. Supported By: Boys Town National Research Hospital Keywords: Disruptive Behavior Disorders, CallousUnemotional Traits, Emotion, Fear, Trauma
128. Dysfunction in Animacy Information Processing in Adolescents with Disruptive Behavior Disorders and Callous-Unemotional Traits Laura Thornton1, Elizabeth Penner2, Kathleen Crum1, Zachary Nolan3, Christopher Adalio4, Stephen Sinclair5, Harma Meffert1, Soonjo Hwang2, R. James Blair6, and Stuart White1 Boys Town National Research Hospital, 2University of Nebraska Medical Center, 3Pennsylvania State University School of Medicine, 4University of California Berkeley, 5 Section on Affective Cognitive Neuroscience, NIMH, NIH, 6Section on Affective Cognitive Neuroscience, NIMH, NIH; Boys Town National Research Hospital
1
127. Amygdala Response to Distress Cues and CallousUnemotional Personality: Moderation by Trauma Harma Meffert1, Kathleen Crum1, Patrick Tyler1, Mary Botkin1, Anna Erway1, Venkata Kolli2, Stuart White1, Kayla Pope3, and R. James Blair1
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
S53
Thursday Abstracts
Results: All scents were perceived as negative in valance. The groups did not differ in LPP amplitude or behavioral ratings prior to treatment. In the veteran group, increased pre-treatment Clinician-Administered PTSD Scale (CAPS) Hyperarousal scores related to an increased early window LPP amplitude in response to the diesel fuel scent (β 5 .52, p 5 .004). Veterans with larger pre-treatment LPP amplitudes across scents showed larger pre- to posttreatment reduction in the CAPS Hyperarousal score, after covarying for pre-treatment CAPS Hyperarousal scores, r(20) 5 2.42, p 5 .05. Conclusions: There were no group-level relationships or treatment changes with behavioral ratings or LPP amplitudes. However, a larger amplitude LPP response to negatively-valanced scents prior to treatment was related to greater improvement in hyperarousal symptoms from the exposure-based treatment. It is possible that emotional responsivity to negative odors may serve as a treatment response moderator in combat veterans with PTSD, particularly for hyperarousal symptoms. Supported By: U.S. Army Military Operations Medical Research Program (08214003) Keywords: PTSD - Posttraumatic Stress Disorder, olfaction, Event-related Potentials, late positive potential, Hyperarousal
124. Functional Architecture of Central Extended Amygdala Networks Rachael Tillman1, Melissa Stockbridge1, Brendon Nacewicz2, Jason Smith1, and Alexander Shackman1 1
University of Maryland - College Park, Wisconsin-Madison
2
University of
Background: The central extended amygdala (EAc)—a circuit encompassing the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a critical 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 neural networks, the functional architecture of the extended amygdala network remains poorly understood. Methods: The use of higher-resolution (2-mm3; no spatial smoothing) ‘resting-state’ multiband fMRI acquired from a large sample of community-dwelling adults (n 5 185; n 5 130 usable; 18-40 years), cutting-edge spatial registration techniques (BBR, SyN/ANTS), and newly developed, anatomically precise seeds, allowed us to compute the intrinsic functional connectivity of the BST and Ce with an unparalleled combination of robustness and specificity. Results: Whole-brain analyses revealed that both poles of the EAc show robust functional connectivity with one another via the sublenticular extended amygdala (‘substantia innominata’), the gray matter region encompassing the amygdalofugal pathway (all ps,.0001, Šidák corrected). Both regions also showed significant vmPFC coupling. BST showed strong connectivity with cingulate territories involved in the adaptive control of anxiety-related behavior (MCC, pgACC), while Ce
S52
showed significant coupling with neighboring amygdala nuclei, anterior hippocampus, and regions of the ventral visual processing stream involved in social processing (e.g. STS). Conclusions: These observations provide a novel neurobiological framework for understanding a range of stresssensitive disorders and set the stage for mechanistic work aimed at developing more effective intervention strategies. Supported By: This was supported by the National Institutes of Health (DA040717, MH107444), University of Wisconsin, and University of Maryland Keywords: Addiction, Amygdala, fear and anxiety, fMRI, extended amygdala (CeA/BST)
125. Alterations in the Neurobehavioral Mechanisms of Fear Extinction and Extinction Recall in Specific Phobia Iris Lange, Liesbet Goossens, Stijn Michielse, Jindra Bakker, Therese van Amelsvoort, and Koen Schruers Maastricht University Background: Fear extinction is the decrease in conditioned fear responses occurring with repeated presentation of a conditioned threat stimulus without reinforcement. Exposurebased treatments are thought to rely on extinction learning mechanisms. Clinical anxiety is however associated with a failure in this process, which may result in the maintenance of conditioned fear responses, and a lower response to therapy. The current study provides novel unpublished data examining whether individuals with a specific phobia (model disorder for excessive fear) show alterations in the neurobehavioral mechanisms of fear extinction and extinction recall. Methods: Individuals aged 16-25 with a spider phobia (SP; n 5 37) and healthy controls (HC; n 5 37) were included. All individuals underwent a 3-day fMRI fear conditioning, extinction and extinction recall paradigm with geometrical shapes as conditioned threat (CS1) and safety (CS-) stimuli. Generalization stimuli (GS) were additionally shown during extinction recall. Fear, valence, shock expectancy and blood-oxygen-level-dependent responses were measured. Results: Results show a trend for a smaller increase in valence for the CS1 from pre-to-post extinction in SP compared to HC (p 5 .08), suggesting impaired extinction learning in SP. Further, a smaller decrease in valence from end of extinction to recall for the CS1 was found for SP, reflecting better extinction retention (p 5 .04). At extinction recall, SP tended to reported higher shock expectancy for GS than HC (p 5 .08). Neuroimaging data show results in the fear extinction network, including the vmPFC, hippocampus, and amygdala. Conclusions: The results point towards impaired extinction learning and reduced safety processing during extinction recall in specific phobia. Supported By: Stichting De Weijerhorst Keywords: Extinction Learning and Recall, Phobia, fMRI
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
Biological Psychiatry
Thursday Abstracts
126. Irritability and Amygdala-Ventral Prefrontal Cortex Connectivity in Children with High Functioning Autism Spectrum Disorder Cynthia Kiefer1, Maria Kryza-Lacombe2, Katrina Cole1, Catherine Lord3, Christopher Monk3, and Jillian Lee Wiggins4 1
Department of Psychology, San Diego State University, SDSU/UCSD Joint Doctoral Program in Clinical Psychology, 3University of Michigan, Department of Psychology, 4 SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego State University 2
Background: Irritability is a common, highly impairing symptom among youth with high functioning autism spectrum disorder (HF-ASD) and predicts long-term adverse outcomes. Impaired processing of emotional faces, found in both autism and irritability, may lead to inappropriate social responses. Indeed, amygdala hyperactivation elicited by emotional faces has been found in autism and irritability in other diagnoses (i.e., bipolar disorder, disruptive mood dysregulation disorder). Yet, little is known about the neural correlates of irritability in HF-ASD, nor how other brain regions within amygdala networks may relate to irritability within HF-ASD. To characterize neural correlates of irritability in HF-ASD, this study investigated amygdala functional connectivity. Methods: Children with HF-ASD (N 5 33, aged 8-19 years) performed an implicit face emotion processing task during fMRI acquisition, in which participants identified the gender of faces with happy, sad, fearful, and neutral expressions. Wholebrain amygdala functional connectivity across emotions was calculated for each individual and correlated with an irritabilitylike measure, the Aggressive Behavior subscale of the Child Behavior Checklist (CBCL), which includes items (e.g., “temper tantrums or hot temper”) shown to comprise an irritability factor conceptualized as low threshold for anger. Results: Whole-brain analyses revealed alterations in right amygdala to ventral prefrontal cortex functional connectivity, which correlated with the irritability-like subscale of the CBCL. Worse irritability-like symptoms related to greater amygdalaprefrontal cortex connectivity (xyz 5 34,62,-2, t(31) 5 3.12, p,.05, k 5 80). Conclusions: Results suggest that the neural substrates of irritability in HF-ASD include amygdala-prefrontal cortex dysfunction, providing evidence that faces may elicit emotion dysregulation in autism, which may lead to irritability. Supported By: Autism Speaks (C.S.M.) and the National Institutes of Health grants U19 HD035482 and MH066496 Keywords: High-functioning autism, Amygdala, fMRI, Functional connectivity, Irritability
Boys Town National Research Hospital, 2Creighton University; University of Nebraska Medical Center, 3Boys Town National Research Hospital; University of Nebraska Medical Center 1
Background: Youth displaying disruptive behavior show amygdala hypo-responsiveness to fearful expressions as a function of a callous-unemotional (CU) personality (i.e., reduced guilt and empathy). This has been related to increased levels of goal-directed antisocial behavior and instrumental aggression. However, some research suggests that trauma exposure may moderate this relationship. Specifically, work has identified two groups of disruptive youth with equivalent high levels of CU-traits, but differing levels of anxiety and trauma exposure. Methods: The objective of the first of two studies was to examine whether trauma exposure influenced the neurobiology underlying fear expression processing in 72 youth with varying levels of disruptive behavior and trauma exposure. Participants performed a gender discrimination task while viewing morphed expressions (0%, 50%, 100%, 150% fear). A linear regression analysis was performed on the BOLD data, using level of CU-traits and trauma exposure as covariates. The second study aimed at examining how the neurobiology underpinning fear expression processing predicted social behavior as a function of trauma exposure. Participants were invited back to complete a social goals task. Results: A significant CU-traits-by-trauma exposure interaction on fear intensity processing within right amygdala was found; CU-traits were negatively associated with fear intensity modulated amygdala responses, but only in low trauma participants. Our second study suggests that stronger fear responsivity in the amygdala predicts prosocial behavior in low trauma youth, whereas stronger fear responsivity predicts non-social behavior (revenge) in high trauma youth. Conclusions: The current data suggest that the pathophysiology associated with CU-personality may depend on trauma exposure. Supported By: Boys Town National Research Hospital Keywords: Disruptive Behavior Disorders, CallousUnemotional Traits, Emotion, Fear, Trauma
128. Dysfunction in Animacy Information Processing in Adolescents with Disruptive Behavior Disorders and Callous-Unemotional Traits Laura Thornton1, Elizabeth Penner2, Kathleen Crum1, Zachary Nolan3, Christopher Adalio4, Stephen Sinclair5, Harma Meffert1, Soonjo Hwang2, R. James Blair6, and Stuart White1 Boys Town National Research Hospital, 2University of Nebraska Medical Center, 3Pennsylvania State University School of Medicine, 4University of California Berkeley, 5 Section on Affective Cognitive Neuroscience, NIMH, NIH, 6Section on Affective Cognitive Neuroscience, NIMH, NIH; Boys Town National Research Hospital
1
127. Amygdala Response to Distress Cues and CallousUnemotional Personality: Moderation by Trauma Harma Meffert1, Kathleen Crum1, Patrick Tyler1, Mary Botkin1, Anna Erway1, Venkata Kolli2, Stuart White1, Kayla Pope3, and R. James Blair1
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
S53