Publications by authors named "Josh M Cisler"

71 Publications

Transcranial direct current stimulation targeting the medial prefrontal cortex modulates functional connectivity and enhances safety learning in obsessive-compulsive disorder: Results from two pilot studies.

Depress Anxiety 2021 Aug 31. Epub 2021 Aug 31.

Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut, USA.

Background: Exposed-based psychotherapy is a mainstay of treatment for obsessive-compulsive disorder (OCD) and anxious psychopathology. The medial prefrontal cortex (mPFC) and the default mode network (DMN), which is anchored by the mPFC, promote safety learning. Neuromodulation targeting the mPFC might augment therapeutic safety learning and enhance response to exposure-based therapies.

Methods: To characterize the effects of mPFC neuromodulation on functional connectivity, 17 community volunteers completed resting-state functional magnetic resonance imaging scans before and after 20 min of frontopolar anodal multifocal transcranial direct current stimulation (tDCS). To examine the effects of tDCS on therapeutic safety learning, 24 patients with OCD completed a pilot randomized clinical trial; they were randomly assigned (double-blind, 50:50) to receive active or sham frontopolar tDCS before completing an in vivo exposure and response prevention (ERP) challenge. Changes in subjective emotional distress during the ERP challenge were used to index therapeutic safety learning.

Results: In community volunteers, frontal pole functional connectivity with the middle and superior frontal gyri increased, while connectivity with the anterior insula and basal ganglia decreased (ps < .001, corrected) after tDCS; functional connectivity between DMN and salience network also decreased after tDCS (ps < .001, corrected). OCD patients who received active tDCS exhibited more rapid therapeutic safety learning (ps < .05) during the ERP challenge than patients who received sham tDCS.

Conclusions: Frontopolar tDCS may modulate mPFC and DMN functional connectivity and can accelerate therapeutic safety learning. Though limited by small samples, these findings motivate further exploration of the effects of frontopolar tDCS on neural and behavioral targets associated with exposure-based psychotherapies.
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http://dx.doi.org/10.1002/da.23212DOI Listing
August 2021

Value estimation and latent-state update-related neural activity during fear conditioning predict posttraumatic stress disorder symptom severity.

Cogn Affect Behav Neurosci 2021 Aug 26. Epub 2021 Aug 26.

Department of Psychiatry, University of Wisconsin, Madison, WI, USA.

Learning theories of posttraumatic stress disorder (PTSD) purport that fear-learning processes, such as those that support fear acquisition and extinction, are impaired. Computational models designed to capture specific processes involved in fear learning have primarily assessed model-free, or trial-and-error, reinforcement learning (RL). Although previous studies indicated that aspects of model-free RL are disrupted among individuals with PTSD, research has yet to identify whether model-based RL, which is inferential and contextually driven, is impaired. Given empirical evidence of aberrant contextual modulation of fear in PTSD, the present study sought to identify whether model-based RL processes are altered during fear conditioning among women with interpersonal violence (IPV)-related PTSD (n = 85) using computational modeling. Model-free, hybrid, and model-based RL models were applied to skin conductance responses (SCR) collected during fear acquisition and extinction, and the model-based RL model was found to provide the best fit to the SCR data. Parameters from the model-based RL model were carried forward to neuroimaging analyses (voxel-wise and independent component analysis). Results revealed that reduced activity within visual processing regions during model-based updating uniquely predicted higher PTSD symptoms. Additionally, after controlling for model-based updating, greater value estimation encoding within the left frontoparietal network during fear acquisition and reduced value estimation encoding within the dorsomedial prefrontal cortex during fear extinction predicted greater PTSD symptoms. Results provide evidence of disrupted RL processes in women with assault-related PTSD, which may contribute to impaired fear and safety learning, and, furthermore, may relate to treatment response (e.g., poorer response to exposure therapy).
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http://dx.doi.org/10.3758/s13415-021-00943-4DOI Listing
August 2021

Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.

Psychoneuroendocrinology 2021 Jul 9;132:105355. Epub 2021 Jul 9.

University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, 1601 Trinity St, Bldg B, Austin, TX 78712, United States.

Introduction: We recently demonstrated that moderate-intensity aerobic exercise delivered during the consolidation of fear extinction learning reduced threat expectancy during a test of extinction recall among women with posttraumatic stress disorder (PTSD). These findings suggest that exercise may be a potential candidate for improving the efficacy of exposure-based therapies, which are hypothesized to work via the mechanisms of fear extinction learning. The purpose of this secondary analysis was to examine whether exercise-induced increases in circulating concentrations of candidate biomarkers: endocannabinoids (anandamide [AEA]; 2-arachidonoylglycerol [2-AG], brain-derived neurotrophic factor (BDNF), and homovanillic acid (HVA), mediate the effects of exercise on extinction recall.

Methods: Participants (N = 35) completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition following extinction training (day 2). Blood was obtained prior to and following EX or CON. Threat expectancy ratings during tests of extinction recall (i.e., initial fear recall and fear recall following reinstatement) were obtained 24 h following EX or CON. Mediation was tested using linear-mixed effects models and bootstrapping of the indirect effect.

Results: Circulating concentrations of AEA and BDNF (but not 2-AG and HVA) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement (AEA 95% CI: -0.623 to -0.005; BDNF 95% CI: -0.941 to -0.005).

Conclusions: Exercise-induced increases in peripheral AEA and BDNF appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD. Future mechanistic research examining these and other biomarkers (e.g., brain-based biomarkers) is warranted.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105355DOI Listing
July 2021

Unique neurocircuitry activation profiles during fear conditioning and extinction among women with posttraumatic stress disorder.

J Psychiatr Res 2021 09 6;141:257-266. Epub 2021 Jul 6.

University of Wisconsin-Madison, USA. Electronic address:

Background: Neurocircuitry models of posttraumatic stress disorder (PTSD) suggest specific alterations in brain structures linked with fear conditioning and extinction. Most models assume a unitary pattern of neurocircuitry dysfunction in PTSD and little attention has focused on defining unique profiles of neurocircuitry engagement (i.e., biotypes), despite known clinical heterogeneity in PTSD. Here, we aim to address this gap using a data-driven approach to characterize unique neurocircuitry profiles among women with PTSD.

Methods: Seventy-six women with PTSD related to assaultive violence exposure competed a task during fMRI that alternated between fear conditioning, where a geometric shape predicted the occurrence of an electric shock, and fear extinction, where the geometric shape no longer predicted electric shock. A multivariate clustering analysis was applied to neurocircuitry patterns constrained within an a priori mask of structures linked with emotion processing. Resulting biotypes were compared on clinical measures of neurocognition, trauma exposure, general mental health symptoms, and PTSD symptoms and on psychophysiological responding during the task.

Results: The clustering analysis identified three biotypes (BT), differentiated by patterns of engagement within salience, default mode, and visual processing networks. BT1 was characterized by higher working memory, fewer general mental health symptoms, and low childhood sexual abuse, and lower PTSD symptom severity. BT2 was characterized by lower verbal IQ but better extinction learning as defined by psychophysiology and threat expectancy. BT3 was characterized by low childhood sexual abuse, anxious arousal, and re-experiencing symptoms.

Conclusion: This data demonstrates unique profiles of neurocircuitry engagement in PTSD, each associated with different clinical characteristics, and suggests further research defining distinct biotypes of PTSD. Clinicaltrials.gov, https://clinicaltrials.gov/ct2/home, NCT02560389.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.007DOI Listing
September 2021

Aerobic exercise reduces anxiety and fear ratings to threat and increases circulating endocannabinoids in women with and without PTSD.

Ment Health Phys Act 2021 Mar 2;20. Epub 2020 Nov 2.

Department of Kinesiology at the University of Wisconsin-Madison, Madison, WI - USA.

Reductions in state anxiety have been reported following an acute bout of aerobic exercise. However, less is known regarding anxiety and fear ratings to specific threatening stimuli following an acute bout of aerobic exercise in women with PTSD. Moreover, the mechanisms responsible for the anxiolytic effects of exercise are not fully understood, although recent studies suggest a role for the endocannabinoid (eCB) system. Thus, this study utilized a randomized, counterbalanced approach to examine anxiety and fear ratings to predictable or unpredictable electric shock administration and circulating concentrations of eCBs and mood states immediately following moderate-intensity aerobic exercise (30 min on treadmill at 70-75% maximum heart rate) and a quiet rest control condition in women with and without a history of trauma, and in women with PTSD (N=42). Results revealed that anxiety and fear ratings to unpredictable and predictable threats were significantly (<.05) lower following exercise compared to quiet rest, with correlational analyses indicating those with greater increases in circulating eCBs had greater reductions in anxiety and fear ratings to unpredictable and predictable threats following exercise. Also, there were significant (<.05) reductions in fatigue, confusion, total mood disturbance, and increases in positive affect following exercise for the entire sample. Non-trauma controls and PTSD groups reported significant (<.05) increases in vigor, with additional mood improvements following exercise for the PTSD group (i.e., decreases in state anxiety, negative affect, tension, anger, and depression). Results from this study suggest that aerobic exercise exerts psychological benefits in women with PTSD, potentially due to exercise-induced increases in circulating concentrations of eCBs.
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http://dx.doi.org/10.1016/j.mhpa.2020.100366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208522PMC
March 2021

Aerobic exercise and consolidation of fear extinction learning among women with posttraumatic stress disorder.

Behav Res Ther 2021 07 27;142:103867. Epub 2021 Apr 27.

University of Wisconsin, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI, 53719-1176, USA. Electronic address:

This study tested whether aerobic exercise delivered during the consolidation window following fear extinction learning reduces the return of fear among women with posttraumatic stress disorder (PTSD). Participants (n=35) completed an initial clinical assessment followed by a 3-day fear acquisition, extinction, and recall protocol. On day 1, participants completed a fear acquisition training task in which one geometric shape (conditioning stimulus; CS+) was paired (with 50% probability) with a mild electric shock (unconditioned stimulus; US), while a different shape (CS-) was never paired with the US. On day 2 (24 h later), participants completed a fear extinction training task in which the CS+ no longer predicted administration of the US. Shortly following extinction, participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity exercise control (CON) condition. On day 3 (24 h later), participants completed fear recall tests assessing the return of fear (spontaneous recovery, renewal, and reinstatement). Fear responding was assessed via threat expectancy ratings and skin conductance responses (SCR). In the threat expectancy ratings, there were no significant differences between groups in spontaneous recovery; however, EX significantly (p=.02) reduced threat expectancy ratings following reinstatement relative to CON. In SCR measures, there were no significant differences between groups in spontaneous recovery, renewal, or reinstatement. These results support a role for moderate-intensity aerobic exercise during the consolidation window in reducing threat expectations following reinstatement in women with PTSD. Research should continue to examine exercise as a potential method for improving the efficacy of exposure-based therapies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04113798.
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http://dx.doi.org/10.1016/j.brat.2021.103867DOI Listing
July 2021

Gray matter volume correlates of adolescent posttraumatic stress disorder: A comparison of manual intervention and automated segmentation in FreeSurfer.

Psychiatry Res Neuroimaging 2021 07 24;313:111297. Epub 2021 Apr 24.

Department of Psychiatry, University of Wisconsin-Madison, Madison, WI United States.

Exposure to early life trauma is common and confers risk for psychological disorders in adolescence, including posttraumatic stress disorder (PTSD). Trauma exposure and PTSD are also consistently linked to alterations in gray matter volume (GMV). Despite the quantity of structural neuroimaging research in trauma-exposed populations, little consensus exists amongst research groups on best practices for image processing method and manual editing procedures. The purpose of this report is to evaluate the utility of manual editing of magnetic resonance (MR) images for detecting PTSD-related group differences in GMV. Here, T1-weighted MR images from adolescent girls aged 11-17 were obtained and analyzed. Two datasets were created from the FreeSurfer reconall pipeline, one of which was manually edited by trained research assistants. Gray matter regions of interest were selected and total volume estimates were entered into linear mixed effects models with method (manual edits or automated) as a within-subjects factor and group dummy-coded with PTSD as the reference group. Consistent with prior literature, individuals with PTSD demonstrated reduced GMV of the amygdala compared to trauma-exposed and non-trauma exposed controls, independent of editing method. Our results demonstrate that amygdala GMV reductions in PTSD are robust to certain methodological choices and do not suggest a benefit to the time-intensive manual editing pipeline in FreeSurfer for quantifying PTSD-related GMV.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205994PMC
July 2021

Differential relationships of PTSD symptom clusters with cortical thickness and grey matter volumes among women with PTSD.

Sci Rep 2021 01 19;11(1):1825. Epub 2021 Jan 19.

Department of Psychiatry, University of WI - Madison, 6001 Research Park Boulevard, Madison, WI, 53719-1176, USA.

Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is more common in women, and interpersonal violence (IPV) exposure is a more potent risk factor for developing PTSD relative to other forms of trauma, most of the existing literature examined combat-exposed men with PTSD. Vertex-wise CT and subcortical GMV analyses were conducted to examine potential differences in a large, well-characterized sample of women with PTSD stemming from IPV-exposure (n = 99) compared to healthy trauma-free women without a diagnosis of PTSD (n = 22). Subgroup analyses were also conducted to determine whether symptom severity within specific PTSD symptom clusters (e.g., re-experiencing, active avoidance, hyperarousal) predict CT and GMV after controlling for comorbid depression and anxiety. Results indicated that a diagnosis of PTSD in women with IPV-exposure did not significantly predict differences in CT across the cortex or GMV in the amygdala or hippocampus compared to healthy controls. However, within the PTSD group, greater re-experiencing symptom severity was associated with decreased CT in the left inferior and middle temporal gyrus, and decreased CT in the right parahippocampal and medial temporal gyrus. In contrast, greater active avoidance symptom severity was associated with greater CT in the left lateral fissure, postcentral gyrus, and middle/lateral occipital cortex, and greater CT in the right paracentral, posterior cingulate, and superior occipital gyrus. In terms of GMV, greater hyperarousal symptom severity was associated with reduced left amygdala GMV, while greater active avoidance symptom severity was associated with greater right amygdala GMV. These findings suggest that structural brain alterations among women with IPV-related PTSD may be driven by symptom severity within specific symptom clusters and that PTSD symptom clusters may have a differential (increased or decreased) association with brain structures.
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http://dx.doi.org/10.1038/s41598-020-80776-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815843PMC
January 2021

Distinct cortical thickness correlates of early life trauma exposure and posttraumatic stress disorder are shared among adolescent and adult females with interpersonal violence exposure.

Neuropsychopharmacology 2021 03 3;46(4):741-749. Epub 2020 Dec 3.

Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.

Early life trauma (ELT) exposure and posttraumatic stress disorder (PTSD) both affect neural structure, which predicts a variety of mental health concerns throughout the lifespan and may present differently between adolescents and adults. However, few studies have identified the relationship between ELT, PTSD, development, and brain structure using cortical thickness (CT). CT may reveal previously obscured alterations that are potentially clinically relevant and, furthermore, could identify specific structural correlates distinct to ELT from PTSD. Two hundred and fifty-three female adolescent and adult survivors of interpersonal violence and non-trauma-exposed demographically matched controls underwent structural MRI at two different sites. Images were processed and CT was estimated using FreeSurfer. Vertex-wise linear model tests were conducted across the cortical surface to investigate whether PTSD and ELT exposure uniquely affect CT, controlling for scanner site. Planned follow-up tests included second-level analyses of clinical symptoms for CT clusters that were significantly related to PTSD or ELT. CT in the middle cingulate cortex was inversely related to ELT in both age groups, such that individuals with more ELT demonstrated less CT in this region. Additionally, CT was significantly greater in the bilateral intraparietal sulcus and left angular gyrus in both adolescents and adults with PTSD. Furthermore, CT in these clusters was also significantly related to clinical symptom severity in the adult PTSD group. This study provides evidence for distinct CT correlates of ELT and PTSD that are present across adolescents and adults, suggesting consistent markers related to ELT and PTSD on gray matter structure in trauma-exposed individuals.
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http://dx.doi.org/10.1038/s41386-020-00918-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027669PMC
March 2021

Frontoparietal network activity during model-based reinforcement learning updates is reduced among adolescents with severe sexual abuse.

J Psychiatr Res 2020 Nov 4. Epub 2020 Nov 4.

Department of Psychiatry, University of Wisconsin, Madison, WI, USA.

Trauma and trauma-related disorders are characterized by impaired learning processes, including reinforcement learning (RL). Identifying which aspects of learning are altered by trauma is critical endeavor, as this may reveal key mechanisms of impairment and potential intervention targets. There are at least two types of RL that have been delineated using computational modeling: model-free and model-based RL. Although these RL processes differentially predict decision-making behavior, most research has examined the impact of trauma on model-free RL. Currently unclear whether model-based RL, which involves building abstract and nuanced representations of stimulus-outcome relationships, is impaired among individuals with a history of trauma. The present study sought to test the hypothesis of impaired model-based RL among adolescent females exposed to assaultive trauma. Participants (n = 60; 29 without a history of assault and 31 with a history of assault with and without PTSD) completed a three-arm bandit task during fMRI acquisition. Two computational models compared the degree to which participants' task behavior fit the use of a model-free versus model-based RL strategy. Although a history of assaultive trauma did not predict poorer model-based RL, greater sexual abuse severity predicted less use of model-based compared to model-free RL. Additionally, severe sexual abuse predicted less left frontoparietal network encoding of model-based RL updates. Altered model-based RL, which supports goal-directed behavior, may be an important route through which clinical impairment emerges among individuals with a history of severe sexual abuse and should be examined further in future studies.
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http://dx.doi.org/10.1016/j.jpsychires.2020.10.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195295PMC
November 2020

Filtering and model-based analysis independently improve skin-conductance response measures in the fMRI environment: Validation in a sample of women with PTSD.

Int J Psychophysiol 2020 12 16;158:86-95. Epub 2020 Oct 16.

Department of Psychiatry, University of Wisconsin-Madison, Madison 53726, WI, USA.

Numerous methods exist for the pre-processing and analysis of skin-conductance response (SCR) data, but there is incomplete consensus on suitability and implementation, particularly with regard to signal filtering in conventional peak score (PS) analysis. This is particularly relevant when SCRs are measured during fMRI, which introduces additional noise and signal variability. Using SCR-fMRI data (n = 65 women) from a fear conditioning experiment, we compare the impact of three nested data processing methods on analysis using conventional PS as well as psychophysiological modeling. To evaluate the different methods, we quantify effect size to recover a benchmark contrast of interest, namely, discriminating SCR magnitude to a conditioned stimulus (CS+) relative to a CS not followed by reinforcement (CS-). Findings suggest that low-pass filtering reduces PS sensitivity (Δd = -20%), while band-pass filtering improves PS sensitivity (Δd = +27%). We also replicate previous findings that a psychophysiological modeling approach yields superior sensitivity to detect contrasts of interest than even the most sensitive PS method (Δd = +110%). Furthermore, we present preliminary evidence that filtering differences may account for a portion of exclusions made on commonly applied metrics, such as below zero discrimination. Despite some limitations of our sample and experimental design, it appears that SCR processing pipelines that include band-pass filtering, ideally with model-based SCR quantification, may increase the validity of SCR response measures, maximize research productivity, and decrease sampling bias by reducing data exclusion.
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http://dx.doi.org/10.1016/j.ijpsycho.2020.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736483PMC
December 2020

L-DOPA and consolidation of fear extinction learning among women with posttraumatic stress disorder.

Transl Psychiatry 2020 08 15;10(1):287. Epub 2020 Aug 15.

University of Arkansas for Medical Sciences, Brain Imaging Research Center, Little Rock, AR, USA.

This study tested whether L-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg L-DOPA/carbidopa (n = 28), or 200/50 mg L-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of L-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that L-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.
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http://dx.doi.org/10.1038/s41398-020-00975-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429959PMC
August 2020

A Pilot Adaptive Neurofeedback Investigation of the Neural Mechanisms of Implicit Emotion Regulation Among Women With PTSD.

Front Syst Neurosci 2020 3;14:40. Epub 2020 Jul 3.

Department of Psychiatry, The University of Wisconsin-Madison, Madison, WI, United States.

Posttraumatic stress disorder (PTSD) is widely associated with deficits in implicit emotion regulation. Recently, adaptive fMRI neurofeedback (A-NF) has been developed as a methodology that offers a unique probe of brain networks that mediate implicit emotion regulation and their impairment in PTSD. We designed an A-NF paradigm in which difficulty of an emotional conflict task (i.e., embedding trauma distractors onto a neutral target stimulus) was controlled by a whole-brain classifier trained to differentiate attention to the trauma distractor vs. target. We exploited this methodology to test whether PTSD was associated with: (1) an altered brain state that differentiates attention towards vs. away from trauma cues; and (2) an altered ability to use concurrent feedback about brain states during an implicit emotion regulation task. Adult women with a current diagnosis of PTSD ( = 10) and healthy control ( = 9) women participated in this task during 3T fMRI. During two initial non-feedback runs used to train a whole-brain classifier, we observed: (1) poorer attention performance in PTSD; and (2) a linear relationship between brain state discrimination and attention performance, which was significantly attenuated among the PTSD group when the task contained trauma cues. During the A-NF phase, the PTSD group demonstrated poorer ability to regulate brain states as per attention instructions, and this poorer ability was related to PTSD symptom severity. Further, PTSD was associated with the heightened encoding of feedback in the insula and hippocampus. These results suggest a novel understanding of whole-brain states and their regulation that underlie emotion regulation deficits in PTSD.
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http://dx.doi.org/10.3389/fnsys.2020.00040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347986PMC
July 2020

Posttraumatic Stress Disorder and the Developing Adolescent Brain.

Biol Psychiatry 2021 01 10;89(2):144-151. Epub 2020 Jun 10.

Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address:

Posttraumatic stress disorder (PTSD) in adolescents is common and debilitating. In contrast to adult PTSD, relatively little is known about the neurobiology of adolescent PTSD, nor about how current treatments may alter adolescent neurodevelopment to allow recovery from PTSD. Improving our understanding of biological mechanisms of adolescent PTSD, taken in the context of neurodevelopment, is crucial for developing novel and personalized treatment approaches. In this review, we highlight prevailing constructs of PTSD and current findings on these domains in adolescent PTSD. Notably, little data exist in adolescent PTSD for prominent adult PTSD constructs, including threat learning and attentional threat bias. Most work to date has examined general threat processing, emotion regulation, and their neural substrates. These studies suggest that adolescent PTSD, while phenomenologically similar to adult PTSD, shows unique neurodevelopmental substrates that may impair recovery but could also be targeted in the context of adolescent neuroplasticity to improve outcomes. Both cross-sectional and longitudinal data suggest abnormal frontolimbic development compared with typically developing youths, a pattern that may differ from resilient youths. Whether current treatments such as trauma-focused psychotherapy engage these targets and restore healthy neurodevelopment remains an open question. We end our review by highlighting emerging areas and knowledge gaps that could be addressed to better characterize the biology underlying adolescent PTSD. Emerging studies in computational modeling of decision making, caregiver-related transmission of traumatic stress, and other areas may offer new targets that could harness adolescent neurobehavioral plasticity to improve resilience and recovery for some of our most vulnerable youths.
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http://dx.doi.org/10.1016/j.biopsych.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725977PMC
January 2021

Altered large-scale functional brain organization in posttraumatic stress disorder: A comprehensive review of univariate and network-level neurocircuitry models of PTSD.

Neuroimage Clin 2020 23;27:102319. Epub 2020 Jun 23.

Neuroscience and Training Program, University of Wisconsin-Madison, United States; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, United States.

Classical neural circuitry models of posttraumatic stress disorder (PTSD) are largely derived from univariate activation studies and implicate the fronto-limbic circuit as a main neural correlate of PTSD symptoms. Though well-supported by human neuroimaging literature, these models are limited in their ability to explain the widely distributed neural and behavioral deficits in PTSD. Emerging interest in the application of large-scale network methods to functional neuroimaging provides a new opportunity to overcome such limitations and conceptualize the neural circuitry of PTSD in the context of network patterns. This review aims to evaluate both the classical neural circuitry model and a new, network-based model of PTSD neural circuitry using a breadth of functional brain organization research in subjects with PTSD. Taken together, this literature suggests global patterns of reduced functional connectivity (FC) in PTSD groups as well as altered FC targets that reside disproportionately in canonical functional networks, especially the default mode network. This provides evidence for an integrative model that includes elements of both the classical models and network-based models to characterize the neural circuitry of PTSD.
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http://dx.doi.org/10.1016/j.nicl.2020.102319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334481PMC
June 2021

Estradiol Modulates Neural and Behavioral Arousal in Women With Posttraumatic Stress Disorder During a Fear Learning and Extinction Task.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 12 30;5(12):1114-1122. Epub 2020 Apr 30.

Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin. Electronic address:

Background: Fear responding in posttraumatic stress disorder (PTSD) is sexually heterogeneous and varies with hormonal fluctuations throughout the menstrual cycle. While research suggests that estrogen levels affect PTSD symptoms among women, there is a dearth of research on modulatory effects of estrogen on fear responding among women with PTSD, and neural outcome measures are lacking.

Methods: A sample of 42 women with PTSD underwent 2 consecutive alternating blocks of fear conditioning and extinction training, during which a CS+ conditioned stimulus, but not a CS-, predicted the occurrence of an electric shock in an acquisition context but not in an extinction context. Assayed saliva determined estradiol levels. Skin conductance response and whole-brain voxelwise activity during functional magnetic resonance imaging were outcome variables in linear mixed-effects models, with estradiol level, PTSD severity, and task contrasts as predictors.

Results: Skin conductance response exhibited a significant estradiol × PTSD severity × habituation interaction (t = 3.180, p = .002), such that PTSD severity was correlated with increased arousal responding between training blocks among women with lower estradiol (t = -3.985, p < .001) but not higher estradiol (t = 0.550, p = .583). Voxelwise activity also demonstrated an identical three-way interaction within dorsomedial prefrontal cortex and anterior insula clusters. The skin conductance response and imaging interactions between PTSD severity and estradiol were not specific to conditioned stimulus type or context.

Conclusions: Estradiol moderated the relationship between PTSD severity and arousal response habituation between fear conditioning and extinction training sessions, such that high estradiol protected against the negative impact of severe PTSD symptoms on fear habituation. These findings suggest that estrogen enhances habituation among women with severe PTSD, potentially influencing the efficacy of extinction-based therapies.
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http://dx.doi.org/10.1016/j.bpsc.2020.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606348PMC
December 2020

Sacrificing reward to avoid threat: Characterizing PTSD in the context of a trauma-related approach-avoidance conflict task.

J Abnorm Psychol 2020 Jul 21;129(5):457-468. Epub 2020 May 21.

Department of Psychiatry, University of Wisconsin-Madison.

Posttraumatic stress disorder (PTSD) is characterized by heightened avoidance, cognitive inflexibility, and impaired reward processing. Maladaptive behavior in PTSD may reflect an imbalance between approach and avoidance, but no research has investigated approach-avoidance conflict (AAC) in PTSD. The current study investigated approach-avoidance behavior in PTSD using a trauma-related AAC (trAAC) task in two independent samples. In Study 1, 43 women with a current diagnosis of PTSD and 18 healthy comparison subjects were recruited from the community. In Study 2, 53 women with trauma exposure and a range of PTSD symptoms were recruited from a correctional institution. Trials were separated into two phases: conflict (the option most likely to win points was most likely to show a trauma-related image) and congruent (the option most likely to win points was least likely to show a trauma-related image). In Study 1, reward obtainment varied with the task manipulation (i.e., fewer points earned during conflict compared to congruent Phase) in PTSD but not healthy subjects. These results indicate that when avoidance is advantageous (congruent phase), individuals with PTSD show increased task performance, whereas when avoidance is maladaptive (conflict phase), individuals with PTSD show increased sacrifice of reward. In Study 2, higher PTSD symptoms predicted decreased reward earning during the conflict phase, again indicating a sacrifice of reward when avoidance is maladaptive. Across both studies, PTSD associated with increased AAC and sacrifice of reward in the presence of trauma-related stimuli. These studies shed light on AAC in PTSD and could inform more targeted therapy approaches. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/abn0000528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393639PMC
July 2020

Semantic Networks and Mechanisms of Exposure Therapy: Implications for the Treatment of Panic Disorder.

Authors:
Josh M Cisler

Am J Psychiatry 2020 03;177(3):197-199

Department of Psychiatry, University of Wisconsin Madison.

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http://dx.doi.org/10.1176/appi.ajp.2019.20010008DOI Listing
March 2020

Biotypes of functional brain engagement during emotion processing differentiate heterogeneity in internalizing symptoms and interpersonal violence histories among adolescent girls.

J Psychiatr Res 2020 02 6;121:197-206. Epub 2019 Dec 6.

University of Wisconsin Madison, Department of Psychiatry, USA. Electronic address:

Youth exposed to early life interpersonal violence (IPV) demonstrate heterogeneous clinical symptoms. Studies based on univariate methods suggest that neurocircuitry related to emotion processing explains heterogeneity in internalizing symptoms. Here, we use a multivariate, data-driven method of identifying distinct functional brain activation profiles (i.e., "biotypes") and test whether these biotypes differentiate internalizing symptoms among IPV-exposed youth. 114 adolescent girls (n = 38 with no IPV exposure or psychopathology; n = 76 with IPV exposure and heterogeneous internalizing symptoms), aged 11-17, completed an emotion processing task during fMRI. To identify distinct biotypes of brain engagement profiles, data-driven clustering analysis was applied to patterns of voxel activation, constrained within a mask of distributed regions implicated in emotion processing. Resulting biotypes (BT1-3) were compared on measures of IPV exposure and internalizing symptoms, as well as symptom reduction during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) among a subset of participants (n = 21). Cluster analyses identified three biotypes, differentiated by engagement of medial prefrontal, anterior insula, hippocampus, parietal, and ventral visual cortex during emotion processing. BT1 exhibited low levels of IPV exposure and internalizing symptoms. BT2 exhibited elevated levels of IPV, except sexual assault, and demonstrated moderate severity across internalizing symptom domains. BT3 exhibited elevated severity across all IPV and internalizing symptom domains. Greater symptom reduction during TF-CBT was associated with increased pre-to post-treatment changes in similarity with BT1. These results demonstrate distinct profiles of emotion processing neurocircuitry that differentiate heterogeneity in internalizing symptoms in IPV-exposed adolescent girls.
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http://dx.doi.org/10.1016/j.jpsychires.2019.12.002DOI Listing
February 2020

Social Trust and Reciprocity Among Adolescent Girls Exposed to Interpersonal Violence.

J Interpers Violence 2019 Oct 14:886260519881522. Epub 2019 Oct 14.

University of Wisconsin-Madison, USA.

Trauma research has traditionally focused on altered emotion regulation and its role in psychopathology, whereas mechanisms of social behavior remain comparatively unexplored, particularly among adolescents. It has been previously reported that adolescents with histories of interpersonal violence (IV) demonstrate disrupted social learning, and the degree to which they are impaired during social interactions requiring trustful behaviors may be associated with their levels of anxiety. In the present study, 52 adolescent females ( = 26 control; = 26 IV-exposed) between ages of 11 and 17 completed a multi-round adaptation of the Trust Game in which they interacted with a confederate peer run by a computer program, alternating between the roles of investor and investee. The task was designed to operationalize the social behaviors of trust and trust reciprocity, where the magnitude of the participants' monetary investment in the confederate during the investor role represented trust while the proportion of investment returned to the confederate in the investee role represented trust reciprocity. IV-exposed and control participants did not differ in trust (i.e., as investors); however, IV-exposed participants without anxiety diagnoses demonstrated lower trust than those with anxiety diagnoses. For trust reciprocity (i.e., as investees), there were again no differences between IV-exposed participants and controls; however, IV-exposed participants with anxiety diagnoses had increased trust reciprocity compared with both other groups. Similarly, caregiver-reported anxiety symptoms were associated with trust reciprocity behaviors among the IV-exposed adolescents. Findings suggest that IV exposure and associated anxiety impacts adolescents' trust behaviors, demonstrating potential mechanisms for maladaptive social behavior among trauma-exposed youth.
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http://dx.doi.org/10.1177/0886260519881522DOI Listing
October 2019

A flexible and generalizable model of online latent-state learning.

PLoS Comput Biol 2019 09 16;15(9):e1007331. Epub 2019 Sep 16.

Department of Psychiatry, University of Wisconsin, Madison, Wisconsin, United States of America.

Many models of classical conditioning fail to describe important phenomena, notably the rapid return of fear after extinction. To address this shortfall, evidence converged on the idea that learning agents rely on latent-state inferences, i.e. an ability to index disparate associations from cues to rewards (or penalties) and infer which index (i.e. latent state) is presently active. Our goal was to develop a model of latent-state inferences that uses latent states to predict rewards from cues efficiently and that can describe behavior in a diverse set of experiments. The resulting model combines a Rescorla-Wagner rule, for which updates to associations are proportional to prediction error, with an approximate Bayesian rule, for which beliefs in latent states are proportional to prior beliefs and an approximate likelihood based on current associations. In simulation, we demonstrate the model's ability to reproduce learning effects both famously explained and not explained by the Rescorla-Wagner model, including rapid return of fear after extinction, the Hall-Pearce effect, partial reinforcement extinction effect, backwards blocking, and memory modification. Lastly, we derive our model as an online algorithm to maximum likelihood estimation, demonstrating it is an efficient approach to outcome prediction. Establishing such a framework is a key step towards quantifying normative and pathological ranges of latent-state inferences in various contexts.
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http://dx.doi.org/10.1371/journal.pcbi.1007331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762208PMC
September 2019

Abnormal Prefrontal Development in Pediatric Posttraumatic Stress Disorder: A Longitudinal Structural and Functional Magnetic Resonance Imaging Study.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 02 16;4(2):171-179. Epub 2018 Aug 16.

Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychiatry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.

Background: Prior studies of pediatric posttraumatic stress disorder (PTSD) have reported cross-sectional and age-related structural and functional brain abnormalities in networks associated with cognitive, affective, and self-referential processing. However, no reported studies have comprehensively examined longitudinal gray matter development and its intrinsic functional correlates in pediatric PTSD.

Methods: Twenty-seven youths with PTSD and 21 nontraumatized typically developing (TD) youths were assessed at baseline and 1-year follow-up. At each visit, youths underwent structural magnetic resonance imaging and resting-state functional magnetic resonance imaging. Regions with volumetric abnormalities in whole-brain structural analyses were identified and used as seeds in exploratory intrinsic connectivity analyses.

Results: Youths with PTSD exhibited sustained reductions in gray matter volume (GMV) in right ventromedial prefrontal cortex (PFC) and bilateral ventrolateral PFC. Group-by-time analyses revealed aberrant longitudinal development in dorsolateral PFC, where typically developing youths exhibited normative decreases in GMV between baseline and follow-up, and youths with PTSD showed increases in GMV. Using these regions as seeds, patients with PTSD exhibited atypical longitudinal decreases in intrinsic PFC-amygdala and PFC-hippocampus connectivity, in contrast to increases in typically developing youths. Specifically, youths with PTSD showed decreasing ventromedial PFC-amygdala connectivity as well as decreasing ventrolateral PFC-hippocampus connectivity over time. Notably, volumetric abnormalities in ventromedial PFC and ventrolateral PFC were predictive of symptom severity.

Conclusions: These findings represent novel longitudinal volumetric and connectivity changes in pediatric PTSD. Atypical prefrontal GMV and prefrontal-amygdala/hippocampus development may underlie persistence of PTSD in youths and could serve as future therapeutic targets.
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http://dx.doi.org/10.1016/j.bpsc.2018.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371792PMC
February 2019

Differential Roles of the Salience Network During Prediction Error Encoding and Facial Emotion Processing Among Female Adolescent Assault Victims.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 04 11;4(4):371-380. Epub 2018 Sep 11.

Brain Imaging Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Background: Early-life assaultive violence exposure is a potent risk factor for posttraumatic stress disorder (PTSD) and other mood and anxiety disorders. Neurocircuitry models posit that increased risk is mediated by heightened emotion processing in a salience network including the dorsal anterior cingulate cortex, anterior insula, and amygdala. However, the processes of reinforcement learning (RL) also engage the salience network and are implicated in responses to early-life trauma and PTSD. To define their relative roles in response to early-life trauma and PTSD symptoms, the current study compared engagement of the salience network during emotion processing and RL as a function of early-life assault exposure.

Methods: Adolescent girls (n = 30 girls who had previously been physically or sexually assaulted; n = 30 healthy girls for comparison) 11 to 17 years of age completed two types of tasks during functional magnetic resonance imaging: a facial emotion processing task and an RL task using either social or nonsocial stimuli. Independent component analysis was used to identify a salience network and characterize its engagement in response to emotion processing and prediction error encoding during the RL tasks.

Results: Assault was related to greater reactivity of the salience network during emotion processing. By contrast, we found lesser encoding of negative prediction errors in the salience network, particularly during the social RL task, in girls who had been assaulted. The dysfunction of salience network activity during emotion processing and prediction error encoding was not associated with PTSD symptoms.

Conclusions: These results suggest that hyper- versus hypoactivity of the salience network among trauma-exposed youths depends on the cognitive-affective domain.
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http://dx.doi.org/10.1016/j.bpsc.2018.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638574PMC
April 2019

The neural representation of the association between comorbid drug use disorders and childhood maltreatment.

Drug Alcohol Depend 2018 11 21;192:215-222. Epub 2018 Sep 21.

Psychiatric Research Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR, 72205, USA.

Background: Comorbidity of drug use disorders (DUD) with other psychopathology is associated with worse functional and treatment outcomes than DUD alone. The present study sought to identify altered functional neural circuitry underlying DUD comorbidity with other psychiatric disorders, and model the relationship of these alterations to childhood trauma (Childhood Trauma Questionnaire) and negative self-beliefs (Beck Depression Inventory).

Methods: A sample of adult men and women (mean = 36.8 years) with childhood maltreatment histories (n = 81) was allocated into the following groups based on psychiatric diagnoses and drug use history: no current or past psychiatric disorders (trauma control sample, n = 20), DUD only (n = 22), psychopathology only (n = 20), and DUD comorbid with other psychiatric illness (DCoP, n = 25).

Results: Multiple regression of seed-based resting-state fMRI, controlling for age and sex, identified a functional connection between the right rostral anterior cingulate cortex (rACC) and left temporoparietal junction (TPJ) that was significantly increased in DCoP females, relative to the other clinical and control groups. Within the DCoP female sample, mediation analysis demonstrated that strength of connectivity between the subgenual cingulate cortex and both the right anterior insula and rostral lateral prefrontal cortex significantly mediated the relationship between increasing physical abuse and self-criticism with age as a moderator.

Conclusions: This study related sex-dependent alterations in functional organization of the prefrontal cortex with DCoP that are, in turn, related to magnitude of negative self-beliefs to childhood trauma exposure. Additionally, DCoP-selective alterations in rACC connectivity suggest that the neural correlates of DCoP do not represent linear additive contributions from two independent disorders.
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http://dx.doi.org/10.1016/j.drugalcdep.2018.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375711PMC
November 2018

Does development moderate the effect of early life assaultive violence on resting-state networks? An exploratory study.

Psychiatry Res Neuroimaging 2018 11 27;281:69-77. Epub 2018 Aug 27.

Brain Imaging Research Center, Psychiatric Research Institute, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA; Department of Psychiatry, University of Wisconsin School of Medicine & Public Health, Madison, WI 53726, USA.

Current neurocircuitry models of PTSD do not account for developmental effects, despite that early life assaultive violence is a potent risk factor for PTSD. Here, we preliminarily evaluated developmental stage as a moderator of the effect of early life assaultive violence on resting-state connectivity amongst regions associated with emotion generation and regulation using fMRI. Participants were adult women (n = 25) and adolescent girls (n = 36) who had or had not experienced early life assaultive violence. We found significant interactions between developmental stage and trauma exposure on resting-state functional connectivity (FC). Left amygdala connectivity with the left ventral anterior cingulate gyrus (BA 32) was reduced among trauma-exposed compared to control adolescents, but increased among trauma-exposed compared to control adults. A corresponding pattern of results was identified for FC between rostral anterior cingulate gyrus seed region and a similar right ventral anterior superior frontal gyrus cluster. Increased FC in both regions for assaulted adult women scaled positively with self-reported emotion regulation difficulties. Our results should be viewed tentatively due to sample limitations, but provide impetus to examine whether neurocircuitry models of PTSD may be strengthened by accounting for developmental stage.
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http://dx.doi.org/10.1016/j.pscychresns.2018.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373177PMC
November 2018

Altered neural encoding of prediction errors in assault-related posttraumatic stress disorder.

J Psychiatr Res 2018 08 12;103:83-90. Epub 2018 May 12.

Neuroscience Training Program, University of Wisconsin-Madison, United States; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, United States.

Posttraumatic stress disorder (PTSD) is widely associated with deficits in extinguishing learned fear responses, which relies on mechanisms of reinforcement learning (e.g., updating expectations based on prediction errors). However, the degree to which PTSD is associated with impairments in general reinforcement learning (i.e., outside of the context of fear stimuli) remains poorly understood. Here, we investigate brain and behavioral differences in general reinforcement learning between adult women with and without a current diagnosis of PTSD. 29 adult females (15 PTSD with exposure to assaultive violence, 14 controls) underwent a neutral reinforcement-learning task (i.e., two arm bandit task) during fMRI. We modeled participant behavior using different adaptations of the Rescorla-Wagner (RW) model and used Independent Component Analysis to identify timecourses for large-scale a priori brain networks. We found that an anticorrelated and risk sensitive RW model best fit participant behavior, with no differences in computational parameters between groups. Women in the PTSD group demonstrated significantly less neural encoding of prediction errors in both a ventral striatum/mPFC and anterior insula network compared to healthy controls. Weakened encoding of prediction errors in the ventral striatum/mPFC and anterior insula during a general reinforcement learning task, outside of the context of fear stimuli, suggests the possibility of a broader conceptualization of learning differences in PTSD than currently proposed in current neurocircuitry models of PTSD.
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http://dx.doi.org/10.1016/j.jpsychires.2018.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008230PMC
August 2018

Large-scale brain organization during facial emotion processing as a function of early life trauma among adolescent girls.

Neuroimage Clin 2018 6;17:778-785. Epub 2017 Dec 6.

University of Arkansas for Medical Sciences, Department of Psychiatry, Brain Imaging Research Center, United States.

Background: A wealth of research has investigated the impact of early life trauma exposure on functional brain activation during facial emotion processing and has often demonstrated amygdala hyperactivity and weakened connectivity between amygdala and medial PFC (mPFC). There have been notably limited investigations linking these previous node-specific findings into larger-scale network models of brain organization.

Method: To address these gaps, we applied graph theoretical analyses to fMRI data collected during a facial emotion processing task among 88 adolescent girls (n = 59 exposed to direct physical or sexual assault; n = 29 healthy controls), aged 11-17, during fMRI. Large-scale organization indices of modularity, assortativity, and global efficiency were calculated for stimulus-specific functional connectivity using an 883 region-of-interest parcellation.

Results: Among the entire sample, more severe early life trauma was associated with more modular and assortative, but less globally efficient, network organization across all stimulus categories. Among the assaulted girls, severity of early life trauma and PTSD diagnoses were both simultaneously related to increased modular brain organization. We also found that more modularized network organization was related both to amygdala hyperactivation and weakened connectivity between amygdala and medial PFC.

Conclusions: These results demonstrate that early life trauma is associated with enhanced brain organization during facial emotion processing and that this pattern of brain organization might explain the commonly observed association between childhood trauma and amygdala hyperactivity and weakened connectivity with mPFC. Implications of these results for neurocircuitry models are discussed.
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http://dx.doi.org/10.1016/j.nicl.2017.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842665PMC
February 2019

Childhood Trauma and Functional Connectivity between Amygdala and Medial Prefrontal Cortex: A Dynamic Functional Connectivity and Large-Scale Network Perspective.

Authors:
Josh M Cisler

Front Syst Neurosci 2017 11;11:29. Epub 2017 May 11.

Department of Psychiatry, University of Wisconsin-Madison, MadisonWI, USA.

Altered functional connectivity (FC) between the medial prefrontal cortex (mPFC) and amygdala is widely implicated as a neural mechanism explaining risk for psychopathology among those exposed to early life trauma. Nonetheless, contemporary neuroimaging research has shifted toward large-scale network models of brain function, and it is not clear how this common bi-nodal finding fits into larger-scale network models. Here, using dynamic functional connectivity (DFC) approaches combined with large-scale network analyses, the larger role of bi-nodal FC between mPFC and amygdala among a sample of adolescent girls is investigated. The sample was comprised of 30 healthy control girls and 26 girls exposed to either physical or sexual assault who underwent a resting-state scan during 3T MRI. DFC using a sliding window approach was used to create weighted, undirected, graphs from the resting-state data following parcellation with a 215 regions-of-interest (ROI) atlas. Using ROI, the predicted finding of lessor FC between mPFC and amygdala as a function of early life trauma was replicated in this sample. By contrast, early life trauma was associated with greater large-scale network modularity. Using a dynamic FC approach, it is also demonstrated that within-subject variability in this bi-nodal FC closely tracks within-subject fluctuations in large-scale network patterns, including connectivity between a limbic and default mode network (in which the amygdala and mPFC nodes belong, respectively) as well as overall modular organization. These results suggest that bi-nodal FC, such as amygdala-mPFC FC, may generally reflect larger-scale network patterns. Future research is necessary to understand whether these associations between nodal FC and large-scale network organization better reflect top-down processes (larger-scale network organization drives bi-nodal FC) or bottom-up processes (bi-nodal FC drives larger-scale network organization) and the related impact of early life trauma.
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http://dx.doi.org/10.3389/fnsys.2017.00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425605PMC
May 2017

Exploring Emotion Regulation in Juveniles Who Have Sexually Offended: An fMRI Study.

J Child Sex Abus 2017 Jan 20;26(1):40-57. Epub 2016 Dec 20.

e Department of Pediatrics , University of Arkansas for Medical Sciences , Little Rock , Arkansas.

This exploratory study compared juveniles who sexually offend to nonoffending juveniles in their capacities to behaviorally and neurologically regulate, or reappraise, negative emotions. Participants were 39 juvenile males, including 10 healthy, nonoffending control subjects and 29 juveniles who sexually offend, comprising 12 juveniles who sexually offend with history of child sexual abuse. Participants completed a clinical assessment and a reappraisal task during functional magnetic resonance imaging. Difficulties in Emotional Regulation Scale results showed significantly less difficulties in emotion regulation among controls compared to juveniles who sexually offend, but when self-rating reappraisal abilities during the functional magnetic resonance imaging, all groups obtained comparable results. The imaging results showed no significant differences in fronto-temporal regions between controls and juveniles who sexually offend. Differences were found in other regions indicated in cognitive control, working memory, and emotional processing between controls and juveniles who sexually offend as well as between juveniles who sexually offend and those without history of child sexual abuse. Findings suggest that juveniles who sexually offend are capable of emotion regulation.
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http://dx.doi.org/10.1080/10538712.2016.1259280DOI Listing
January 2017

Modes of Large-Scale Brain Network Organization during Threat Processing and Posttraumatic Stress Disorder Symptom Reduction during TF-CBT among Adolescent Girls.

PLoS One 2016 9;11(8):e0159620. Epub 2016 Aug 9.

Brain Imaging Research Center, Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, United States of America.

Posttraumatic stress disorder (PTSD) is often chronic and disabling across the lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and mediating neural mechanisms are not well understood. Here, we test whether PTSD symptom reduction during TF-CBT is associated with individual differences in large-scale brain network organization during emotion processing. Twenty adolescent girls, aged 11-16, with PTSD related to assaultive violence completed a 12-session protocol of TF-CBT. Participants completed an emotion processing task, in which neutral and fearful facial expressions were presented either overtly or covertly during 3T fMRI, before and after treatment. Analyses focused on characterizing network properties of modularity, assortativity, and global efficiency within an 824 region-of-interest brain parcellation separately during each of the task blocks using weighted functional connectivity matrices. We similarly analyzed an existing dataset of healthy adolescent girls undergoing an identical emotion processing task to characterize normative network organization. Pre-treatment individual differences in modularity, assortativity, and global efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction. Patients who responded better to treatment had greater network modularity and assortativity but lesser efficiency, a pattern that closely resembled the control participants. At a group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, but this was more pronounced among participants with less symptom improvement. The results support the hypothesis that modularized and resilient brain organization during emotion processing operate as mechanisms enabling symptom reduction during TF-CBT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159620PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978452PMC
July 2017
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