Publications by authors named "Robin Aupperle"

65 Publications

Baseline sleep quality moderates symptom improvement in veterans with comorbid PTSD and TBI receiving trauma-focused treatment.

Behav Res Ther 2021 May 29;143:103892. Epub 2021 May 29.

Psychology Service, VA San Diego Healthcare System, 3350 La Jolla Village Dr, San Diego, CA, 92161, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, 3350 La Jolla Village Dr, San Diego, CA, 92161, USA; Department of Psychiatry, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA. Electronic address:

Poor sleep quality is common among Veterans with posttraumatic stress disorder (PTSD) and history of traumatic brain injury (TBI). However, the relationship between sleep quality and treatment outcomes following trauma-focused interventions is less well-understood in this population. We sought to better understand whether 1) sleep quality changed as a result of trauma-focused treatment and 2) if baseline sleep quality moderated psychological and neurobehavioral treatment outcomes. Our sample consisted of 100 Iraq/Afghanistan era Veterans with PTSD and history of mild to moderate TBI who were randomized to one of two trauma-focused treatments: 1) Cognitive Processing Therapy (CPT) or 2) combined CPT and Cognitive Symptom Management and Rehabilitation Therapy (SMART-CPT). Self-reported sleep quality, psychiatric symptoms (PTSD and depression), and neurobehavioral concerns were assessed at multiple timepoints throughout the study. Multilevel modeling showed sleep quality did not improve, regardless of treatment condition. However, worse baseline sleep quality was associated with less improvement in PTSD symptoms and cognitive complaints. There was no effect of baseline sleep quality on change in depression symptoms. These findings suggest that more targeted treatments to address sleep quality either prior to or in conjunction with trauma-focused therapy may help to improve treatment outcomes for Veterans with comorbid PTSD and TBI history.
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http://dx.doi.org/10.1016/j.brat.2021.103892DOI Listing
May 2021

Long-term stability of computational parameters during approach-avoidance conflict in a transdiagnostic psychiatric patient sample.

Sci Rep 2021 Jun 3;11(1):11783. Epub 2021 Jun 3.

Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK, 74136, USA.

Maladaptive behavior during approach-avoidance conflict (AAC) is common to multiple psychiatric disorders. Using computational modeling, we previously reported that individuals with depression, anxiety, and substance use disorders (DEP/ANX; SUDs) exhibited differences in decision uncertainty and sensitivity to negative outcomes versus reward (emotional conflict) relative to healthy controls (HCs). However, it remains unknown whether these computational parameters and group differences are stable over time. We analyzed 1-year follow-up data from a subset of the same participants (N = 325) to assess parameter stability and relationships to other clinical and task measures. We assessed group differences in the entire sample as well as a subset matched for age and IQ across HCs (N = 48), SUDs (N = 29), and DEP/ANX (N = 121). We also assessed 2-3 week reliability in a separate sample of 30 HCs. Emotional conflict and decision uncertainty parameters showed moderate 1-year intra-class correlations (.52 and .46, respectively) and moderate to excellent correlations over the shorter period (.84 and .54, respectively). Similar to previous baseline findings, parameters correlated with multiple response time measures (ps < .001) and self-reported anxiety (r = .30, p < .001) and decision difficulty (r = .44, p < .001). Linear mixed effects analyses revealed that patients remained higher in decision uncertainty (SUDs, p = .009) and lower in emotional conflict (SUDs, p = .004, DEP/ANX, p = .02) relative to HCs. This computational modelling approach may therefore offer relatively stable markers of transdiagnostic psychopathology.
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http://dx.doi.org/10.1038/s41598-021-91308-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175390PMC
June 2021

Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial.

Brain Behav Immun 2021 May 27. Epub 2021 May 27.

Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK 74136 USA; School of Community Medicine, University of Tulsa, 800 S. Tucker Dr., Tulsa, OK 74104 USA. Electronic address:

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have shown initial promise in producing antidepressant effects. This is perhaps due to these drugs being peroxisome proliferator-activated receptor gamma (PPARγ) agonists, in addition to their inhibition of cyclooxygenase enzymes. Some, albeit mixed, evidence suggests that PPARγ agonists have antidepressant effects in humans and animals. This double-blind, placebo-controlled, pharmacologic functional magnetic resonance imaging (ph-fMRI) study aimed to elucidate the impact of ibuprofen on emotion-related neural activity and determine whether observed effects were due to changes in PPARγ gene expression. Twenty healthy volunteers completed an emotional face matching task during three fMRI sessions, conducted one week apart. Placebo, 200 mg, or 600 mg ibuprofen was administered 1 h prior to each scan in a pseudo-randomized order. Peripheral blood mononuclear cells were collected at each session to isolate RNA for PPARγ gene expression. At the doses used, ibuprofen did not significantly change PPARγ gene expression. Ibuprofen dose was associated with decreased blood oxygen level-dependent (BOLD) activation in the dorsolateral prefrontal cortex and fusiform gyrus during emotional face processing (faces-shapes). Additionally, PPARγ gene expression was associated with increased BOLD activation in the insula and transverse and superior temporal gyri (faces-shapes). No interaction effects between ibuprofen dose and PPARγ gene expression on BOLD activation were observed. Thus, results suggest that ibuprofen and PPARγ may have independent effects on emotional neurocircuitry. Future studies are needed to further delineate the roles of ibuprofen and PPARγ in exerting antidepressant effects in healthy as well as clinical populations.
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http://dx.doi.org/10.1016/j.bbi.2021.05.023DOI Listing
May 2021

It is never as good the second time around: Brain areas involved in salience processing habituate during repeated drug cue exposure in treatment engaged abstinent methamphetamine and opioid users.

Neuroimage 2021 May 19;238:118180. Epub 2021 May 19.

Laureate Institute for Brain Research (LIBR), 6655 South Yale Ave, Tulsa, OK 74136, USA.

The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118180DOI Listing
May 2021

Neurocognitive Empowerment for Addiction Treatment (NEAT): study protocol for a randomized controlled trial.

Trials 2021 May 7;22(1):330. Epub 2021 May 7.

Laureate Institute for Brain Research, 6655 South Yale Ave., Tulsa, OK, 74136, USA.

Background: Neurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed "Neurocognitive Empowerment for Addiction Treatment" (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making.

Method/design: In a single-blind randomized controlled trial (RCT), 80 female opioid and/or methamphetamine users will be recruited from an addiction recovery program providing an alternative to incarceration for women with substance use-related offenses. Eight groups of 9-12 participants will be randomized into NEAT or treatment-as-usual (TAU). NEAT involves 14 90-min sessions, delivered twice weekly. The primary outcome is change in self-reported drug craving from before to after intervention using Obsessive Compulsive Drug Use Scale. Secondary and exploratory outcomes include additional psychological, neurocognitive, and structural and functional neuroimaging measures. Clinical measures will be performed at five time points (pre- and post-intervention, 3-, 6-, and 12-month follow-up); neuroimaging measures will be completed at pre- and post-intervention.

Discussion: The present RCT is the first study to examine the efficacy of an adjunctive neurocognitive rehabilitation and awareness program for addiction. Results from this study will provide initial information concerning potential clinical efficacy of the treatment, as well as delineate neural mechanisms potentially targeted by this novel intervention.

Trial Registration: ClinicalTrials.gov NCT03922646 . Registered on 22 April 2019.
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http://dx.doi.org/10.1186/s13063-021-05268-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106153PMC
May 2021

Extracurricular Activities, Screen Media Activity, and Sleep May Be Modifiable Factors Related to Children's Cognitive Functioning: Evidence From the ABCD Study.

Child Dev 2021 Apr 26. Epub 2021 Apr 26.

Laureate Institute for Brain Research.

This study used a machine learning framework in conjunction with a large battery of measures from 9,718 school-age children (ages 9-11) from the Adolescent Brain Cognitive Development (ABCD) Study to identify factors associated with fluid cognitive functioning (FCF), or the capacity to learn, solve problems, and adapt to novel situations. The identified algorithm explained 14.74% of the variance in FCF, replicating previously reported socioeconomic and mental health contributors to FCF, and adding novel and potentially modifiable contributors, including extracurricular involvement, screen media activity, and sleep duration. Pragmatic interventions targeting these contributors may enhance cognitive performance and protect against their negative impact on FCF in children.
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http://dx.doi.org/10.1111/cdev.13578DOI Listing
April 2021

The effect of a mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: a randomized feasibility study.

BMC Complement Med Ther 2021 Apr 15;21(1):123. Epub 2021 Apr 15.

Laureate Institute for Brain Research, 6655 S Yale Avenue, Tulsa, OK, 74136, USA.

Background: Early life stress (ELS) has been linked to poor mental and physical health outcomes in adolescence and adulthood. Mindfulness reduces symptoms of depression and anxiety and improves cognitive and social outcomes in both youth and adults. However, little is known whether mindfulness can mitigate against the adverse neurobiological and psychological effects of ELS. This study aimed to examine the feasibility of conducting a group mindfulness intervention in adolescents with ELS and provide preliminary indication of potential effects on stress-related biomarkers and mental health symptoms.

Methods: Forty adolescents were randomized to receive either eight sessions of Mindfulness-Based Stress Reduction for Teens in group format (MBSR-T; n = 21) or Treatment as Usual Control group (CTRL; n = 17). Outcomes were assessed at baseline and follow-up and included measures associated with neurobiological functioning (immune and endocrine biomarkers) and self-reported mental health (depressive) symptoms. Linear mixed effects models were used to assess the effects of group and time on these outcome measures.

Results: Sixteen of the 21 adolescents completed the intervention, attending an average of 6.5 sessions. The model examining cortisol responses to stress induction revealed medium effects trending toward significance (Cohen's d = .56) for anticipatory cortisol levels in the MBSR-T relative to CTRL groups. No significant effects were found in models examining C-reactive protein or interleukin 6 inflammatory markers. The model examining depressive symptoms revealed a medium effect for symptom reduction (Cohen's d = .69) in the MBSR-T relative to CTRL groups.

Conclusions: This study demonstrated feasibility of conducting a group-based MBSR-T intervention for adolescents with ELS. There was some evidence for efficacy on a symptom level with potential subtle changes on a biological level. Future larger studies are needed to determine the efficacy of group-based mindfulness interventions in this population.

Trial Registration: Identifier # NCT03633903 , registered 16/08/2018.
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http://dx.doi.org/10.1186/s12906-021-03295-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050904PMC
April 2021

Gastric symptoms and low perceived maternal warmth are associated with eating disorder symptoms in young adolescent girls.

Int J Eat Disord 2021 Jun 9;54(6):1009-1018. Epub 2021 Apr 9.

Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.

Objective: This study sought to determine whether gastric symptoms are associated with later eating disorder (ED) symptoms during early adolescence, and whether this relationship is moderated by parental warmth/acceptance and/or the child's sex.

Method: Longitudinal data from the Adolescent Brain Cognitive Development Study were utilized. Participants ages 9-10 years old (N = 4,950; 2,370 female) completed measures at baseline and 1 year later (Y1). At baseline, gastric symptoms were measured by parent-reported items from the Child Behavior Checklist (CBCL), and perceived parental acceptance was measured by youth report on the Children's Report of Parent Behavior Inventory (CRPBI) Acceptance subscale separately for mothers and fathers. ED symptoms at Y1 were assessed by parent report on a computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Linear mixed-effects models were conducted separately for maternal and paternal acceptance to test relationships among variables.

Results: A three-way interaction between baseline gastric symptoms, sex, and maternal acceptance predicted Y1 ED symptoms (𝛽 = 0.08; p < .01). Post-hoc analyses revealed that the interaction between gastric symptoms and maternal acceptance was significant for girls only (𝛽 = -0.06, p < .01), such that low maternal acceptance was associated with a stronger relationship between baseline gastric symptoms and Y1 ED symptoms. No statistically significant main effects or interactions were found in the model for paternal acceptance.

Discussion: Gastric symptoms and low perceived maternal acceptance may interact to result in heightened risk for EDs in young adolescent girls.
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http://dx.doi.org/10.1002/eat.23516DOI Listing
June 2021

Test-retest reliability of approach-avoidance conflict decision-making during functional magnetic resonance imaging in healthy adults.

Hum Brain Mapp 2021 Jun 2;42(8):2347-2361. Epub 2021 Mar 2.

Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.

Neural and behavioral mechanisms during approach-avoidance conflict decision-making are relevant across various psychiatric disorders, particularly anxiety disorders. Studies using approach-avoidance conflict paradigms in healthy adults have identified preliminary neural mechanisms, but findings must be replicated and demonstrated as reliable before further application. This study sought to replicate previous findings and examine test-retest reliability of behavioral (approach behavior, reaction time) and neural (regions of interest [ROIs]) responses during an approach-avoidance conflict task conducted during functional magnetic resonance imaging (fMRI). Thirty healthy adults completed an approach-avoidance conflict task during fMRI on two occasions (mean interval: 17 days; range: 11-32). Effects of task condition during three task phases (decision-making, affective outcome and monetary reward) and intraclass correlation coefficients (ICCs) were calculated across time points. Results replicated that approach behavior was modulated by conflict during decision-making. ROI activations were replicated such that dorsal anterior cingulate cortex (dACC) was modulated by conflict during decision-making, and dACC, striatum, and anterior insula were modulated by valence during affective outcomes (p's <.0083). Approach behavior during conflict demonstrated excellent reliability (ICCs ≥.77). Activation of dACC during conflict decision-making and anterior insula during negative outcomes demonstrated fair reliability (ICCs = .51 and .54), and dACC and striatum activation demonstrated good reliability during negative outcomes (ICCs = .63 and .69). Two additional ROIs (amygdala, left dorsolateral prefrontal cortex) showed good reliability during negative outcomes (ICCs ≥.60). These results characterize several specific behavioral and neuroimaging responses that are replicable and sufficiently reliable during approach-avoidance conflict decision-making to support future utility.
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http://dx.doi.org/10.1002/hbm.25371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090786PMC
June 2021

Latent variables for region of interest activation during the monetary incentive delay task.

Neuroimage 2021 04 24;230:117796. Epub 2021 Jan 24.

Laureate Institute for Brain Research, 6655 South Yale Avenue, Tulsa, OK 74136, USA; Department of Community Medicine, Oxley Health Sciences, University of Tulsa, 800 South Tucker Drive, Tulsa, OK 74104, USA.

Background: The Monetary Incentive Delay task (MID) has been used extensively to probe anticipatory reward processes. However, individual differences evident during this task may relate to other constructs such as general arousal or valence processing (i.e., anticipation of negative versus positive outcomes). This investigation used a latent variable approach to parse activation patterns during the MID within a transdiagnostic clinical sample.

Methods: Participants were drawn from the first 500 individuals recruited for the Tulsa-1000 (T1000), a naturalistic longitudinal study of 1000 participants aged 18-55 (n = 476 with MID data). We employed a multiview latent analysis method, group factor analysis, to characterize factors within and across variable sets consisting of: (1) region of interest (ROI)-based blood oxygenation level-dependent (BOLD) contrasts during reward and loss anticipation; and (2) self-report measures of positive and negative valence and related constructs.

Results: Three factors comprised of ROI indicators emerged to accounted for >43% of variance and loaded on variables representing: (1) general arousal or general activation; (2) valence, with dissociable responses to anticipation of win versus loss; and (3) region-specific activation, with dissociable activation in salience versus perceptual brain networks. Two additional factors were comprised of self-report variables, which appeared to represent arousal and valence.

Conclusions: Results indicate that multiview techniques to identify latent variables offer a novel approach for differentiating brain activation patterns during task engagement. Such approaches may offer insight into neural processing patterns through dimension reduction, be useful for probing individual differences, and aid in the development of optimal explanatory or predictive frameworks.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110176PMC
April 2021

Independent and Synergistic Associations Between TBI Characteristics and PTSD Symptom Clusters on Cognitive Performance and Postconcussive Symptoms in Iraq and Afghanistan Veterans.

J Neuropsychiatry Clin Neurosci 2021 14;33(2):98-108. Epub 2021 Jan 14.

Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego (Jurick, Crocker, Twamley, Schiehser, Jak); Department of Psychiatry, University of California San Diego (Jurick, Merritt, Glassman, Twamley, Schiehser, Jak); VA San Diego Healthcare System, San Diego (Jurick, Crocker, Merritt, Glassman, Twamley, Schiehser, Jak); San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology (Sanderson-Cimino, Keller); PsychArmor Institute, San Diego (Rodgers); and the Laureate Institute for Brain Research, University of Tulsa, Oklahoma (Aupperle).

Objective: The investigators sought to evaluate the independent and interactive associations between mild traumatic brain injury (mTBI) characteristics and posttraumatic stress disorder (PTSD) symptoms with regard to postconcussive symptoms and cognition among treatment-seeking veterans of the U.S. conflicts in Iraq and Afghanistan.

Methods: Sixty-seven Iraq and Afghanistan veterans who had a history of mTBI and comorbid PTSD were grouped based on injury mechanism (blast versus nonblast) and number of lifetime mTBIs (one to two versus three or more). Independent associations between mTBI characteristics and PTSD symptom clusters were evaluated with regard to cognition and postconcussive symptoms. Follow-up analyses were conducted to determine any interactive associations between TBI characteristics and PTSD symptom clusters.

Results: Higher PTSD symptoms, particularly hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. No direct relationships were observed between PTSD symptom clusters and memory or processing speed. The relationship between hyperarousal and processing speed was moderated by lifetime mTBIs, such that those with a history of at least three mTBIs demonstrated a negative association between hyperarousal and processing speed. Blast-related mTBI history was associated with reduced processing speed, compared with non-blast-related mTBI. However, an interaction was observed such that among those with blast-related mTBI history, higher re-experiencing symptoms were associated with poorer processing speed, whereas veterans without history of blast-related mTBI did not demonstrate an association between processing speed and re-experiencing symptoms.

Conclusions: Higher hyperarousal and re-experiencing symptoms were associated with reduced processing speed among veterans with repetitive and blast-related mTBI history, respectively. PTSD symptoms, specifically hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. Limited associations were found between injury characteristics and cognition chronically following mTBI. However, these results support synergistic effects of specific PTSD symptom clusters and TBI characteristics.
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http://dx.doi.org/10.1176/appi.neuropsych.20050128DOI Listing
January 2021

Behavioral activation therapy for depression is associated with a reduction in the concentration of circulating quinolinic acid.

Psychol Med 2020 Nov 25:1-10. Epub 2020 Nov 25.

Laureate Institute for Brain Research, Tulsa, OK, USA.

Background: An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.

Methods: Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).

Results: BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). The change in KynA/QA was nominally associated with the magnitude of change in PROMIS-D scores (p = 0.074, Cohen's f2 = 0.054). Baseline KynA/QA did not predict response to BA therapy.

Conclusion: The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
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http://dx.doi.org/10.1017/S0033291720004389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144244PMC
November 2020

Greater decision uncertainty characterizes a transdiagnostic patient sample during approach-avoidance conflict: a computational modelling approach.

J Psychiatry Neurosci 2021 01 4;46(1):E74-E87. Epub 2021 Jan 4.

From the Laureate Institute for Brain Research, Tulsa, OK, USA (Smith, Kirlic, Stewart, Touthang, Kuplicki, Khalsa, Feinstein, Paulus, Aupperle); and the Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA (Stewart, Khalsa, Paulus, Aupperle).

Background: Imbalances in approach-avoidance conflict (AAC) decision-making (e.g., sacrificing rewards to avoid negative outcomes) are considered central to multiple psychiatric disorders. We used computational modelling to examine 2 factors that are often not distinguished in descriptive analyses of AAC: decision uncertainty and sensitivity to negative outcomes versus rewards (emotional conflict).

Methods: A previously validated AAC task was completed by 478 participants, including healthy controls ( = 59), people with substance use disorders ( = 159) and people with depression and/or anxiety disorders who did not have substance use disorders ( = 260). Using an active inference model, we estimated individual-level values for a model parameter that reflected decision uncertainty and another that reflected emotional conflict. We also repeated analyses in a subsample (59 healthy controls, 161 people with depression and/or anxiety disorders, 56 people with substance use disorders) that was propensity-matched for age and general intelligence.

Results: The model showed high accuracy (72%). As further validation, parameters correlated with reaction times and self-reported task motivations in expected directions. The emotional conflict parameter further correlated with self-reported anxiety during the task ( = 0.32, < 0.001), and the decision uncertainty parameter correlated with self-reported difficulty making decisions ( = 0.45, < 0.001). Compared to healthy controls, people with depression and/or anxiety disorders and people with substance use disorders showed higher decision uncertainty in the propensity-matched sample ( = 2.16, = 0.03, and = 2.88, = 0.005, respectively), with analogous results in the full sample; people with substance use disorders also showed lower emotional conflict in the full sample ( = 3.17, = 0.002).

Limitations: This study was limited by heterogeneity of the clinical sample and an inability to examine learning.

Conclusion: These results suggest that reduced confidence in how to act, rather than increased emotional conflict, may explain maladaptive approach-avoidance behaviours in people with psychiatric disorders.
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http://dx.doi.org/10.1503/jpn.200032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955838PMC
January 2021

Visual cortical regions show sufficient test-retest reliability while salience regions are unreliable during emotional face processing.

Neuroimage 2020 10 20;220:117077. Epub 2020 Jun 20.

Laureate Institute for Brain Research, Tulsa, OK, United States; Department of Community Medicine, University of Tulsa, Tulsa, OK, United States. Electronic address:

Functional magnetic resonance imaging studies frequently use emotional face processing tasks to probe neural circuitry related to psychiatric disorders and treatments with an emphasis on regions within the salience network (e.g., amygdala). Findings across previous test-retest reliability studies of emotional face processing have shown high variability, potentially due to differences in data analytic approaches. The present study comprehensively examined the test-retest reliability of an emotional faces task utilizing multiple approaches to region of interest (ROI) analysis and by examining voxel-wise reliability across the entire brain for both neural activation and functional connectivity. Analyses included 42 healthy adult participants who completed an fMRI scan concurrent with an emotional faces task on two separate days with an average of 25.52 days between scans. Intraclass correlation coefficients (ICCs) were calculated for the 'FACES-SHAPES' and 'FACES' (compared to implicit baseline) contrasts across the following: anatomical ROIs identified from a publicly available brain atlas (i.e., Brainnetome), functional ROIs consisting of 5-mm spheres centered on peak voxels from a publicly available meta-analytic database (i.e., Neurosynth), and whole-brain, voxel-wise analysis. Whole-brain, voxel-wise analyses of functional connectivity were also conducted using both anatomical and functional seed ROIs. While group-averaged neural activation maps were consistent across time, only one anatomical ROI and two functional ROIs showed good or excellent individual-level reliability for neural activation. The anatomical ROI was the right medioventral fusiform gyrus for the FACES contrast (ICC ​= ​0.60). The functional ROIs were the left and the right fusiform face area (FFA) for both FACES-SHAPES and FACES (Left FFA ICCs ​= ​0.69 & 0.79; Right FFA ICCs ​= ​0.68 & 0.66). Poor reliability (ICCs ​< ​0.4) was identified for almost all other anatomical and functional ROIs, with some exceptions showing fair reliability (ICCs ​= ​0.4-0.59). Whole-brain voxel-wise analysis of neural activation identified voxels with good (ICCs ​= ​0.6-0.74) to excellent reliability (ICCs ​> ​0.75) that were primarily located in visual cortex, with several clusters in bilateral dorsal lateral prefrontal cortex (DLPFC). Whole-brain voxel-wise analyses of functional connectivity for amygdala and fusiform gyrus identified very few voxels with good to excellent reliability using both anatomical and functional seed ROIs. Exceptions included clusters in right cerebellum and right DLPFC that showed reliable connectivity with left amygdala (ICCs ​> ​0.6). In conclusion, results indicate that visual cortical regions demonstrate good reliability at the individual level for neural activation, but reliability is generally poor for salience regions often focused on within psychiatric research (e.g., amygdala). Given these findings, future clinical neuroimaging studies using emotional faces tasks to examine individual differences might instead focus on visual regions and their role in psychiatric disorders.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875460PMC
October 2020

Women with Major Depressive Disorder, Irrespective of Comorbid Anxiety Disorders, Show Blunted Bilateral Frontal Responses during Win and Loss Anticipation.

J Affect Disord 2020 08 11;273:157-166. Epub 2020 May 11.

Laureate Institute for Brain Research, 6655 South Yale Avenue, Tulsa, OK, 74136, USA; Department of Community Medicine, Oxley Health Sciences, University of Tulsa, 800 South Tucker Drive, Tulsa, OK, 74104, USA.

Background: Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized.

Methods: This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal.

Results: CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker.

Limitations: This was a cross-sectional analysis restricted to women.

Conclusions: Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD.
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http://dx.doi.org/10.1016/j.jad.2020.04.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306441PMC
August 2020

Dark Times: The Role of Negative Reinforcement in Methamphetamine Addiction.

Front Psychiatry 2020 17;11:114. Epub 2020 Mar 17.

Laureate Institute for Brain Research, Tulsa, OK, United States.

Methamphetamine use is associated with substantial adverse outcomes including poor mental and physical health, financial difficulties, and societal costs. Despite deleterious long-term consequences associated with methamphetamine, many people use drugs for short-term reduction of unpleasant physical or emotional sensations. By removing these aversive states, drug use behaviors are negatively reinforced. Abstinence from methamphetamine can then result in a return to previous aversive emotional states linked to withdrawal and craving, often contributing to an increased likelihood for relapse. This negative reinforcement cycle is hypothesized to be a motivating and maintaining factor for addiction. Thus, this review highlights the current evidence for negative reinforcement mechanisms in methamphetamine use disorder by integrating studies of subjective experience, behavior, functional magnetic resonance imaging, positron emission tomography, and event-related potentials and examining the efficacy of treatments targeting aspects of negative reinforcement. Overall, the literature demonstrates that individuals who use methamphetamine have diminished cognitive control and process emotions, loss of reward, and interoceptive information differently than non-using individuals. These differences are reflected in behavioral and subjective experiments as well as brain-based experiments which report significant differences in various frontal regions, insula, anterior cingulate cortex, and striatum. Together, the results suggest methamphetamine users have an altered experience of negative outcomes, difficulties employing effective emotion regulation, and difficulty engaging in adaptive or goal-directed decision-making. Suggestions for future research to improve our understanding of how negative reinforcement contributes to methamphetamine addiction and to develop effective interventions are provided.
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http://dx.doi.org/10.3389/fpsyt.2020.00114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090143PMC
March 2020

Web-Based Graphic Representation of the Life Course of Mental Health: Cross-Sectional Study Across the Spectrum of Mood, Anxiety, Eating, and Substance Use Disorders.

JMIR Ment Health 2020 Jan 28;7(1):e16919. Epub 2020 Jan 28.

Laureate Institute for Brain Research, Tulsa, OK, United States.

Background: Although patient history is essential for informing mental health assessment, diagnosis, and prognosis, there is a dearth of standardized instruments measuring time-dependent factors relevant to psychiatric disorders. Previous research has demonstrated the potential utility of graphical representations, termed life charts, for depicting the complexity of the course of mental illness. However, the implementation of these assessments is limited by the exclusive focus on specific mental illnesses (ie, bipolar disorder) and the lack of intuitive graphical interfaces for data collection and visualization.

Objective: This study aimed to develop and test the utility of the Tulsa Life Chart (TLC) as a Web-based, structured approach for obtaining and graphically representing historical information on psychosocial and mental health events relevant across a spectrum of psychiatric disorders.

Methods: The TLC interview was completed at baseline by 499 participants of the Tulsa 1000, a longitudinal study of individuals with depressive, anxiety, substance use, or eating disorders and healthy comparisons (HCs). All data were entered electronically, and a 1-page electronic and interactive graphical representation was developed using the Google Visualization Application Programming Interface. For 8 distinct life epochs (periods of approximately 5-10 years), the TLC assessed the following factors: school attendance, hobbies, jobs, social support, substance use, mental health treatment, family structure changes, negative and positive events, and epoch and event-related mood ratings. We used generalized linear mixed models (GLMMs) to evaluate trajectories of each domain over time and by sex, age, and diagnosis, using case examples and Web-based interactive graphs to visualize data.

Results: GLMM analyses revealed main or interaction effects of epoch and diagnosis for all domains. Epoch by diagnosis interactions were identified for mood ratings and the number of negative-versus-positive events (all P values <.001), with all psychiatric groups reporting worse mood and greater negative-versus-positive events than HCs. These differences were most robust at different epochs, depending on diagnosis. There were also diagnosis and epoch main effects for substance use, mental health treatment received, social support, and hobbies (P<.001). User experience ratings (each on a 1-5 scale) revealed that participants found the TLC pleasant to complete (mean 3.07, SD 1.26) and useful for understanding their mental health (mean 3.07, SD 1.26), and that they were likely to recommend it to others (mean 3.42, SD 0.85).

Conclusions: The TLC provides a structured, Web-based transdiagnostic assessment of psychosocial history relevant for the diagnosis and treatment of psychiatric disorders. Interactive, 1-page graphical representations of the TLC allow for the efficient communication of historical life information that would be useful for clinicians, patients, and family members.
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http://dx.doi.org/10.2196/16919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013650PMC
January 2020

Corrigendum to "Always on my mind: Cross-brain associations of mental health symptoms during simultaneous parent-child scanning" [Dev. Cognit. Neurosci. 40 (December) (2019) 100729].

Dev Cogn Neurosci 2020 Feb 26;41:100751. Epub 2019 Dec 26.

Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK, 74136, United States; Department of Human Development and Family Sciences, Oklahoma State University - Tulsa, 700 N. Greenwood Ave., Tulsa, OK, 74106, United States.

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http://dx.doi.org/10.1016/j.dcn.2019.100751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994623PMC
February 2020

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

Trials 2020 Jan 6;21(1):17. Epub 2020 Jan 6.

Laureate Institute for Brain Research, 6655 South Yale Avenue, Tulsa, OK, 74136, USA.

Background: Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder.

Methods/design: We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods.

Discussion: This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome.

Trial Registration: The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.
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http://dx.doi.org/10.1186/s13063-019-3802-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943897PMC
January 2020

Always on my mind: Cross-brain associations of mental health symptoms during simultaneous parent-child scanning.

Dev Cogn Neurosci 2019 12 5;40:100729. Epub 2019 Nov 5.

Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK 74136, United States; Department of Human Development and Family Sciences, Oklahoma State University - Tulsa, 700 N. Greenwood Ave., Tulsa, OK 74106, United States.

How parents manifest symptoms of anxiety or depression may affect how children learn to modulate their own distress, thereby influencing the children's risk for developing an anxiety or mood disorder. Conversely, children's mental health symptoms may impact parents' experiences of negative emotions. Therefore, mental health symptoms can have bidirectional effects in parent-child relationships, particularly during moments of distress or frustration (e.g., when a parent or child makes a costly mistake). The present study used simultaneous functional magnetic resonance imaging (fMRI) of parent-adolescent dyads to examine how brain activity when responding to each other's costly errors (i.e., dyadic error processing) may be associated with symptoms of anxiety and depression. While undergoing simultaneous fMRI scans, healthy dyads completed a task involving feigned errors that indicated their family member made a costly mistake. Inter-brain, random-effects multivariate modeling revealed that parents who exhibited decreased medial prefrontal cortex and posterior cingulate cortex activation when viewing their child's costly error response had children with more symptoms of depression and anxiety. Adolescents with increased anterior insula activation when viewing a costly error made by their parent had more anxious parents. These results reveal cross-brain associations between mental health symptomatology and brain activity during parent-child dyadic error processing.
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http://dx.doi.org/10.1016/j.dcn.2019.100729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934088PMC
December 2019

A pragmatic clinical trial examining the impact of a resilience program on college student mental health.

Depress Anxiety 2020 03 4;37(3):202-213. Epub 2019 Nov 4.

Laureate Institute for Brain Research, Tulsa, Oklahoma.

Background: One in three college students experience significant depression or anxiety interfering with daily functioning. Resilience programs that can be administered to all students offer an opportunity for addressing this public health problem. The current study objective was to assess the benefit of a brief, universal resilience program for first-year college students.

Method: First-year students at a private, midwestern university participated. This trial used a pragmatic design, delivering the intervention within university-identified orientation courses and was not randomized. The four-session resilience program included goal-building, mindfulness, and resilience skills. The comparison was orientation-as-usual. Primary outcomes included PROMIS® Depression and Anxiety and Connor-Davidson Resilience Scale. Secondary and exploratory outcomes included the Perceived Stress Scale, Emotion Regulation, and Cognitive Behavioral Therapy (CBT) Skills Questionnaires, and Freiburg Mindfulness Inventory. Time by treatment interactions at post-training and semester-end were examined using linear mixed models.

Results: Analysis included 252 students, 126 who completed resilience programming and a matched comparison sample. Resilience programming did not relate to improvements in depression at post-training (CI: -2.53 to 1.02; p = .404, d =-0.08), but did at semester-end (95% CI: -4.27 to -0.72; p = .006, d = -0.25) and improvements in perceived stress were observed at post-training (CI: -3.31 to -0.44; p = .011, d = -0.24) and semester-end (CI: -3.30 to -0.41; p = .013, d = -0.24). Emotion regulation, mindfulness, and CBT skills increased, with CBT skills mediating clinical improvements.

Conclusions: Universal implementation of a brief, resilience intervention may be effective for improving college student mental health.
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http://dx.doi.org/10.1002/da.22969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054149PMC
March 2020

Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry.

Brain Behav Immun 2020 01 8;83:163-171. Epub 2019 Oct 8.

Janssen Research & Development, 3210 Merryfield Row, San Diego, CA 92121, USA.

Appetite change is a defining feature of major depressive disorder (MDD), yet little neuroscientific evidence exists to explain why some individuals experience increased appetite when they become depressed while others experience decreased appetite. Previous research suggests depression-related appetite changes can be indicative of underlying neural and inflammatory differences among MDD subtypes. The present study explores the relationship between systemic inflammation and brain circuitry supporting food hedonics for individuals with MDD. Sixty-four participants (31 current, unmedicated MDD and 33 healthy controls [HC]) provided blood samples for analysis of an inflammatory marker, C-reactive protein (CRP), and completed a functional magnetic resonance imaging (fMRI) scan in which they rated the perceived pleasantness of various food stimuli. Random-effects multivariate modeling was used to explore group differences in the relationship between CRP and the coupling between brain activity and inferred food pleasantness (i.e., strength of the relationship between activity and pleasantness ratings). Results revealed that for MDD with increased appetite, higher CRP in blood related to greater coupling between orbitofrontal cortex and anterior insula activity and inferred food pleasantness. Compared to HC, all MDD exhibited a stronger positive association between CRP and coupling between activity in striatum and inferred food pleasantness. These findings suggest that for individuals with MDD, systemic low-grade inflammation is associated with differences in reward and interoceptive-related neural circuitry when making hedonic inferences about food stimuli. In sum, altered immunologic states may affect appetite and inferences about food reward in individuals with MDD and provide evidence for physiological subtypes of MDD.
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http://dx.doi.org/10.1016/j.bbi.2019.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937709PMC
January 2020

The Electrical Aftermath: Brain Signals of Posttraumatic Stress Disorder Filtered Through a Clinical Lens.

Front Psychiatry 2019 31;10:368. Epub 2019 May 31.

Laureate Institute for Brain Research, Tulsa, OK, United States.

This review aims to identify patterns of electrical signals identified using electroencephalography (EEG) linked to posttraumatic stress disorder (PTSD) diagnosis and symptom dimensions. We filter EEG findings through a clinical lens, evaluating nuances in findings according to study criteria and participant characteristics. Within the EEG frequency domain, greater right than left parietal asymmetry in alpha band power is the most promising marker of PTSD symptoms and is linked to exaggerated physiological arousal that may impair filtering of environmental distractors. The most consistent findings within the EEG time domain focused on event related potentials (ERPs) include: 1) exaggerated frontocentral responses (contingent negative variation, mismatch negativity, and P3a amplitudes) to task-irrelevant distractors, and 2) attenuated parietal responses (P3b amplitudes) to task-relevant target stimuli. These findings suggest that some individuals with PTSD suffer from attention dysregulation, which could contribute to problems concentrating on daily tasks and goals in lieu of threatening distractors. Future research investigating the utility of alpha asymmetry and frontoparietal ERPs as diagnostic and predictive biomarkers or intervention targets are recommended.
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http://dx.doi.org/10.3389/fpsyt.2019.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555259PMC
May 2019

Machine Learning Analysis of the Relationships Between Gray Matter Volume and Childhood Trauma in a Transdiagnostic Community-Based Sample.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 08 13;4(8):734-742. Epub 2019 Mar 13.

Laureate Institute for Brain Research, Tulsa, Oklahoma; Department of Community Medicine, University of Tulsa, Tulsa, Oklahoma; Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma.

Background: Childhood trauma is a significant risk factor for adult psychopathology. Previous investigations have implicated childhood trauma-related structural changes in anterior cingulate, dorsolateral prefrontal and orbitofrontal cortex, and hippocampus. Using a large transdiagnostic community sample, the goal of this investigation was to differentially associate regional gray matter (GM) volume with childhood trauma severity specifically, distinct from adult psychopathology.

Methods: A total of 577 non-treatment-seeking adults (n = 207 men) completed diagnostic, childhood trauma, and structural magnetic resonance imaging assessments with regional GM volume estimated using FreeSurfer. Elastic net analysis was conducted in a nested cross-validation framework, with GM volumes, adult psychopathology, age, education, sex, and magnetic resonance imaging coil type as potential predictors for childhood trauma severity.

Results: Elastic net identified age, education, sex, medical condition, adult psychopathology, and 13 GM regions as predictors of childhood trauma severity. GM regions identified included right caudate; left pallidum; bilateral insula and cingulate sulcus; left superior, inferior, and orbital frontal regions; and regions within temporal and parietal lobes and cerebellum.

Conclusions: Results from this large, transdiagnostic sample implicate GM volume in regions central to current neurobiological theories of trauma (e.g., prefrontal cortex) as well as additional regions involved in reward, interoceptive, attentional, and sensory processing (e.g., striatal, insula, and parietal/occipital cortices). Future longitudinal studies examining the functional impact of structural changes in this broader network of regions are needed to clarify the role each may play in longer-term outcomes following trauma.
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http://dx.doi.org/10.1016/j.bpsc.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688962PMC
August 2019

Forging Neuroimaging Targets for Recovery in Opioid Use Disorder.

Front Psychiatry 2019 7;10:117. Epub 2019 Mar 7.

Laureate Institute for Brain Research, Tulsa, OK, United States.

The United States is in the midst of an opioid epidemic and lacks a range of successful interventions to reduce this public health burden. Many individuals with opioid use disorder (OUD) consume drugs to relieve physical and/or emotional pain, a pattern that may increasingly result in death. The field of addiction research lacks a comprehensive understanding of physiological and neural mechanisms instantiating this cycle of in OUD, resulting in limited interventions that successfully promote abstinence and recovery. Given the urgency of the opioid crisis, the present review highlights faulty brain circuitry and processes associated with OUD within the context of the (1). This model underscores processes as crucial to the maintenance and exacerbation of chronic substance use together with and processes. This review focuses on cross-sectional as well as longitudinal studies of relapse and treatment outcome that employ magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRs), brain stimulation methods, and/or electroencephalography (EEG) explored in frequency and time domains (the latter measured by event-related potentials, or ERPs). We discuss strengths and limitations of this neuroimaging work with respect to study design and individual differences that may influence interpretation of findings (e.g., opioid use chronicity/recency, comorbid symptoms, and biological sex). Lastly, we translate gaps in the OUD literature, particularly with respect to processes, into future research directions involving operant and classical conditioning involving aversion/stress. Overall, opioid-related stimuli may lessen their hold on frontocingulate mechanisms implicated in as a function of prolonged abstinence and that degree of frontocingulate impairment may predict treatment outcome. In addition, longitudinal studies suggest that brain stimulation/drug treatments and prolonged abstinence can change brain responses during and to reduce salience of drug cues, which may attenuate further craving and relapse. Incorporating this neuroscience-derived knowledge with the may offer a useful plan for delineating specific neurobiological targets for OUD treatment.
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http://dx.doi.org/10.3389/fpsyt.2019.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417368PMC
March 2019

Computer-Based Executive Function Training for Combat Veterans With PTSD: A Pilot Clinical Trial Assessing Feasibility and Predictors of Dropout.

Front Psychiatry 2019 1;10:62. Epub 2019 Mar 1.

Laureate Institute for Brain Research, Tulsa, OK, United States.

While evidence-based PTSD treatments are often efficacious, 20-50% of individuals continue to experience significant symptoms following treatment. Further, these treatments do not directly target associated neuropsychological deficits. Here, we describe the methods and feasibility for computer-based executive function training (EFT), a potential alternative or adjunctive PTSD treatment. Male combat veterans with full or partial PTSD ( = 20) and combat-exposed controls (used for normative comparison; = 20) completed clinical, neuropsychological and functional neuroimaging assessments. Those with PTSD were assigned to EFT ( = 13) or placebo training (word games; = 7) at home for 6 weeks, followed by repeat assessment. Baseline predictors of treatment completion were explored using logistic regressions. Individual feedback and changes in clinical symptoms, neuropsychological function, and neural activation patterns are described. Dropout rates for EFT and placebo training were 38.5 and 57.1%, respectively. Baseline clinical severity and brain activation (i.e., prefrontal-insula-amygdala networks) during an emotional anticipation task were predictive of treatment completion. Decreases in clinical symptoms were observed following treatment in both groups. EFT participants improved on training tasks but not on traditional neuropsychological assessments. All training completers indicated liking EFT, and indicated they would engage in EFT (alone or as adjunctive treatment) if offered. Results provide an initial framework to explore the feasibility of placebo-controlled, computerized, home-based executive function training (EFT) on psychological and neuropsychological function and brain activation in combat veterans with PTSD. Clinical severity and neural reactivity to emotional stimuli may indicate which veterans will complete home-based computerized interventions. While EFT may serve as a potential alternative or adjunctive PTSD treatment, further research is warranted to address compliance and determine whether EFT may benefit functioning above and beyond placebo interventions.
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http://dx.doi.org/10.3389/fpsyt.2019.00062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405637PMC
March 2019

SMART-CPT for veterans with comorbid post-traumatic stress disorder and history of traumatic brain injury: a randomised controlled trial.

J Neurol Neurosurg Psychiatry 2019 03 15;90(3):333-341. Epub 2018 Dec 15.

Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, California, USA.

Objective: To better concurrently address emotional and neuropsychological symptoms common in veterans with comorbid post-traumatic stress disorder (PTSD) and history of traumatic brain injury (TBI), we integrated components of compensatory cognitive training from the Cognitive Symptom Management and Rehabilitation Therapy (CogSMART) programme into cognitive processing therapy (CPT) for PTSD to create a hybrid treatment, SMART-CPT (CogSMART+CPT). This study compared the efficacy of standard CPT with SMART-CPT for treatment of veterans with comorbid PTSD and history of TBI reporting cognitive symptoms.

Methods: One hundred veterans with PTSD, a history of mild to moderate TBI and current cognitive complaints were randomised and received individually delivered CPT or SMART-CPT for 12 weeks. Participants underwent psychological, neurobehavioural and neuropsychological assessments at baseline, on completion of treatment and 3 months after treatment.

Results: Both CPT and SMART-CPT resulted in clinically significant reductions in PTSD and postconcussive symptomatology and improvements in quality of life. SMART-CPT resulted in additional improvements in the neuropsychological domains of attention/working memory, verbal learning/memory and novel problem solving.

Conclusion: SMART-CPT, a mental health intervention for PTSD, combined with compensatory cognitive training strategies, reduces PTSD and neurobehavioural symptoms and also provides added value by improving cognitive functioning.
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http://dx.doi.org/10.1136/jnnp-2018-319315DOI Listing
March 2019

Evidence Over Dogma: Embracing an Expanding Repertoire of PTSD Treatment Options.

Authors:
Robin L Aupperle

Am J Psychiatry 2018 10;175(10):927-928

From the Laureate Institute for Brain Research and the School of Community Medicine, University of Tulsa, Tulsa, Okla.

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http://dx.doi.org/10.1176/appi.ajp.2018.18060675DOI Listing
October 2018

Latent variable analysis of negative affect and its contributions to neural responses during shock anticipation.

Neuropsychopharmacology 2019 03 22;44(4):695-702. Epub 2018 Aug 22.

Laureate Institute for Brain Research, Tulsa, OK, USA.

Negative affect is considered an important factor in the etiology of depression and anxiety, and is highly related to pain. However, negative affect is not a unitary construct. To identify specific targets for treatment development, we aimed to derive latent variables of negative affect and test their unique contributions to affective processing during anticipation of unpredictable, painful shock. Eighty-three subjects (43 with depression and anxiety spectrum disorders and 40 healthy controls) completed self-report measures of negative valence and underwent neuroimaging while exploring computer-simulated contexts with and without the threat of a painful, but tolerable, shock. Principal component analysis (PCA) extracted distinct components of general negative affect (GNA) and pain-related negative affect (PNA). While elevated GNA and PNA were both indicative of depression and anxiety disorders, greater PNA was more strongly related to task-specific anxious reactivity during shock anticipation. GNA was associated with increased precuneus and middle frontal gyrus activity, whereas PNA was related to increased bilateral anterior insula activity. Anterior insula activity mediated the relationship between PNA and task-specific anxious reactivity. In conclusion, GNA and PNA have distinct neural signatures and uniquely contribute to anxious anticipation. PNA, via insula activity, may relate to arousal in ways that could contribute to affective dysregulation, and thus may be an important treatment target.
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http://dx.doi.org/10.1038/s41386-018-0187-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372706PMC
March 2019