Cancer Epidemiology in Hispanic Populations: An Analysis of Funded Observational Research at the National Cancer Institute.

BACKGROUND: More than 62 million people self-identified as Hispanic/Latino (H/L) in the 2020 United States census. The U.S. H/L population has higher burden of certain cancers compared with their non-Hispanic White counterparts. METHODS: Key term search using the NIH Query/View/Report (QVR) system, along with Research, Condition, and Disease Categorization codes identified cancer epidemiology research grants in H/L populations funded by the NCI as a primary or secondary funder from fiscal years 2016 through 2021. Three reviewers identified eligible grants based on specified inclusion/exclusion criteria and a codebook for consistency extracting key characteristics. RESULTS: A total of 450 grants were identified through the QVR system using key words related to H/Ls; 41 cancer epidemiology grants remained after applying exclusion criteria. These grants contained specific aims focused on H/Ls (32%) or included H/Ls as part of a racial/ethnic comparison (68%). NCI was the primary funder of the majority of the grants (85%), and most of the research grants focused on cancer etiology (44%) and/or survivorship (49%). Few grants (10%) investigated environmental exposures. CONCLUSIONS: This article provides an overview of NCI-funded cancer epidemiology research in H/L populations from 2016 to 2021. Future cancer epidemiology research should reflect the changing dynamics of the U.S. demography with diverse, representative populations and well-characterized ethnicity. IMPACT: Research that carefully measures the relevant biological, environmental, behavioral, psychologic, sociocultural, and clinical risk factors will be critical to better understanding the nuanced patterns influencing cancer-related outcomes in the heterogenous H/L population.

Advancing rapid cycle research in cancer care delivery: a National Cancer Institute workshop report.

Generating actionable research findings quickly and efficiently is critical for improving the delivery of cancer-related care and outcomes. To address this issue, the National Cancer Institute convened subject matter experts, researchers, clinicians, and patients for a 2-day virtual meeting in February 2022. The purpose of this meeting was to identify how rapid cycle interventional research methods can be used to generate findings useful in improving routine clinical practice. The meeting yielded an initial conceptualization of rapid cycle interventional research as being comprised of 6 key elements: use of iterative study designs; reliance on proximal primary outcomes; early and continued engagement with community and clinical partners; use of existing data sources to measure primary outcomes; facilitative features of the study setting and context; and consideration of appropriate rigor relative to intended use of findings. The meeting also identified the types of study designs that can be leveraged to conduct rapid cycle interventional research and provided examples of these; considered this approach from the perspective of key partners; described the clinical and data infrastructure, research resources, and key collaborations needed to support this work; identified research topics best addressed using this approach; and considered needed methodological advances. The National Cancer Institute is committed to exploring opportunities to encourage further development and application of this research approach as a means for better promoting improvements in the delivery of cancer-related care.

Brain-behavioral adaptability predicts response to cognitive behavioral therapy for emotional disorders: A person-centered event-related potential study.

Single-trial-level analyses afford the ability to link neural indices of elaborative attention (such as the late positive potential [LPP], an event-related potential) with downstream markers of attentional processing (such as reaction time [RT]). This approach can provide useful information about individual differences in information processing, such as the ability to adapt behavior based on attentional demands ("brain-behavioral adaptability"). Anxiety and depression are associated with maladaptive information processing implicating aberrant cognition-emotion interactions, but whether brain-behavioral adaptability predicts response to psychotherapy is not known. We used a novel person-centered, trial-level analysis approach to link neural indices of stimulus processing to behavioral responses and to predict treatment outcome. Thirty-nine patients with anxiety and/or depression received 12 weeks of cognitive behavioral therapy (CBT). Prior to treatment, patients performed a speeded reaction-time task involving briefly-presented pairs of aversive and neutral pictures while electroencephalography was recorded. Multilevel modeling demonstrated that larger LPPs predicted slower responses on subsequent trials, suggesting that increased attention to the task-irrelevant nature of pictures interfered with reaction time on subsequent trials. Whereas using LPP and RT averages did not distinguish CBT responders from nonresponders, in trial-level analyses individuals who demonstrated greater ability to benefit behaviorally (i.e., faster RT) from smaller LPPs on the previous trial (greater brain-behavioral adaptability) were more likely to respond to treatment and showed greater improvements in depressive symptoms. These results highlight the utility of trial-level analyses to elucidate variability in within-subjects, brain-behavioral attentional coupling in the context of emotion processing, in predicting response to CBT for emotional disorders.

Emotion-based brain mechanisms and predictors for SSRI and CBT treatment of anxiety and depression: a randomized trial.

Mechanisms and predictors for the successful treatment of anxiety and depression have been elusive, limiting the effectiveness of existing treatments and curtailing the development of new interventions. In this study, we evaluated the utility of three widely used neural probes of emotion (experience, regulation, and perception) in their ability to predict symptom improvement and correlate with symptom change following two first-line treatments-selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Fifty-five treatment-seeking adults with anxiety and/or depression were randomized to 12 weeks of SSRI or CBT treatment (ClinicalTrials.gov identifier: NCT01903447). Functional magnetic resonance imaging (fMRI) was used to examine frontolimbic brain function during emotion experience, regulation, and perception, as probed by the Emotion Regulation Task (ERT; emotion experience and regulation) and emotional face assessment task (EFAT; emotion perception). Brain function was then related to anxiety and depression symptom change. Results showed that both SSRI and CBT treatments similarly attenuated insula and amygdala activity during emotion perception, and greater treatment-related decrease in insula and amygdala activity was correlated with greater reduction in anxiety symptoms. Both treatments also reduced amygdala activity during emotion experience but brain change did not correlate with symptom change. Lastly, greater pre-treatment insula and amygdala activity during emotion perception predicted greater anxiety and depression symptom improvement. Thus, limbic activity during emotion perception is reduced by both SSRI and CBT treatments, and predicts anxiety and depression symptom improvement. Critically, neural reactivity during emotion perception may be a non-treatment-specific mechanism for symptom improvement.

The current state of funded NIH grants in implementation science in genomic medicine: a portfolio analysis.

PURPOSE: Implementation science offers methods to evaluate the translation of genomic medicine research into practice. The extent to which the National Institutes of Health (NIH) human genomics grant portfolio includes implementation science is unknown. This brief report's objective is to describe recently funded implementation science studies in genomic medicine in the NIH grant portfolio, and identify remaining gaps. METHODS: We identified investigator-initiated NIH research grants on implementation science in genomic medicine (funding initiated 2012-2016). A codebook was adapted from the literature, three authors coded grants, and descriptive statistics were calculated for each code. RESULTS: Forty-two grants fit the inclusion criteria (~1.75% of investigator-initiated genomics grants). The majority of included grants proposed qualitative and/or quantitative methods with cross-sectional study designs, and described clinical settings and primarily white, non-Hispanic study populations. Most grants were in oncology and examined genetic testing for risk assessment. Finally, grants lacked the use of implementation science frameworks, and most examined uptake of genomic medicine and/or assessed patient-centeredness. CONCLUSION: We identified large gaps in implementation science studies in genomic medicine in the funded NIH portfolio over the past 5 years. To move the genomics field forward, investigator-initiated research grants should employ rigorous implementation science methods within diverse settings and populations.

Impact of PTSD on post-concussive symptoms, neuropsychological functioning, and pain in post-9/11 veterans with mild traumatic brain injury.

Prior work suggested that post-traumatic stress disorder (PTSD) worsens post-concussive symptoms (PCS), neuropsychological functioning, and pain-related outcomes in post-9/11 veterans. However, the impact of PTSD in the context of mild traumatic brain injury (mTBI) is not entirely clear. We evaluated possible differences among veterans with deployment-related mTBI with and without PTSD, and a comparison group. We hypothesized that veterans with comorbid mTBI and PTSD would report more PCS, perform worse on neuropsychological tasks, and report greater pain intensity and maladaptive pain coping relative to those without PTSD. Ninety (15 female, 75 male) post-9/11 veterans completed measures of psychiatric functioning, PCS, deployment-related mTBI, pain intensity, pain coping, and a brief neuropsychological evaluation. Veterans with comorbid mTBI and PTSD reported significantly higher PCS across domains, and greater pain intensity and maladaptive coping. They also performed more poorly on measures of recall, but not on measures of attention, encoding, or executive functioning. Findings suggest that PTSD results in greater PCS in the context of mTBI, and is associated with greater pain catastrophizing, worse recall, greater pain intensity, and greater illness-focused coping than in mTBI alone. PCS symptoms, recall, and pain coping may be of clinical importance for post-9/11 veterans with the "polytrauma triad."

Neural Responsiveness to Reward as an Index of Depressive Symptom Change Following Cognitive-Behavioral Therapy and SSRI Treatment.

OBJECTIVE: Reward positivity (RewP), a neurophysiologic index of reward responsivity, is consistently reduced in participants with depression and, to a lesser extent, anxiety. It remains unknown, however, whether RewP can be altered as psychiatric symptoms change with treatment. The current study addressed this question by examining differences in RewP within patients before and after 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral therapy (CBT). We also examined the utility of RewP as a predictor of symptom change during CBT and SSRI treatment. METHODS: Participants were recruited between 2014 and 2017 and included adults with a primary DSM-5 anxiety or depressive disorder (n = 63) and healthy controls (n = 25). At baseline and 12 weeks, participants completed a monetary award task while electroencephalogram (EEG) was recorded. Between EEG sessions, patients completed CBT or SSRI treatment. RESULTS: At baseline, higher levels of depressive symptoms were associated with a more attenuated RewP. We found no significant differences between patients and healthy controls in the degree of RewP change across the 12 weeks; however, among patients, the extent of increase in RewP robustly correlated with the extent of decline in depressive (t = -2.21, P = .03) and anxiety (t = -2.57, P = .02) symptoms following CBT and SSRI treatment. Additionally, a more attenuated RewP at baseline predicted a greater reduction in depressive symptoms following treatment with SSRIs (t = -2.04, P < .05), but not after CBT. CONCLUSIONS: These findings highlight neural responsiveness to reward as both a mechanism and a predictor of depressive symptom change that may be used serve as an objective index of symptom improvement. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01903447.

Individual differences in combat experiences and error-related brain activity in OEF/OIF/OND veterans.

Increased error-related negativity (ERN) has been implicated in the pathophysiology of multiple forms of psychopathology. Although there is increasing evidence that the ERN can be shaped by environment and experience, no studies to date have examined this question in a clinical sample. In the current study, we examined the influence of combat exposure on the ERN using electroencephalogram (EEG) in a sample of military veterans with a high prevalence of psychopathology. Participants included sixty-seven U.S. military veterans from Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). The degree of combat exposure was assessed using the Deployment Risk and Resilience Inventory-2 (DRRI-2) and Combat Exposure Scale (CES). A well-validated flanker task was used to elicit the ERN during continuous EEG recording. Results revealed that veterans who reported experiencing greater combat exposure exhibited a more enhanced ERN, even when adjusting for broad anxiety and posttraumatic stress disorder (PTSD) symptoms. The association between combat exposure and ERN was not moderated by PTSD symptom severity. The current study demonstrates that greater combat exposure is associated with a more enhanced ERN among OEF/OIF/OND veterans. This enhanced ERN may be one mechanism that places veterans at greater risk for developing psychiatric disorders following exposure to combat. Future longitudinal studies are needed to directly test whether the ERN mediates the relation between level of combat exposure and the development of internalizing disorders.

Trait attentional control modulates neurofunctional response to threat distractors in anxiety and depression.

Accumulating data suggest attentional control capability varies across psychiatric diagnostic boundaries. The Attentional Control Scale (ACS) assesses self-reported trait attentional control (TAC) and tracks the anterior attention system. Greater TAC is associated with less negative affect, however, its mechanisms in anxiety and depression are poorly understood. Therefore, we examined whether individual differences in TAC modulated top-down mechanisms in a clinical sample. During fMRI, 104 patients with social anxiety, generalized anxiety, and/or major depression and 34 healthy participants completed a validated attentional control paradigm comprising strings of letters superimposed on threatening and neutral face distractors. In the low perceptual load condition, a target letter was in a string of identical letters. In the high load condition, a target letter was in a mixed letter string. Whole-brain regression results for low load revealed more activation to threat (vs. neutral) distractors in the pregenual anterior cingulate cortex was predicted by better TAC (i.e., higher ACS scores). For high load, regression results showed less activation to threat (vs. neutral) distractors in the inferior frontal gyrus was predicted by better TAC. An exploratory whole-brain ANOVA revealed a main effect of group in the superior temporal gyrus and a main effect of perceptual load in parietal, frontal, and limbic regions. No other effects were detected and activation derived from significant ANOVA results did not correlate with ACS scores. In conclusion, regression findings suggest individual differences in brain-behavioral ACS-related activity in frontal structures may be useful in identifying phenotypes in internalizing conditions.

Convergence of fMRI and ERP measures of emotional face processing in combat-exposed U. S. military veterans.

The late positive potential (LPP) and fMRI blood-oxygen-level dependent (BOLD) activity can provide complementary measures of the processing of affective and social stimuli. Separate lines of research using these measures have often employed the same stimuli, paradigms, and samples; however, there remains relatively little understanding of the way in which individual differences in one of these measures relates to the other, and all prior research has been conducted in psychiatrically healthy samples and using emotional scenes (not faces). Here, 32 combat-exposed U. S. military veterans with varying levels of posttraumatic stress symptomatology viewed affective social stimuli (angry, fearful, and happy faces) and geometric shapes during separate EEG and fMRI BOLD recordings. Temporospatial principal component analysis was used to quantify the face-elicited LPP in a data-driven manner, prior to conducting whole-brain correlations between resulting positivities and fMRI BOLD elicited by faces. Participants with larger positivities to fearful faces (> shapes) showed increased activation in the amygdala; larger positivities to angry and happy faces (> shapes) were associated with increased BOLD activation in the posterior fusiform gyrus and inferior temporal gyrus, respectively. Across all face types, larger positivities were associated with increased activation in the fusiform "face" area. Correlations using mean area amplitude LPPs showed an association with increased activation in the anterior insula for angry faces (> shapes). LPP-BOLD associations were not moderated by PTSD. Findings provide the first evidence of correspondence between face-elicited LPP and BOLD activation across a range of (normal to disordered) psychiatric health.

Error-related Brain Activity as a Treatment Moderator and Index of Symptom Change during Cognitive-Behavioral Therapy or Selective Serotonin Reuptake Inhibitors.

Increased neural error monitoring, as measured by the error-related negativity (ERN), is a transdiagnostic neurobiological marker of anxiety. To date, little is known about whether the ERN can inform the choice between first-line anxiety disorder treatments and whether the ERN changes following treatment completion. The aim of the study was to therefore assess whether the ERN is a treatment moderator and index of symptom change during cognitive-behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs). Participants included adult volunteers (M age=25.8±8.5; 67% female) with principal anxiety disorders (n=60) or no lifetime history of Axis I psychopathology (ie, healthy controls; n=26). A flanker task was used to elicit the ERN at baseline and 12 weeks later, following either CBT or SSRIs in the patient sample. Results indicated that baseline ERN was a significant treatment moderator such that a more enhanced baseline ERN was associated with greater reduction in anxiety symptoms within individuals who received CBT but not SSRIs. Results also revealed that the ERN increased pre- to post-treatment among patients randomized to SSRIs, but remained stable among patients randomized to CBT and healthy controls. Together, these novel findings highlight that ERN may help guide treatment decisions regarding engagement in CBT or SSRIs, especially among individuals with an enhanced ERN. The findings also suggest that SSRIs have the capacity to alter individual differences in the ERN, providing evidence that the ERN is not entirely static in patients with anxiety disorders.

Neural response to errors is associated with problematic alcohol use over time in combat-exposed returning veterans: An event-related potential study.

BACKGROUND: Currently, we do not have biomarkers to help identify individuals at-risk for chronic, problematic alcohol use, especially among veteran populations, who have notoriously high rates of alcohol use. One biomarker that may predict individuals at risk for chronic, problematic alcohol use is error-related brain activity. We examined longitudinal associations between the error-related negativity (ERN), an event-related potential observed following the commission of errors, and problematic alcohol use among U.S. military veterans returning from recent conflicts in Iraq and Afghanistan. METHODS: Forty-six military veterans, aged 18-55 years, completed a well-validated flanker task known to elicit the ERN at baseline. Problematic alcohol use and other clinically relevant variables were assessed at baseline, 3-, 6-, 9-, 12-, 15-, 18-, 21-months, and 2 years. RESULTS: Results indicated that the ERN magnitude was associated with problematic alcohol use over time, even after controlling for relevant clinical variables. Specifically, veterans with a smaller ERN magnitude evidenced a decline in problematic alcohol use over time, while veterans with a larger ERN magnitude had no change in their problematic alcohol use across the follow-up. In addition, exploratory analyses found that treatment engagement during the study did not moderate these relationships. CONCLUSIONS: Our findings provide preliminary evidence that ERN can be used as a predictor of problematic alcohol use over time. Therefore, neural response to errors could help to identify individuals at risk for continued problematic alcohol use for intervention efforts and suggests that error processing may be an important therapeutic target within Alcohol Use Disorder intervention efforts.

Neural indices of emotional reactivity and regulation predict course of PTSD symptoms in combat-exposed veterans.

After diagnosis, veterans with posttraumatic stress disorder (PTSD) display significant variability in the natural course of illness (Bonanno et al., 2012)). Cross-sectional work reveals that abnormal neural response during emotion reactivity-measured using the late positive potential (LPP)-correlates with PTSD symptom severity; however, whether the LPP during emotional reactivity and regulation predicts symptoms over time is unknown. The current study examined the LPP during emotion reactivity and regulation as predictors of PTSD symptoms over one year in OEF/OIF/OND combat-exposed veterans. At baseline, participants completed an Emotion Regulation Task (ERT) during electroencephalogram recording. The Clinician Administered PTSD Scale (CAPS) was completed at baseline (N=86), 6-months (N=54) and 1-year (N=49) later. During ERT, participants viewed negative pictures; partway through they were instructed to "reappraise" (i.e., reduce negative affect/regulate) or "look" (i.e., passively react). Change in LPP during emotional reactivity (ΔLPP-E) and reappraisal (ΔLPP-R) were calculated and used in multilevel mixed modeling to predict CAPS over time. Findings demonstrated that deficiency in reappraisal (ΔLPP-R) predicted more overall symptoms over time, while greater neural responses to emotion (ΔLPP-E) and greater change in neural response as a function of reappraisal (ΔLPP-R) predicted a decline in avoidance symptoms over time. Together, results support the utility of neural markers of emotional reactivity and regulation as predictors of PTSD symptoms-and change in symptoms-across one year.

Studying de-implementation in health: an analysis of funded research grants.

BACKGROUND: Studying de-implementation-defined herein as reducing or stopping the use of a health service or practice provided to patients by healthcare practitioners and systems-has gained traction in recent years. De-implementing ineffective, unproven, harmful, overused, inappropriate, and/or low-value health services and practices is important for mitigating patient harm, improving processes of care, and reducing healthcare costs. A better understanding of the state-of-the-science is needed to guide future objectives and funding initiatives. To this end, we characterized de-implementation research grants funded by the United States (US) National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ). METHODS: We used systematic methods to search, identify, and describe de-implementation research grants funded across all 27 NIH Institutes and Centers (ICs) and AHRQ from fiscal year 2000 through 2017. Eleven key terms and three funding opportunity announcements were used to search for research grants in the NIH Query, View and Report (QVR) system. Two coders identified eligible grants based on inclusion/exclusion criteria. A codebook was developed, pilot tested, and revised before coding the full grant applications of the final sample. RESULTS: A total of 1277 grants were identified through the QVR system; 542 remained after removing duplicates. After the multistep eligibility assessment and review process, 20 grant applications were coded. Many grants were funded by NIH (n = 15), with fewer funded by AHRQ, and a majority were funded between fiscal years 2015 and 2016 (n = 11). Grant proposals focused on de-implementing a range of health services and practices (e.g., medications, therapies, screening tests) across various health areas (e.g., cancer, cardiovascular disease) and delivery settings (e.g., hospitals, nursing homes, schools). Grants proposed to use a variety of study designs and research methods (e.g., experimental, observational, mixed methods) to accomplish study aims. CONCLUSIONS: Based on the systematic portfolio analysis of NIH- and AHRQ-funded research grants over the past 17 years, relatively few have focused on studying the de-implementation of ineffective, unproven, harmful, overused, inappropriate, and/or low-value health services and practices provided to patients by healthcare practitioners and systems. Strategies for raising the profile and growing the field of research on de-implementation are discussed.

PTSD symptoms are associated with visual retrieval performance in OEF/OIF/OND veterans.

Posttraumatic stress disorder (PTSD) is associated with poorer performance on neuropsychological tests in veterans. However, prior studies have generally compared individuals with PTSD to control groups, often excluding individuals with moderate symptoms. The present study evaluated neuropsychological performance among OEF/OIF/OND veterans as a function of overall PTSD severity, while also exploring potential associations between cognitive performance and PTSD symptom clusters. Using a brief neuropsychological battery, clinical interviews, and self-report instruments, we evaluated neuropsychological and psychiatric functioning in 90 OEF/OIF/OND veterans. When controlling for the effects of premorbid intellectual functioning and combat exposure, higher PTSD severity predicted worse visual retrieval performance, but not attention, verbal retrieval, visual learning, or executive functioning performance. A trend was observed where higher PTSD symptoms predicted worse verbal learning performance. All PTSD symptom clusters were associated with visual retrieval performance within the full sample. Avoidance and numbing symptoms were associated with verbal learning in the full sample. Findings suggest that among OEF/OIF/OND veterans with a range of PTSD symptoms, the assessment of visual memory may have implications for clinical practice.

Predicting cognitive behavioral therapy response in social anxiety disorder with anterior cingulate cortex and amygdala during emotion regulation.

BACKGROUND: Cognitive Behavioral Therapy (CBT) for social anxiety disorder (SAD) and other internalizing conditions attempts to improve emotion regulation. Accumulating data indicate anterior cingulate cortex (ACC), and to a lesser extent amygdala, activation in various tasks predicts treatment outcome. However, little is known about ACC and amygdala activation to emotion regulation in predicting clinical improvement following CBT in SAD. METHODS: Before treatment, 38 SAD patients completed implicit and explicit emotion regulation paradigms during fMRI. Implicit regulation involved attentional control over negative distractors. Explicit regulation comprised cognitive reappraisal to negative images. Pre-CBT brain activity was circumscribed to anatomical-based ACC sub-regions (rostral, dorsal) and amygdala masks, which were submitted to ROC curves to examine predictive validity as well as correlational analysis to evaluate prognostic change in symptom severity. RESULTS: More rostral (rACC) activity in implicit regulation and less rACC activity during explicit regulation distinguished responders (34%) from non-responders. Greater amygdala response in implicit regulation also foretold responder status. Baseline rACC and amygdala activity during attentional control correlated with pre-to-post CBT change in symptom severity such that more activation was related to greater decline in symptoms. No significant correlations were observed for explicit regulation. CONCLUSIONS: Across forms of regulation, rACC activity predicted responder status whereas amygdala as a neuromarker was limited to implicit regulation. While the direction of effects (enhanced vs. reduced) in rACC activity was task-dependent, results suggest SAD patients with deficient regulation benefited more from CBT. Findings support previous studies involving patients with depression and suggest the rACC may be a viable marker of clinical improvement in SAD.

Prefrontal and amygdala engagement during emotional reactivity and regulation in generalized anxiety disorder.

BACKGROUND: Emotion dysregulation is prominent in generalized anxiety disorder (GAD), characterized clinically by exaggerated reactivity to negative stimuli and difficulty in down-regulating this response. Although limited research implicates frontolimbic disturbances in GAD, whether neural aberrations occur during emotional reactivity, regulation, or both is not well understood. METHODS: During functional magnetic resonance imaging (fMRI), 30 individuals with GAD and 30 healthy controls (HC) completed a well-validated explicit emotion regulation task designed to measure emotional reactivity and regulation of reactivity. During the task, participants viewed negative images ('Look-Negative' condition) and, on some trials, used a cognitive strategy to reduce negative affective response ('Reappraise' condition). RESULTS: Results from an Analysis of Variance corrected for whole brain multiple comparisons showed a significant group x condition interaction in the left amygdala and left inferior frontal gyrus (IFG). Results from post-hoc analyses showed that the GAD group engaged these regions to a greater extent than HCs during Look-Negative but not Reappraise. Behaviorally, the GAD group reported feeling more negative than the HC group in each condition, although both groups reported reduced negative affect following regulation. LIMITATIONS: As comorbidity was permitted, the presence of concurrent disorders, like other anxiety disorders and depression, detracts our ability to classify neural engagement particular to GAD alone. CONCLUSIONS: Individuals with GAD exhibited over-engagement of amygdala and frontal regions during the viewing of negative images, compared to HCs. Together, these aberrations may indicate that deficits in emotional reactivity rather than regulation contribute to emotion dysregulation in those with GAD.

Neurofunctional correlates of behavioral inhibition system sensitivity during attentional control are modulated by perceptual load.

Although the Behavioral Inhibition System (BIS) is associated with threat-sensitivity, little is known about its neurofunctional correlates during cognitive control over task-irrelevant threat distractors. Thirty non-clinical participants, who ranged in BIS sensitivity, completed an attentional control paradigm during fMRI. The paradigm varied in cognitive demand with low perceptual load comprising identical target letters and high perceptual load comprising a target letter in a mixed letter string; each superimposed on threatening and neutral face distractors. Whole-brain results indicated that individuals with higher, relative to lower BIS sensitivity, exhibited enhanced dorsolateral prefrontal cortex activation to angry (vs. neutral) and enhanced dorsal anterior cingulate cortex activation to fearful (vs. neutral) face distractors under low load whereas no differences in activation were observed under high load. These findings are consistent with literature indicating that the BIS is involved in conflict processing, including between cognitive and emotional or motivational goals.