Heartbeat-evoked neural response abnormalities in generalized anxiety disorder during peripheral adrenergic stimulation.

Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat-evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, µg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 µg isoproterenol infusion, the GAD group (n = 24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the healthy comparison (HC) group (n = 24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than the HC group during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 µg isoproterenol infusion. Using analyzable blood oxygenation level-dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing in prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.

Cognitive control as a potential neural mechanism of protective role of spirituality in anxiety disorders among American Indian people: An ERP study.

Research suggests that traditional cultural factors are protective against mental health conditions in American Indian (AI) populations. This study aims to determine if cognitive control is a neurocognitive mechanism of the protective role of spirituality in AI people with generalized anxiety disorder (GAD). Participants self-identified as AI (n = 52) and included individuals with GAD (n = 16) and without GAD (n = 36). Electroencephalography was collected during a stop-signal task to probe cognitive control using the P3 event-related potential. Higher levels of spirituality attenuated the processing efficiency disruption among individuals with GAD as indicated by P3 amplitudes closer to that of individuals without GAD.

Heartbeat-evoked neural response abnormalities in generalized anxiety disorder during peripheral adrenergic stimulation.

Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, µg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 µg isoproterenol infusion, the GAD group (n=24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the HC group (n=24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than HC during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 µg isoproterenol infusion. Using analyzable blood oxygenation level dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing according to prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.

Resilience and health in American Indians and Alaska Natives: A scoping review of the literature.

American Indians and Alaska Natives suffer from disproportionately high rates of chronic mental and physical health conditions. These health inequities are linked to colonization and its downstream consequences. Most of the American Indian and Alaska Native health inequities research uses a deficit framework, failing to acknowledge the resilience of American Indian and Alaska Native people despite challenging historical and current contexts. This scoping review is based on a conceptual model which acknowledges the context of colonization and its consequences (psychological and health risk factors). However, rather than focusing on health risk, we focus on protective factors across three identified domains (social, psychological, and cultural/spiritual), and summarize documented relationships between these resilience factors and health outcomes. Based on the scoping review of the literature, we note gaps in extant knowledge and recommend future directions. The findings summarized here can be used to inform and shape future interventions which aim to optimize health and well-being in American Indian and Alaska Native peoples.

Parieto-occipital ERP indicators of gut mechanosensation in humans.

Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the body's interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with faster stimulation detection and reduced reaction time variability. Capsule stimulation induced late neural responses in parieto-occipital electrodes near the midline. Moreover, these 'gastric evoked potentials' showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. Our results replicated in a separate experiment, and abdominal X-ray imaging localized most capsule stimulations to the gastroduodenal segments. Combined with our prior observation that a Bayesian model is capable of estimating computational parameters of gut-brain mechanosensation, these findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut feelings and gut-brain interactions in healthy and clinical populations.

Impulsivity in amphetamine use disorder: Examination of sex differences.

AIMS: This study aimed to test whether there are sex differences in the relationship between impulsivity and amphetamine use disorder (AMP). DESIGN: A naturalistic cross-sectional design was used. SETTING: The Tulsa 1000 study was held in Tulsa, OK, USA. PARTICIPANTS: There were two groups in this study: AMP+ (29F, 20M) and AMP- (57F, 33M). MEASUREMENTS: This project focuses on data related to impulsivity: UPPS-P impulsive behavior scale and a stop signal task (SST) during functional magnetic resonance imaging (fMRI) recording. Group, sex and their interaction were compared for UPPS-P ratings and SST fMRI and behavioral responses. FINDINGS: AMP+ reported higher UPPS-P positive and negative urgency scores (Ps < 0.001; r = 0.56 and 0.51) and displayed greater bilateral insula and amygdala responses across correct SST trials (Ps < 0.001, g range = 0.57-0.81) than AMP-. fMRI results indicated that AMP+ exhibited larger right anterior/middle insula, amygdala and nucleus accumbens signals during successful difficult stop trials than AMP- (Ps < 0.01; g = 0.63, 0.54 and 0.44, respectively). Crucially, two group × sex effects emerged: (a) within females, AMP+ reported larger UPPS-P lack of premeditation scores than AMP- (P < 0.001, r = 0.51), and (b) within males, AMP+ showed greater left middle insula signals than AMP- across correct SST trials (P = 0.01, g = 0.78). CONCLUSIONS: Both female and male amphetamine users appear to be characterized by rash action in the presence of positive and negative mood states as well as heightened recruitment of right hemisphere regions during behavioral inhibition. In contrast, planning ahead may be particularly difficult for female amphetamine users, whereas male amphetamine users may need to recruit additional left hemisphere resources during inhibitory processing.

Striatal hypoactivation during monetary loss anticipation in individuals with substance use disorders in a heterogenous urban American Indian sample.

Research suggests that disproportionate exposure to risk factors places American Indian (AI) peoples at higher risk for substance use disorders (SUD). Although SUD is linked to striatal prioritization of drug rewards over other appetitive stimuli, there are gaps in the literature related to the investigation of aversive valuation processing, and inclusion of AI samples. To address these gaps, this study compared striatal anticipatory gain and loss processing between AI-identified with SUD (SUD+; n = 52) and without SUD (SUD-; n = 35) groups from the Tulsa 1000 study who completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. Results indicated that striatal activations in the nucleus accumbens (NAcc), caudate, and putamen were greatest for anticipating gains (ps < 0.001) but showed no group differences. In contrast to gains, the SUD+ exhibited lower NAcc (p = .01, d =0.53) and putamen (p = .04, d =0.40) activation to anticipating large losses than the comparison group. Within SUD+ , lower striatal responses during loss anticipations were associated with slower MID reaction times (NAcc: r = -0.43; putamen: r = -0.35) during loss trials. This is among the first imaging studies to examine underlying neural mechanisms associated with SUD within AIs. Attenuated loss processing provides initial evidence of a potential mechanism wherein blunted prediction of aversive consequences may be a defining feature of SUD that can inform future prevention and intervention targets.

Conceptualizing Indigenous strengths-based health and wellness research using group concept mapping.

BACKGROUND: In recent years public health research has shifted to more strengths or asset-based approaches to health research but there is little understanding of what this concept means to Indigenous researchers. Therefore our purpose was to define an Indigenous strengths-based approach to health and well-being research. METHODS: Using Group Concept Mapping, Indigenous health researchers (N = 27) participated in three-phases. Phase 1: Participants provided 218 unique responses to the focus prompt "Indigenous Strengths-Based Health and Wellness Research…" Redundancies and irrelevant statements were removed using content analysis, resulting in a final set of 94 statements. Phase 2: Participants sorted statements into groupings and named these groupings. Participants rated each statement based on importance using a 4-point scale. Hierarchical cluster analysis was used to create clusters based on how statements were grouped by participants. Phase 3: Two virtual meetings were held to share and invite researchers to collaboratively interpret results. RESULTS: A six-cluster map representing the meaning of Indigenous strengths-based health and wellness research was created. Results of mean rating analysis showed all six clusters were rated on average as moderately important. CONCLUSIONS: The definition of Indigenous strengths-based health research, created through collaboration with leading AI/AN health researchers, centers Indigenous knowledges and cultures while shifting the research narrative from one of illness to one of flourishing and relationality. This framework offers actionable steps to researchers, public health practitioners, funders, and institutions to promote relational, strengths-based research that has the potential to promote Indigenous health and wellness at individual, family, community, and population levels.

The influence of self-focused attention on emotional picture processing: An ERP study.

Research has documented neurophysiological indicators of anticipation (Stimulus Preceding Negativity [SPN]) and perception (Late Positive Potential [LPP]) of threat, yet little is known as to how self-focused attention manipulations influence emotion processing within the context of cued picture viewing. With self-referent attention moderating attention to external stimuli, it is necessary to document how self-focused attention impacts attention and the ability to emotionally process external threat. The goal of the present study was to evaluate the impact of self-focused attention on the anticipation and perceptual processing of unpleasant pictures within a cued-picture viewing paradigm among 33 participants. Overall, the results suggest that the self-focused attention manipulations disrupted anticipation but not processing of pictures, as indexed by the SPN and LPP respectively. Self-focused attention appears to disrupt the preparatory attention for upcoming unpleasant stimuli, potentially through loading cognitive resources or activation of associative defensive responding. Collectively, these findings demonstrate the impact of self-focused attention within the context of emotional picture processing and suggest further areas of investigation.

Five recommendations for using large-scale publicly available data to advance health among American Indian peoples: the Adolescent Brain and Cognitive Development (ABCD) StudySM as an illustrative case.

American Indian and Alaska Native (AIAN) populations have suffered a history of exploitation and abuse within the context of mental health research and related fields. This history is rooted in assimilation policies, historical trauma, and cultural loss, and is promulgated through discrimination and disregard for traditional culture and community knowledge. In recognition of this history, it is imperative for researchers to utilize culturally sensitive approaches that consider the context of tribal communities to better address mental health issues for AIAN individuals. The public availability of data from large-scale studies creates both opportunities and challenges when studying mental health within AIAN populations. This manuscript has two goals; first, showcase an example of problematic use of Adolescent Brain Cognitive Development (ABCD) StudySM data to promulgate stereotypes about AIAN individuals and, second, in partnership with collaborators from Cherokee Nation, we provide five recommendations for utilizing data from publicly available datasets to advance health research in AIAN populations. Specifically, we argue for the consideration of (1) the heterogeneity of the communities represented, (2) the importance of focusing on AIAN health and well-being, (3) engagement of relevant communities and AIAN community leaders, (4) consideration of historical and ongoing injustices, and (5) engagement with AIAN regulatory agencies or review boards. These recommendations are founded on principles from broader indigenous research efforts emphasizing community-engaged research and principles of Indigenous Data Sovereignty and Governance.

Coping in the Clinic: Effects of Clinically Elevated Anxiety on Dynamic Neurophysiological Mechanisms of Escape/Avoidance Preparation.

BACKGROUND: Treatments for anxiety and related disorders target exaggerated escape/avoidance as a core feature, but current methods fail to improve escape/avoidance habits for many treatment-seeking individuals. To support developing tools that increase treatment efficacy by targeting mechanisms more directly, the current work examined potential distinctions in the neurophysiologies of escape and avoidance and tested how clinical anxiety affects these neurophysiologies. METHODS: Twenty-five treatment-seeking individuals with varied principal diagnoses (e.g., generalized anxiety disorder, posttraumatic stress disorder) and 20 non-treatment-seeking control subjects participated. In the study task, approximately 5.25-second cues predicted aversive images that could be avoided (blocked by a button press before image onset), escaped (ended by a button press after image onset), or not controlled. To examine neural processing and defensive response modulation, anticipatory event-related potentials were derived, and startle reflexes were probed throughout each cue. RESULTS: Multidimensional profiles were observed such that 1) anticipatory event-related potential enhancement was only reliable during avoidance preparation, and event-related potentials potentially reflected perceived/instrumental control; and 2) startle reflexes were inhibited during avoidance preparation, relatively enhanced during escape preparation, and further enhanced during uncontrollable anticipation, thus potentially reflecting fear-related activation. Treatment-seeking status, then, did not affect cortical processing, but it did moderate context-dependent fear (if individuals with severe depression were excluded) such that treatment-seeking individuals without depression showed exaggerated startle during escape, but not avoidance, preparation. CONCLUSIONS: Data suggest a specific effect of anxiety on fear system activation during preparation to escape aversion. This effect warrants further investigation as a precision target for interventions that directly modulate the specific underlying neural circuitry.

Neural processes of inhibitory control in American Indian peoples are associated with reduced mental health problems.

American Indians (AI) experience disproportionately high prevalence of suicide and substance use disorders (SUD). However, accounting for risk burden (e.g. historical trauma and discrimination), the likelihood of mental health disorders or SUD is similar or decreased compared with the broader population. Such findings have spurred psychological research examining the protective factors, but no studies have investigated its potential neural mechanisms. Inhibitory control is one of the potential neurobehavioral construct with demonstrated protective effects, but has not been examined in neuroimaging studies with AI populations specifically. We examined the incidence of suicidal thoughts and behaviors (STB) and SUD among AI (n = 76) and propensity matched (sex, age, income, IQ proxy and trauma exposure) non-Hispanic White (NHW) participants (n = 76). Among the AI sample, functional magnetic resonance imaging (fMRI) data recorded during the stop-signal task (SST) was examined in relation to STB and SUDs. AIs relative to NHW subjects displayed lower incidence of STB. AIs with no reported STBs showed greater activity in executive control regions during the SST compared with AI who endorsed STB. AI without SUD demonstrated lower activity relative to those individual reporting SUD. Results are consistent with a growing body of literature demonstrating the high level of risk burden driving disparate prevalence of mental health concerns in AI. Furthermore, differential activation during inhibitory control processing in AI individuals without STB may represent a neural mechanism of protective effects against mental health problems in AI. Future research is needed to elucidate sociocultural factors contributing protection against mental health outcomes in AIs and further delineate neural mechanisms with respect to specific concerns (e.g. SUD vs STB).

Repetitive negative thinking is associated with impaired verbal learning but not executive functioning in individuals with eating disorders.

Objective: Repetitive negative thinking (RNT) is an important symptom in the development and maintenance of eating disorders (EDs). RNT Research on RNT's effect on cognition in EDs is scarce. This investigation focused on associations between RNT and cognition in individuals with EDs. Methods: Ruminative Response Scale (RRS) was used from Tulsa-1000 study (T-1000) data (eating disorders-ED, Major Depressive Disorder-MDD, and healthy subjects) who were propensity matched to examine associations with cognitive performance. RNT was examined across groups and we quantified the associations between scores for RNT, depression, executive function, and learning/memory from the T-1000 study. A linear regression analysis was conducted to determine predictors of disability. Results: RNT was similar in ED and MDD participants, and more intense than in controls. RNT was significantly correlated with verbal learning/memory in the control (r = 0.514, p = 0.006) and ED groups (r = -0.447, p = 0.020), but this relationship had opposite slopes in either group. Increased RNT was associated with decreased verbal learning/memory ability in ED participants while in controls, increased RNT was associated with increased ability. Comorbid depression in the ED group acted as a potential moderator of the above relationship between RNT and EF. Among ED patients, depressive symptom severity was the best predictor of disability. Discussion: The differential association of RNT with cognitive abilities in ED and MDD patients suggests depression is not a mediator of RNT-mediated cognitive dysfunction in EDs. This necessitates a better understanding of the mechanistic relationship between RNT and diverse types of cognitive functioning.

Active coping strategies and less pre-pandemic alcohol use relate to college student mental health during the COVID-19 pandemic.

Objective: To further delineate risk and resilience factors contributing to trajectories of mental health symptoms experienced by college students through the pandemic. Participants: n = 183 college students (67.2% female). Methods: Linear mixed models examined time effects on depression and anxiety. Propensity-matched subgroups exhibiting "increased" versus "low and stable" depression symptoms from before to after the pandemic-onset were compared on pre-pandemic demographic and psychological factors and COVID-related experiences and coping strategies. Results: Students experienced worsening of mental health symptoms throughout the pandemic, particularly during Fall 2020 compared with Fall 2019 (Depression scale d = -0.43 [95% CI: -0.65 to -0.21]). The propensity-matched subgroup exhibiting relative resilience ("low and stable" symptoms) reported less alcohol use prior to the pandemic, greater use of active coping strategies, and less of an impact on their college progress. Conclusions: Results point to several potential targets of screening and intervention to decrease residual impacts of the pandemic.

Limits to the generalizability of resting-state functional magnetic resonance imaging studies of youth: An examination of ABCD Study® baseline data.

This study examined how resting-state functional magnetic resonance imaging (rs-fMRI) data quality and availability relate to clinical and sociodemographic variables within the Adolescent Brain Cognitive Development Study. A sample of participants with an adequate sample of quality baseline rs-fMRI data containing low average motion (framewise displacement ≤ 0.15; low-noise; n = 4,356) was compared to a sample of participants without an adequate sample of quality data and/or containing high average motion (higher-noise; n = 7,437) using Chi-squared analyses and t-tests. A linear mixed model examined relationships between clinical and sociodemographic characteristics and average head motion in the sample with low-noise data. Relative to the sample with higher-noise data, the low-noise sample included more females, youth identified by parents as non-Hispanic white, and youth with married parents, higher parent education, and greater household incomes (ORs = 1.32-1.42). Youth in the low-noise sample were also older and had higher neurocognitive skills, lower BMIs, and fewer externalizing and neurodevelopmental problems (ds = 0.12-0.30). Within the low-noise sample, several clinical and demographic characteristics related to motion. Thus, participants with low-noise rs-fMRI data may be less representative of the general population and motion may remain a confound in this sample. Future rs-fMRI studies of youth should consider these limitations in the design and analysis stages in order to optimize the representativeness and clinical relevance of analyses and results.

Increasing Native Research Leadership Through an Early Career Development Program.

Inequities impact American Indian, Alaska Native, and Native Hawaiian populations across various health conditions; in particular, many Native communities bear a disproportionate burden of substance use disorder. Such inequities persist despite concerted efforts of communities and significant research directed toward prevention and intervention. One factor hampering these efforts is the underrepresentation of researchers who are themselves Native and uniquely equipped to respond to the needs of their communities. This paper describes the innovative Native Children's Research Exchange (NCRE) Scholars program, now entering its ninth year of successful career development support for emerging Native scholars. We summarize the history of NCRE Scholars, outline the mentoring and training approaches taken to meet the unique needs of early-career Native scholars, and present key progress of program alumni. The current cohort of Scholars provide first-person perspectives on how four key program elements have supported their career development to date. NCRE Scholars has been an effective approach for supporting the next generation of Native research leaders and for helping to build an essential mass of Native researchers prepared to respond to Native community health priority needs.

Documenting the late positive potential towards self-imagery within social anxiety.

Models of social anxiety propose that negative self-imagery is a maintenance factor of psychopathology, yet the mechanisms of this relationship are unclear. One proposed mechanism is attention towards self-images. However, self-image creation does not occur in isolation and is likely influenced by other mechanisms, such as anticipatory processing (AP). The current study aimed to investigate how trait social anxiety and AP influence motivated attention during self-imagery (i.e., late-positive potential; LPP). Participants (N = 40) with a mean age of 18.95 (SD = 1.22) completed AP manipulations and a self-imagery task. Results revealed that participants with high levels of social anxiety who engaged in AP demonstrated blunted LPP activity in the late time window (6000-10,000 ms) relative to those who engaged in Distraction. These results suggest that motivated attention towards self-imagery may be impacted by anticipatory processing, but less influenced by the valence of self-imagery. Given previous research has been limited in methodology, this study expands upon current research by documenting the neural mechanisms of self-imagery manipulations within social anxiety.

Independent Psychometric Evaluation and Predictive Utility of The Social Anxiety Questionnaire.

The Social Anxiety Questionnaire (SAQ) is a 10-item measure of social anxiety developed to comprehensively and concisely target the mechanisms described in Clark and Wells' model of social anxiety and address the breadth of social anxiety symptoms which may not all be encompassed in existing questionnaires. The aim of the current studies is to independently investigate the factor structure of the SAQ (i.e., Study 1 and 2) and determine its predictive validity and utility (i.e., Study 3 and 4). Data were collected across 4 studies to evaluate the factor structure and utility. Overall, the results suggest that a total summed score of the SAQ appeared to capture unique aspects of social anxiety that may not be captured using a single measure and appears to provide utility in experimental manipulations of theoretical maintenance factors. The current study was limited by a convenience sample and future research should continue to document the psychometric properties and clinical utility of this novel measure of social anxiety. The SAQ may show promise in both correlational and experimental research but future research should consider further evaluation of its utility.