Research Letter: Concussion-Related General Startle Suppression in Adolescent Athletes.

OBJECTIVES: We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but no current symptoms. We hypothesized that individuals with recent concussion would have a suppressed startle response compared to healthy controls. METHODS: We conducted a cross-sectional study on 49 adolescent athletes with a recent concussion (n = 20; age: 14.6 ± 1.6 years; 60% female), a concussion history > 1 year prior (n = 16; age: 14.8 ± 2.0 years; 44% female), and healthy controls (n = 13; age: 13.3 ± 2.8 years; 54% female). We measured the eyeblink of the general startle reflex via electromyography activity of the orbicularis oculi muscle using electrodes placed under the right eye. Measurement sessions included twelve 103 decibel acoustic startle probes ~50 milliseconds in duration delivered ~15-25 seconds apart. The primary dependent variable was mean startle magnitude (µV), and group was the primary independent variable. We used a one-way analysis of variance followed by a Tukey post hoc test to compare mean startle magnitude between groups. RESULTS: Mean startle magnitude significantly differed (F = 5.49, P = .007) among the groups. Mean startle magnitude was significantly suppressed for the concussion (P = .01) and concussion history groups (P = .02) compared to healthy controls. There was no significant difference between the recent concussion and concussion history groups (P = 1.00). CONCLUSION: Our results provide novel evidence for startle suppression in adolescent athletes following concussion. The concussion history group had an attenuated startle response beyond resolution of their recovery, suggesting there may be lingering physiological dysfunction.

Whose Signals Are Being Amplified? Toward a More Equitable Clinical Psychophysiology.

Research using psychophysiological methods holds great promise for refining clinical assessment, identifying risk factors, and informing treatment. Unfortunately, unique methodological features of existing approaches limit inclusive research participation and, consequently, generalizability. This brief overview and commentary provides a snapshot of the current state of representation in clinical psychophysiology, with a focus on the forms and consequences of ongoing exclusion of Black participants. We illustrate issues of inequity and exclusion that are unique to clinical psychophysiology, considering intersections among social constructions of Blackness and biased design of current technology used to measure electroencephalography, skin conductance, and other signals. We then highlight work by groups dedicated to quantifying and addressing these limitations. We discuss the need for reflection and input from a wider variety of stakeholders to develop and refine new technologies, given the risk of further widening disparities. Finally, we provide broad recommendations for clinical psychophysiology research.

Sociability Alcohol Expectancies Shape Predictions of Drinking Behavior and Anxiety in a Novel Affective Forecasting Task.

Background: Existing work proposes that people with higher social anxiety symptoms and sociability alcohol expectancies believe alcohol can lower their anxiety. However, studies have primarily analyzed retrospective reports, not anticipatory motives. Since predictions of future emotion (i.e., affective forecasts) strongly influence behavior, it is critical to understand how people predict alcohol will influence their anxiety. Additionally, intolerance of uncertainty (IU) is related to the use of alcohol as a coping tool, but there is a dearth of work testing whether IU influences alcohol-related forecasts. Objectives: Utilizing a novel affective forecasting task, we tested the prediction that social anxiety symptoms, sociability alcohol expectancies, and IU would relate to predictions about alcohol use. In an initial study and preregistered replication, participants imagined themselves in stressful social scenarios and forecasted how anxious they would feel when drinking and when sober. In the replication, participants also forecasted whether they would drink in the imagined scenarios. Results: Contrary to hypotheses, social anxiety symptoms and IU did not significantly predict higher forecasted anxiety across studies, nor did they predict forecasted drinking. Exploratory analyses showed that participants with higher sociability alcohol expectancies forecasted being more likely to drink, and forecasted feeling less anxious when drinking (versus being sober). Even after statistically controlling for social anxiety, the effect of sociability expectancies remained significant in predicting forecasted anxiety and forecasted drinking. Conclusions: Clinicians could consider specifically targeting sociability expectancies for alcohol use difficulties, and future research should continue utilizing affective forecasting paradigms to test links between social anxiety, alcohol expectancies, and alcohol-use problems.

Unconditioned response to a naturally aversive stimulus is associated with sensitized defensive responding and self-reported fearful traits in a PTSD sample.

Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue (CS-) in trauma-exposed individuals during fear acquisition. However, the relationships of UCR with defensive responses during extinction training, posttraumatic stress disorder (PTSD) symptom severity, and fearful traits in trauma-exposed individuals are not known. In a sample of 100 trauma-exposed adults with a continuum of PTSD severity, we recorded startle responses and skin conductance responses (SCR) during fear acquisition and extinction training using a 140 psi, 250-ms air blast to the larynx as the unconditioned stimulus. We explored dimensional associations of two different measures of UCR (unconditioned startle and unconditioned SCR) with conditioned defensive responding to CS+ and CS-, conditioned fear (CS+ minus CS-), PTSD symptom severity, and a measure of fearful traits (composite of fear survey schedule, anxiety sensitivity index, and Connor-Davidson resilience scale). Unconditioned startle was positively associated with startle potentiation to the threat cue and the safety cue across both learning phases (CS+ Acquisition, CS- Acquisition, CS+ Extinction Training, CS- Extinction Training) and with fearful traits. Unconditioned SCR was positively associated with SCR to the CS+ and CS- and SCR difference score during Acquisition. Neither type of UCR was associated with PTSD symptom severity. Our findings suggest that UCR, particularly unconditioned startle to a naturally aversive stimulus, may inform research on biomarkers and treatment targets for symptoms of pervasive and persistent fear in trauma-exposed individuals.

Acute nicotine abstinence amplifies subjective withdrawal symptoms and threat-evoked fear and anxiety, but not extended amygdala reactivity.

Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Mechanistic work in animals implicates the central extended amygdala (EAc)-including the central nucleus of the amygdala and the neighboring bed nucleus of the stria terminalis-but the translational relevance of these discoveries remains unexplored. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science.

Multiverse analyses of fear acquisition and extinction retention in posttraumatic stress disorder.

Persistent fear is a cardinal feature of posttraumatic stress disorder (PTSD), and deficient fear extinction retention is a proposed illness mechanism and target of exposure-based therapy. However, evidence for deficient fear extinction in PTSD has been mixed using laboratory paradigms, which may relate to underidentified methodological variation across studies. We reviewed the literature to identify parameters that differ across studies of fear extinction retention in PTSD. We then performed Multiverse Analysis in a new sample, to quantify the impact of those methodological parameters on statistical findings. In 25 PTSD patients (15 female) and 36 trauma-exposed non-PTSD controls (TENC) (20 female), we recorded skin conductance response (SCR) during fear acquisition and extinction learning (day 1) and extinction recall (day 2). A first Multiverse Analysis examined the effects of methodological parameters identified by the literature review on comparisons of SCR-based fear extinction retention in PTSD versus TENC. A second Multiverse Analysis examined the effects of those methodological parameters on comparisons of SCR to a danger cue (CS+) versus safety cue (CS-) during fear acquisition. Both the literature review and the Multiverse Analysis yielded inconsistent findings for fear extinction retention in PTSD versus TENC, and most analyses found no statistically significant group difference. By contrast, significantly elevated SCR to CS+ versus CS- was consistently found across all analyses in the literature review and the Multiverse Analysis of new data. We discuss methodological parameters that may most contribute to inconsistent findings of fear extinction retention deficit in PTSD and implications for future clinical research.

Alcohol's effects during uncertain and uncontrollable stressors in the laboratory.

Alcohol's effects on reactivity to stressors depends on the nature of the stressor and the reactivity being assessed. Research identifying characteristics of stressors that modulate reactivity and clarifies the neurobehavioral, cognitive, and affective components of this reactivity may help prevent, reduce or treat the negative impacts of acute and chronic alcohol use with implications for other psychopathology involving maladaptive reactivity to stressors. We used a novel, multi-measure, cued electric shock stressor paradigm in a greater university community sample of adult recreational drinkers to test how alcohol (N=64), compared to No-alcohol (N=64), effects reactivity to stressors that vary in both their perceived certainty and controllability. Preregistered analyses suggested alcohol significantly dampened subjective anxiety (self-report) and defensive reactivity (startle potentiation) more during uncertain than during certain stressors regardless of controllability, suggesting that stressor uncertainty -but not uncontrollability- may be sufficient to enhance alcohol's stress reactivity dampening and thus negative reinforcement potential.

Leveraging the Strengths of Psychologists With Lived Experience of Psychopathology.

Psychopathology is a common element of the human experience, and psychological scientists are not immune. Recent empirical data demonstrate that a significant proportion of clinical, counseling, and school psychology faculty and graduate students have lived experience, both past and present, of psychopathology. This commentary compliments these findings by leveraging the perspectives of the authors and signatories, who have personal lived experience of psychopathology, to improve professional inclusivity in these fields. By "coming out proud," the authors aim to foster discussion, research, and inclusion efforts as they relate to psychopathology experiences in psychological science. To that end, the authors describe considerations related to disclosure of lived experience, identify barriers to inclusion, and provide concrete recommendations for personal and systemic changes to improve recognition and acceptance of psychopathology lived experience among psychologists.

Motives and Consequences of Alcohol Use in People With Social Anxiety Disorder: A Daily Diary Study.

People with social anxiety disorder (SAD) are at increased risk for alcohol-related problems. Most research exploring social anxiety and alcohol use has examined negative drinking consequences, with less consideration of positive consequences-namely positive social experiences-that may reinforce alcohol use. In this daily diary study, we examined how adults diagnosed with SAD (N = 26) and a psychologically healthy control group (N = 28) experienced positive drinking consequences in naturally occurring drinking episodes during the study period. For 14 consecutive days, participants answered questions about alcohol use, motives for drinking, and positive consequences of drinking. On days when participants drank, those with SAD were more likely than healthy controls to perceive a reduction in anxiety, but the two groups did not differ in their likelihood of experiencing positive social drinking consequences. For both groups, on days when they were more motivated to drink to enhance social experiences (affiliation motives) or cope with distress (coping motives), they were more likely to obtain positive consequences from drinking. Compared to controls, participants with SAD endorsed stronger trait and daily coping motives (anxiety-coping, social anxiety-coping, and depression-coping). Results are discussed in the context of reinforcement mechanisms that may maintain social anxiety and alcohol use.

Intolerance of uncertainty and physiological responses during instructed uncertain threat: A multi-lab investigation.

Individuals with high self-reported Intolerance of uncertainty (IU) tend to interpret uncertainty negatively. Recent research has been inconclusive on evidence of an association between IU and physiological responses during instructed uncertain threat. To address this gap, we conducted secondary analyses of IU and physiology data recorded during instructed uncertain threat tasks from two lab sites (Wisconsin-Madison; n = 128; Yale, n = 95). No IU-related effects were observed for orbicularis oculi activity (auditory startle-reflex). Higher IU was associated with: (1) greater corrugator supercilii activity to predictable and unpredictable threat of shock, compared to the safety from shock, and (2) poorer discriminatory skin conductance response between the unpredictable threat of shock, relative to the safety from shock. These findings suggest that IU-related biases may be captured differently depending on the physiological measure during instructed uncertain threat. Implications of these findings for neurobiological models of uncertainty and anticipation in anxiety are discussed.

#EEGManyLabs: Investigating the replicability of influential EEG experiments.

There is growing awareness across the neuroscience community that the replicability of findings about the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardised analysis pipelines. Inspired by recent efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalography (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound influence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and selection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations.

Psychophysiological correlates of anxious apprehension: Trait worry is associated with startle response to threat.

Worry is a form of repetitive negative thought that is closely associated with anxiety disorders. Worry has been described as anxious apprehension and conceptualized as reflecting heightened anticipation of potentially threatening future events. However, it is unclear whether people who tend to worry show heightened physiological reactivity when anticipating threat, especially if the threat is uncertain. In the current study, community participants (n = 52) completed a threat anticipation task featuring uncertain threat, certain threat, and safety while the startle response to auditory probes was measured. Self-reported tendency to worry was assessed using the Penn State Worry Questionnaire, and anxiety disorder status was assessed via a clinical interview. A repeated-measures general linear model showed a main effect of threat level on the startle response, as well as a significant three-way interaction among threat level, worry, and anxiety disorder status. Follow-up tests showed that higher worry was associated with blunted startle responses to threat but particularly to uncertain threat among participants with a history of anxiety disorders. Worry did not moderate startle responding in participants without a history of anxiety disorders. These results indicate that psychophysiological correlates of worry depend on clinical status and suggest that trait worry is associated with physiological blunting to threat in individuals with a history of anxiety disorders, particularly when threat is uncertain. Implications for theoretical models of worry are discussed.

Acute alcohol administration dampens central extended amygdala reactivity.

Alcohol use is common, imposes a staggering burden on public health, and often resists treatment. The central extended amygdala (EAc)-including the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce)-plays a key role in prominent neuroscientific models of alcohol drinking, but the relevance of these regions to acute alcohol consumption in humans remains poorly understood. Using a single-blind, randomized-groups design, multiband fMRI data were acquired from 49 social drinkers while they performed a well-established emotional faces paradigm after consuming either alcohol or placebo. Relative to placebo, alcohol significantly dampened reactivity to emotional faces in the BST. To rigorously assess potential regional differences in activation, data were extracted from unbiased, anatomically predefined regions of interest. Analyses revealed similar levels of dampening in the BST and Ce. In short, alcohol transiently reduces reactivity to emotional faces and it does so similarly across the two major divisions of the human EAc. These observations reinforce the translational relevance of addiction models derived from preclinical work in rodents and provide new insights into the neural systems most relevant to the consumption of alcohol and to the initial development of alcohol abuse in humans.

Alcohol's effects on emotionally motivated attention, defensive reactivity and subjective anxiety during uncertain threats.

Developing a better understanding of how and under what circumstances alcohol affects the emotions, cognitions and neural functions that precede and contribute to dangerous behaviors during intoxication may help to reduce their occurrence. Alcohol intoxication has recently been shown to reduce defensive reactivity and anxiety more during uncertain vs certain threat. However, alcohol's effects on emotionally motivated attention to these threats are unknown. Alcohol may disrupt both affective response to and attentional processing of uncertain threats making intoxicated individuals less able to avoid dangerous and costly behaviors. To test this possibility, we examined the effects of a broad range of blood alcohol concentrations on 96 participants' sub-cortically mediated defensive reactivity (startle potentiation), retrospective subjective anxiety (self-report) and cortically assessed emotionally motivated attention (probe P3 event related potential) while they experienced visually cued uncertain and certain location electric shock threat. As predicted, alcohol decreased defensive reactivity and subjective anxiety more during uncertain vs certain threat. In a novel finding, alcohol dampened emotionally motivated attention during uncertain but not certain threat. This effect appeared independent of alcohol's effects on defensive reactivity and subjective anxiety. These results suggest that alcohol intoxication dampens processing of uncertain threats while leaving processing of certain threats intact.

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans.

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol-dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol-dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to nonalcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent premorbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. (PsycINFO Database Record

Psychometric properties of startle and corrugator response in NPU, affective picture viewing, and resting state tasks.

The current study provides a comprehensive evaluation of critical psychometric properties of commonly used psychophysiology laboratory tasks/measures within the NIMH RDoC. Participants (N = 128) completed the no-shock, predictable shock, unpredictable shock (NPU) task, affective picture viewing task, and resting state task at two study visits separated by 1 week. We examined potentiation/modulation scores in NPU (predictable or unpredictable shock vs. no-shock) and affective picture viewing tasks (pleasant or unpleasant vs. neutral pictures) for startle and corrugator responses with two commonly used quantification methods. We quantified startle potentiation/modulation scores with raw and standardized responses. We quantified corrugator potentiation/modulation in the time and frequency domains. We quantified general startle reactivity in the resting state task as the mean raw startle response during the task. For these three tasks, two measures, and two quantification methods, we evaluated effect size robustness and stability, internal consistency (i.e., split-half reliability), and 1-week temporal stability. The psychometric properties of startle potentiation in the NPU task were good, but concerns were noted for corrugator potentiation in this task. Some concerns also were noted for the psychometric properties of both startle and corrugator modulation in the affective picture viewing task, in particular, for pleasant picture modulation. Psychometric properties of general startle reactivity in the resting state task were good. Some salient differences in the psychometric properties of the NPU and affective picture viewing tasks were observed within and across quantification methods.