Early Life Stress, Coping, and Cardiovascular Reactivity to Acute Social Stress.

OBJECTIVE: Early life stress (ELS) occurring during childhood and adolescence is an established risk factor for later cardiovascular disease and dysregulated reactivity to acute social stress. This study examined whether ELS associations with baseline cardiovascular functioning, cardiovascular stress reactivity and recovery, and emotional stress reactivity vary across levels of emotion-oriented, task-oriented, and avoidant coping styles. METHODS: The sample included 1027 adolescents and young adults (mean age = 19.29 years; 50% female; 64% Black, 34% non-Hispanic White) who reported on their ELS exposure and coping styles. Participants completed a standardized acute social stress test (the Trier Social Stress Test [TSST]), with heart rate (HR) and blood pressure (BP) measured before, during, and after the TSST. Self-reports of negative emotions during the TSST indexed emotional stress reactivity. RESULTS: Multiple regression models adjusting for demographic factors and body mass index showed that ELS was associated with lower HR stress reactivity, avoidant coping was related to lower systolic BP and diastolic BP during stress and lower systolic BP during recovery, and higher emotion-oriented coping and lower task-oriented coping predicted greater emotional stress reactivity. A consistent pattern emerged where emotion-oriented coping amplified the associations between ELS and maladaptive stress responses (blunted cardiovascular stress reactivity and recovery; enhanced emotional stress reactivity), whereas lower levels of emotion-oriented coping were associated with resilient profiles among those who experienced ELS (lower resting HR, lower emotional stress reactivity, average HR and BP stress reactivity and recovery). However, low levels of emotion-oriented coping also conferred a risk of higher BP during recovery for those with high levels of ELS. CONCLUSIONS: These results suggest that low to moderate levels of emotion-oriented coping promote optimal cardiovascular and emotional reactivity to acute stress among individuals exposed to ELS.

Development of Dynamic Measures to Assess Balance Confidence and State Anxiety While Walking at Increasing Speeds in Young and Older Adults.

The purpose of this study was to determine the test-retest reliability and construct validity of tools to assess how balance confidence (BC) and state anxiety (SA) change with progressively increasing walking speeds. Sixteen young adults and 15 older adults attended two sessions. Individuals began walking on a treadmill at 0.4 m/s Participants chose to continue increasing the treadmill speed (up to 2.0 m/s) or to discontinue the protocol while rating their BC and SA after completing each speed. BC at participants' fastest speed attempted demonstrated high and moderate test-retest reliability among young (intraclass correlation coefficient [ICC] = .908) and older adults (ICC = .704). SA for young adults and older adults was good (ICC = .833) and fair (ICC = .490), respectively. Our measures also correlated with measures of dynamic stability while walking for young (r = -.67, p = .008) and older adults (r = .54, p = .046). Our dynamic measures of BC and SA are valid and reliable in young and older adults.

Violence exposure, affective style, and stress-induced changes in resting state functional connectivity.

Chronic childhood stress is linked to greater susceptibility to internalizing disorders in adulthood. Specifically, chronic stress leads to changes in brain connectivity patterns, and, in turn, affects psychological functioning. Violence exposure, a chronic stressor, increases stress reactivity and disrupts emotion regulation processes. However, it is unclear to what extent violence exposure affects the neural circuitry underlying emotion regulation. Individual differences in affective style also moderate the impact of stress on psychological function and can thus alter the relationship between violence exposure and brain function. Resting-state functional connectivity (rsFC) is an index of intrinsic brain activity. Stress-induced changes in rsFC between the amygdala, hippocampus, and prefrontal cortex (PFC) are associated with emotion dysregulation and may elucidate how affective style modulates the relationship between violence exposure and brain connectivity. Therefore, the present study examined the impact of violence exposure and affective style on stress-induced changes in rsFC. Participants (n = 233) completed two 6-minute resting-state functional magnetic resonance imaging scans, one before (pre-stress) and one after (post-stress) a psychosocial stress task. The bilateral amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) were used as seed regions for rsFC analyses. Significant stress-induced changes in the prefrontal, fronto-limbic, and parieto-limbic rsFC were observed. Further, pre-stress to post-stress differences in rsFC varied with violence exposure and affective style. These findings suggest that prefrontal, fronto-limbic, and parieto-limbic connectivity is associated with the emotional response to stress and provide new insight into the neural mechanisms through which affective style moderates the impact violence exposure has on the brain.

Reproducibility of whole-brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy.

Assessing brain temperature can provide important information about disease processes (e.g., stroke, trauma) and therapeutic effects (e.g., cerebral hypothermia treatment). Whole-brain magnetic resonance spectroscopic imaging (WB-MRSI) is increasingly used to quantify brain metabolites across the entire brain. However, its feasibility and reliability for estimating brain temperature needs further validation. Therefore, the present study evaluates the reproducibility of WB-MRSI for temperature mapping as well as metabolite quantification across the whole brain in healthy volunteers. Ten healthy adults were scanned on three occasions 1 week apart. Brain temperature, along with four commonly assessed brain metabolites-total N-acetyl-aspartate (tNAA), total creatine (tCr), total choline (tCho) and myo-inositol (mI)-were measured from WB-MRSI data. Reproducibility was evaluated using the coefficient of variation (CV). The measured mean (range) of the intra-subject CVs was 0.9% (0.6%-1.6%) for brain temperature mapping, and 4.7% (2.5%-15.7%), 6.4% (2.4%-18.9%) and 14.2% (4.4%-52.6%) for tNAA, tCho and mI, respectively, with reference to tCr. Consistently larger variability was found when using H2 O as the reference for metabolite quantifications: 7.8% (3.3%-17.8%), 7.8% (3.1%-18.0%), 9.8% (3.7%-31.0%) and 17.0% (5.9%-54.0%) for tNAA, tCr, tCho and mI, respectively. Further, the larger the brain region (indicated by a greater number of voxels within that region), the better the reproducibility for both temperature and metabolite estimates. Our results demonstrate good reproducibility of whole-brain temperature and metabolite measurements using the WB-MRSI technique.

Negative life experiences contribute to racial differences in the neural response to threat.

Threat-related emotional function is supported by a neural circuit that includes the prefrontal cortex (PFC), hippocampus, and amygdala. The function of this neural circuit is altered by negative life experiences, which can potentially affect threat-related emotional processes. Notably, Black-American individuals disproportionately endure negative life experiences compared to White-American individuals. However, the relationships among negative life experiences, race, and the neural substrates that support threat-related emotional function remains unclear. Therefore, the current study investigated whether the brain function that supports threat-related emotional processes varies with racial differences in negative life experiences. In the present study, adolescent violence exposure, family income, and neighborhood disadvantage were measured prospectively (i.e., at 11-19 years of age) for Black-American and White-American volunteers. Participants then, as young adults (i.e., 18-23 years of age), completed a Pavlovian fear conditioning task during functional magnetic resonance imaging (fMRI). Cued and non-cued threats were presented during the conditioning task and behavioral (threat expectancy) and psychophysiological responses (skin conductance response; SCR) were recorded simultaneously with fMRI. Racial differences were observed in neural (fMRI activity), behavioral (threat expectancy), and psychophysiological (SCR) responses to threat. These threat-elicited responses also varied with negative life experiences (violence exposure, family income, and neighborhood disadvantage). Notably, racial differences in brain activity to threat were smaller after accounting for negative life experiences. The present findings suggest that racial differences in the neural and behavioral response to threat are due, in part, to exposure to negative life experiences and may provide new insight into the mechanisms underlying racial disparities in mental health.

Anticipatory prefrontal cortex activity underlies stress-induced changes in Pavlovian fear conditioning.

Excessive stress exposure often leads to emotional dysfunction, characterized by disruptions in healthy emotional learning, expression, and regulation processes. A prefrontal cortex (PFC)-amygdala circuit appears to underlie these important emotional processes. However, limited human neuroimaging research has investigated whether these brain regions underlie the altered emotional function that develops with stress. Therefore, the present study used functional magnetic resonance imaging (fMRI) to investigate stress-induced changes in PFC-amygdala function during Pavlovian fear conditioning. Participants completed a variant of the Montreal Imaging Stress Task (MIST) followed (25 min later) by a Pavlovian fear conditioning task during fMRI. Self-reported stress to the MIST was used to identify three stress-reactivity groups (Low, Medium, and High). Psychophysiological, behavioral, and fMRI signal responses were compared between the three stress-reactivity groups during fear conditioning. Fear learning, indexed via participant expectation of the unconditioned stimulus during conditioning, increased with stress reactivity. Further, the High stress-reactivity group demonstrated greater autonomic arousal (i.e., skin conductance response, SCR) to both conditioned and unconditioned stimuli compared to the Low and Medium stress-reactivity groups. Finally, the High stress group did not regulate the emotional response to threat. More specifically, the High stress-reactivity group did not show a negative relationship between conditioned and unconditioned SCRs. Stress-induced changes in these emotional processes paralleled changes in dorsolateral, dorsomedial, and ventromedial PFC function. These findings demonstrate that acute stress facilitates fear learning, enhances autonomic arousal, and impairs emotion regulation, and suggests these stress-induced changes in emotional function are mediated by the PFC.

Comparison of reproducibility of single voxel spectroscopy and whole-brain magnetic resonance spectroscopy imaging at 3T.

To date, single voxel spectroscopy (SVS) is the most commonly used MRS technique. SVS is relatively easy to use and provides automated and immediate access to the resulting spectra. However, it is also limited in spatial coverage. A new and very promising MRS technique allows for whole-brain MR spectroscopic imaging (WB-MRSI) with much improved spatial resolution. Establishing the reproducibility of data obtained using SVS and WB-MRSI is an important first step for using these techniques to evaluate longitudinal changes in metabolite concentration. The purpose of this study was to assess and directly compare the reproducibility of metabolite quantification at 3T using SVS and WB-MRSI in 'hand-knob' areas of motor cortices and hippocampi in healthy volunteers. Ten healthy adults were scanned using both SVS and WB-MRSI on three occasions one week apart. N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were quantified using SVS and WB-MRSI with reference to both Cr and H2 O. The reproducibility of each technique was evaluated using the coefficient of variation (CV), and the correspondence between the two techniques was assessed using Pearson correlation analysis. The measured mean (range) intra-subject CVs for SVS were 5.90 (2.65-10.66)% for metabolites (i.e. NAA, Cho, mI) relative to Cr, and 8.46 (4.21-21.07)% for metabolites (NAA, Cr, Cho, mI) relative to H2 O. The mean (range) CVs for WB-MRSI were 7.56 (2.78-11.41)% for metabolites relative to Cr, and 7.79 (4.57-14.11)% for metabolites relative to H2 O. Significant positive correlations were observed between metabolites quantified using SVS and WB-MRSI techniques when the Cr but not H2 O reference was used. The results demonstrate that reproducibilities of SVS and WB-MRSI are similar for quantifying the four major metabolites (NAA, Cr, Cho, mI); both SVS and WB-MRSI exhibited good reproducibility. Our findings add reference information for choosing the appropriate 1 H-MRS technique in future studies.

Relationships between study habits, burnout, and general surgery resident performance on the American Board of Surgery In-Training Examination.

BACKGROUND: The American Board of Surgery In-Training Examination (ABSITE) is used by programs to evaluate the knowledge and readiness of trainees to sit for the general surgery qualifying examination. It is often used as a tool for resident promotion and may be used by fellowship programs to evaluate candidates. Burnout has been associated with job performance and satisfaction; however, its presence and effects on surgical trainees' performance are not well studied. We sought to understand factors including burnout and study habits that may contribute to performance on the ABSITE examination. METHODS: Anonymous electronic surveys were distributed to all residents at 10 surgical residency programs (n = 326). Questions included demographics as well as study habits, career interests, residency characteristics, and burnout scores using the Oldenburg Burnout Inventory, which assesses burnout because of both exhaustion and disengagement. These surveys were then linked to the individual's 2016 ABSITE and United States Medical Licensing Examination (USMLE) step 1 and 2 scores provided by the programs to determine factors associated with successful ABSITE performance. RESULTS: In total, 48% (n = 157) of the residents completed the survey. Of those completing the survey, 48 (31%) scored in the highest ABSITE quartile (≥75th percentile) and 109 (69%) scored less than the 75th percentile. In univariate analyses, those in the highest ABSITE quartile had significantly higher USMLE step 1 and step 2 scores (P < 0.001), significantly lower burnout scores (disengagement, P < 0.01; exhaustion, P < 0.04), and held opinions that the ABSITE was important for improving their surgical knowledge (P < 0.01). They also read more frequently to prepare for the ABSITE (P < 0.001), had more disciplined study habits (P < 0.001), were more likely to study at the hospital or other public settings (e.g., library, coffee shop compared with at home; P < 0.04), and used active rather than passive study strategies (P < 0.04). Gender, marital status, having children, and debt burden had no correlation with examination success. Backward stepwise multiple regression analysis identified the following independent predictors of ABSITE scores: study location (P < 0.0001), frequency of reading (P = 0.0001), Oldenburg Burnout Inventory exhaustion (P = 0.02), and USMLE step 1 and 2 scores (P = 0.007 and 0.0001, respectively). CONCLUSIONS: Residents who perform higher on the ABSITE have a regular study schedule throughout the year, report less burnout because of exhaustion, study away from home, and have shown success in prior standardized tests. Further study is needed to determine the effects of burnout on clinical duties, career advancement, and satisfaction.

Neural mechanisms of human temporal fear conditioning.

Learning the temporal relationship between a warning cue (conditioned stimulus; CS) and aversive threat (unconditioned stimulus; UCS) is an important aspect of Pavlovian conditioning. Although prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support Pavlovian conditioning, it remains unclear whether these regions support time-related processes important for this type of associative learning. Elucidating the neural substrates of temporal conditioning is important for a complete understanding of the Pavlovian conditioning process. Therefore, the present study used a temporal Pavlovian conditioning procedure to investigate brain activity that mediates the formation of temporal associations. During fMRI, twenty-three healthy volunteers completed a temporal conditioning procedure and a control task that does not support conditioning. Specifically, during the temporal conditioning procedure, the UCS was presented at fixed intervals (ITI: 20s) while in the control condition the UCS was presented at random intervals (Average ITI: 20s, ITI Range: 6-34s). We observed greater skin conductance responses and expectancy of the UCS during fixed (i.e., temporal conditioning) relative to random (i.e., control procedure) interval trials. These findings demonstrate fixed trials support temporal conditioning, while random trials do not. During fixed interval trials, greater conditioned fMRI signal responses were observed within dorsolateral prefrontal cortex, inferior parietal lobule, inferior and middle temporal cortex, hippocampus, and amygdala. The current findings suggest these brain regions constitute a neural circuit that encodes the temporal information necessary for Pavlovian fear conditioning.

Affective state and locus of control modulate the neural response to threat.

The ability to regulate the emotional response to threat is critical to healthy emotional function. However, the response to threat varies considerably from person-to-person. This variability may be partially explained by differences in emotional processes, such as locus of control and affective state, which vary across individuals. Although the basic neural circuitry that mediates the response to threat has been described, the impact individual differences in affective state and locus of control have on that response is not well characterized. Understanding how these factors influence the neural response to threat would provide new insight into processes that mediate emotional function. Therefore, the present study used a Pavlovian conditioning procedure to investigate the influence individual differences in locus of control, positive affect, and negative affect have on the brain and behavioral responses to predictable and unpredictable threats. Thirty-two healthy volunteers participated in a fear conditioning study in which predictable and unpredictable threats (i.e., unconditioned stimulus) were presented during functional magnetic resonance imaging (fMRI). Locus of control showed a linear relationship with learning-related ventromedial prefrontal cortex (PFC) activity such that the more external an individual's locus of control, the greater their differential response to predictable versus unpredictable threat. In addition, positive and negative affectivity showed a curvilinear relationship with dorsolateral PFC, dorsomedial PFC, and insula activity, such that those with high or low affectivity showed reduced regional activity compared to those with an intermediate level of affectivity. Further, activity within the PFC, as well as other regions including the amygdala, were linked with the peripheral emotional response as indexed by skin conductance and electromyography. The current findings demonstrate that the neural response to threat within brain regions that mediate the peripheral emotional response is modulated by an individual's affective state as well as their perceptions of an event's causality.

Controllability modulates the neural response to predictable but not unpredictable threat in humans.

Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

Hippocampal gray matter volume in young adulthood varies with adolescent alcohol use.

Adolescent substance use is linked with negative future outcomes (e.g., depression, anxiety, substance use disorder). Given that the brain undergoes significant maturation during adolescence, this developmental period may represent a time of particular vulnerability to substance use. Neuroimaging research has largely focused on heavy or binge patterns of substance use; thus, relatively less is known about the neural impact of a broader range of adolescent substance use. Characterizing the neural impact of a broader range of adolescent substance use may inform prevention and treatment efforts. The present study investigated relationships between adolescent substance use trajectories (i.e., alcohol, tobacco, and cannabis) and gray matter volume in young adulthood. Substance use was assessed in 1,594 participants at ages 11, 13, 16, and 19. Following the last assessment, 320 participants completed a single magnetic resonance imaging session to assess brain gray matter volume. Latent growth curve models were used to estimate growth parameters characterizing alcohol, tobacco, and cannabis use trajectories for each participant. These growth parameters (i.e., intercept, linear slope, and quadratic slope) were then used as predictors of gray matter volume. The gray matter volume of the hippocampus was positively associated with age 14 alcohol use (i.e., intercept) but not other trajectories (i.e., progression or acceleration) or substances (tobacco or cannabis). These results provide new insight into the neural impact of distinct adolescent alcohol, tobacco, and cannabis use trajectories, which may help to refine prevention and treatment efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Human trace fear conditioning: right-lateralized cortical activity supports trace-interval processes.

Pavlovian conditioning requires the convergence and simultaneous activation of neural circuitry that supports conditioned stimulus (CS) and unconditioned stimulus (US) processes. However, in trace conditioning, the CS and US are separated by a period of time called the trace interval, and thus do not overlap. Therefore, determining brain regions that support associative learning by maintaining a CS representation during the trace interval is an important issue for conditioning research. Prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support trace-conditioning processes. However, relatively little is known about whether this activity is specific to the trace CS, the trace interval, or both periods of time. The present study was designed to disentangle the hemodynamic response produced by the trace CS from that associated with the trace interval, in order to identify learning-related activation during these distinct components of a trace-conditioning trial. Trace-conditioned activity was observed within dorsomedial prefrontal cortex (PFC), dorsolateral PFC, insula, inferior parietal lobule (IPL), and posterior cingulate (PCC). Each of these regions showed learning-related activity during the trace CS, while trace-interval activity was only observed within a subset of these areas (i.e., dorsomedial PFC, PCC, right dorsolateral PFC, right IPL, right superior/middle temporal gyrus, and bilateral insula). Trace-interval activity was greater in right than in left dorsolateral PFC, IPL, and superior/middle temporal gyrus. These findings indicate that components of the prefrontal, cingulate, insular, and parietal cortices support trace-interval processes, as well as suggesting that a right-lateralized fronto-parietal circuit may play a unique role in trace conditioning.

Abnormal ECG patterns in chronic post-war PTSD patients: a pilot study.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric syndrome associated with high levels of sympathetic activation of the autonomic nervous system. Individuals diagnosed with PTSD have a high propensity for electrocardiogram (ECG) abnormalities, atrioventricular conductive defects, and cerebrovascular incidents. PURPOSE: The aim of this study was to investigate ECG abnormalities in post-war PTSD patients. METHOD: This pilot study compared patients diagnosed with chronic post-war PTSD (n = 30) to patients diagnosed with major depressive disorder (MDD; n = 24) and healthy controls (n = 20). Following the completion of the Structured Clinical Interview for the DSM (SCID), participants were assessed with a standard 12-lead ECG. RESULTS: ECG abnormalities were observed in 66.7% of PTSD patients and 70.8% of MDD patients. In contrast, only 28.6% of the healthy control group showed ECG abnormalities. Multivariate logistic regression was used to adjust for participants' sex, smoking rate, education level, disease duration, and marital status. The results indicated that PTSD and MDD patients were more likely to have ECG abnormalities than the normal population (odds ratio for PTSD = 12.7, 95% confidence interval 1.9-83.9; and odds ratio for MDD = 14.9, 95% confidence interval 1.3-170.5). CONCLUSION: PTSD and MDD patients showed elevated rates of ECG abnormalities compared to healthy controls. These findings have important implications for the medical treatment of PTSD and MDD given that both of these patient groups appear to be at increased risk of cardiovascular disorder.

Lexical decision and the number of morphemes and affixes.

There has been a considerable amount of research looking at the effects of both syllable number and syllable frequency on lexical decision and word naming times. Recently, there has also been an increased interest in morphological variables, but there have been no large scale studies that have examined the role of the number of morphemes in lexical decision for nonwords. This is partly because of the difficulty of identifying morphemes in nonwords. We present a program that identifies the presence of affixes and, therefore, can be used to count the number of morpheme-like elements in a nonword. We then used the program to measure the importance of affixes/morphemes in predicting lexical decision in nonwords. The results suggested that morphemes have an important role in lexical decision for both words and nonwords.

Hippocampal and amygdala volumes vary with residential proximity to toxicants at Birmingham, Alabama's 35th Avenue Superfund site.

Exposure to environmental toxicants have serious implications for the general health and well-being of children, particularly during pivotal neurodevelopmental stages. The Environmental Protection Agency's (EPA) Superfund program has identified several areas (Superfund sites) across the United States with high levels of environmental toxicants, which affect the health of many residents in nearby communities. Exposure to these environmental toxicants has been linked to changes in the structure and function of the brain. However, limited research has investigated the relationship between the proximity of childhood homes to a Superfund site and the development of subcortical structures like the hippocampus and amygdala. The present study investigated the hippocampal and amygdala volumes of young adults in relation to the proximity of their childhood homes to Birmingham, Alabama's 35th Avenue Superfund site. Forty participants who either lived within or adjacent to the Superfund site (Proximal group; n = 20) or who lived elsewhere in the greater Birmingham metropolitan area (Distal group; n = 20) were included in this study. Both groups were matched on age, sex, race, and years of education. Magnetic resonance imaging (MRI) was used to compare the gray matter volume of the hippocampus and amygdala between groups. Differences in bilateral hippocampal and left amygdala volumes were observed. Specifically, hippocampal and amygdala volumes were greater in the Proximal than Distal group. These findings suggest that the proximity of children's homes to environmental toxicants may impact the development of the hippocampus and amygdala. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Stress-induced Changes in Autonomic Reactivity Vary with Adolescent Violence Exposure and Resting-state Functional Connectivity.

Exposure to violence during childhood can lead to functional changes in brain regions that are important for emotion expression and regulation, which may increase susceptibility to internalizing disorders in adulthood. Specifically, childhood violence exposure can disrupt the functional connectivity among brain regions that include the prefrontal cortex (PFC), hippocampus, and amygdala. Together, these regions are important for modulating autonomic responses to stress. However, it is unclear to what extent changes in brain connectivity relate to autonomic stress reactivity and how the relationship between brain connectivity and autonomic responses to stress varies with childhood violence exposure. Thus, the present study examined whether stress-induced changes in autonomic responses (e.g., heart rate, skin conductance level (SCL)) varied with amygdala-, hippocampus-, and ventromedial prefrontal cortex (vmPFC)-whole brain resting-state functional connectivity (rsFC) as a function of violence exposure. Two hundred and ninety-seven participants completed two resting-state functional magnetic resonance imaging scans prior to (pre-stress) and after (post-stress) a psychosocial stress task. Heart rate and SCL were recorded during each scan. Post-stress heart rate varied negatively with post-stress amygdala-inferior parietal lobule rsFC and positively with post-stress hippocampus-anterior cingulate cortex rsFC among those exposed to high, but not low, levels of violence. Results from the present study suggest that post-stress fronto-limbic and parieto-limbic rsFC modulates heart rate and may underlie differences in the stress response among those exposed to high levels of violence.

Consensus design of a calibration experiment for human fear conditioning.

Fear conditioning is a widely used laboratory model to investigate learning, memory, and psychopathology across species. The quantification of learning in this paradigm is heterogeneous in humans and psychometric properties of different quantification methods can be difficult to establish. To overcome this obstacle, calibration is a standard metrological procedure in which well-defined values of a latent variable are generated in an established experimental paradigm. These intended values then serve as validity criterion to rank methods. Here, we develop a calibration protocol for human fear conditioning. Based on a literature review, series of workshops, and survey of N = 96 experts, we propose a calibration experiment and settings for 25 design variables to calibrate the measurement of fear conditioning. Design variables were chosen to be as theory-free as possible and allow wide applicability in different experimental contexts. Besides establishing a specific calibration procedure, the general calibration process we outline may serve as a blueprint for calibration efforts in other subfields of behavioral neuroscience that need measurement refinement.

Neural mechanisms underlying the conditioned diminution of the unconditioned fear response.

Recognizing cues that predict an aversive event allows one to react more effectively under threatening conditions, and minimizes the reaction to the threat itself. This is demonstrated during Pavlovian fear conditioning when the unconditioned response (UCR) to a predictable unconditioned stimulus (UCS) is diminished compared to the UCR to an unpredictable UCS. The present study investigated the functional magnetic resonance imaging (fMRI) signal response associated with Pavlovian conditioned UCR diminution to better understand the relationship between individual differences in behavior and the neural mechanisms of the threat-related emotional response. Healthy volunteers participated in a fear conditioning study in which trait anxiety, skin conductance response (SCR), UCS expectancy, and the fMRI signal were assessed. During acquisition trials, a tone (CS+) was paired with a white noise UCS and a second tone (CS-) was presented without the UCS. Test trials consisted of the CS+ paired with the UCS, CS- paired with the UCS, and presentations of the UCS alone to assess conditioned UCR diminution. UCR diminution was observed within the dorsolateral PFC, dorsomedial PFC, cingulate cortex, inferior parietal lobule (IPL), anterior insula, and amygdala. The threat-related activity within the dorsolateral PFC, dorsomedial PFC, posterior cingulate cortex, and IPL varied with individual differences in trait anxiety. In addition, anticipatory (i.e. CS elicited) activity within the PFC showed an inverse relationship with threat-related (i.e. UCS elicited) activity within the PFC, IPL, and amygdala. Further, the emotional response (indexed via SCR) elicited by the threat was closely linked to amygdala activity. These findings are consistent with the view that the amygdala and PFC support learning-related processes that influence the emotional response evoked by a threat.

Stress-Induced Changes in Effective Connectivity During Regulation of the Emotional Response to Threat.

Background: Stress-related disruption of emotion regulation appears to involve the prefrontal cortex (PFC) and amygdala. However, the interactions between brain regions that mediate stress-induced changes in emotion regulation remain unclear. The present study builds upon prior work that assessed stress-induced changes in the neurobehavioral response to threat by investigating effective connectivity between these brain regions. Methods: Participants completed the Montreal Imaging Stress Task followed by a Pavlovian fear conditioning procedure during functional magnetic resonance imaging. Stress ratings and psychophysiological responses were used to assess stress reactivity. Effective connectivity during fear conditioning was identified using multivariate autoregressive modeling. Effective connectivity values were calculated during threat presentations that were either predictable (preceded by a warning cue) or unpredictable (no warning cue). Results: A neural hub within the dorsomedial PFC (dmPFC) showed greater effective connectivity to other PFC regions, inferior parietal lobule, insula, and amygdala during predictable than unpredictable threat. The dmPFC also showed greater connectivity to different dorsolateral PFC and amygdala regions during unpredictable than predictable threat. Stress ratings varied with connectivity differences from the dmPFC to the amygdala. Connectivity from dmPFC to amygdala was greater in general during unpredictable than predictable threat, however, this connectivity increased during predictable compared with unpredictable threat as stress reactivity increased. Conclusions: Our findings suggest that acute stress disrupts connectivity underlying top-down emotion regulation of the threat response. Furthermore, increased connectivity between the dmPFC and amygdala may play a critical role in stress-induced changes in the emotional response to threat. Impact statement The present study builds upon prior work that assessed stress-induced changes in the human neurobehavioral response to threat by demonstrating that increased top-down connectivity from the dorsomedial prefrontal cortex to the amygdala varies with individual differences in stress reactivity. These findings provide novel evidence in humans of stress-induced disruption of a specific top-down corticolimbic circuit during active emotion regulation processes, which may play a causal role in the long-term effects of chronic or excessive stress exposure.