State-of-the-art Dashboards on Clinical Indicator Data to Support Reflection on Practice: Scoping Review.

BACKGROUND: There is an increasing interest in using routinely collected eHealth data to support reflective practice and long-term professional learning. Studies have evaluated the impact of dashboards on clinician decision-making, task completion time, user satisfaction, and adherence to clinical guidelines. OBJECTIVE: This scoping review aims to summarize the literature on dashboards based on patient administrative, medical, and surgical data for clinicians to support reflective practice. METHODS: A scoping review was conducted using the Arksey and O'Malley framework. A search was conducted in 5 electronic databases (MEDLINE, Embase, Scopus, ACM Digital Library, and Web of Science) to identify studies that met the inclusion criteria. Study selection and characterization were performed by 2 independent reviewers (BB and CP). One reviewer extracted the data that were analyzed descriptively to map the available evidence. RESULTS: A total of 18 dashboards from 8 countries were assessed. Purposes for the dashboards were designed for performance improvement (10/18, 56%), to support quality and safety initiatives (6/18, 33%), and management and operations (4/18, 22%). Data visualizations were primarily designed for team use (12/18, 67%) rather than individual clinicians (4/18, 22%). Evaluation methods varied among asking the clinicians directly (11/18, 61%), observing user behavior through clinical indicators and use log data (14/18, 78%), and usability testing (4/18, 22%). The studies reported high scores on standard usability questionnaires, favorable surveys, and interview feedback. Improvements to underlying clinical indicators were observed in 78% (7/9) of the studies, whereas 22% (2/9) of the studies reported no significant changes in performance. CONCLUSIONS: This scoping review maps the current literature landscape on dashboards based on routinely collected clinical indicator data. Although there were common data visualization techniques and clinical indicators used across studies, there was diversity in the design of the dashboards and their evaluation. There was a lack of detail regarding the design processes documented for reproducibility. We identified a lack of interface features to support clinicians in making sense of and reflecting on their personal performance data.

Hepatitis A Virus Infections Among Men Who Have Sex with Men - Eight U.S. States, 2017-2018.

During 1995-2011, the overall incidence of hepatitis A decreased by 95% in the United States from 12 cases per 100,000 population during 1995 to 0.4 cases per 100,000 population during 2011, and then plateaued during 2012─2015. The incidence increased by 294% during 2016-2018 compared with the incidence during 2013-2015, with most cases occurring among populations at high risk for hepatitis A infection, including persons who use illicit drugs (injection and noninjection), persons who experience homelessness, and men who have sex with men (MSM) (1-3). Previous outbreaks among persons who use illicit drugs and MSM led to recommendations issued in 1996 by the Advisory Committee on Immunization Practices (ACIP) for routine hepatitis A vaccination of persons in these populations (4). Despite these long-standing recommendations, vaccination coverage rates among MSM remain low (5). In 2017, the New York City Department of Health and Mental Hygiene contacted CDC after public health officials noted an increase in hepatitis A infections among MSM. Laboratory testing* of clinical specimens identified strains of the hepatitis A virus (HAV) that subsequently matched strains recovered from MSM in other states. During January 1, 2017-October 31, 2018, CDC received reports of 260 cases of hepatitis A among MSM from health departments in eight states, a substantial increase from the 16 cases reported from all 50 states during 2013-2015. Forty-eight percent (124 of 258) of MSM patients were hospitalized for a median of 3 days. No deaths were reported. In response to these cases, CDC supported state and local health departments with public health intervention efforts to decrease HAV transmission among MSM populations. These efforts included organizing multistate calls among health departments to share information, providing guidance on developing targeted outreach and managing supplies for vaccine campaigns, and conducting laboratory testing of clinical specimens. Targeted outreach for MSM to increase awareness about hepatitis A infection and improve access to vaccination services, such as providing convenient locations for vaccination, are needed to prevent outbreaks among MSM.

Protracted Outbreak of Salmonella Newport Infections Linked to Ground Beef: Possible Role of Dairy Cows - 21 States, 2016-2017.

In January 2017, CDC identified a cluster of Salmonella enterica serotype Newport infections with isolates sharing an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern, JJPX01.0010 (pattern 10), through PulseNet, the national molecular subtyping network for foodborne disease surveillance. This report summarizes the investigation by CDC, state and local health and agriculture departments, and the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS) and discusses the possible role of dairy cows as a reservoir for strains of Salmonella that persistently cause human illness. This investigation combined epidemiologic and whole genome sequencing (WGS) data to link the outbreak to contaminated ground beef; dairy cows were hypothesized to be the ultimate source of Salmonella contamination.

Outbreak of Fluoroquinolone-Resistant Campylobacter jejuni Infections Associated with Raw Milk Consumption from a Herdshare Dairy - Colorado, 2016.

In August 2016, a local public health agency (LPHA) notified the Colorado Department of Public Health and Environment (CDPHE) of two culture-confirmed cases of Campylobacter infection among persons who consumed raw (unpasteurized) milk from the same herdshare dairy. In Colorado, the sale of raw milk is illegal; however, herdshare programs, in which a member can purchase a share of a herd of cows or goats, are legal and are not regulated by state or local authorities. In coordination with LPHAs, CDPHE conducted an outbreak investigation that identified 12 confirmed and five probable cases of Campylobacter jejuni infection. Pulsed-field gel electrophoresis (PFGE) patterns for the 10 cases with available isolates were identical using the enzyme Sma. In addition, two milk samples (one from the dairy and one obtained from an ill shareholder) also tested positive for the outbreak strain. Five C. jejuni isolates sent to CDC for antimicrobial susceptibility testing were resistant to ciprofloxacin, tetracycline, and nalidixic acid (1). Although shareholders were notified of the outbreak and cautioned against drinking the milk on multiple occasions, milk distribution was not discontinued. Although its distribution is legal through herdshare programs, drinking raw milk is inherently risky (2). The role of public health in implementing control measures associated with a product that is known to be unsafe remains undefined.

Platelet-rich plasma for tissue regeneration can be stored at room temperature for at least five days.

BACKGROUND: Autologous platelet-rich plasma (PRP) is gaining increasing use as a wound healing promoter in a variety of clinical settings, including dentistry. Fresh PRP is often used, necessitating daily draws. The present study investigates the possibility of using stored PRP without having to freeze it by storing PRP under variable conditions and assessing growth factor release as a surrogate marker of continued viability. METHODS: Freshly drawn PRP was stored in oxygen permeable and non-oxygen permeable containers under conditions of constant agitation with or without added prostaglandin, intermittent agitation and no agitation, over an 8-day period. Serial platelet counts, mean platelet volume, platelet distribution width and platelet-large cell ratio, and collagen-induced aggregometry were undertaken. Once collagen-induced aggregation had gone to completion, the plasma was centrifuged to pellet platelet material and the supernatants separated and frozen for batched analysis of released platelet-derived growth factor-BB (PDGF-BB). RESULTS: As would be anticipated, platelet counts, percentage aggregation and PDGF-BB levels all reduced over time. Platelet parameters suggested that platelets were more stable in the non-oxygen permeable containers, possibly due to pH drift and a degree of microaggregate formation in the oxygen permeable containers. CONCLUSION: Although platelet integrity and PDGF-BB fell over time, the intermittently agitated non-oxygen permeable container appeared to retain better platelet integrity and function, and PDGF-BB release, than other storage conditions, with potential for clinical use for 5-8 days.

Notes from the Field: Typhoid Fever Outbreak Associated with an Asymptomatic Carrier at a Restaurant - Weld County, Colorado, 2015.

On September 11, 2015, a single case of typhoid fever, caused by Salmonella Typhi infection, was reported to the Colorado Department of Public Health and Environment (CDPHE). Because the patient (patient A) had symptom onset September 2 and had traveled internationally for 4 days 60 days before symptom onset, the case initially was thought to be travel-associated* (1,2). On October 1, a second case of S. Typhi infection was reported in patient B, with symptom onset September 20. Patient B reported no international travel or contact with ill persons or known carriers. Patients A and B resided approximately 6 miles (10 kilometers) apart and had no discernible epidemiologic connection. Family members of patients A and B tested negative for S. Typhi. CDPHE and the Weld County Department of Public Health and Environment (WCDPHE) investigated to 1) determine whether these cases represented a larger outbreak, 2) identify common exposure sources, and 3) stop transmission. Investigators determined that the typhoid fever in both patients and in a third patient (patient C) was associated with eating in the same restaurant during a 5-day period.

Reduction of autonomic regulation in children and adolescents with conversion disorders.

OBJECTIVE: Conversion symptoms--functional neurological disturbances of body function--occur in association with extreme arousal, often in the context of emotional distress. The mechanisms that determine how and why such symptoms occur remain unknown. In this study, we used cardiac measures to assess arousal and cardiac autonomic regulation in children and adolescents who presented with acute conversion symptoms. METHODS: Heart rate was recorded in 57 children and adolescents (41 girls; 8.5-18 years old) with acute conversion symptoms and 57 age- and sex-matched healthy controls, during a resting condition and then during tasks involving cognitive and emotional activation. Arousal and autonomic regulation were assessed by measures of heart rate and heart rate variability. Psychological measures included attachment and emotional distress. RESULTS: Children and adolescents with conversion symptoms displayed higher autonomic arousal than did the controls, both at baseline and during task conditions (higher heart rate: baseline mean [standard deviation] = 82 [9.49] versus 74 [10.79] beats/min, p < .001; lower root mean squared successive differences-heart rate variability: 45.35 [27.97] versus 58.62 [25.69] ms(2), p = .012; and lower high-frequency heart rate variability: 6.50 [1.19] versus 7.01 [0.95] ln[ms(2)] p = .017), and decreased autonomic regulation (attenuation of heart rate increases across tasks). The baseline pattern of increased autonomic arousal was especially pronounced in children with coercive-preoccupied patterns of attachment. Autonomic measures were not correlated with measures of emotional distress. CONCLUSIONS: High autonomic arousal may be a precondition for generating conversion symptoms. Functional dysregulations of the cardiac, respiratory, and circulatory systems may mediate fainting episodes and nonepileptic seizures, and aberrant patterns of functional connectivity between motor areas and central arousal systems may be responsible for generating motor conversion symptoms.

Conversion disorder in children and adolescents: a disorder of cognitive control.

OBJECTIVE: To assess cognitive function in children and adolescents presenting with acute conversion symptoms. METHODS: Fifty-seven participants aged 8.5-18 years (41 girls and 16 boys) with conversion symptoms and 57 age- and gender-matched healthy controls completed the IntegNeuro neurocognitive battery, an estimate of intelligence, and self-report measures of subjective emotional distress. RESULTS: Participants with conversion symptoms showed poorer performance within attention, executive function, and memory domains. Poorer performance was reflected in more errors on specific tests: Switching of Attention (t(79) = 2.17, p = .03); Verbal Interference (t(72) = 2.64, p = .01); Go/No-Go (t(73) = 2.20, p = .03); Memory Recall and Verbal Learning (interference errors for memory recall; t(61) = 3.13, p < .01); and short-delay recall (t(75) = 2.05, p < .01) and long-delay recall (t(62) = 2.24, p = .03). Poorer performance was also reflected in a reduced span of working memory on the Digit Span Test for both forward recall span (t(103) = -3.64, p < .001) and backward recall span (t(100) = -3.22, p < .01). There was no difference between participants and controls on IQ estimate (t(94) = -589, p = .56), and there was no correlation between cognitive function and perceived distress. CONCLUSIONS: Children and adolescents with acute conversion symptoms have a reduced capacity to manipulate and retain information, to block interfering information, and to inhibit responses, all of which are required for effective attention, executive function, and memory.

Specific biases for identifying facial expression of emotion in children and adolescents with conversion disorders.

OBJECTIVE: This study aimed to assess how children and adolescents with conversion disorders identify universal facial expressions of emotion and to determine whether identification of emotion in faces relates to subjective emotional distress. METHODS: Fifty-seven participants (41 girls and 16 boys) aged 8.5 to 18 years with conversion disorders and 57 age- and sex-matched healthy controls completed a computerized task in which their accuracy and reaction times for identifying facial expressions were recorded. To isolate the effect of individual emotional expressions, participants' reaction times for each emotion (fear, anger, sadness, disgust, and happiness) were subtracted from their reaction times for the neutral control face. Participants also completed self-report measures of subjective emotional distress. RESULTS: Children/Adolescents with conversion disorders showed faster reaction times for identifying expressions of sadness (t(112) = -2.2, p = .03; 444 [609] versus 713 [695], p = .03) and slower reactions times for happy expressions (t(99.3) = 2.28, p ≤ .024; -33 [35] versus 174 [51], p = .024), compared with controls (F(33.75, 419.81) = 3.76, p < .001). There were no significant correlations (at the corrected p value of .01) between reaction times and subjective reports of perceived distress (r values ranged from 092 to 0.221; p > .018). There were also no differences in identification accuracy for any emotion (p > .82). CONCLUSIONS: The observation of faster reaction times to sad faces in children and adolescents with conversion disorders suggests increased vigilance and motor readiness to emotional signals that are potential threats to self or to close others. These effects may occur before conscious processing.

Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis.

BACKGROUND: Depression is associated with an increase in the likelihood of cardiac events; however, studies investigating the relationship between depression and heart rate variability (HRV) have generally focused on patients with cardiovascular disease (CVD). The objective of the current report is to examine with meta-analysis the impact of depression and antidepressant treatment on HRV in depressed patients without CVD. METHODS: Studies comparing 1) HRV in patients with major depressive disorder and healthy control subjects and 2) the HRV of patients with major depressive disorder before and after treatment were considered for meta-analysis. RESULTS: Meta-analyses were based on 18 articles that met inclusion criteria, comprising a total of 673 depressed participants and 407 healthy comparison participants. Participants with depression had lower HRV (time frequency: Hedges' g = -.301, p < .001; high frequency: Hedges' g = -.293, p < .001; nonlinear: Hedges' g = -1.955, p = .05; Valsalva ratio: Hedges' g = -.712, p < .001) than healthy control subjects, and depression severity was negatively correlated with HRV (r = -.354, p < .001). Tricyclic medication decreased HRV, although serotonin reuptake inhibitors, mirtazapine, and nefazodone had no significant impact on HRV despite patient response to treatment. CONCLUSIONS: Depression without CVD is associated with reduced HRV, which decreases with increasing depression severity, most apparent with nonlinear measures of HRV. Critically, a variety of antidepressant treatments do not resolve these decreases despite resolution of symptoms, highlighting that antidepressant medications might not have HRV-mediated cardioprotective effects and the need to identify individuals at risk among patients in remission.

Neural synchrony in patients with a first episode of schizophrenia: tracking relations with grey matter and symptom profile.

BACKGROUND: Although schizophrenia has been characterized by disruptions to neural synchrony, it remains unknown whether these disturbances are related to symptoms and loss of grey matter. We examined relations between 40 Hz Gamma band synchrony and grey matter in patients with schizophrenia at first episode and after 2.5 years. METHODS: From an initial recruitment of 35 medicated patients with a first episode of schizophrenia, 25 patients completed clinical and oddball task-elicited Gamma synchrony within 3 months of health service contact and again after 2.5 years, 23 completed magnetic resonance imaging (MRI) at these time points, and 13 completed all sessions. We compared patients with 35 matched healthy controls. We identified early (0-150 ms) and late (250-500 ms) peaks in Gamma synchrony locked to oddball targets, and we analyzed MRI data using voxel-based morphometry. We evaluated group and test-retest differences using repeated-measures analyses of variance. RESULTS: Compared with controls, at first contact, patients with a first episode of schizophrenia showed a disruption to the laterality of early Gamma synchrony and global reduction in late Gamma synchrony, with a corresponding loss of fronto-temporal-parietal grey matter. Gamma synchrony was increased at follow-up among patients with a first episode of schizophrenia. It related negatively to further loss of grey matter, but positively to improvement in reality distortion symptoms. These relations could not be explained by medication dose. LIMITATIONS: Our study did not include unmedicated patients or normative follow-up testing. CONCLUSION: Gamma synchrony may track the progression of schizophrenia from first episode. An increase in Gamma synchrony over time might reflect an attempt to adapt to a progressive loss of cortical grey matter and associated changes in cognitive and emotional function.

Disturbances in selective information processing associated with the BDNF Val66Met polymorphism: evidence from cognition, the P300 and fronto-hippocampal systems.

In this study, we examined whether the Met allele of the BDNF Val66Met polymorphism is associated with selective disruptions to task-relevant information processing. In 475 non-clinical participants for whom BDNF genotype status was determined we used the 'IntegNeuro' computerized battery of neuropsychological tests to assess cognitive performance, an auditory oddball task to elicit the P300 event-related potential (ERP) and, in smaller subsets of these subjects, high resolution structural MRI imaging to quantify fronto-hippocampal grey matter (n=161), and functional magnetic resonance imaging to assess fronto-hippocampal BOLD activation (n=37). Met/Met (MM) homozygotes had higher verbal recall errors, in the absence of differences in attention, executive function, verbal ability or sensori-motor function. Further, MM homozygotes demonstrated a slowed P300 ERP during the oddball task, with corresponding alterations in hippocampal and lateral prefrontal activation, and a localized reduction in hippocampal grey matter. These results are consistent with a subtle impact of the Met allele on fronto-hippocampal systems involved in selective information processing of stimulus context and memory updating within the normal population. The findings also indicate that heritable endophenotypes such as the P300 have value in elucidating genotype-phenotype relationships.

Integrating objective gene-brain-behavior markers of psychiatric disorders.

There is little consensus about which objective markers should be used to assess major psychiatric disorders, and predict/evaluate treatment response for these disorders. Clinical practice relies instead on subjective signs and symptoms, such that there is a "translational gap" between research findings and clinical practice. This gap arises from: a) a lack of integrative theoretical models which provide a basis for understanding links between gene-brain-behavior mechanisms and clinical entities; b) the reliance on studying one measure at a time so that linkages between markers are their specificity are not established; and c) the lack of a definitive understanding of what constitutes normative function. Here, we draw on a standardized methodology for acquiring multiple sources of genomic, brain and behavioral data in the same subjects, to propose candidate markers of selected psychiatric disorders: depression, post-traumatic stress disorder, schizophrenia, attention-deficit/hyperactivity disorder and dementia disorders. This methodology has been used to establish a standardized international database which provides a comprehensive framework and the basis for testing hypotheses derived from an integrative theoretical model of the brain. Using this normative base, we present preliminary findings for a number of disorders in relation to the proposed markers. Establishing these objective markers will be the first step towards determining their sensitivity, specificity and treatment prediction in individual patients.

Mapping frontal-limbic correlates of orienting to change detection.

Orienting responses are elicited by salient stimuli, and may be indexed by skin conductance responses. Concurrent functional magnetic resonance imaging and skin conductance response recording was used to identify neural correlates of orienting to abrupt sensory change (infrequent high pitch oddball 'target' tones embedded in frequent lower pitch 'standard' tones) in 16 healthy participants. 'With skin conductance response' responses to targets were distinguished by preferentially greater activity in the amygdala and ventral medial and lateral frontal cortical regions. By contrast, 'without skin conductance response' responses elicited distinctive activity in the dorsal lateral frontal cortex and supramarginal gyrus. These findings suggest that orienting to unexpected sensory change elicits a network for appraising salience and novelty, whereas, in the absence of orienting, a parallel network for sensory and context evaluation is preferentially engaged.

The mellow years?: neural basis of improving emotional stability over age.

Contrary to the pervasive negative stereotypes of human aging, emotional functions may improve with advancing age. However, the brain mechanisms underlying changes in emotional function over age remain unknown. Here, we demonstrate that emotional stability improves linearly over seven decades (12-79 years) of the human lifespan. We used both functional magnetic resonance imaging and event-related potential recording to examine the neural basis of this improvement. With these multimodal techniques, we show that better stability is predicted by a shift toward greater medial prefrontal control over negative emotional input associated with increased activity later in the processing sequence (beyond 200 ms after stimulus) and less control over positive input, related to a decrease in early activity (within 150 ms). This shift was independent from gray matter loss, indexed by structural magnetic resonance data. We propose an integrative model in which accumulated life experience and the motivation for meaning over acquisition in older age contribute to plasticity of medial prefrontal systems, achieving a greater selective control over emotional functions.

Pathways for fear perception: modulation of amygdala activity by thalamo-cortical systems.

Effective perception of fear signals is crucial for human survival and the importance of the amygdala in this process is well documented. Animal, lesion and neuroimaging studies indicate that incoming sensory signals of fear travel from thalamus to amygdala via two neural pathways: a direct subcortical route and an indirect pathway via the sensory cortex. Other lines of research have demonstrated prefrontal modulation of the amygdala. However, no study to date has examined the prefrontal modulation of the thalamo-cortico-amygdala pathways in vivo. We used psychophysiological and physiophysiological interactions to examine the functional connectivity within thalamus, amygdala and sensory (inferior occipital, fusiform) cortices, and the modulation of these networks by the anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI) data were acquired for 28 healthy control subjects during a fear perception task, with neutral as the 'baseline' control condition. Main effect analysis, using a region of interest (ROI) approach, confirmed that these regions are part of a distributed neural system for fear perception. Psychophysiological interactions revealed an inverse functional connectivity between occipito-temporal visual regions and the left amygdala, but a positive connectivity between these visual region and the right amygdala, suggesting that there is a hemispheric specialization in the transfer of fear signals from sensory cortices to amygdala. Physiophysiological interactions revealed a dorsal-ventral division in ACC modulation of the thalamus-sensory cortex pathway. While the dorsal ACC showed a positive modulation of this pathway, the ventral ACC exhibited an inverse relationship. In addition, both the dorsal and ventral ACC showed an inverse interaction with the direct thalamus-amygdala pathway. These findings suggest that thalamo-amygdala and cortical regions are involved in a dynamic interplay, with functional differentiation in both lateralized and ventral/dorsal gradients. Breakdowns in these interactions may give rise to affect-related symptoms seen in a range of neuropsychiatric disorders.

A direct brainstem-amygdala-cortical 'alarm' system for subliminal signals of fear.

We examined whether consciously undetected fear signals engage a collateral brainstem pathway to the amygdala and prefrontal cortex in the intact human brain, using functional neuroimaging. 'Blindsight' lesion patients can respond to visual fear signals independently from conscious experience, suggesting that these signals reach the amygdala via a direct pathway that bypasses the primary visual cortex. Electrophysiological evidence points to concomitant involvement of prefrontal regions in automatic orienting to subliminal signals of fear, which may reflect innervation arising from brainstem arousal systems. To approximate blindsight in 22 healthy subjects, facial signals of fear were presented briefly (16.7 ms) and masked such that conscious detection was prevented. Results revealed that subliminal fear signals elicited activity in the brainstem region encompassing the superior colliculus and locus coeruleus, pulvinar and amygdala, and in fronto-temporal regions associated with orienting. These findings suggest that crude sensory input from the superior colliculo-pulvinar visual pathway to the amygdala may allow for sufficient appraisal of fear signals to innervate the locus coeruleus. The engagement of the locus coeruleus could explain the observation of diffuse fronto-temporal cortical activity, given its role in evoking collateral ascending noradrenergic efferents to the subcortical amygdala and prefrontal cortex. This network may represent an evolutionary adaptive neural 'alarm' system for rapid alerting to sources of threat, without the need for conscious appraisal.

Sex differences in functional connectivity in first-episode and chronic schizophrenia patients.

OBJECTIVE: There has been consistent evidence for a lower incidence and milder course of schizophrenia in women, yet there have been very few investigations of sex differences in brain function in this disorder. This study used a new high-temporal-resolution measure of functional brain connectivity to test the prediction that female patients would show relatively greater inter- and intrahemispheric connectivity than male patients, particularly in the early stage of schizophrenia. METHOD: Forty patients with chronic schizophrenia (20 women and 20 men) and 24 patients with first-episode schizophrenia (12 women and 12 men) and their respective matched comparison groups completed a conventional auditory oddball task. Phase synchronous gamma (40 Hz) activity was extracted from EEG recording during the task and time-locked to the oddball (target) stimuli. RESULTS: Chronic schizophrenia subjects showed a reduction in global functional connectivity (lower gamma phase synchrony) relative to their matched healthy subjects. Unexpectedly, this reduction was most apparent in female patients. By contrast, while first-episode patients showed a general reduction in the speed of frontal connectivity, the speed of global connectivity was relatively faster in female patients. CONCLUSIONS: This is the first study to investigate sex differences in schizophrenia that used the functional connectivity measure of gamma phase synchrony. The results suggest that in female patients with schizophrenia, additional breakdowns in brain network connectivity may develop with illness chronicity.

The dynamics of cortico-amygdala and autonomic activity over the experimental time course of fear perception.

Human neuroimaging studies implicate the amygdala, medial prefrontal and somatosensory-related cortices as key neural components in the perception of facial fear signals. Yet, their temporal sequence and interaction with autonomic arousal is not known. We used simultaneous functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) recording in 22 healthy subjects to examine central and autonomic responses to repeated fearful expressions. Phasic SCRs followed a U-shape pattern across early, middle and late presentations of fear stimuli. fMRI data revealed a concomitant temporal sequence of preferential somatosensory insula, dorsomedial prefrontal cortex and left amygdala engagement. These findings suggest that sustained cortico-amygdala and autonomic responses may serve to prime the emotional content of fear signals, and differentiate them from initial stimulus novelty.