Association Between Duration of SARS-CoV-2 Positivity and Long COVID.

In an observational study, we analyzed 1293 healthcare workers previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 34.1% developed postacute sequelae of SARS-CoV-2 infection (also known as long COVID). Using a multivariate logistic regression model, we demonstrate that the likelihood of developing long COVID in infected individuals rises with the increasing of duration of infection and that 3 doses of the BNT162b2 vaccine are protective, even during the Omicron wave.

Point process temporal structure characterizes electrodermal activity.

Electrodermal activity (EDA) is a direct readout of the body's sympathetic nervous system measured as sweat-induced changes in the skin's electrical conductance. There is growing interest in using EDA to track physiological conditions such as stress levels, sleep quality, and emotional states. Standardized EDA data analysis methods are readily available. However, none considers an established physiological feature of EDA. The sympathetically mediated pulsatile changes in skin sweat measured as EDA resemble an integrate-and-fire process. An integrate-and-fire process modeled as a Gaussian random walk with drift diffusion yields an inverse Gaussian model as the interpulse interval distribution. Therefore, we chose an inverse Gaussian model as our principal probability model to characterize EDA interpulse interval distributions. To analyze deviations from the inverse Gaussian model, we considered a broader model set: the generalized inverse Gaussian distribution, which includes the inverse Gaussian and other diffusion and nondiffusion models; the lognormal distribution which has heavier tails (lower settling rates) than the inverse Gaussian; and the gamma and exponential probability distributions which have lighter tails (higher settling rates) than the inverse Gaussian. To assess the validity of these probability models we recorded and analyzed EDA measurements in 11 healthy volunteers during 1 h of quiet wakefulness. Each of the 11 time series was accurately described by an inverse Gaussian model measured by Kolmogorov-Smirnov measures. Our broader model set offered a useful framework to enhance further statistical descriptions of EDA. Our findings establish that a physiologically based inverse Gaussian probability model provides a parsimonious and accurate description of EDA.

CT-based radiomics can identify physiological modifications of bone structure related to subjects' age and sex.

PURPOSE: Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners. MATERIALS AND METHODS: We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions. RESULTS: The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years). CONCLUSION: Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis.

Functional assessment of bidirectional cortical and peripheral neural control on heartbeat dynamics: A brain-heart study on thermal stress.

The study of functional Brain-Heart Interplay (BHI) from non-invasive recordings has gained much interest in recent years. Previous endeavors aimed at understanding how the two dynamical systems exchange information, providing novel holistic biomarkers and important insights on essential cognitive aspects and neural system functioning. However, the interplay between cardiac sympathovagal and cortical oscillations still has much room for further investigation. In this study, we introduce a new computational framework for a functional BHI assessment, namely the Sympatho-Vagal Synthetic Data Generation Model, combining cortical (electroencephalography, EEG) and peripheral (cardiac sympathovagal) neural dynamics. The causal, bidirectional neural control on heartbeat dynamics was quantified on data gathered from 26 human volunteers undergoing a cold-pressor test. Results show that thermal stress induces heart-to-brain functional interplay sustained by EEG oscillations in the delta and gamma bands, primarily originating from sympathetic activity, whereas brain-to-heart interplay originates over central brain regions through sympathovagal control. The proposed methodology provides a viable computational tool for the functional assessment of the causal interplay between cortical and cardiac neural control.

Elementary integrate-and-fire process underlies pulse amplitudes in Electrodermal activity.

Electrodermal activity (EDA) is a direct read-out of sweat-induced changes in the skin's electrical conductance. Sympathetically-mediated pulsatile changes in skin sweat measured as EDA resemble an integrate-and-fire process, which yields an inverse Gaussian model as the inter-pulse interval distribution. We have previously showed that the inter-pulse intervals in EDA follow an inverse Gaussian distribution. However, the statistical structure of EDA pulse amplitudes has not yet been characterized based on the physiology. Expanding upon the integrate-and-fire nature of sweat glands, we hypothesized that the amplitude of an EDA pulse is proportional to the excess volume of sweat produced compared to what is required to just reach the surface of the skin. We modeled this as the difference of two inverse Gaussian models for each pulse, one which represents the time required to produce just enough sweat to rise to the surface of the skin and one which represents the time requires to produce the actual volume of sweat. We proposed and tested a series of four simplifications of our hypothesis, ranging from a single difference of inverse Gaussians to a single simple inverse Gaussian. We also tested four additional models for comparison, including the lognormal and gamma distributions. All models were tested on EDA data from two subject cohorts, 11 healthy volunteers during 1 hour of quiet wakefulness and a different set of 11 healthy volunteers during approximately 3 hours of controlled propofol sedation. All four models which represent simplifications of our hypothesis outperformed other models across all 22 subjects, as measured by Akaike's Information Criterion (AIC), as well as mean and maximum distance from the diagonal on a quantile-quantile plot. Our broader model set of four simplifications offered a useful framework to enhance further statistical descriptions of EDA pulse amplitudes. Some of the simplifications prioritize fit near the mode of the distribution, while others prioritize fit near the tail. With this new insight, we can summarize the physiologically-relevant amplitude information in EDA with at most four parameters. Our findings establish that physiologically based probability models provide parsimonious and accurate description of temporal and amplitude characteristics in EDA.

Psychophysics and computational modeling of feature-continuous motion perception.

Sensory decision-making is frequently studied using categorical tasks, even though the feature space of most stimuli is continuous. Recently, it has become more common to measure feature perception in a gradual fashion, say when studying motion perception across the full space of directions. However, continuous reports can be contaminated by perceptual or motor biases. Here, we examined such biases on perceptual reports by comparing two response methods. With the first method, participants reported motion direction in a motor reference frame by moving a trackball. With the second method, participants used a perceptual frame of reference with a perceptual comparison stimulus. We tested biases using three different versions of random dot kinematograms. We found strong and systematic biases in responses when reporting the direction in a motor frame of reference. For the perceptual frame of reference, these systematic biases were not evident. Independent of the response method, we also detected a systematic misperception where subjects sometimes confuse the physical stimulus direction with its opposite direction. This was confirmed using a von Mises mixture model that estimated the contribution of veridical perception, misperception, and guessing. Importantly, the more sensitive perceptual reporting method revealed that, with increasing levels of sensory evidence, perceptual performance increases not only in the form of higher detection probability, but under certain conditions also in the form of increased precision.

A Novel Approach for Segment-Length Selection Based on Stationarity to Perform Effective Connectivity Analysis Applied to Resting-State EEG Signals.

Connectivity among different areas within the brain is a topic that has been notably studied in the last decade. In particular, EEG-derived measures of effective connectivity examine the directionalities and the exerted influences raised from the interactions among neural sources that are masked out on EEG signals. This is usually performed by fitting multivariate autoregressive models that rely on the stationarity that is assumed to be maintained over shorter bits of the signals. However, despite being a central condition, the selection process of a segment length that guarantees stationary conditions has not been systematically addressed within the effective connectivity framework, and thus, plenty of works consider different window sizes and provide a diversity of connectivity results. In this study, a segment-size-selection procedure based on fourth-order statistics is proposed to make an informed decision on the appropriate window size that guarantees stationarity both in temporal and spatial terms. Specifically, kurtosis is estimated as a function of the window size and used to measure stationarity. A search algorithm is implemented to find the segments with similar stationary properties while maximizing the number of channels that exhibit the same properties and grouping them accordingly. This approach is tested on EEG signals recorded from six healthy subjects during resting-state conditions, and the results obtained from the proposed method are compared to those obtained using the classical approach for mapping effective connectivity. The results show that the proposed method highlights the influence that arises in the Default Mode Network circuit by selecting a window of 4 s, which provides, overall, the most uniform stationary properties across channels.

A polysomnography study examining the association between sleep and postoperative delirium in older hospitalized cardiac surgical patients.

Hospitalized older patients who undergo elective cardiac surgery with cardiopulmonary bypass are prone to postoperative delirium. Self-reported shorter sleep and longer sleep have been associated with impaired cognition. Few data exist to guide us on whether shorter or longer sleep is associated with postoperative delirium in this hospitalized cohort. This was a prospective, single-site, observational study of hospitalized patients (>60 years) scheduled to undergo elective major cardiac surgery with cardiopulmonary bypass (n = 16). We collected and analysed overnight polysomnography data using the Somté PSG device and assessed for delirium twice a day until postoperative day 3 using the long version of the confusion assessment method and a structured chart review. We also assessed subjective sleep quality using the Pittsburg Sleep Quality Index. The delirium median preoperative hospital stay of 9 [Q1, Q3: 7, 11] days was similar to the non-delirium preoperative hospital stay of 7 [4, 9] days (p = .154). The incidence of delirium was 45.5% (10/22) in the entire study cohort and 50% (8/16) in the final cohort with clean polysomnography data. The preoperative delirium median total sleep time of 323.8 [Q1, Q3: 280.3, 382.1] min was longer than the non-delirium median total sleep time of 254.3 [210.9, 278.1] min (p = .046). This was accounted for by a longer delirium median non-rapid eye movement (REM) stage 2 sleep duration of 282.3 [229.8, 328.8] min compared to the non-delirium median non-REM stage 2 sleep duration of 202.5 [174.4, 208.9] min (p = .012). Markov chain modelling confirmed these findings. There were no differences in measures of sleep quality assessed by the Pittsburg Sleep Quality Index. Polysomnography measures of sleep obtained the night preceding surgery in hospitalized older patients scheduled for elective major cardiac surgery with cardiopulmonary bypass are suggestive of an association between longer sleep duration and postoperative delirium.

Advanced computation in cardiovascular physiology: new challenges and opportunities.

Recent developments in computational physiology have successfully exploited advanced signal processing and artificial intelligence tools for predicting or uncovering characteristic features of physiological and pathological states in humans. While these advanced tools have demonstrated excellent diagnostic capabilities, the high complexity of these computational 'black boxes' may severely limit scientific inference, especially in terms of biological insight about both physiology and pathological aberrations. This theme issue highlights current challenges and opportunities of advanced computational tools for processing dynamical data reflecting autonomic nervous system dynamics, with a specific focus on cardiovascular control physiology and pathology. This includes the development and adaptation of complex signal processing methods, multivariate cardiovascular models, multiscale and nonlinear models for central-peripheral dynamics, as well as deep and transfer learning algorithms applied to large datasets. The width of this perspective highlights the issues of specificity in heartbeat-related features and supports the need for an imminent transition from the black-box paradigm to explainable and personalized clinical models in cardiovascular research. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

A novel artificial intelligence based intensive care unit monitoring system: using physiological waveforms to identify sepsis.

A massive amount of multimodal data are continuously collected in the intensive care unit (ICU) along each patient stay, offering a great opportunity for the development of smart monitoring devices based on artificial intelligence (AI). The two main sources of relevant information collected in the ICU are the electronic health records (EHRs) and vital sign waveforms continuously recorded at the bedside. While EHRs are already widely processed by AI algorithms for prompt diagnosis and prognosis, AI-based assessments of the patients' pathophysiological state using waveforms are less developed, and their use is still limited to real-time monitoring for basic visual vital sign feedback at the bedside. This study uses data from the MIMIC-III database (PhysioNet) to propose a novel AI approach in ICU patient monitoring that incorporates features estimated by a closed-loop cardiovascular model, with the specific goal of identifying sepsis within the first hour of admission. Our top benchmark results (AUROC = 0.92, AUPRC = 0.90) suggest that features derived by cardiovascular control models may play a key role in identifying sepsis, by continuous monitoring performed through advanced multivariate modelling of vital sign waveforms. This work lays foundations for a deeper data integration paradigm which will help clinicians in their decision-making processes. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Functional brain-heart interplay extends to the multifractal domain.

The study of functional brain-heart interplay has provided meaningful insights in cardiology and neuroscience. Regarding biosignal processing, this interplay involves predominantly neural and heartbeat linear dynamics expressed via time and frequency domain-related features. However, the dynamics of central and autonomous nervous systems show nonlinear and multifractal behaviours, and the extent to which this behaviour influences brain-heart interactions is currently unknown. Here, we report a novel signal processing framework aimed at quantifying nonlinear functional brain-heart interplay in the non-Gaussian and multifractal domains that combines electroencephalography (EEG) and heart rate variability series. This framework relies on a maximal information coefficient analysis between nonlinear multiscale features derived from EEG spectra and from an inhomogeneous point-process model for heartbeat dynamics. Experimental results were gathered from 24 healthy volunteers during a resting state and a cold pressor test, revealing that synchronous changes between brain and heartbeat multifractal spectra occur at higher EEG frequency bands and through nonlinear/complex cardiovascular control. We conclude that significant bodily, sympathovagal changes such as those elicited by cold-pressure stimuli affect the functional brain-heart interplay beyond second-order statistics, thus extending it to multifractal dynamics. These results provide a platform to define novel nervous-system-targeted biomarkers. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Lateralization of directional brain-heart information transfer during visual emotional elicitation.

Previous studies have characterized the physiological interactions between central nervous system (brain) and peripheral cardiovascular system (heart) during affective elicitation in healthy subjects; however, questions related to the directionality of this functional interplay have been gaining less attention from the scientific community. Here, we explore brain-heart interactions during visual emotional elicitation in healthy subjects using measures of Granger causality (GC), a widely used descriptor of causal influences between two dynamical systems. The proposed approach inferences causality between instantaneous cardiovagal dynamics estimated from inhomogeneous point-process models of the heartbeat and high-density electroencephalogram (EEG) dynamics in 22 healthy subjects who underwent pleasant/unpleasant affective elicitation by watching pictures from the International Affective Picture System database. Particularly, we calculated the GC indexes between the EEG spectrogram in the canonical θ-, α-, ß-, and γ-bands and both the instantaneous mean heart rate and its continuous parasympathetic modulations (i.e., the instantaneous HF power). Thus we looked for significant statistical differences among GC values estimated during the resting state, neutral elicitation, and pleasant/unpleasant arousing elicitation. As compared with resting state, coupling strength increases significantly in the left hemisphere during positive stimuli and in the right hemisphere during negative stimuli. Our results further reveal a correlation between emotional valence and lateralization of the dynamical information transfer going from brain-to-heart, mainly localized in the prefrontal, somatosensory, and posterior cortexes, and of the information transfer from heart-to-brain, mainly reflected into the fronto-parietal cortex oscillations in the γ-band (30-45 Hz).

A Parsimonious Granger Causality Formulation for Capturing Arbitrarily Long Multivariate Associations.

High-frequency neuroelectric signals like electroencephalography (EEG) or magnetoencephalography (MEG) provide a unique opportunity to infer causal relationships between local activity of brain areas. While causal inference is commonly performed through classical Granger causality (GC) based on multivariate autoregressive models, this method may encounter important limitations (e.g., data paucity) in the case of high dimensional data from densely connected systems like the brain. Additionally, physiological signals often present long-range dependencies which commonly require high autoregressive model orders/number of parameters. We present a generalization of autoregressive models for GC estimation based on Wiener-Volterra decompositions with Laguerre polynomials as basis functions. In this basis, the introduction of only one additional global parameter allows to capture arbitrary long dependencies without increasing model order, hence retaining model simplicity, linearity and ease of parameters estimation. We validate our method in synthetic data generated from families of complex, densely connected networks and demonstrate superior performance as compared to classical GC. Additionally, we apply our framework to studying the directed human brain connectome through MEG data from 89 subjects drawn from the Human Connectome Project (HCP) database, showing that it is able to reproduce current knowledge as well as to uncover previously unknown directed influences between cortical and limbic brain regions.

Patient-Specific Classification of ICU Sedation Levels From Heart Rate Variability.

OBJECTIVE: To develop a personalizable algorithm to discriminate between sedation levels in ICU patients based on heart rate variability. DESIGN: Multicenter, pilot study. SETTING: Several ICUs at Massachusetts General Hospital, Boston, MA. PATIENTS: We gathered 21,912 hours of routine electrocardiogram recordings from a heterogenous group of 70 adult ICU patients. All patients included in the study were mechanically ventilated and were receiving sedatives. MEASUREMENTS AND MAIN RESULTS: As "ground truth" for developing our method, we used Richmond Agitation Sedation Scale scores grouped into four levels denoted "comatose" (-5), "deeply sedated" (-4 to -3), "lightly sedated" (-2 to 0), and "agitated" (+1 to +4). We trained a support vector machine learning algorithm to calculate the probability of each sedation level from heart rate variability measures derived from the electrocardiogram. To estimate algorithm performance, we calculated leave-one-subject out cross-validated accuracy. The patient-independent version of the proposed system discriminated between the four sedation levels with an overall accuracy of 59%. Upon personalizing the system supplementing the training data with patient-specific calibration data, consisting of an individual's labeled heart rate variability epochs from the preceding 24 hours, accuracy improved to 67%. The personalized system discriminated between light- and deep-sedation states with an average accuracy of 75%. CONCLUSIONS: With further refinement, the methodology reported herein could lead to a fully automated system for depth of sedation monitoring. By enabling monitoring to be continuous, such technology may help clinical staff to monitor sedation levels more effectively and to reduce complications related to over- and under sedation.

Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea.

While autonomic outflow is an important co-factor of nausea physiology, central control of this outflow is poorly understood. We evaluated sympathetic (skin conductance level) and cardiovagal (high-frequency heart rate variability) modulation, collected synchronously with functional MRI (fMRI) data during nauseogenic visual stimulation aimed to induce vection in susceptible individuals. Autonomic data guided analysis of neuroimaging data, using a stimulus-based (analysis windows set by visual stimulation protocol) and percept-based (windows set by subjects' ratings) approach. Increased sympathetic and decreased parasympathetic modulation was associated with robust and anti-correlated brain activity in response to nausea. Specifically, greater autonomic response was associated with reduced fMRI signal in brain regions such as the insula, suggesting an inhibitory relationship with premotor brainstem nuclei. Interestingly, some sympathetic/parasympathetic specificity was noted. Activity in default mode network and visual motion areas was anti-correlated with parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical activity was anti-correlated with sympathetic outflow during recovery, soon after cessation of nauseogenic stimulation. These results suggest divergent central autonomic control for sympathetic and parasympathetic response to nausea. Autonomic outflow and the central autonomic network underlying ANS response to nausea may be an important determinant of overall nausea intensity and, ultimately, a potential therapeutic target.

Likelihood methods for point processes with refractoriness.

Likelihood-based encoding models founded on point processes have received significant attention in the literature because of their ability to reveal the information encoded by spiking neural populations. We propose an approximation to the likelihood of a point-process model of neurons that holds under assumptions about the continuous time process that are physiologically reasonable for neural spike trains: the presence of a refractory period, the predictability of the conditional intensity function, and its integrability. These are properties that apply to a large class of point processes arising in applications other than neuroscience. The proposed approach has several advantages over conventional ones. In particular, one can use standard fitting procedures for generalized linear models based on iteratively reweighted least squares while improving the accuracy of the approximation to the likelihood and reducing bias in the estimation of the parameters of the underlying continuous-time model. As a result, the proposed approach can use a larger bin size to achieve the same accuracy as conventional approaches would with a smaller bin size. This is particularly important when analyzing neural data with high mean and instantaneous firing rates. We demonstrate these claims on simulated and real neural spiking activity. By allowing a substantive increase in the required bin size, our algorithm has the potential to lower the barrier to the use of point-process methods in an increasing number of applications.

Identifying prognostic factors for survival in intensive care unit patients with SIRS or sepsis by machine learning analysis on electronic health records.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) and sepsis are the most common causes of in-hospital death. However, the characteristics associated with the improvement in the patient conditions during the ICU stay were not fully elucidated for each population as well as the possible differences between the two. GOAL: The aim of this study is to highlight the differences between the prognostic clinical features for the survival of patients diagnosed with SIRS and those of patients diagnosed with sepsis by using a multi-variable predictive modeling approach with a reduced set of easily available measurements collected at the admission to the intensive care unit (ICU). METHODS: Data were collected from 1,257 patients (816 non-sepsis SIRS and 441 sepsis) admitted to the ICU. We compared the performance of five machine learning models in predicting patient survival. Matthews correlation coefficient (MCC) was used to evaluate model performances and feature importance, and by applying Monte Carlo stratified Cross-Validation. RESULTS: Extreme Gradient Boosting (MCC = 0.489) and Logistic Regression (MCC = 0.533) achieved the highest results for SIRS and sepsis cohorts, respectively. In order of importance, APACHE II, mean platelet volume (MPV), eosinophil counts (EoC), and C-reactive protein (CRP) showed higher importance for predicting sepsis patient survival, whereas, SOFA, APACHE II, platelet counts (PLTC), and CRP obtained higher importance in the SIRS cohort. CONCLUSION: By using complete blood count parameters as predictors of ICU patient survival, machine learning models can accurately predict the survival of SIRS and sepsis ICU patients. Interestingly, feature importance highlights the role of CRP and APACHE II in both SIRS and sepsis populations. In addition, MPV and EoC are shown to be important features for the sepsis population only, whereas SOFA and PLTC have higher importance for SIRS patients.

Comparative Assessment of Physiological Responses to Emotional Elicitation by Auditory and Visual Stimuli.

The study of emotions through the analysis of the induced physiological responses gained increasing interest in the past decades. Emotion-related studies usually employ films or video clips, but these stimuli do not give the possibility to properly separate and assess the emotional content provided by sight or hearing in terms of physiological responses. In this study we have devised an experimental protocol to elicit emotions by using, separately and jointly, pictures and sounds from the widely used International Affective Pictures System and International Affective Digital Sounds databases. We processed galvanic skin response, electrocardiogram, blood volume pulse, pupillary signal and electroencephalogram from 21 subjects to extract both autonomic and central nervous system indices to assess physiological responses in relation to three types of stimulation: auditory, visual, and auditory/visual. Results show a higher galvanic skin response to sounds compared to images. Electrocardiogram and blood volume pulse show different trends between auditory and visual stimuli. The electroencephalographic signal reveals a greater attention paid by the subjects when listening to sounds compared to watching images. In conclusion, these results suggest that emotional responses increase during auditory stimulation at both central and peripheral levels, demonstrating the importance of sounds for emotion recognition experiments and also opening the possibility toward the extension of auditory stimuli in other fields of psychophysiology. Clinical and Translational Impact Statement- These findings corroborate auditory stimuli's importance in eliciting emotions, supporting their use in studying affective responses, e.g., mood disorder diagnosis, human-machine interaction, and emotional perception in pathology.

CT Cadaveric dataset for Radiomics features stability assessment in lumbar vertebrae.

Radiomics features (RFs) studies have showed limitations in the reproducibility of RFs in different acquisition settings. To date, reproducibility studies using CT images mainly rely on phantoms, due to the harness of patient exposure to X-rays. The provided CadAIver dataset has the aims of evaluating how CT scanner parameters effect radiomics features on cadaveric donor. The dataset comprises 112 unique CT acquisitions of a cadaveric truck acquired on 3 different CT scanners varying KV, mA, field-of-view, and reconstruction kernel settings. Technical validation of the CadAIver dataset comprises a comprehensive univariate and multivariate GLM approach to assess stability of each RFs extracted from lumbar vertebrae. The complete dataset is publicly available to be applied for future research in the RFs field, and could foster the creation of a collaborative open CT image database to increase the sample size, the range of available scanners, and the available body districts.

Brain correlates of phasic autonomic response to acupuncture stimulation: an event-related fMRI study.

Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR-) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR- was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR-. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR-, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli.