History of concussion and lowered heart rate variability at rest beyond symptom recovery:a systematic review and meta-analysis

Introduction: Concussion is a growing concern in worldwide sporting culture. Heart rate variability (HRV) is closely tied with autonomic nervous system (ANS) deficits that arise from a concussion. The objective of this review was to determine if a history of concussion (HOC) can impact HRV values in the time-domain in individuals at rest. This review works to add to the literature surrounding HRV testing and if it can be used to check for brain vulnerabilities beyond the recovery of concussion symptoms. Materials and methods: The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. A computer based systematic review scanned articles dating from 1996 to June 2023 through PubMed, Cochrane Library, Google Scholar, and EMBASE databases. A risk of bias assessment was conducted using the ROBINS-E tool. The average difference in time between heartbeats (MeanNN), the standard deviation of the differences (SDNN), and the root mean squared of the successive intervals (RMSSD) were measured. Results: Six total studies were found that fit the inclusion criteria including a total of 242 participants (133 without HOC, 109 with HOC). The average age of the control group was 23.3 ± 8.2, while the average age of the history of TBI group was 25.4 ± 9.7, with no significant difference between the groups (p = 0.202). Four of the studies reported no significant difference in any of the three measures, while two of the studies reported significant difference for all three measures. The meta-analysis was conducted and found that MeanNN (p = 0.03) and RMSSD (p = 0.04) reached statistical significance, while SDNN did not (p = 0.11). Conclusion: The results of this meta-analysis showed significant difference in two of the three HRV time-domain parameters evaluated. It demonstrates that there can be lowered HRV values that expand beyond the recovery of symptoms, reflecting an extensive period of ANS susceptibility after a concussion. This may be an important variable in determining an athlete’s return to play (RTP). Lack of homogenous study populations and testing methods introduces potential for bias and confounding factors, such as gender or age. Future studies should focus on baseline tests to compare individuals to themselves rather than matched controls

Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder

Background: Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. Methods: We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed-based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. Results: Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. Conclusions: Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD

Correlates finding of heart rate changes in fMRI data

Tato diplomová práce pojednává o problematice hledání korelátů změn tepové frekvence v datech funkční magnetické rezonance. Nejprve je popsán princip funkční magnetické rezonance, vznik BOLD signálu, akvizice dat, jejich předzpracování a analýza. Dále je popsána variabilita tepové frekvence a její vliv na data funkční magnetické rezonance. V praktické části se práce věnuje předzpracování časových průběhů tepové frekvence do podoby využitelné k hledání korelátů mezi variabilitou tepové frekvence a daty získaných z funkční magnetické rezonance pomocí obecného lineárního modelu. Popis postupu při statistické analýze a vyhodnocení získaných výsledků (hledaných korelátů) je provedeno v závěru práce.This master’s thesis deals with problematic of correlates finding of heart rate changes in fMRI data. The first part describes principle of fMRI, creation of BOLD signal, data acquisition, their pre-processing and analysis. The next part describes heart rate variability and its impact on fMRI data. The following section is dedicated to pre-processing of heart rate time series to the form, which can be used in correlates finding of heart rate variability and fMRI data with generalized linear model. The process of statistical testing and its result with discussion can be found in the last part of this thesis.

The central autonomic network at rest: Uncovering functional MRI correlates of time-varying autonomic outflow.

Peripheral measures of autonomic nervous system (ANS) activity at rest have been extensively employed as putative biomarkers of autonomic cardiac control. However, a comprehensive characterization of the brain-based central autonomic network (CAN) sustaining cardiovascular oscillations at rest is missing, limiting the interpretability of these ANS measures as biomarkers of cardiac control. We evaluated combined cardiac and fMRI data from 34 healthy subjects from the Human Connectome Project to detect brain areas functionally linked to cardiovagal modulation at rest. Specifically, we combined voxel-wise fMRI analysis with instantaneous heartbeat and spectral estimates obtained from inhomogeneous linear point-process models. We found exclusively negative associations between cardiac parasympathetic activity at rest and a widespread network including bilateral anterior insulae, right dorsal middle and left posterior insula, right parietal operculum, bilateral medial dorsal and ventrolateral posterior thalamic nuclei, anterior and posterior mid-cingulate cortex, medial frontal gyrus/pre-supplementary motor area. Conversely, we found only positive associations between instantaneous heart rate and brain activity in areas including frontopolar cortex, dorsomedial prefrontal cortex, anterior, middle and posterior cingulate cortices, superior frontal gyrus, and precuneus. Taken together, our data suggests a much wider involvement of diverse brain areas in the CAN at rest than previously thought, which could reflect a differential (both spatially and directionally) CAN activation according to the underlying task. Our insight into CAN activity at rest also allows the investigation of its impairment in clinical populations in which task-based fMRI is difficult to obtain (e.g., comatose patients or infants).This work was supported by the US National Institutes for Health (NIH), Office of the Director (OT2-OD023867 to VN); National Center for Complementary and Integrative Health (NCCIH), NIH (P01-AT009965, R61-AT009306, R33-AT009306, R01-AT007550 to VN); the National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH (R01-AR064367 to VN); the Medical Research Council (MRC), UK (MR/P01271X/1 to LP); the American Heart Association (16GRNT26420084 to RB)

Brain-heart pathways to blood pressure-related hypoalgesia

OBJECTIVE: High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging (fMRI) and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain. METHODS: Eighteen participants (10 women; 32.7 ± 6.5 years) underwent BP monitoring over one week at home, and individual pain thresholds were determined in the lab. Subsequently, participants were administered unpredictable painful and non-painful electrocutaneous shocks (stimulus type), timed to occur either at systole or diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience. RESULTS: Subjective pain was lower for painful stimuli administered at systole compared to diastole, F1, 2283 = 4.82; p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F1, 2164 = 10.47; p < 0.0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type x cardiac phase interaction emerged except for a small cluster located in the right parietal cortex. CONCLUSIONS: We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral and lingual gyrus, regions typically involved in the cognitive aspects of pain experience

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer\u27s Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer\u27s Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults

Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults

The ability to regulate emotion is crucial to promote well-being. Evidence suggests that the medial prefrontal cortex (mPFC) and adjacent anterior cingulate (ACC) modulate amygdala activity during emotion regulation. Yet less is known about whether the amygdala-mPFC circuit is linked with regulation of the autonomic nervous system and whether the relationship differs across the adult lifespan. The current study tested the hypothesis that heart rate variability (HRV) reflects the strength of mPFC-amygdala interaction across younger and older adults. We recorded participants’ heart rates at baseline and examined whether baseline HRV was associated with amygdala-mPFC functional connectivity during rest. We found that higher HRV was associated with stronger functional connectivity between the amygdala and the mPFC during rest across younger and older adults. In addition to this age-invariant pattern, there was an age-related change, such that greater HRV was linked with stronger functional connectivity between amygdala and ventrolateral PFC (vlPFC) in younger than in older adults. These results are in line with past evidence that vlPFC is involved in emotion regulation especially in younger adults. Taken together, our results support the neurovisceral integration model and suggest that higher heart rate variability is associated with neural mechanisms that support successful emotional regulation across the adult lifespan

Altered Local and Large-Scale Dynamic Functional Connectivity Variability in Posttraumatic Stress Disorder: A Resting-State fMRI Study

Posttraumatic stress disorder (PTSD) is a psychiatric condition that can emerge after exposure to an exceedingly traumatic event. Previous neuroimaging studies have indicated that PTSD is characterized by aberrant resting-state functional connectivity (FC). However, few existing studies on PTSD have examined dynamic changes in resting-state FC related to network formation, interaction, and dissolution over time. In this study, we compared the dynamic resting-state local and large-scale FC between PTSD patients (n = 22) and healthy controls (HC; n = 22; conducted as standard deviation in resting-state local and large-scale FC over a series of sliding windows). Local dynamic FC was examined by calculating the dynamic regional homogeneity (dReHo), and large-scale dynamic FC (dFC) was investigated between regions with significant dReHo group differences. For the PTSD patients, we also investigated the relationship between symptom severity and dFC/dReHo. Our results showed that PTSD patients were characterized by I) increased dynamic (more variable) dReHo in left precuneus (PCu); II) increased dynamic (more variable) dFC between the left PCu and left insula; and III) decreased dFC between left PCu and left inferior parietal lobe (IPL), and decreased dFC between left PCu and right PCu. However, there is no significant correlation between the clinical indicators and dReHo/dFC after the family-wise-error (FWE) correction. These findings provided the initial evidence that PTSD is characterized by aberrant patterns of fluctuating communication within brain system such as the default mode network (DMN) and among different brain systems such as the salience network and the DMN