Exogenous Attention to Emotional Stimuli Presenting Realistic (3D) Looming Motion.

Previous research shows that dynamic stimuli, on the one hand, and emotional stimuli, on the other, capture exogenous attention due to their biological relevance. Through neural (ERPs) and behavioral measures (reaction times and errors), the present study explored the combined effect of looming motion and emotional content on attentional capture. To this end, 3D-recreated static and dynamic animals assessed as emotional (positive or negative) or neutral were presented as distractors while 71 volunteers performed a line orientation task. We observed a two-phase effect: firstly (before 300 ms), early components of ERPs (P1p and N2po) showed enhanced exogenous attentional capture by looming positive distractors and static threatening animals. Thereafter, dynamic and static threatening distractors received enhanced endogenous attention as revealed by both late ERP activity (LPC) and behavioral (errors) responses. These effects are likely explained by both the emotional valence and the distance of the stimulus at each moment.

Incidental Attitude Formation via the Surveillance Task: A Preregistered Replication of the Olson and Fazio (2001) Study.

Evaluative conditioning is one of the most widely studied procedures for establishing and changing attitudes. The surveillance task is a highly cited evaluative-conditioning paradigm and one that is claimed to generate attitudes without awareness. The potential for evaluative-conditioning effects to occur without awareness continues to fuel conceptual, theoretical, and applied developments. Yet few published studies have used this task, and most are characterized by small samples and small effect sizes. We conducted a high-powered (N = 1,478 adult participants), preregistered close replication of the original surveillance-task study (Olson & Fazio, 2001). We obtained evidence for a small evaluative-conditioning effect when "aware" participants were excluded using the original criterion-therefore replicating the original effect. However, no such effect emerged when three other awareness criteria were used. We suggest that there is a need for caution when using evidence from the surveillance-task effect to make theoretical and practical claims about "unaware" evaluative-conditioning effects.

Retinotopy of emotion: Perception of negatively valenced stimuli presented at different spatial locations as revealed by event-related potentials.

Scarce previous data on how the location where an emotional stimulus appears in the visual scene modulates its perception suggest that, for functional reasons, a perceptual advantage may exist, vertically, for stimuli presented at the lower visual field (LoVF) and, horizontally, for stimuli presented at the left visual field (LeVF). However, this issue has been explored through a limited number of spatial locations, usually in a single spatial dimension (e.g., horizontal) and invariant eccentricities. Event-related potentials (ERPs) were recorded from 39 participants perceiving brief neutral (wheels) and emotional stimuli (spiders) presented at 17 different locations, one foveal and 16 at different peripheral coordinates. As a secondary scope, we explored the role of the magnocellular (M) and the parvocellular (P) visual pathways by presenting an isoluminant/heterochromatic (P-biased) and a heteroluminant/isochromatic version (M-biased) of each stimulus. Emo > Neu effects were observed in PN1 (120 ms) for stimuli located at fovea, and in PN2 (215 ms) for stimuli located both at fovea and diverse peripheral regions. A factorial approach to these effects further revealed that: (a) emotional stimuli presented in the periphery are efficiently perceived, without evident decrease from para- to perifovea; (b) peripheral Emo > Neu effects are reflected 95 ms later than foveal Emo > Neu effects in ERPs; (c) LoVF is more involved than UVF in these effects; (d) our data fail to support the LeVF advantage previously reported, and (e) Emo > Neu effects were significant for both M and P stimuli.

Platelet-derived bio-products: Classification update, applications, concerns and new perspectives.

Platelet derived bio-products in the form of platelet rich plasma, plasma rich in growth factors, or plasma-free platelet releasates, are being studied worldwide with the aim of proving their efficacy in tissue regeneration within many different clinical areas, such as traumatology, maxillofacial surgery, ophthalmology, dermatology and otorhinolaryngology, amongst others. The current lack of consensus in the preparation method and application form, or in the quality assessment of each bio-product, precludes adequate interpretation of the relevance of reported clinical outcomes, and, while many in clinicians are very positive about them, many are sceptic. Relevant aspects of these products are considered to propose a classification nomenclature which would aid a comprehensive comparison of clinical outcomes of bio-products of the same characteristics. Finally, the uses of platelet-derived bio-products in in vitro culture (for cell therapy purposes) as a substitute of animal-origin sera, and other future perspectives of applications of platelet-derived bio-products are discussed.

Ultrafast Cortical Gain Adaptation in the Human Brain by Trial-To-Trial Changes of Associative Strength in Fear Learning.

In fear conditioning, more efficient sensory processing of a stimulus (the conditioned stimulus, CS) that has acquired motivational relevance by being paired with an aversive event (the unconditioned stimulus, US) has been associated with increased cortical gain in early sensory brain areas (Miskovic and Keil, 2012). Further, this sensory gain modulation related to short-term plasticity changes occurs independently of aware cognitive anticipation of the aversive US, pointing toward implicit learning mechanisms (Moratti and Keil, 2009). However, it is unknown how quickly the implicit learning of CS-US associations results in the adaptation of cortical gain. Here, using steady-state visually evoked fields derived from human Magnetoencephalography (MEG) recordings in two experiments (N = 33, 17 females and 16 males), we show that stimulus-driven neuromagnetic oscillatory activity increases and decreases quickly as a function of associative strength within three or four trials, as predicted by a computationally implemented Rescorla-Wagner model with the highest learning rate. These ultrafast cortical gain adaptations are restricted to early visual cortex using a delay fear conditioning procedure. Short interval (500 ms) trace conditioning resulted in the same ultrafast activity modulations by associative strength, but in a complex occipito-parieto-temporo-frontal network. Granger causal analysis revealed that reverberating top-down and bottom-up influences between anterior and posterior brain regions during trace conditioning characterized this network. Critically, in both delay and trace conditioning, ultrafast cortical gain modulations as a function of associative strength occurred independently of conscious US anticipation.SIGNIFICANCE STATEMENT In ever-changing environments, learned associations between a cue and an aversive consequence must change under new stimulus-consequence contingencies to be adaptive. What predicts potential dangers now might be meaningless in the next situation. Predictive cues are prioritized, as reflected by increased sensory cortex activity for these cues. However, this modulation also must adapt to altered stimulus-consequence contingencies. Here, we show that human visual cortex activity can be modulated quickly according to ultrafast contingency changes within a few learning trials. This finding extends to frontal brain regions when the cue and the aversive event are separated in time. Critically, this ultrafast updating process occurs orthogonally to aware aversive outcome anticipation and therefore relies on unconscious implicit learning mechanisms.

Implementation of a closed platelet-rich-plasma preparation method using the local blood bank infrastructure at the Principality of Asturias (Spain): Back to basic methodology and a demographics perspective after 1 year.

Platelet-rich plasma (PRP) is used with increasing demand as autologous adjuvant therapy in many areas of regenerative medicine, thanks to the platelet rich content of growth factors and bio-active molecules. However, to date there is a lack of consensus on PRP preparation methods, on processing and application forms, on clinical application guidelines and on knowledge-based composition at the cellular and molecular level, making difficult the assessment of clinical results from different groups in different clinical areas. Here we describe the implementation of PRP production on a closed-system using the infrastructure of a certified blood bank, detailing methodology, and validation and production results 1 year after its implementation. Our methodology provides a reproducible, safe, practical and yet affordable PRP bio-product that will allow further studies to better define PRP applications in regenerative medicine and personalized therapeutic regimes.

Magnocellular Bias in Exogenous Attention to Biologically Salient Stimuli as Revealed by Manipulating Their Luminosity and Color.

Exogenous attention is a set of mechanisms that allow us to detect and reorient toward salient events-such as appetitive or aversive-that appear out of the current focus of attention. The nature of these mechanisms, particularly the involvement of the parvocellular and magnocellular visual processing systems, was explored. Thirty-four participants performed a demanding digit categorization task while salient (spiders or S) and neutral (wheels or W) stimuli were presented as distractors under two figure-ground formats: heterochromatic/isoluminant (exclusively processed by the parvocellular system, Par trials) and isochromatic/heteroluminant (preferentially processed by the magnocellular system, Mag trials). This resulted in four conditions: SPar, SMag, WPar, and WMag. Behavioral (RTs and error rates in the task) and electrophysiological (ERPs) indices of exogenous attention were analyzed. Behavior showed greater attentional capture by SMag than by SPar distractors and enhanced modulation of SMag capture as fear of spiders reported by participants increased. ERPs reflected a sequence from magnocellular dominant (P1p, ≃120 msec) to both magnocellular and parvocellular processing (N2p and P2a, ≃200 msec). Importantly, amplitudes in one N2p subcomponent were greater to SMag than to SPar and WMag distractors, indicating greater magnocellular sensitivity to saliency. Taking together, results support a magnocellular bias in exogenous attention toward distractors of any nature during initial processing, a bias that remains in later stages when biologically salient distractors are present.

DNA copy number profiling reveals different patterns of chromosomal instability within colorectal cancer according to the age of onset.

Chromosomal instability resulting in copy number alterations is a hallmark of colorectal cancer (CRC). However, few studies have attempted to characterize the chromosomal changes occurring in early-onset CRC in order to compare them with those taking place within the more extensively studied late-onset CRC subset. Our aim was to characterize the genomic profiles of these two groups of colorectal tumors and to compare them to each other. Array comparative genomic hybridization profiling of 146 colorectal tumors (60 early-onset and 86 late-onset) in combination with an unsupervised analysis was used to define common and specific copy number alterations. We found a number of important differences between the chromosomal instability profiles of each age subset. Thus, losses at 1p36, 1p12, 1q21, 9p13, 14q11, 16p13, and 16p12 were significantly more frequent in younger patients, whereas gains at 7q11 and 7q22 were more frequent in older patients. Moreover, the unsupervised analysis stratified the tumors into two clusters, each one of which was enriched in patients from one of the age subsets. Our findings confirm the existence of substantial differences between the chromosomal instability profiles of the two groups which are more important from a qualitative point of view. Further studies are needed to understand the clinicopathological implications of these dissimilarities.

Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a complex inflammatory vascular disease. There are currently limited treatment options for AAA when surgery is inapplicable. Therefore, insights into molecular mechanisms underlying AAA pathogenesis may reveal therapeutic targets that could be manipulated pharmacologically or biologically to halt disease progression. Using an elastase-induced AAA mouse model, we previously established that the complement alternative pathway (AP) plays a critical role in the development of AAA. However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding directly to target surfaces. In this study, we sought to determine whether properdin serves as a focal point for the initiation of the AP complement activation in AAA. Using a properdin loss of function mutation in mice and a mutant form of the complement factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin is required for the development of elastase-induced AAA in its primary role as a convertase stabilizer. Unexpectedly, we find that, in AAA, natural IgG antibodies direct AP-mediated complement activation. The absence of IgG abrogates C3 deposition in elastase-perfused aortic wall and protects animals from AAA development. We also determine that blockade of properdin activity prevents aneurysm formation. These results indicate that an innate immune response to self-antigens activates the complement system and initiates the inflammatory cascade in AAA. Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growth.

Evaluation of bioaccumulation kinetics of gold nanorods in vital mammalian organs by means of total reflection X-ray fluorescence spectrometry.

This work presents the first application of total-reflection X-ray fluorescence (TXRF) spectrometry, a new and powerful alternative analytical method, to evaluation of the bioaccumulation kinetics of gold nanorods (GNRs) in various tissues upon intravenous administration in mice. The analytical parameters for developed methodology by TXRF were evaluated by means of the parallel analysis of bovine liver certified reference material samples (BCR-185R) doped with 10 µg/g gold. The average values (n = 5) achieved for gold measurements in lyophilized tissue weight were as follows: recovery 99.7%, expanded uncertainty (k = 2) 7%, repeatability 1.7%, detection limit 112 ng/g, and quantification limit 370 ng/g. The GNR bioaccumulation kinetics was analyzed in several vital mammalian organs such as liver, spleen, brain, and lung at different times. Additionally, urine samples were analyzed to study the kinetics of elimination of the GNRs by this excretion route. The main achievement was clearly differentiating two kinds of behaviors. GNRs were quickly bioaccumulated by highly vascular filtration organs such as liver and spleen, while GNRs do not show a bioaccumulation rates in brain and lung for the period of time investigated. In parallel, urine also shows a lack of GNR accumulation. TXRF has proven to be a powerful, versatile, and precise analytical technique for the evaluation of GNRs content in biological systems and, in a more general way, for any kind of metallic nanoparticles.

Potential impact of metal oxide nanoparticles on the immune system: The role of integrins, L-selectin and the chemokine receptor CXCR4.

The impact of metal oxide nanoparticles (NPs) on the immune system has been studied in vitro using human peripheral blood lymphocytes (PBLs). Metal oxide NPs (ZnO, CeO2, TiO2 and Al2O3) induced changes in the expression levels of adhesion molecules and the C-X-C chemokine receptor type 4 (CXCR4) in these cells. Proliferation studies were carried out with CFSE in response to PHA, finding an increase in T-cell proliferation upon cell exposure to TiO2 and Al2O3 NPs. For ZnO NPs, a decrease in the chemotactic response to SDF-1α was observed. No changes were found in basophil activation and leukocyte oxidative burst after phagocytosis. Despite the absence of cytotoxicity, metal oxide NPs are not inert; they alter the expression levels of adhesion molecules and chemokine receptors, key actors in the immune response, and affect important cell functions such as T-cell proliferative response to mitogens and chemotaxis. FROM THE CLINICAL EDITOR: This study demonstrates the immune-modulating effects of four different metal nanoparticles in a human peripheral blood lymphocyte model system. These effects were clearly present even though these nanoparticles did not display cytotocity in ex vivo experiments.

Learning to suppress a distractor may not be unconscious.

The additional singleton task has become a popular paradigm to explore visual statistical learning and selective attention. In this task, participants are instructed to find a different-shaped target among a series of distractors as fast as possible. In some trials, the search display includes a singleton distractor with a different color, making search more difficult. This singleton distractor appears more often in one location than in the remaining locations. The typical results of these experiments show that participants learn to ignore the area of the screen that is more likely to contain the singleton distractor. It is often claimed that this learning takes place unconsciously, because at the end of the experiment participants seem to be unable to identify the location where the singleton distractor appeared most frequently during the task. In the present study, we tested participants' awareness in three high-powered experiments using alternative measures. Contrary to previous studies, the results show clear evidence of explicit knowledge about which area of the display was more likely to contain the singleton distractor, suggesting that this type of learning might not be unconscious.

The role of working memory in probabilistic cuing of visual search.

In a typical probabilistic cuing experiment, participants are asked to find a visual target among a series of distractors. Although participants are not informed about this, the target appears more frequently in one region of the display, resulting in faster search times for targets located in this region. This bias is thought to depend on a habit-like attentional control mechanism, unconstrained by the availability of working memory (WM) resources. However, the only study that has explored this feature in the past suffers from methodological shortcomings that leave the results open to alternative explanations. In three experiments, we aimed to confirm whether probabilistic cuing is unaffected by visual, spatial, and spatiotemporal WM load. For each experiment, one group of participants performed the visual search task during the retention interval of a WM task (high-load group), whereas another group of participants (no-load group) carried out the visual search task after the WM task. We hypothesized that the probabilistic cuing effect would be larger for the no-load group compared to the high-load group. This hypothesis was confirmed in one experiment, but exploratory analyses suggest that the results can be highly dependent on the analytic approach, casting doubts on its robustness. Overall, our results provide partial support for the hypothesis that probabilistic cuing is not affected by a secondary task. However, given that some analyses reveal an effect of WM load, we conclude that it might be premature to rule out the possibility that the expression of this attentional bias requires WM resources. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

End-on PEGylation of heparin: Effect on anticoagulant activity and complexation with protamine.

Heparin is the most common anticoagulant used in clinical practice but shows some downsides such as short half-life (for the high molecular weight heparin) and secondary effects. On the other hand, its low molecular weight analogue cannot be neutralized with protamine, and therefore cannot be used in some treatments. To address these issues, we conjugated polyethylene glycol (PEG) to heparin reducing end (end-on) via oxime ligation and studied the interactions of the conjugate (Hep-b-PEG) with antithrombin III (AT) and protamine. Isothermal titration calorimetry showed that Hep-b-PEG maintains the affinity to AT. Dynamic light scattering demonstrated that the Hep-b-PEG formed colloidal stable nanocomplexes with protamine instead of large multi-molecular aggregates, associated with heparin side effects. The in vitro (human plasma) and in vivo experiments (Sprague Dawley rats) evidenced an extended half-life and higher anticoagulant activity of the conjugate when compared to unmodified heparin.

Association between Gray-Scale Ultrasound Imaging and Serological Creatine Kinase for Quantifying Exercise-Induced Muscle Damage: An Observational Study.

Limited evidence has verified if ultrasound imaging (US) can detect post-exercise muscle damage based on size, shape, and brightness metrics. This study aimed to analyze the correlation between creatine kinase (CK) concentration and (as a biomarker of muscle damage) changes in US gray-scale metrics after an exercise-induced muscle damage protocol. An observational study was conducted at a private university lab located in Madrid. Twenty-five untrained and asymptomatic volunteers were enrolled in this study. Baseline demographic data and body composition metrics were collected. In addition, the rectus femoris US data and CK concentration were assessed at baseline and after inducing muscle damage (24 and 48 h later). After calculating time differences for all the outcomes, the correlation between the changes observed with US and biomarkers was assessed. Significant CK concentration increases were found 24 h (p = 0.003) and 48 h (p < 0.001) after exercise. However, no significant changes in muscle size, shape, or brightness were found in any location (p > 0.05 for all). In addition, no significant associations were found between CK changes and US changes (p > 0.05 for all). Gray-scale US is not a sensitive tool for detecting muscle damage, as a protocol of exercise-induced muscle damage confirmed with CK produced no significant gray-scale US changes after 24 or 48 h. In addition, US and CK changes after 24 and 48 h were not associated with each other.

Aerobic Exercise and Neuropathic Pain: Insights from Animal Models and Implications for Human Therapy.

This narrative review explores the complex relationship between aerobic exercise (AE) and neuropathic pain (NP), particularly focusing on peripheral neuropathies of mechanical origin. Pain, a multifaceted phenomenon, significantly impacts functionality and distress. The International Association for the Study of Pain's definition highlights pain's biopsychosocial nature, emphasizing the importance of patient articulation. Neuropathic pain, arising from various underlying processes, presents unique challenges in diagnosis and treatment. Our methodology involved a comprehensive literature search in the PubMed and SCOPUS databases, focusing on studies relating AE to NP, specifically in peripheral neuropathies caused by mechanical forces. The search yielded 28 articles and 1 book, primarily animal model studies, providing insights into the efficacy of AE in NP management. Results from animal models demonstrate that AE, particularly in forms like no-incline treadmill and swimming, effectively reduces mechanical allodynia and thermal hypersensitivity associated with NP. AE influences neurophysiological mechanisms underlying NP, modulating neurotrophins, cytokines, and glial cell activity. These findings suggest AE's potential in attenuating neurophysiological alterations in NP. However, human model studies are scarce, limiting the direct extrapolation of these findings to human neuropathic conditions. The few available studies indicate AE's potential benefits in peripheral NP, but a lack of specificity in these studies necessitates further research. In conclusion, while animal models show promising results regarding AE's role in mitigating NP symptoms and influencing underlying neurophysiological mechanisms, more human-centric research is required. This review underscores the need for targeted clinical trials to fully understand and harness AE's therapeutic potential in human neuropathic pain, especially of mechanical origin.

Is probabilistic cuing of visual search an inflexible attentional habit? A meta-analytic review.

In studies on probabilistic cuing of visual search, participants search for a target among several distractors and report some feature of the target. In a biased stage the target appears more frequently in one specific area of the search display. Eventually, participants become faster at finding the target in that rich region compared to the sparse region. In some experiments, this stage is followed by an unbiased stage, where the target is evenly located across all regions of the display. Despite this change in the spatial distribution of targets, search speed usually remains faster when the target is located in the previously rich region. The persistence of the bias even when it is no longer advantageous has been taken as evidence that this phenomenon is an attentional habit. The aim of this meta-analysis was to test whether the magnitude of probabilistic cuing decreases from the biased to the unbiased stage. A meta-analysis of 42 studies confirmed that probabilistic cuing during the unbiased stage was roughly half the size of cuing during the biased stage, and this decrease persisted even after correcting for publication bias. Thus, the evidence supporting the claim that probabilistic cuing is an attentional habit might not be as compelling as previously thought.

Clinical Response After Treatment of Knee Osteoarthritis With a Standardized, Closed-System, Low-Cost Platelet-Rich Plasma Product: 1-Year Outcomes.

Background: Intra-articular infiltration of platelet-rich plasma (PRP) is an alternative therapeutic option to classic hyaluronic acid for the treatment of symptomatic knee osteoarthritis (KOA). However, variation in preparation methods and quality assessment of PRP makes the study of its real clinical efficacy difficult. Purpose: To (1) evaluate the clinical efficacy of a characterized PRP product prepared in a standardized manner and in a closed-system for the treatment of KOA and to (2) evaluate the association of the clinical response to PRP-related variables. Study Design: Case series; Level of evidence, 4. Methods: We recruited 130 patients with nonoperative KOA and evaluated them for 1 year. PRP was prepared from a donation of autologous blood, obtaining 3 aliquots of approximately 10mL of product, which were frozen, allowing platelet disruption, platelet factor release, and long-term storage, until administration. Patients were treated 3 consecutive times every 4 weeks with an intra-articular PRP knee injection under sterile conditions. Complete blood count was performed on the whole-blood sample and the processed PRP before freezing it, for product quality assessment. Patients were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and basic satisfaction scale at 3 months, 6 months, and 1 year after intervention. Results: Quality assessment confirmed a leukocyte-poor PRP product (white blood cell count, 0.09 ± 0.09 × 109/L) with a high platelet purity (platelet count, 630.86 ± 191.75 × 109/L). WOMAC scores improved, and basic satisfaction was achieved in 70% of patients. No adverse events were reported. No correlations were observed between PRP quality parameters and clinical results. PRP complete treatment production costs were €108/US$125 (€36/US$41.6 per injection). Conclusion: This standardized PRP production method resulted in improved WOMAC scores at 1 year postoperatively in 70% of patients with KOA. This technique was safe and affordable and ensured consecutive infiltrations with the same product to each patient.

The role of working memory in contextual cueing of visual attention.

It is usually easier to find objects in familiar contexts that we have seen before. The type of learning that underlies this facilitation, known as contextual cueing, has been understood as an incidental and automatic process given that, among other reasons, it seems to be independent of working memory (WM) resources. This claim has found support in previous research showing that contextual cueing can be acquired latently, while participants perform a demanding WM task. However, previous studies have not always found this pattern of results and, in general, the available evidence is far from conclusive. The aim of the present study was to clarify the role of WM in contextual learning with two large-sample, confirmatory experiments. Our results show a robust contextual cueing effect even when visuospatial working memory resources were recruited by a demanding secondary task.

Heart-brain synchronization breakdown in Parkinson's disease.

Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson's disease (PD) but their relationship with central autonomic network (CAN) activity is not fully understood. We analyzed the synchronization between HRV and brain activity in 31 PD patients and 21 age-matched healthy controls using blood-oxygen-level-dependent (BOLD) signals from resting-state functional brain MRI and HRV metrics from finger plethysmography recorded for 7.40 min. We additionally quantified autonomic symptoms (SCOPA-AUT) and objective autonomic cardiovascular parameters (blood pressure and heart rate) during deep breathing, Valsalva, and head-up tilt, which were used to classify the clinical severity of dysautonomia. We evaluated HRV and BOLD signals synchronization (HRV-BOLD-sync) with Pearson lagged cross-correlations and Fisher's statistics for combining window-length-dependent HRV-BOLD-Sync Maps and assessed their association with clinical dysautonomia. HRV-BOLD-sync was lower significantly in PD than in controls in various brain regions within CAN or in networks involved in autonomic modulation. Moreover, heart-brain synchronization index (HBSI), which quantifies heart-brain synchronization at a single-subject level, showed an inverse exposure-response relationship with dysautonomia severity, finding the lowest HBSI in patients with severe dysautonomia, followed by moderate, mild, and, lastly, controls. Importantly, HBSI was associated in PD, but not in controls, with Valsalva pressure recovery time (sympathetic), deep breathing E/I ratio (cardiovagal), and SCOPA-AUT. Our findings support the existence of heart-brain de-synchronization in PD with an impact on clinically relevant autonomic outcomes.