Psychophysiology

The olfactory and intranasal trigeminal systems interact closely, influencing chemosensory perception, yet the mechanisms underlying their interaction remain poorly understood and have been studied mainly in young adults. We aimed to characterize olfactory-trigeminal interactions in aging by comparing electrophysiological and behavioral responses under ipsilateral and contralateral olfactory-trigeminal co-stimulation, to determine the relative contributions of peripheral and central mechanisms. Using chemosensory event-related potentials and a localization task, 44 healthy older adults (66.3 {+/-} 4.6 years; 29 women) were tested under four conditions: pure trigeminal (carbon dioxide; CO2), pure olfactory (2-phenylethanol; PEA), ipsilateral co-stimulation (PEA+CO2 in the same nostril), and contralateral co-stimulation (PEA+CO2 in opposite nostrils). Ipsilateral, but not contralateral olfactory-trigeminal co-stimulation, improved trigeminal localization performance and induced larger late positive component amplitudes. Together, these findings suggest that olfactory-trigeminal interactions are driven primarily by peripheral rather than central mechanisms. This study also provides normative CSERP data for healthy older adults.

Laboratory stress tasks are widely used to assess individual differences in acute stress reactivity, yet it remains unclear how these responses correspond to stress experienced in everyday life. Here, we combined the Montreal imaging stress task (MIST) with ecological momentary assessment (EMA) over three months to assess acute and everyday stress in 67 healthy women. Greater within-person variability in everyday stress, but not average stress levels, were associated with stronger overall stress-related brain responses (b = 0.73, p = .039), with a whole-brain association particularly evident in the bilateral caudate (rROI = .32, pcluster.FWE < .001). Greater everyday stress variability was also associated with stronger stress-related functional connectivity between the ventromedial prefrontal cortex (vmPFC) and parietal and posterior medial regions (pcluster.FWE < .001). We conclude that acute neural stress responses relate more closely to fluctuations in perceived stress than to how stressed an individual feels on average. This suggests that laboratory stress tasks capture acute stress responsivity that is distinct from average stress exposure, highlighting the importance of considering what these tasks measure when interpreting individual differences in acute stress responses.

Background: Bipolar disorder is associated with persistent social, cognitive, and functional impairment during euthymia, yet the neural mechanisms underlying these deficits remain unclear. Alterations to self-referential processing are a candidate mechanism, but existing electrophysiological studies rely on emotionally valenced paradigms that potentially confound self-processing with emotional biases. Methods: We analysed electroencephalography from 28 patients with bipolar disorder (type I or II) and 28 age- and sex-matched healthy controls during an emotionally neutral colour judgment task with self-related (preference) and non-self-related (similarity) conditions. Late positive potentials, temporal generalisation decoding, and frequency band decoding (theta, alpha, beta) were used to characterise the temporal dynamics and oscillatory correlates of self versus non-self processing. Results: Controls showed higher overall event-related potential amplitudes and greater self versus non-self differentiation than patients (condition by group interaction, 337 to 946 ms). Broadband temporal generalisation decoding revealed extensive cross-temporal generalisation of the self versus non-self representation in controls, spanning most of the trial, but no significant generalisation in patients. Frequency analyses showed that alpha and beta carried self versus non-self information in both groups, with broader extent in controls, and that anterior theta carried this information in patients but not controls. Exploratory correlations linked decoding measures to rumination and anxiety but not to manic symptoms. Conclusions: The neural representation distinguishing self-referential from externally guided processing was both smaller in amplitude and less temporally sustained in bipolar disorder. Reduced persistence is not detectable by conventional amplitude analyses, and may bear on the self-related and social cognitive difficulties reported in this population.

Introduction: Decision making for selecting an object or a course of action from possible alternatives largely depends on our perceptual ability modulated by attention. When multiple stimuli appear close together in time, processing one stimulus can temporarily impair the processing of another due to temporal limitations of attention. Observers frequently fail to detect the second target (T2) presented within a few hundred milliseconds after the first target (T1) in a stream of stimuli, which is commonly known as attentional blink (AB). Existing theories attribute this perceptual lapse to T1 processing, distractor interference, or transient attentional gating; however, the computations underlying suppressive mechanism remains unresolved. We investigated whether pupil-size could reveal the underlying mechanisms of AB and predict conscious perception on a trial-by-trial basis. Methods: Pupil diameter and gaze locations were recorded using an infrared eye tracker. Machine learning techniques were used to classify trials when T2 was detected versus when it was not, after correct identification of T1, during an AB task from the pupil dynamics, which also yielded attentional episode (AE) associated with each element in the stream of visual stimuli when deconvolved. Results: Cross-validating classifiers achieved near-perfect accuracy not only in distinguishing but also predicting perceptual outcomes on a single-trial basis. AEs exhibited greater power when T2 was detected than when it was missed; the differential power in AEs on a logarithmic scale was highly synced with the differential pupil size. Conclusions: Collectively, these findings establish a framework for predicting attention-driven perceptual outcomes from pupil-dynamics at finer time-scale.

BACKGROUND: An individual's adaptation to threatening environments under uncertainty is reflected in stress responses. Predictability (the ability to anticipate events) and controllability (the ability to control outcomes) are central to how one adapts, yet their joint influence on aversive learning remains unclear. METHODS: Thirty healthy adults completed a probabilistic aversive learning task in which cue-outcome contingencies varied across levels of predictability and controllability, i.e. whether shock intensity depended on prediction accuracy. Prediction accuracy, reaction time, subjective stress ratings, and skin conductance responses were recorded throughout. Trial-wise learning dynamics were estimated using the Volatile Kalman Filter. RESULTS: Prediction accuracy reduced as environments became less predictable and negatively associated with higher learning rates across predictability levels, with the strongest relationship observed in highly predictable blocks. Skin conductance responses showed that moderately predictable environments elicited responses like those in highly predictable environments when accurate predictions reduced shock intensity, but resembled responses in unpredictable environments when shock intensity was uncontrollable. Model comparison revealed a double dissociation between subjective stress ratings and skin conductance responses. Subjective ratings were best explained by model-derived volatility when prediction accuracy determined shock intensity and by belief uncertainty when it was independent of prediction accuracy, whereas skin conductance responses showed the reverse pattern. Reaction times were best explained by belief uncertainty when predictions influenced shock intensity. Higher anxiety was associated with elevated learning rates in highly and moderately predictable blocks when predictions did not control shock intensity.

During wakefulness, we are used to perceive the environment through our senses, act on it and take these inputs to update our experiences and build the perceptions. When the inputs are not longer accurate or structured, people would sometimes have hallucinatory experiences. Whether such experiences are associated with distinct patterns of thought, and how they relate to large scale brain dynamics, remains unclear. To address these questions, we combined experience sampling protocol with EEG recording during multimodal Ganzfeld, where participants were exposed to unstructured, uniform visual and auditory stimulation. Participants repeatedly reported the complexity of their visual experiences together with ongoing thoughts related to perceptual belief, prediction perception mismatch, active updating, and prior mentation. EEG microstates were extracted to characterize the temporal dynamics of large-scale brain networks. We found that visual complexity was related to all four dimensions, but partly distinct in simple and complex visual experiences. These phenomenological changes were accompanied by distinct, and often nonlinear, dynamics of large-scale brain networks involved in visual processing, salience detection, and internally directed cognition. It also indicates that this paradigm might be a valuable model for investigating the mechanisms underlying hallucinatory experiences in psychosis.

Tactile imagery has attracted growing fundamental and clinical interest. Previous studies often investigated neural and functional similarities between imagined and actual touch. Several functional aspects of touch, such as differences between active and passive touch, between different haptic features during active touch or sensitivity of different body parts for passive touch, have also been explored in tactile imagery. Furthermore, considerable individual differences in the ability to engage in tactile imagery have been observed. However, several important aspects, involving different imagery components and a wide variety of touch qualities remain to be explored within a single comprehensive study. The current study therefore aims to provide a wide-ranging assessment of tactile imagery in terms of imagery processing components (vividness, maintenance, transformation), type of touch (active versus passive) and touch qualities (object properties for active touch, different tactile sensations across body sites for passive touch). We developed a comprehensive questionnaire containing 72 items to assess tactile imagery ability. 136 healthy participants were asked to imagine different touch types and rate imagery vividness and their ability to maintain and transform each sensation on 5-point Likert-scales. Active touch varied by object (plastic bottle, modeling clay, sponge) and property (temperature, weight, texture, resistance). Passive touch varied by body site (lip, shin, sole of the foot, lower back) and sensation (stroking, vibration, pinching). Overall, participants were able to perform tactile imagery: the vast majority reported at least some imagery across touch types. Individual variability was substantial: scores bridged both ends of the scale. Active tactile imagery differed significantly between objects, depending on tactile property. Object-property pairs with particularly strong imagery were bottle-temperature, bottle-weight and sponge-texture, whereas bottle-resistance elicited weaker imagery, as did temperature and weight for both sponge and clay. Passive tactile imagery was significantly stronger for body sites with higher receptor density (i.e. lip and foot). Imagery of stroking was significantly weaker than vibration and pinching. Active and passive imagery showed a strong, positive correlation, though some participants had relatively strong active imagery, but weaker passive imagery, or vice versa. Our findings confirm that tactile imagery ability varies across individuals and touch types, underlining the importance of a comprehensive imagery ability assessment tool specific to the tactile domain.

Anxiety-related traits (ARTs) have been linked to altered fear learning, but previous studies have typically examined different experimental phases and response systems, limiting the comparability of findings and the accumulation of consistent evidence. Here, we comprehensively examined associations between ARTs and fear conditioning across acquisition, extinction and renewal and across subjective, physiological and neural response systems in a well-powered sample (N = 267) using a two-day differential conditioning paradigm. ARTs were operationalized as a composite of trait anxiety, neuroticism, and intolerance of uncertainty and conditioned responding was assessed using skin conductance responses, fear-potentiated startle, US expectancy ratings, fear ratings, and functional magnetic resonance imaging. Higher ARTs were consistently associated with elevated subjective fear and US expectancy to both threat and safety cues during extinction and renewal, without corresponding elevations in physiological responding. At the same time, ARTs were not associated with threat-safety discrimination in subjective or physiological measures across phases, while neural associations were limited to reduced dorsal anterior cingulate cortex discrimination during early renewal. These findings suggest that ARTs are characterized by a CS unspecific cognitive bias toward heightened threat expectancy and evaluation rather than altered associative fear learning, highlighting the importance of distinguishing conditioned discrimination from general levels of responding across response systems.

Despite its strong link to neuropsychiatric conditions, frustration remains critically understudied in humans and animals alike. Therefore, there is an urgent need to develop tools to understand and therapeutically target frustration-related functions. Interestingly, humans and rats respond similarly during frustrative nonreward by increasing barpress durations. We previously validated barpress duration in rat operant tasks as a reliable measure of frustration-related behavior; however, it is wellknown that in addition to duration of responding, emotional states such as frustration alter other aspects of responding such as force of pressing. One-dimensional, static measures such as maximum force could miss rich information contained within operant data. Thus, the objective of this study is to apply machine learning (ML) to force/time profiles to discriminate frustration-related barpresses from non-frustration-related barpresses. Results showed an AUROC for FR1 (i.e., non-frustrated) vs. extinction (frustrated condition) for individual barpresses of 0.65 that improved to 0.84 with a chunk size of 10. The model generalized well to progressive ratio responding, a different kind of frustration procedure. We conclude that force/time profiling does provide utility beyond one dimensional measures of duration or force separately, meaning that we can indeed infer the internal state of frustration from behavior using ML techniques. Importantly, this project will also serve as proof-of-concept for applying ML to predict other internal states from barpress data.

Kinaesthetic motor imagery (kMI) is widely used in sport to enhance motor performance by engaging cortical sensorimotor networks. Neurofeedback may further support kMI, but the optimal neural target to reinforce remains unclear. Maximal sensorimotor event-related desynchronisation (SMR-ERD) represents a relevant target as it may index sensorimotor cortex engagement, yet sport expertise has been associated with reduced SMR-ERD, potentially reflecting neural efficiency. The optimal neurofeedback target may therefore depend on sport expertise, movement expertise, and individual kMI ability. This study examined how these factors influence sensorimotor activity during kMI. We compared 17 basketball players (Experts) and 16 individuals without formal basketball training (Novices). kMI ability and frequency of use were assessed using questionnaires, while SMR-ERD was quantified using electroencephalography (EEG) during kMI. Participants imagined either a basketball-specific movement (Free throw), for which only Experts had extensive experience, or a generic movement (Box lifting), familiar to both groups. Experts reported greater kMI ability and more frequent kMI use than Novices. Only Experts exhibited significant and sustained SMR-ERD during kMI. Moreover, SMR-ERD was stronger in Experts than Novices specifically during Free throw kMI, corresponding to their movement of expertise. Nonetheless, within the Expert group, higher kMI ability was associated with reduced SMR-ERD. These findings suggest that sport expertise initially enhances voluntary recruitment of sensorimotor networks during kMI, whereas greater kMI ability may subsequently promote neural efficiency, resulting in reduced overall sensorimotor cortical activation. These results highlight the need to tailor kMI-based neurofeedback training to users' sport expertise and kMI ability levels.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is frequently complicated by delayed cerebral ischaemia (DCI), for which current therapies incompletely target the underlying multifactorial pathophysiology. Transauricular vagus nerve stimulation (taVNS) modulates inflammatory, vasoactive and autonomic pathways and may attenuate secondary brain injury after aSAH. Methods: We conducted a prospective, single-centre, single-blind, randomised, sham-controlled pilot trial in adults within 5 days of aneurysm securing for non-traumatic aSAH. Participants were allocated 1:1 to active taVNS (left tragus) or sham (left earlobe) using a portable device delivered for 45 minutes twice daily over 5 days. Primary outcomes were safety (taVNS-related serious adverse events), acceptability, and compliance; secondary outcomes included inflammatory biomarkers, DCI, in-hospital complications, and functional outcomes to 1 month. Results: Thirty patients were randomised (16 taVNS, 14 sham), with numerically more severe aSAH at baseline in the taVNS arm. No taVNS-related serious adverse events occurred; side effects were generally mild and transient, and over 80% of planned sessions were completed. TaVNS produced greater reductions in serum tumour necrosis factor- and trends towards reductions in interleukin-1{beta} and interleukin-10, with numerically fewer DCI events (6.6% vs 35.7%) and neurological impairments (16.7% vs 53.8%), although functional outcomes were not statistically different at 1 month. Conclusions: Early taVNS after aSAH is safe, acceptable, and feasible in the neurocritical care setting and shows biologically plausible signals warranting evaluation in larger multi-centre trials.

Past studies using transcranial magnetic stimulation have shown larger motor-evoked potentials when people observe someone lifting a heavy object than when they observe someone lifting a light one. This means that observers may engage their own motor system in proportion to the perceived effort. However, the different responses during the observation of light and heavy objects may have been influenced by predictable trial sequences within blocked presentation, making it unclear whether corticospinal excitability reflects online processing of kinematics or is affected by top-down expectations. In this Registered Report, 57 right-handed participants passively observed videos of a precision grip and lift of heavy and light objects while receiving a single-pulse TMS to the left primary motor cortex during the lift phase of the movement. Motor-evoked potentials were recorded from the right first dorsal interosseous muscle. The study compared two main observation contexts: a predictable trial sequence in which repeated videos of the same lifts were presented in a blocked order, and an unpredictable one in which videos were presented semi-randomly and participants could rely only on kinematic cues to perceive the weight of the lifted object. In both conditions, the same videos of lifts of equivalent-looking heavy and light objects were used and only the order of presentation differed. Contrary to our predictions, in the blocked (predictable) condition, there was no significant difference in MEPs elicited by light and heavy lifts. In the unpredictable condition, participants showed greater corticospinal excitability during the observation of the light lifts compared to the heavy lifts. This suggests that in the absence of predictable information, the corticospinal system was sensitive to the observed kinematics, but contrary to previous findings, its excitability varied inversely with the object weight.

Background: Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition lacking mechanistically grounded interventions. Here, we tested whether transcranial photobiomodulation (tPBM) can restore neural homeostasis in ADHD patients. Methods: In a randomized, double-blind, sham-controlled crossover design, 28 young adults with ADHD completed a two-week intervention, receiving active (150 mW) and sham (0 mW) stimulation over the right prefrontal cortex for 16 minutes with concurrent electroencephalography (EEG) recording, alongside 29 healthy controls providing a normative reference. Results: Behaviorally, tPBM improved working memory K scores in the ADHD group, with performance closer to typical levels. Across sensor and source levels, tPBM progressively increased relative alpha power, steepened the aperiodic exponent, and enhanced neural complexity, as indexed by multiscale entropy, with widespread effects spanning frontoparietal and attention systems, extending to sensory and default-mode regions, collectively indicating a shift toward normative neural dynamics. Notably, these changes--consistent with rebalanced excitation/inhibition dynamics--predict behavioral improvements in working memory. Conclusions: Together, our findings identify tPBM as a candidate approach for restoring excitation/inhibition balance and normalizing large-scale neural dynamics in ADHD patients, providing a mechanistic foundation for its therapeutic potential.

This study investigated bidirectional associations between maternal sleep and depressive symptoms from preconception to postpartum, and whether infant sleep mediated or moderated these associations. We used data from the Generation R Next Study (N=2,294). Maternal sleep (specifically general sleep disturbance, latency, quality, duration, and midpoint) and depressive symptoms were prospectively assessed at five timepoints from preconception to 12-month postpartum. Sleep was self-assessed with the General Sleep Disturbance Scale and Munich Chronotype Questionnaire; depressive symptoms with the Adult Self Report depression/anxiety subscale and Edinburgh Postnatal Depression Scale. Infant sleep (specifically night awakenings, nocturnal sleep duration, and latency) was parent-reported at 1-month postpartum using the Brief Infant Sleep Questionnaire. Bidirectional associations were examined using Autoregressive Latent Trajectory Models with Structured Residuals. The role of infant sleep was examined using mediation and moderation analyses. We found that maternal sleep and depressive symptoms were both stable over time. For sleep quality and disturbance, bidirectional associations suggested slightly stronger effects from depression to sleep (sleep quality:{beta}depression[-&gt;]sleep quality=0.11, 95%CI:0.07 - 0.14; general sleep disturbance:{beta}depression[-&gt;]sleep disturbance=0.14, 95%CI:0.10 - 0.18) than from sleep to depression ({beta}sleep quality/disturbance[-&gt;]depression=0.07 for both, 95%CIs:0.03 - 0.11). For latency, effects were comparable in both directions ({beta}depression[-&gt;]sleep latency=0.06, 95%CI:0.03 - 0.09; {beta}sleep latency[-&gt;]depression=0.05, 95%CI:0.01 - 0.09). The association between depressive symptoms and sleep latency was both mediated (9.7%) and moderated (p<0.05) by infant sleep latency. In conclusion, general maternal sleep disturbance, sleep quality, and sleep latency showed bidirectional associations with depressive symptoms from preconception/early pregnancy onwards. Infant sleep latency may represent a potential modifiable factor within this cycle.

Abstract Introduction: Despite advances in pain management, effective analgesics in pain situations remain elusive. Opioids and non-opioids carry risks of neurotoxic and psychedelic effects with adverse physiological outcomes. Indian instrumental music (IIM) mitigates subacute pain by rewiring neurochemical synergy as an evidence-based, non-invasive, non-pharmacological system to mitigate pain. Objective: Investigating therapeutic efficacy of IIM in mitigating subacute pain by analyzing behavioral, peripheral, and central neurochemical re-tuning. Methods: Mice were divided into Control, Pain, Pain+Music, and Music groups. Pre-treatment behavioral parameters were compared with those observed after 14 days IIM exposure. Evaluations included nociceptive latencies (hot-plate/tail-flick), locomotion (Open Field Test), and anxiety (Elevated Plus Maze). Molecular analyses quantified peripheral neuropeptides (SP, NK-1R, CGRP), serum cortisol, spinal neurotrophic factor, neurotransmitters (glutamate, GABA, dopamine (DA), 5-HT), BDNF, and mRNA expression of BDNF, Ntrk1R/2R, and D1R in cortex, thalamus, hippocampus and hypothalamus. All procedures adhered to IAEC guidelines. Results: IIM yielded 3.9-4.4-fold antinociceptive improvements, 3.3-fold locomotor restoration, and 3.6-4.9-fold anxiolysis. 14 days IIM exposure reduced peripheral nociceptive-neuropeptides 1.3-2.0-fold (SP, NK-1R, CGRP), serum cortisol 1.3-fold, and spinal glutamate, serotonin levels 1.5- and 1.3-fold. An enhanced expression of spinal GABA, DA about 1.5-fold, and BDNF by 1.3-fold was observed after music listening. Brain-region-specific differential mRNA-expression at cortex, thalamus, hypothalamus and hippocampus revealed the neuromodulatory impact of rhythmic music in a formalin-induced murine pain-model. Conclusion: Gross reduction of pain parameters demonstrates therapeutic potential of IIM as multilevel neuromodulator to suppress the multidimensional stressor, pain, via peripheral desensitization, spinal E-I balance, and differential calibration of BDNF/Trk/D1R plasticity at specific brain-regions. Keywords: Pain, Non-Pharmacological Method, Indian Instrumental Music (IIM), Behavior, Neurotransmitters, Neuroplasticity, mRNA Expression.

Background Sleep, mood, and affective states are mutually connected. There is a paucity of studies, however, that have considered bidirectional relationships between daily sleep-affective dyads in naturalistic settings, particularly for shift workers. Objective To evaluate the dynamic and temporal interplay of daily smartphone-based self-reported sleep measurements, dimensions of affective experience and cognitive processing in UK shift working nurses. Methods The EClocker Study prospectively monitored 102 National Health Service (NHS) nurses (aged 25-61 years, 83.3% female) working standard (day shift) and non-standard (fast rotating shifts) schedules over a two-week period. Smartphone-based Experience Sampling Methodology (ESM) recorded daily sleep, mood, momentary affect and cognitive attentional functioning. Self-reported burnout, emotional dysregulation, emotion reactivity and affective dimensions (positive and negative) were also collected. Findings Overall, NHS nurses reported a high prevalence of depressive symptoms, stress, burnout and sleep-circadian rhythm disturbances. Generalised Additive Modelling (GAMs) revealed that NHS nurses higher perceived sleep quality predicted better next-day mood state, while better daytime mood was associated with reduced sleep onset latency, such that participants reported falling asleep faster. In contrast, daytime mood or affect (positive and negative) had no substantial, direct impact on nurses subjective sleep parameters (sleep quality, sleep duration, sleep efficiency). Exposure to fast rotating night shifts across the two-week study was associated with more frequent response errors on a Choice Reaction Time (CRT) cognitive task, while daytime somnolence did not adversely influence nurses momentary reaction time speeds or attentional function. Conclusions Clinically relevant sleep impairments, insomnia-related symptoms, elevated stress, and poor mood were pervasive in a sample of UK NHS nurses, regardless of shift type. Sleep quality impacted next-day mood and daytime mood impacted sleep latency, while rotating shifts led to an increase in cognitive errors. Recognising the impact of shiftwork and designing interventions to promote better sleep quality offer potential to enhance mood and performance in healthcare professionals. Clinical implications We need to implement and evaluate interventions that regularise sleep patterns and promote sleep quality to alleviate mood symptoms among frontline NHS shift workers.

Background Limited heart rate rise contributes to reduced exercise tolerance for people who have heart failure with reduced ejection fraction (HFrEF), yet rate-adaptive pacing does not improve functional capacity due to an attenuated force-frequency relationship (FFR). How the FFR relates to total peripheral resistance and sympathetic tone in HFrEF is unknown. Methods In a prospective, observational study, participants with HFrEF and controls underwent an incremental pacing protocol, during which heart rate was increased from 50 to 140 beats per minute. At each heart rate increment LV contractility was measured by echocardiography to determine the FFR, as well as continuous beat-to-beat measurement of systolic and diastolic blood pressures with a plethysmography device to determine cardiac output, total peripheral resistance and blood pressure variability (BPV). A microneurography study was then conducted to measure muscle sympathetic nerve activity (MSNA) during incremental pacing. Results A total of 157 participants with HFrEF and 55 controls (mean age 71.1{+/-}1.4 years, 172 (81.1%) male) underwent the pacing protocol. We observed single units in seven of 11 participants who participated in the microneurography study. In both groups, LV contractility and cardiac output increased until the peak of the FFR, after which these declined. We observed a reduction in total peripheral resistance, blood pressure variability, MSNA frequency and incidence coinciding with the peak of the FFR, beyond which these increased. Whilst these relationships were present in both groups, they were more evident in participants with HFrEF. Conclusions For people with HFrEF there is a bidirectional relationship between heart rate and sympathetic activation, with a nadir of sympathetic tone occurring at the peak of the FFR. Both excessively low and high heart rates are accompanied by greater sympathetic activation. Taken together, these data suggest that optimal heart rate targets for HFrEF are likely to be individual.

BackgroundLocomotor adaptation is essential for adjusting walking patterns to complex environments. This study investigated locomotor adaptation deficits in people with Parkinsons disease (PD) and examined oscillatory activity in the globus pallidus internus (GPi) during walking adaptation. We hypothesized that elevated beta-band activity in the GPi is associated with reduced locomotor adaptability in PD. MethodsTwelve PD patients with GPi deep brain stimulation (DBS) (eleven bilateral and one unilateral) were included. Local field potentials (LFPs) were recorded from DBS electrodes during split-belt treadmill walking. Patients were tested in the medication-off, DBS-off state. Locomotor adaptation was measured as the change in step length asymmetry during split-belt walking, with smaller changes indicating greater adaptation deficits. ResultsWe found that GPi high beta (20-30 Hz) and low gamma (30-60 Hz) oscillations were modulated during split-belt walking. Compared to adapters, non-adapters showed decreased movement-related beta suppression during walking. Across participants, beta activity in the GPi contralateral to the fast leg was negatively associated with adaptation magnitude (Spearmans {rho} = -0.65 to -0.75). ConclusionsGPi oscillations are dynamically modulated during locomotor adaptation in PD. Increased beta activity may underlie impaired sensorimotor adaptation during walking. These findings provide novel insight into basal ganglia mechanisms of gait adaptation in PD and suggest that elevated GPi beta activity may serve as a marker of locomotor adaptation deficits.

Coronary flow waveforms have a distinct diastolic-dominant shape with periods of low or retrograde flow during systole. While the general waveform shape has been attributed to complex interactions between cardiac and vascular mechanics, there is limited research into the variability in coronary flow waveforms and what this variability may reveal about cardiac function. This work presents a shape analysis of left anterior descending artery (LAD) flow waveforms using Fourier transforms and Singular Value Decomposition (SVD) performed on baseline data collected from 32 pigs. Pigs included in the study reflect two breeds (Ossabaw and Yorkshire) and three different experimental conditions (lean-control, lean-paced, and obese-paced). Fourier transforms were used to decompose the waveforms into 15 harmonics for each pig. An SVD analysis is then used to extract temporal patterns of the waveforms. Correlations between pig-specific coefficients for the SVD modes and clinical metrics were used to investigate physiological explanations of LAD waveform variability. Temporal LAD flow patterns of the second SVD mode are significantly correlated with heart rate. The third SVD mode significantly correlates with mean blood pressure and maximum hyperemic flow. Furthermore, the fourth SVD mode is weakly correlated with left-ventricular end diastolic pressure and endocardial-epicardial flow ratios. This work demonstrates that LAD flow waveforms can be broken down into temporal patterns that correlate with physiological features. Furthermore, this shape-analysis method allows for waveform reconstruction and simplifies visualization of the temporal patterns identified using SVD, an advantage over existing methods that focus on characterizing flow waveforms by points of interest.

Background Understanding the mechanisms underlying brain aging and age-related pathological changes is essential for advancing brain health research. Our group previously developed a mechanistic mathematical model of healthy brain, Chamberland et al. (2024) that integrates key biological processes involved in normal aging, from which Alzheimer's disease (AD) related changes may emerge naturally. Objectives To characterize and validate this brain model by evaluating its sensitivity, calibrating its parameters, and assessing generalizability in independent populations. Methods The model represents the evolution of key biological processes associated with brain aging, including amyloid beta (A{beta}), tau pathologies, neuroinflammation, and neuronal death. After identifying the 30 most influential parameters, we calibrated the model using cognitively normal (CN) participants from the AD Neuroimaging Initiative (ADNI) database (n = 211) by minimizing a loss function composed of three outcomes (AB) plaques, tau tangles, and neuronal density). The calibrated model was then applied to the UK Biobank cohort (n = 35,899) of normal controls (aged 44-82 years). The effects of sex and APOE were evaluated using stratified simulations. Results Parameter calibration significantly reduced the prediction errors for A{beta} and tau. Neuronal density predictions showed strong agreement in the UK Biobank cohort. The variance decomposition identified APOE status as a major contributor to variability in A{beta}. Conclusion Our validated brain health model links mechanistic pathways with population data and reproduces neuronal density patterns in an independent cohort. These findings support its use as a framework for studying brain aging and investigating how Alzheimer's disease related pathological changes may emerge with aging.