Direct access to specific autobiographical memories is lower in healthy middle-aged to older adult Apolipoprotein E ε4 carriers compared to non-carriers.

Recent research suggests that the retrieval of autobiographical memories among cognitively healthy middle-aged and older adults is sensitive to the Apolipoprotein E ε4 (APOE4) allele, a genetic marker that increases the risk of Alzheimer's disease (AD) dementia. However, whether the APOE4-associated alteration in autobiographical memory retrieval encompasses rapid (i.e. direct retrieval) or iterative (i.e. generative retrieval) processes remains unclear. In the present study, 39 APOE4 carriers and 45 non-carriers (ages 60-80) who scored within normal limits on neuropsychological testing were cued to generate specific autobiographical events. We examined group differences in direct and generative retrieval and correlated direct and generative retrieval rates with performance on neuropsychological tests. Direct retrieval rates were lower in the APOE4 carriers compared to non-carriers. Episodic memory positively correlated with direct retrieval rates across the sample, though this relationship became non-significant when factoring in age and sex. There were no significant findings related to successful generative retrieval rates and its efficiency. In summary, compared to non-carriers, cognitively unimpaired middle-aged to older adult APOE4 carriers demonstrated greater difficulty, rapidly reconstructing specific autobiographical events without the support of semantic memory, suggesting that early autobiographical memory retrieval processes demonstrate vulnerability to AD-related risk factors.

Biosymbiotic haptic feedback - Sustained long term human machine interfaces.

Haptic technology permeates diverse fields and is receiving renewed attention for VR and AR applications. Advances in flexible electronics, facilitate the integration of haptic technologies into soft wearable systems, however, because of small footprint requirements face challenges of operational time requiring either large batteries, wired connections or frequent recharge, restricting the utility of haptic devices to short-duration tasks or low duty cycles, prohibiting continuously assisting applications. Currently many chronic applications are not investigated because of this technological gap. Here, we address wireless power and operation challenges with a biosymbiotic approach enabling continuous operation without user intervention, facilitated by wireless power transfer, eliminating the need for large batteries, and offering long-term haptic feedback without adhesive attachment to the body. These capabilities enable haptic feedback for robotic surgery training and posture correction over weeks of use with neural net computation. The demonstrations showcase that this device class expands use beyond conventional brick and strap or epidermally attached devices enabling new fields of use for imperceptible therapeutic and assistive haptic technologies supporting care and disease management.

Machine learning prediction model for postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) continues to be a major cause of morbidity following colorectal surgery. Despite best efforts, the incidence of POI in colorectal surgery remains high (~30%). This study aimed to investigate machine learning techniques to identify risk factors for POI in colorectal surgery patients, to help guide further preventative strategies. METHODS: A TRIPOD-guideline-compliant retrospective study was conducted for major colorectal surgery patients at a single tertial care centre (2018-2022). The primary outcome was the occurrence of POI, defined as not achieving GI-2 (outcome measure of time to first stool and tolerance of oral diet) by day four. Multivariate logistic regression, decision trees, radial basis function and multilayer perceptron (MLP) models were trained using a random allocation of patients to training/testing data sets (80/20). The area under the receiver operating characteristic (AUROC) curves were used to evaluate model performance. RESULTS: Of 504 colorectal surgery patients, 183 (36%) experienced POI. Multivariate logistic regression, decision trees, radial basis function and MLP models returned an AUROC of 0.722, 0.706, 0.712 and 0.800, respectively. The MLP model had the highest sensitivity and specificity values. In addition to well-known risk factors for POI, such as postoperative hypokalaemia, surgical approach, and opioid use, the MLP model identified sarcopenia (ranked 4/30) as a potentially modifiable risk factor for POI. CONCLUSION: MLP outperformed other models in predicting POI. Machine learning can provide valuable insights into the importance and ranking of specific predictive variables for POI. Further research into the predictive value of preoperative sarcopenia for POI is required.

Can irony regulate negative emotion? Evidence from behaviour and ERPs.

This study used ratings and event-related potentials (ERPs) to compare the mechanisms through which verbal irony and cognitive reappraisal mitigate negative emotion. Verbal irony is when the literal meaning of words contrasts with their intended meaning. Cognitive reappraisal is when we reconsider emotional stimuli to make them less intense. Our hypothesis was that cognitive reappraisal is a potential mechanism through which irony reduces negative emotion. Participants viewed mildly negative pictures first, then read an ironic or literal statement about it in one block, and used cognitive reappraisal of or attending to the picture in the other block. Participants then viewed the picture for a second time, before rating how negative they felt. Behaviourally, irony reduced negative feelings more than literal statements, and reappraisal reduced negative feelings more than attending, with a larger reduction from reappraisal than from irony. In ERPs, irony elicited a prolonged N400 compared to literal, indexing an initial contrast between picture and word affect and sustained processing of their combination. Cognitive reappraisal elicited a larger late positivity compared to attending at the instruction screen. No differences were found during second picture presentation. These findings suggest that irony and cognitive reappraisal can reduce negative affect in different ways.

On the relationship between unprompted thought and affective well-being: A systematic review and meta-analysis.

There is a growing recognition that thoughts often arise independently of external demands. These thoughts can span from reminiscing your last vacation to contemplating career goals to fantasizing about meeting your favorite musician. Often referred to as mind wandering, such frequently occurring unprompted thoughts have widespread impact on our daily functions, with the dominant narrative converging on a negative relationship between unprompted thought and affective well-being. In this systematic review of 76 studies, we implemented a meta-analysis and qualitative review to elucidate if and when unprompted thought is indeed negatively associated with affective well-being in adults. Using a multilevel mixed-model approach on 386 effect sizes from 23,168 participants across 64 studies, our meta-analyses indicated an overall relationship between unprompted thought and worse affective well-being (r¯ = -.18, 95% CI [-.23, -.14]); however, the magnitude and direction of this relationship changed when considering specific aspects of the phenomenon (including thought content and intentionality) and methodological approaches (including questionnaires vs. experience sampling). The qualitative review further contextualizes this relationship by revealing the nuances of how and when unprompted thought is associated with affective well-being. Taken together, our meta-analysis and qualitative review indicate that the commonly reported relationship between unprompted thought and affective well-being is contingent upon the content and conceptualization of unprompted thought, as well as the methodological and analytic approaches implemented. Based on these findings, we propose emerging directions for future empirical and theoretical work that highlight the importance of accounting for when, how, and for whom unprompted thought is associated with affective well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Retrieving autobiographical memories in autobiographical contexts: are age-related differences in narrated episodic specificity present outside of the laboratory?

The Autobiographical Interview, a method for evaluating detailed memory of real-world events, reliably detects differences in episodic specificity at retrieval between young and older adults in the laboratory. Whether this age-associated reduction in episodic specificity for autobiographical event retrieval is present outside of the laboratory remains poorly understood. We used a videoconference format to administer the Autobiographical Interview to cognitively unimpaired older adults (N = 49, M = 69.5, SD = 5.94) and young adults (N = 54, M = 22.5, SD = 4.19) who were in their homes at the time of retrieval. Relative to young adults, older adults showed reduced episodic specificity in their home environment, as reflected by fewer episodic or "internal" details (t (101) = 3.23, p = 0.009) and more "external" details (i.e., semantic, language-based details) (t (101) = 3.60, p = 0.003). These findings, along with detail subtype profiles in the narratives, bolster the ecological validity of the Autobiographical Interview and add promise to the use of virtual cognitive testing to improve the accessibility, participant diversity, scalability, and ecological validity of memory research.

Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach.

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Wireless Battery-free and Fully Implantable Organ Interfaces.

Advances in soft materials, miniaturized electronics, sensors, stimulators, radios, and battery-free power supplies are resulting in a new generation of fully implantable organ interfaces that leverage volumetric reduction and soft mechanics by eliminating electrochemical power storage. This device class offers the ability to provide high-fidelity readouts of physiological processes, enables stimulation, and allows control over organs to realize new therapeutic and diagnostic paradigms. Driven by seamless integration with connected infrastructure, these devices enable personalized digital medicine. Key to advances are carefully designed material, electrophysical, electrochemical, and electromagnetic systems that form implantables with mechanical properties closely matched to the target organ to deliver functionality that supports high-fidelity sensors and stimulators. The elimination of electrochemical power supplies enables control over device operation, anywhere from acute, to lifetimes matching the target subject with physical dimensions that supports imperceptible operation. This review provides a comprehensive overview of the basic building blocks of battery-free organ interfaces and related topics such as implantation, delivery, sterilization, and user acceptance. State of the art examples categorized by organ system and an outlook of interconnection and advanced strategies for computation leveraging the consistent power influx to elevate functionality of this device class over current battery-powered strategies is highlighted.

Biosymbiotic platform for chronic long-range monitoring of biosignals in limited resource settings.

Remote patient monitoring is a critical component of digital medicine, and the COVID-19 pandemic has further highlighted its importance. Wearable sensors aimed at noninvasive extraction and transmission of high-fidelity physiological data provide an avenue toward at-home diagnostics and therapeutics; however, the infrastructure requirements for such devices limit their use to areas with well-established connectivity. This accentuates the socioeconomic and geopolitical gap in digital health technology and points toward a need to provide access in areas that have limited resources. Low-power wide area network (LPWAN) protocols, such as LoRa, may provide an avenue toward connectivity in these settings; however, there has been limited work on realizing wearable devices with this functionality because of power and electromagnetic constraints. In this work, we introduce wearables with electromagnetic, electronic, and mechanical features provided by a biosymbiotic platform to realize high-fidelity biosignals transmission of 15 miles without the need for satellite infrastructure. The platform implements wireless power transfer for interaction-free recharging, enabling long-term and uninterrupted use over weeks without the need for the user to interact with the devices. This work presents demonstration of a continuously wearable device with this long-range capability that has the potential to serve resource-constrained and remote areas, providing equitable access to digital health.

Recent advances in the neuroscience of spontaneous and off-task thought: implications for mental health.

People spend a remarkable 30-50% of awake life thinking about something other than what they are currently doing. These experiences of being "off-task" can be described as spontaneous thought when mental dynamics are relatively flexible. Here we review recent neuroscience developments in this area and consider implications for mental wellbeing and illness. We provide updated overviews of the roles of the default mode network and large-scale network dynamics, and we discuss emerging candidate mechanisms involving hippocampal memory (sharp-wave ripples, replay) and neuromodulatory (noradrenergic and serotonergic) systems. We explore how distinct brain states can be associated with or give rise to adaptive and maladaptive forms of thought linked to distinguishable mental health outcomes. We conclude by outlining new directions in the neuroscience of spontaneous and off-task thought that may clarify mechanisms, lead to personalized biomarkers, and facilitate therapy developments toward the goals of better understanding and improving mental health.

Fully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation.

Electrical stimulation of the neuromuscular system holds promise for both scientific and therapeutic biomedical applications. Supplying and maintaining the power necessary to drive stimulation chronically is a fundamental challenge in these applications, especially when high voltages or currents are required. Wireless systems, in which energy is supplied through near field power transfer, could eliminate complications caused by battery packs or external connections, but currently do not provide the harvested power and voltages required for applications such as muscle stimulation. Here, we introduce a passive resonator optimized power transfer design that overcomes these limitations, enabling voltage compliances of ± 20 V and power over 300 mW at device volumes of 0.2 cm2, thereby improving power transfer 500% over previous systems. We show that this improved performance enables multichannel, biphasic, current-controlled operation at clinically relevant voltage and current ranges with digital control and telemetry in freely behaving animals. Preliminary chronic results indicate that implanted devices remain operational over 6 weeks in both intact and spinal cord injured rats and are capable of producing fine control of spinal and muscle stimulation.

Brain mediators of biased social learning of self-perception in social anxiety disorder.

Social anxiety disorder (SAD) is characterized by an excessive fear of social evaluation and a persistently negative view of the self. Here we test the hypothesis that negative biases in brain responses and in social learning of self-related information contribute to the negative self-image and low self-esteem characteristic of SAD. Adult participants diagnosed with social anxiety (N = 21) and matched controls (N = 23) rated their performance and received social feedback following a stressful public speaking task. We investigated how positive versus negative social feedback altered self-evaluation and state self-esteem and used functional Magnetic Resonance Imaging (fMRI) to characterize brain responses to positive versus negative feedback. Compared to controls, participants with SAD updated their self-evaluation and state self-esteem significantly more based on negative compared to positive social feedback. Responses in the frontoparietal network correlated with and mirrored these behavioral effects, with greater responses to positive than negative feedback in non-anxious controls but not in participants with SAD. Responses to social feedback in the anterior insula and other areas mediated the effects of negative versus positive feedback on changes in self-evaluation. In non-anxious participants, frontoparietal brain areas may contribute to a positive social learning bias. In SAD, frontoparietal areas are less recruited overall and less attuned to positive feedback, possibly reflecting differences in attention allocation and cognitive regulation. More negatively biased brain responses and social learning could contribute to maintaining a negative self-image in SAD and other internalizing disorders, thereby offering important new targets for interventions.

A pull to be close: The differentiating effects of oxytocin and grief stimulus type on approach behavior in complicated grief.

Theoretical models of complicated grief (CG) suggest that maladaptive motivational tendencies (e.g., perseverative proximity-seeking of the deceased; excessive avoidance of reminders) interfere with a person's ability to recover from their loved one's death. Due in part to conflicting evidence, little mechanistic understanding of how these behaviors develop in grief exists. We sought to (1) identify behavioral differences between CG and non-CG groups based on approach/avoidance bias for grief-, deceased-, and social-related stimuli, and (2) test the role of the neuropeptide oxytocin in shaping approach/avoidance bias. Widowed older adults with (n = 17) and without (n = 22) CG completed an approach/avoidance task measuring implicit bias for both personalized and non-specific grief-related stimuli (among other stimuli). In a double-blinded, randomized, counterbalanced design, each participant attended both an intranasal oxytocin session and a placebo session. Aims were to (1) identify differential effects of CG and stimulus type on implicit approach/avoidance bias [placebo session], and (2) investigate interactive effects of CG, stimulus type, and oxytocin vs. placebo on approach/avoidance bias [both sessions]. In the placebo session, participants in the non-CG group demonstrated an approach bias across all stimuli. Intranasal oxytocin had an overall slowing effect on the CG group's response times. Further, oxytocin decreased avoidance bias in response to photos of the deceased spouse in the CG group only. Findings support the hypothesis that oxytocin has a differential effect on motivational tendency in CG compared to non-CG, strengthening evidence for its role in CG. Findings also emphasize the need to consider differences in personalized vs. generic stimuli when designing grief-relevant tasks.

A dorsomedial prefrontal cortex-based dynamic functional connectivity model of rumination.

Rumination is a cognitive style characterized by repetitive thoughts about one's negative internal states and is a common symptom of depression. Previous studies have linked trait rumination to alterations in the default mode network, but predictive brain markers of rumination are lacking. Here, we adopt a predictive modeling approach to develop a neuroimaging marker of rumination based on the variance of dynamic resting-state functional connectivity and test it across 5 diverse subclinical and clinical samples (total n = 288). A whole-brain marker based on dynamic connectivity with the dorsomedial prefrontal cortex (dmPFC) emerges as generalizable across the subclinical datasets. A refined marker consisting of the most important features from a virtual lesion analysis further predicts depression scores of adults with major depressive disorder (n = 35). This study highlights the role of the dmPFC in trait rumination and provides a dynamic functional connectivity marker for rumination.

Dreams share phenomenological similarities with task-unrelated thoughts and relate to variation in trait rumination and COVID-19 concern.

While recent neurocognitive theories have proposed links between dreams and waking life, it remains unclear what kinds of waking thoughts are most similar in their phenomenological characteristics to those of dreams. To investigate this question and examine relevance of dreams to significant personal concerns and dispositional mental health traits, we employed ecological momentary assessment and trait questionnaires across 719 young adults who completed the study during the COVID-19 pandemic, a time marked by considerable societal concern. Across the group and at the level of individual differences, dreams showed the highest correspondence with task-unrelated thoughts. Participants who self-reported greater COVID-19 concern rated their dreams as more negative and unconstructive, a relationship which was moderated by trait rumination. Furthermore, dreams perceived as more negative unconstructive and immersive in nature associated with increased trait rumination beyond variation in rumination explained by waking task-unrelated thoughts alone. Together, these results point to similarities between perceived characteristics of dreams and task-unrelated thoughts, and support a relationship between dreams, current concerns, and mental health.

Past and future episodic detail retrieval is reduced among clinically normal older adults at higher genetic risk for late-onset Alzheimer's disease.

OBJECTIVE: Remembering and imagining personal events that are rich in episodic (i.e., event-specific) detail is compromised in older adults who have mild cognitive impairment, a known risk factor for Alzheimer's disease dementia. Less clear is whether lower episodic detail generation is associated with higher risk for Alzheimer's disease dementia before mild clinical decline is detectable. METHOD: We compared past and future autobiographical thinking in clinically normal older adult carriers of the Alzheimer's disease-associated apolipoprotein E e4 allele (APOE4; n = 39) to demographically and neuropsychologically similar non-APOE4 carriers (n = 43). RESULTS: APOE4 carriers showed a significant reduction for episodic details when remembering past events (d = .47) and imagining future events (d = .46), but not for nonepisodic details. CONCLUSIONS: These findings suggest that APOE4 is associated with a selective reduction of episodic detail during past and future autobiographical thinking among clinically normal older adults. Reduced episodic detail generation, therefore, may be an early cognitive associate of higher risk for Alzheimer's disease dementia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dwelling in prolonged grief: Resting state functional connectivity during oxytocin and placebo administration.

Clinical theories of adaptation in bereavement highlight a need for flexible shifting between mental states. However, prolonged motivational salience of the deceased partner may be a complicating factor, particularly when coupled with perseverative thinking about the loss. We investigated how prolonged grief symptoms might relate to resting state functional brain network connectivity in a sample of older adults (n = 38) who experienced the death of a partner 6-36 months prior, and whether intranasal oxytocin (as a neuropeptide involved in pair-bonding) had differential effects in participants with higher prolonged grief symptoms. Higher scores on the Inventory of Complicated Grief (ICG) were associated with lower anticorrelation (i.e., higher functional connectivity) between the defaultretrosplenial - cingulo-operculardACC network pair. Intranasal oxytocin increased functional connectivity in the same defaultretrosplenial - cingulo-operculardACC circuit but ICG scores did not moderate effects of oxytocin, contrary to our prediction. Higher ICG scores were associated with longer dwell time in a dynamic functional connectivity state featuring positive correlations among default, frontoparietal, and cingulo-opercular networks, across both placebo and oxytocin sessions. Dwell time was not significantly affected by oxytocin, and higher prolonged grief symptoms were not associated with more variability in dynamic functional connectivity states over the scan. Results offer preliminary evidence that prolonged grief symptoms in older adults are associated with patterns of static and time-varying functional network connectivity and may specifically involve a default network-salience-related circuit that is sensitive to oxytocin.

Wireless, fully implantable cardiac stimulation and recording with on-device computation for closed-loop pacing and defibrillation.

Monitoring and control of cardiac function are critical for investigation of cardiovascular pathophysiology and developing life-saving therapies. However, chronic stimulation of the heart in freely moving small animal subjects, which offer a variety of genotypes and phenotypes, is currently difficult. Specifically, real-time control of cardiac function with high spatial and temporal resolution is currently not possible. Here, we introduce a wireless battery-free device with on-board computation for real-time cardiac control with multisite stimulation enabling optogenetic modulation of the entire rodent heart. Seamless integration of the biointerface with the heart is enabled by machine learning-guided design of ultrathin arrays. Long-term pacing, recording, and on-board computation are demonstrated in freely moving animals. This device class enables new heart failure models and offers a platform to test real-time therapeutic paradigms over chronic time scales by providing means to control cardiac function continuously over the lifetime of the subject.

Wearable flexible body matched electromagnetic sensors for personalized non-invasive glucose monitoring.

This work introduces novel body-matched, vasculature-inspired, quasi-antenna-arrays that act as electromagnetic sensors to instantaneously, continuously, and wirelessly sense glucose variations in the bloodstream. The proposed sensors are personalized, leverage electromagnetic waves, and are coupled with a custom machine-learning-based signal-processing module. These sensors are flexible, and embedded in wearable garments such as socks, which provide conformity to curved skin surfaces and movement resilience. The entire wearable system is calibrated against temperature, humidity, and movement resulting in high accuracy in glucose variations tracking. In-Vivo experiments on diabetic rats and pigs exhibit a 100% diagnostic accuracy over a wide range of glucose variations. Human trials on patients with diabetes and healthy individuals reveal a clinical accuracy of continuous glucose monitoring of 99.01% in twenty-eight subjects who underwent Oral Glucose Tolerance Tests. Hence, our approach ensures the continuous tracking of glucose variations from hypo-to-hyper glycemic levels with great fidelity.