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.

Speaking Well and Feeling Good: Age-Related Differences in the Affective Language of Resting State Thought.

Despite the prevalence and importance of resting state thought for daily functioning and psychological well-being, it remains unclear how such thoughts differ between young and older adults. Age-related differences in the affective tone of resting state thoughts, including the affective language used to describe them, could be a novel manifestation of the positivity effect, with implications for well-being. To examine this possibility, a total of 77 young adults (M = 24.9 years, 18-35 years) and 74 cognitively normal older adults (M = 68.6 years, 58-83 years) spoke their thoughts freely during a think-aloud paradigm across two studies. The emotional properties of spoken words and participants' retrospective self-reported affective experiences were computed and examined for age differences and relationships with psychological well-being. Study 1, conducted before the start of the COVID-19 pandemic, revealed that older adults exhibited more diversity of positive, but not negative, affectively tinged words compared to young adults and more positive self-reported thoughts. Despite being conducted virtually during the COVID-19 pandemic, study 2 replicated many of study 1's findings, generalizing results across samples and study contexts. In an aggregated analysis of both samples, positive diversity predicted higher well-being beyond other metrics of affective tone, and the relationship between positive diversity and well-being was not moderated by age. Considering that older adults also exhibited higher well-being, these results hint at the possibility that cognitively healthy older adults' propensity to experience more diverse positive concepts during natural periods of restful thought may partly underlie age-related differences in well-being and reveal a novel expression of the positivity effect. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00239-z.

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.

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).

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.

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.

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 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.

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.

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).

When self comes to a wandering mind: Brain representations and dynamics of self-generated concepts in spontaneous thought.

Self-relevant concepts are major building blocks of spontaneous thought, and their dynamics in a natural stream of thought are likely to reveal one's internal states that are important for mental health. Here, we conducted a functional magnetic resonance imaging experiment (n = 62) to examine brain representations and dynamics of self-generated concepts in the context of spontaneous thought using a newly developed free association-based thought sampling task. The dynamics of conceptual associations were predictive of individual differences in general negative affectivity, replicating across multiple datasets (n = 196). Reflecting on self-generated concepts strongly engaged brain regions linked to autobiographical memory, conceptual processes, emotion, and autonomic regulation, including the medial prefrontal and medial temporal subcortical structures. Multivariate pattern-based predictive modeling revealed that the neural representations of valence became more person-specific as the level of perceived self-relevance increased. Overall, this study sheds light on how self-generated concepts in spontaneous thought construct inner affective states and idiosyncrasies.

Functional connectivity with medial temporal regions differs across cultures during post-encoding rest.

Connectivity of the brain at rest can reflect individual differences and impact behavioral outcomes, including memory. The present study investigated how culture influences functional connectivity with regions of the medial temporal lobe. In this study, 46 Americans and 59 East Asians completed a resting state scan after encoding pictures of objects. To investigate cross-cultural differences in resting state functional connectivity, left parahippocampal gyrus (anterior and posterior regions) and left hippocampus were selected as seed regions. These regions were selected, because they were previously implicated in a study of cultural differences during the successful encoding of detailed memories. Results revealed that left posterior parahippocampal gyrus had stronger connectivity with temporo-occipital regions for East Asians compared with Americans and stronger connectivity with parieto-occipital regions for Americans compared with East Asians. Left anterior parahippocampal gyrus had stronger connectivity with temporal regions for East Asians than Americans and stronger connectivity with frontal regions for Americans than East Asians. Although connectivity did not relate to memory performance, patterns did relate to cultural values. The degree of independent self-construal and subjective value of tradition were associated with functional connectivity involving left anterior parahippocampal gyrus. Findings are discussed in terms of potential cultural differences in memory consolidation or more general trait or state-based processes, such as holistic versus analytic processing.

Task-unrelated thought increases after consumption of COVID-19 and general news.

Task-unrelated thoughts (TUTs) are frequent distractions from our everyday tasks, which can reduce productivity and safety during task performance. This necessitates the examination of factors that modulate TUT occurrence in daily life. One factor that has previously been implicated as a source of TUT is personally salient concerns. External factors such as news media serve as cues for these concerns, potentially increasing TUT occurrence. However, this has not been thoroughly examined in everyday life settings. We thus utilized Ecological Momentary Assessment to survey participants throughout the day for ten days, on their TUTs and news consumption in two separate studies. Study 1 focused on the impact of news related to the Coronavirus Disease (COVID-19) pandemic, as a common and global concern. We found that TUT occurrence was significantly predicted by COVID-19 news consumption, such that TUT occurrence increased with COVID-19 news consumption. To extend these findings, we implemented Study 2 using similar methods, but focusing on the consumption of news media in general. TUT occurrence was predicted by general news consumption, with an increase in reports of TUT following consumption of news media in general. We thus extended the association found between TUT and COVID-19-related news in Study 1, to any news topic in Study 2. We speculate that the increase in TUTs was due to heightened salience of current concerns, cued by the news. These findings highlight the importance of considering when we choose to consume news media and the value of examining contextual factors when studying TUTs in daily life.

Associations Between Age and Resting State Connectivity Are Partially Dependent Upon Cardiovascular Fitness.

Previous research suggests a marked impact of aging on structural and functional connectivity within the frontoparietal control network (FPCN) and default mode network (DMN). As aging is also associated with reductions in cardiovascular fitness, age-related network connectivity differences reported by past studies could be partially due to age-related declines in fitness. Here, we use data collected as part of a 16-week exercise intervention to explore relationships between fitness and functional connectivity. Young and older adults completed baseline assessments including cardiovascular fitness, health and functioning measures, and an fMRI session. Scan data were acquired on a Siemens 3T MRI scanner with a 32-channel head coil. Results from regression analyses indicated that average connectivity did not differ between young and older adults. However, individual ROI-to-ROI connectivity analyses indicated weaker functional correlations for older adults between specific regions in the FPCN and DMN and, critically, many of these differences were attenuated when fitness was accounted for. Taken together, findings suggest that fitness exerts regional rather than global effects on network connectivity.

Individual differences in the relationship between episodic detail generation and resting state functional connectivity vary with age.

The ability to generate episodic details while recollecting autobiographical events is believed to depend on a collection of brain regions that form a posterior medial network (PMN). How age-related differences in episodic detail generation relate to the PMN, however, remains unclear. The present study sought to examine individual differences, and the role of age, in PMN resting state functional connectivity (rsFC) associations with episodic detail generation. Late middle-aged and older adults (N = 41, ages 52-81), and young adults (N = 21, ages 19-35) were asked to describe recent personal events, and these memory narratives were coded for episodic, semantic and 'miscellaneous' details. Independent components analysis and regions-of-interest analyses were used to assess rsFC within the PMN separately for anterior connections (hippocampal and medial prefrontal) and posterior connections (hippocampal, parahippocampal and parieto-occipital), as these connections purportedly serve different functional roles in episodic detail generation. Compared to younger adults, older adults produced memory narratives with lower episodic specificity (ratio of episodic:total details) and a greater amount of semantic detail. Among the older adults, episodic detail amounts and episodic specificity were reduced with increasing age. There were no significant age differences in PMN rsFC. Stronger anterior PMN rsFC was related to lower episodic detail in the older adult group, but not in the young. Among the older adults, increasing age brought on an association between increased anterior PMN rsFC and reduced episodic specificity. In contrast, increasing age brought on an association between increased posterior PMN rsFC and increased semantic detail. The present study provides evidence that functional connectivity within the PMN, particularly anterior PMN, tracks individual differences in the amount of episodic details retrieved by older adults. Furthermore, these brain-behavior relationships appear to be age-specific, indicating that some process within aging alters the nature of how anterior PMN rsFC and episodic detail relate to each other. Whether this process entails an age-related loss of integrity to the PMN, or an age-related shift toward semantic retrieval, remains to be determined.

Efficacy and fMRI-based response predictors to mindfulness-based cognitive therapy in obsessive-compulsive disorder: Study protocol for a randomised clinical trial.

BACKGROUND: Around 40-50% of patients with obsessive-compulsive disorder (OCD) suffer from obsessions and compulsions after receiving first-line treatments. Mindfulness-based cognitive therapy (MBCT) has been proposed as a reasonable augmentation strategy for OCD. MBCT trains to decentre from distressful thoughts and emotions by focusing on them voluntarily and with consciousness. This practice develops alternative ways to deal with obsessions, which could increase non-reactivity behaviours and, in turn, reduce compulsions. This study aims to investigate the efficacy of MBCT to improve OCD symptoms. Secondly, it pursues to investigate which socio-demographic, clinical, and neurobiological characteristics mediate or moderate the MBCT response; and identify potential biomarkers of positive/negative response. METHODS: This study is a randomised clinical trial (RCT) of 60 OCD patients who do not respond to first-line treatments. Participants will be randomised to either an MBCT program or treatment as usual. The MBCT group will undergo 10 weekly sessions of 120min. Principal outcome: change in OCD severity symptoms using clinician and self-reported measures. Also, participants will undergo a comprehensive evaluation assessing comorbid clinical variables, neuropsychological functioning and thought content. Finally, a comprehensive neuroimaging protocol using structural and functional magnetic resonance imaging will be acquired in a 3T scanner. All data will be obtained at baseline and post-intervention. DISCUSSION: This study will assess the efficacy of mindfulness in OCD patients who do not achieve clinical recovery after usual treatment. It is the first RCT in this subject examining clinical, neuropsychological and neuroimaging variables to examine the neural patterns associated with the MBCT response. CLINICAL TRIALS REGISTRATION: NCT03128749.

Tormenting thoughts: The posterior cingulate sulcus of the default mode network regulates valence of thoughts and activity in the brain's pain network during music listening.

Many individuals spend a significant amount of their time "mind-wandering". Mind-wandering often includes spontaneous, nonintentional thought, and a neural correlate of this kind of thought is the default mode network (DMN). Thoughts during mind-wandering can have positive or negative valence, but only little is known about the neural correlates of positive or negative thoughts. We used resting-state functional magnetic resonance imaging (fMRI) and music to evoke mind-wandering in n = 33 participants, with positive-sounding music eliciting thoughts with more positive valence and negative-sounding music eliciting thoughts with more negative valence. Applying purely data-driven analysis methods, we show that medial orbitofrontal cortex (mOFC, part of the ventromedial prefrontal cortex) and the posterior cingulate sulcus (likely area 23c of the posterior cingulate cortex), two sub-regions of the DMN, modulate the valence of thought-contents during mind-wandering. In addition, across two independent experiments, we observed that the posterior cingulate sulcus, a region involved in pain, shows valence-specific functional connectivity with core regions of the brain's putative pain network. Our results suggest that two DMN regions (mOFC and posterior cingulate sulcus) support the formation of negative spontaneous, nonintentional thoughts, and that the interplay between these structures with regions of the putative pain network forms a neural mechanism by which thoughts can become painful.