Locus coeruleus integrity is related to an exploitation-based decision-making bias in older adulthood.

Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus integrity. Critically, we demonstrate that an exploitation bias in older adulthood, assessed with a foraging task, is sensitive and specific to lower locus coeruleus integrity. Because the locus coeruleus is uniquely vulnerable to Alzheimer's disease pathology, our findings suggest that aging, and a presymptomatic trajectory of Alzheimer's related decline, may fundamentally alter decision-making abilities in later life.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex.

Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy-where it plays a central role in the integrative processes underpinning complex, human-defining cognition-the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression and recent evidence suggests that, during early brain development, 5-HT2AR signalling on neural progenitor cells stimulates their proliferation-a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signalling plays a major role in both human cortical expansion and functioning. Owing to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.

Hippocampus and temporal pole functional connectivity is associated with age and individual differences in autobiographical memory.

Recollection of one's personal past, or autobiographical memory (AM), varies across individuals and across the life span. This manifests in the amount of episodic content recalled during AM, which may reflect differences in associated functional brain networks. We take an individual differences approach to examine resting-state functional connectivity of temporal lobe regions known to coordinate AM content retrieval with the default network (anterior and posterior hippocampus, temporal pole) and test for associations with AM. Multiecho resting-state functional magnetic resonance imaging (fMRI) and autobiographical interviews were collected for 158 younger and 105 older healthy adults. Interviews were scored for internal (episodic) and external (semantic) details. Age group differences in connectivity profiles revealed that older adults had lower connectivity within anterior hippocampus, posterior hippocampus, and temporal pole but greater connectivity with regions across the default network compared with younger adults. This pattern was positively related to posterior hippocampal volumes in older adults, which were smaller than younger adult volumes. Connectivity associations with AM showed two significant patterns. The first dissociated connectivity related to internal vs. external AM across participants. Internal AM was related to anterior hippocampus and temporal pole connectivity with orbitofrontal cortex and connectivity within posterior hippocampus. External AM was related to temporal pole connectivity with regions across the lateral temporal cortex. In the second pattern, younger adults displayed temporal pole connectivity with regions throughout the default network associated with more detailed AMs overall. Our findings provide evidence for discrete ensembles of brain regions that scale with systematic variation in recollective styles across the healthy adult life span.

Precision Mapping of the Default Network Reveals Common and Distinct (Inter)activity for Autobiographical Memory and Theory of Mind.

The default network is widely implicated as a common neural substrate for self-generated thought, such as remembering one's past (autobiographical memory) and imagining the thoughts and feelings of others (theory of mind). Findings that the default network comprises subnetworks of regions - some commonly and some distinctly involved across processes - suggest that one's own experiences inform their understanding of others. With the advent of precision fMRI methods, however, it is unclear if this shared substrate is observed instead due to traditional group analysis methods. We investigated this possibility using a novel combination of methodological strategies. Twenty-three participants underwent multi-echo resting-state and task fMRI. We used their resting-state scans to conduct cortical parcellation sensitive to individual variation but preserving our ability to conduct group analysis. Using multivariate analyses, we assessed the functional activation and connectivity profiles of default network regions while participants engaged in autobiographical memory, theory of mind, or a sensorimotor control condition. Across the default network, we observed stronger activity associated with both autobiographical memory and theory of mind compared to the control condition. Nonetheless, we also observed that some regions showed preferential activity to either experimental condition, in line with past work. The connectivity results similarly indicated shared and distinct functional profiles. Our results support that autobiographical memory and theory of mind - two theoretically important and widely-studied domains of social cognition - evoke common and distinct aspects of the default network even when ensuring high fidelity to individual-specific characteristics.

Heritability of individualized cortical network topography.

Human cortex is patterned by a complex and interdigitated web of large-scale functional networks. Recent methodological breakthroughs reveal variation in the size, shape, and spatial topography of cortical networks across individuals. While spatial network organization emerges across development, is stable over time, and is predictive of behavior, it is not yet clear to what extent genetic factors underlie interindividual differences in network topography. Here, leveraging a nonlinear multidimensional estimation of heritability, we provide evidence that individual variability in the size and topographic organization of cortical networks are under genetic control. Using twin and family data from the Human Connectome Project (n = 1,023), we find increased variability and reduced heritability in the size of heteromodal association networks (h2 : M = 0.34, SD = 0.070), relative to unimodal sensory/motor cortex (h2 : M = 0.40, SD = 0.097). We then demonstrate that the spatial layout of cortical networks is influenced by genetics, using our multidimensional estimation of heritability (h2-multi; M = 0.14, SD = 0.015). However, topographic heritability did not differ between heteromodal and unimodal networks. Genetic factors had a regionally variable influence on brain organization, such that the heritability of network topography was greatest in prefrontal, precuneus, and posterior parietal cortex. Taken together, these data are consistent with relaxed genetic control of association cortices relative to primary sensory/motor regions and have implications for understanding population-level variability in brain functioning, guiding both individualized prediction and the interpretation of analyses that integrate genetics and neuroimaging.

Structural white matter properties and cognitive resilience to tau pathology.

INTRODUCTION: We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset. METHODS: We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic network and default mode network moderate the association between amyloid-ß/tau pathology and cognitive decline. We also investigated whether demographic and health/risk factors are associated with white matter properties. RESULTS: Higher global efficiency of the limbic network, as well as free-water corrected diffusion measures within the tracts of both networks, attenuated the impact of tau pathology on memory decline. Education, age, sex, white matter hyperintensities, and vascular risk factors were associated with white matter properties of both networks. DISCUSSION: White matter can influence cognitive resilience against tau pathology, and promoting education and vascular health may enhance optimal white matter properties. HIGHLIGHTS: Aß and tau were associated with longitudinal memory change over ∼7.5 years. White matter properties attenuated the impact of tau pathology on memory change. Health/risk factors were associated with white matter properties.

Analyzing the Factor Structure of the Toronto Empathy Questionnaire: Dimensionality, Reliability, Validity, Measurement Invariance and One-Year Stability of the German Version.

In the face of heterogeneity in the measurement of empathy, the Toronto Empathy Questionnaire (TEQ; Spreng et al., Journal of Personality Assessment, 91(1), 62-71 (2009)) was developed as a brief unidimensional tool by statistically forming a consensus from existing measures of the construct. The present study aimed to (1) validate a German version of the TEQ, and (2) contribute empirical evidence to the ongoing debate regarding a singular versus multidimensional factor structure of the TEQ. One cross-sectional and two longitudinal studies were performed, with a total of 1,075 participants. Our initial exploratory factor analyses suggested either a one- or a two-factor structure (with the two-factors clustering straight and reverse-scored items); the two-factor model outperformed the one-factor model using confirmatory factor analyses. However, after negated items were replaced by positively reworded alternatives, both models fit the data equally well. A comparison of the correlation patterns with numerous external measures indicated that a second factor of the TEQ is a methodological artifact of item wording. Finally, a unidimensional TEQ scale showed sufficient internal consistency, two-week test-retest reliability, one-year stability, as well as convergent and discriminant validity with measures of empathy, emotion recognition, emotion regulation, altruism, social desirability, and the Big Five personality traits.

Taking stock of the past: A psychometric evaluation of the Autobiographical Interview.

Autobiographical memory (AM) involves a rich phenomenological re-experiencing of a spatio-temporal event from the past, which is challenging to objectively quantify. The Autobiographical Interview (AI; Levine et al. Psychology and Aging, 17(4), 677-689, 2002) is a manualized performance-based assessment designed to quantify episodic (internal) and semantic (external) features of recalled and verbally conveyed prior experiences. The AI has been widely adopted, yet has not undergone a comprehensive psychometric validation. We investigated the reliability, validity, association to individual differences measures, and factor structure in healthy younger and older adults (N = 352). Evidence for the AI's reliability was strong: the subjective scoring protocol showed high inter-rater reliability and previously identified age effects were replicated. Internal consistency across timepoints was robust, suggesting stability in recollection. Central to our validation, internal AI scores were positively correlated with standard, performance-based measures of episodic memory, demonstrating convergent validity. The two-factor structure for the AI was not well supported by confirmatory factor analysis. Adjusting internal and external detail scores for the number of words spoken (detail density) improved trait estimation of AM performance. Overall, the AI demonstrated sound psychometric properties for inquiry into the qualities of autobiographical remembering.

Revealing robust neural correlates of conscious and unconscious visual processing: Activation likelihood estimation meta-analyses.

Our ability to consciously perceive information from the visual scene relies on a myriad of intrinsic neural mechanisms. Functional neuroimaging studies have sought to identify the neural correlates of conscious visual processing and to further dissociate from those pertaining to preconscious and unconscious visual processing. However, delineating what core brain regions are involved in eliciting a conscious percept remains a challenge, particularly regarding the role of prefrontal-parietal regions. We performed a systematic search of the literature that yielded a total of 54 functional neuroimaging studies. We conducted two quantitative meta-analyses using activation likelihood estimation to identify reliable patterns of activation engaged by i. conscious (n = 45 studies, comprising 704 participants) and ii. unconscious (n = 16 studies, comprising 262 participants) visual processing during various task performances. Results of the meta-analysis specific to conscious percepts quantitatively revealed reliable activations across a constellation of regions comprising the bilateral inferior frontal junction, intraparietal sulcus, dorsal anterior cingulate, angular gyrus, temporo-occipital cortex and anterior insula. Neurosynth reverse inference revealed conscious visual processing to be intertwined with cognitive terms related to attention, cognitive control and working memory. Results of the meta-analysis on unconscious percepts revealed consistent activations in the lateral occipital complex, intraparietal sulcus and precuneus. These findings highlight the notion that conscious visual processing readily engages higher-level regions including the inferior frontal junction and unconscious processing reliably recruits posterior regions, mainly the lateral occipital complex.

Conscientiousness associated with efficiency of the salience/ventral attention network: Replication in three samples using individualized parcellation.

Conscientiousness, and related constructs impulsivity and self-control, have been related to structural and functional properties of regions in the prefrontal cortex (PFC) and anterior insula. Network-based conceptions of brain function suggest that these regions belong to a single large-scale network, labeled the salience/ventral attention network (SVAN). The current study tested associations between conscientiousness and resting-state functional connectivity in this network using two community samples (N's = 244 and 239) and data from the Human Connectome Project (N = 1000). Individualized parcellation was used to improve functional localization accuracy and facilitate replication. Functional connectivity was measured using an index of network efficiency, a graph theoretical measure quantifying the capacity for parallel information transfer within a network. Efficiency of a set of parcels in the SVAN was significantly associated with conscientiousness in all samples. Findings are consistent with a theory of conscientiousness as a function of variation in neural networks underlying effective prioritization of goals.

Age differences in the functional architecture of the human brain.

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience-dependent changes, or both, is uncertain. We employed a multimethod strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n = 181) and older (n = 120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multiscale, multimethod approaches to characterize the architecture of functional brain aging.

Social Prescription Interventions Addressing Social Isolation and Loneliness in Older Adults: Meta-Review Integrating On-the-Ground Resources.

BACKGROUND: Social prescription programs represent a viable solution to linking primary care patients to nonmedical community resources for improving patient well-being. However, their success depends on the integration of patient needs with local resources. This integration could be accelerated by digital tools that use expressive ontology to organize knowledge resources, thus enabling the seamless navigation of diverse community interventions and services tailored to the needs of individual users. This infrastructure bears particular relevance for older adults, who experience a range of social needs that impact their health, including social isolation and loneliness. An essential first step in enabling knowledge mobilization and the successful implementation of social prescription initiatives to meet the social needs of older adults is to incorporate the evidence-based academic literature on what works, with on-the-ground solutions in the community. OBJECTIVE: This study aims to integrate scientific evidence with on-the-ground knowledge to build a comprehensive list of intervention terms and keywords related to reducing social isolation and loneliness in older adults. METHODS: A meta-review was conducted using a search strategy combining terms related to older adult population, social isolation and loneliness, and study types relevant to reviews using 5 databases. Review extraction included intervention characteristics, outcomes (social [eg, loneliness, social isolation, and social support] or mental health [eg, psychological well-being, depression, and anxiety]), and effectiveness (reported as consistent, mixed, or not supported). Terms related to identified intervention types were extracted from the reviewed literature as well as descriptions of corresponding community services in Montréal, Canada, available from web-based regional, municipal, and community data sources. RESULTS: The meta-review identified 11 intervention types addressing social isolation and loneliness in older adults by either increasing social interactions, providing instrumental support, promoting mental and physical well-being, or providing home and community care. Group-based social activities, support groups with educational elements, recreational activities, and training or use of information and communication technologies were the most effective in improving outcomes. Examples of most intervention types were found in community data sources. Terms derived from the literature that were the most commonly congruent with those describing existing community services were related to telehealth, recreational activities, and psychological therapy. However, several discrepancies were observed between review-based terms and those addressing the available services. CONCLUSIONS: A range of interventions found to be effective at addressing social isolation and loneliness or their impact on mental health were identified from the literature, and many of these interventions were represented in services available to older residents in Montréal, Canada. However, different terms were occasionally used to describe or categorize similar services across data sources. Establishing an efficient means of identifying and structuring such sources is important to facilitate referrals and help-seeking behaviors of older adults and for strategic planning of resources.

Temporal pole volume is associated with episodic autobiographical memory in healthy older adults.

Recollection of personal past events differs across the lifespan. Older individuals recall fewer episodic details and convey more semantic information than young. Here we examine how gray matter volumes in temporal lobe regions integral to episodic and semantic memory (hippocampus and temporal poles, respectively) are related to age differences in autobiographical recollection. Gray matter volumes were obtained in healthy young (n = 158) and old (n = 105) adults. The temporal pole was demarcated and hippocampus segmented into anterior and posterior regions to test for volume differences between age groups. The Autobiographical Interview was administered to measure episodic and semantic autobiographical memory. Volume associations with episodic and semantic autobiographical memory were then assessed. Brain volumes were smaller for older adults in the posterior hippocampus. Autobiographical memory was less episodic and more semanticized for older versus younger adults. Older adults also showed positive associations between temporal pole volumes and episodic autobiographical recall; in the young, temporal pole volume was positively associated with performance on standard laboratory measures of semantic memory. Exploratory analyses revealed that age-related episodic autobiographical memory associations with anterior hippocampal volumes depended on sex. These findings suggest that age differences in brain structures implicated in episodic and semantic memory may portend reorganization of neural circuits to support autobiographical memory in later life.

Brain Dynamics Underlying Cognitive Flexibility Across the Lifespan.

The neural mechanisms contributing to flexible cognition and behavior and how they change with development and aging are incompletely understood. The current study explored intrinsic brain dynamics across the lifespan using resting-state fMRI data (n = 601, 6-85 years) and examined the interactions between age and brain dynamics among three neurocognitive networks (midcingulo-insular network, M-CIN; medial frontoparietal network, M-FPN; and lateral frontoparietal network, L-FPN) in relation to behavioral measures of cognitive flexibility. Hierarchical multiple regression analysis revealed brain dynamics among a brain state characterized by co-activation of the L-FPN and M-FPN, and brain state transitions, moderated the relationship between quadratic effects of age and cognitive flexibility as measured by scores on the Delis-Kaplan Executive Function System (D-KEFS) test. Furthermore, simple slope analyses of significant interactions revealed children and older adults were more likely to exhibit brain dynamic patterns associated with poorer cognitive flexibility compared with younger adults. Our findings link changes in cognitive flexibility observed with age with the underlying brain dynamics supporting these changes. Preventative and intervention measures should prioritize targeting these networks with cognitive flexibility training to promote optimal outcomes across the lifespan.

Gradients of structure-function tethering across neocortex.

The white matter architecture of the brain imparts a distinct signature on neuronal coactivation patterns. Interregional projections promote synchrony among distant neuronal populations, giving rise to richly patterned functional networks. A variety of statistical, communication, and biophysical models have been proposed to study the relationship between brain structure and function, but the link is not yet known. In the present report we seek to relate the structural and functional connection profiles of individual brain areas. We apply a simple multilinear model that incorporates information about spatial proximity, routing, and diffusion between brain regions to predict their functional connectivity. We find that structure-function relationships vary markedly across the neocortex. Structure and function correspond closely in unimodal, primary sensory, and motor regions, but diverge in transmodal cortex, particularly the default mode and salience networks. The divergence between structure and function systematically follows functional and cytoarchitectonic hierarchies. Altogether, the present results demonstrate that structural and functional networks do not align uniformly across the brain, but gradually uncouple in higher-order polysensory areas.

Troubled past: A critical psychometric assessment of the self-report Survey of Autobiographical Memory (SAM).

The Survey of Autobiographical Memory (SAM) was designed as an easy-to-administer measure of self-perceived autobiographical memory (AM) recollection capacity. We provide a comprehensive psychometric evaluation of the SAM in younger and older adults. First, we evaluated the reliability of the SAM as a measure of self-perceived recollective capacity. Next, we tested whether the SAM was a valid measure of episodic and autobiographical memory performance, as assessed with widely used performance-based measures. Finally, we investigated associations between the SAM, cognitive measures and self-reported assessments of psychological functioning. The SAM demonstrated reliability as a self-report measure of perceived recollective capacity. High internal consistency was observed across subscales, with the exception of SAM-semantic. Evidence for independence among the subscales was mixed: SAM-episodic and SAM-semantic items showed poor correspondence with respective subscales. Good correspondence was observed between the future and spatial items and their SAM subscales. The SAM showed limited associations with AM performance as measured by the Autobiographical Interview (AI), yet was broadly associated with self-reported AI event vividness. SAM scores were weakly associated with performance-based memory measures and were age-invariant, inconsistent with known age effects on declarative memory. Converging evidence indicated that SAM-episodic and SAM-semantic subscales are not independent and should not be interpreted as specific measures of episodic or semantic memory. The SAM was robustly associated with self-efficacy, suggesting an association with confidence in domain general self-report abilities. We urge caution in the use and interpretation of the SAM as a measure of AM, pending revision and further psychometric validation.

Longitudinal Basal Forebrain Degeneration Interacts with TREM2/C3 Biomarkers of Inflammation in Presymptomatic Alzheimer's Disease.

Cholinergic inputs originating from the peripheral nervous system regulate the inflammatory immune responses of macrophages during clearance of blood-based pathogens. Because microglia are involved in clearing amyloid and tau pathology from the central nervous system, we hypothesized that cholinergic input originating from the basal forebrain might similarly regulate inflammatory immune responses to these pathologies in the aging brain. To explore this hypothesis, we leveraged the Alzheimer's Disease Neuroimaging Initiative dataset. Cognitively normal older male and female human adults were differentiated according to the relative concentration of phosphorylated tau and amyloid in their cerebrospinal fluid, yielding neurotypical and preclinical, cognitively healthy, subgroups. We then tracked these two groups longitudinally with structural MRI and biomarkers of inflammation, including soluble sTREM2 levels in the CSF and complement C3 expression in the blood transcriptome. Longitudinal loss of basal forebrain volume was larger in the preclinical compared with the neurotypical subgroup. Across preclinical adults, loss of basal forebrain volume was associated with greater longitudinal accumulation of sTREM2 and higher peripheral blood C3 expression. None of these relationships were attributable to degeneration in the whole-brain gray matter volume. Preclinical APOE e4 carriers exhibited the largest loss of basal forebrain volume and highest C3 expression. Consistent with the known anti-inflammatory influence of the peripheral cholinergic pathways on macrophages, our findings indicate that a loss of central cholinergic input originating from the basal forebrain might remove a key check on microglial inflammation induced by amyloid and tau accumulation.SIGNIFICANCE STATEMENT In the peripheral nervous system, cholinergic modulation holds the reactivity of macrophages to blood-based pathogens in check, promoting clearance while preventing runaway inflammation and immune-triggered cell death. Microglia are the brain's resident macrophages and play an important role in clearing accumulated amyloid and tau from neurons. Here, we demonstrate that a loss of cholinergic integrity in the CNS, indexed by longitudinal decreases of basal forebrain volume, interacts with multiple biomarkers of inflammation in cognitively normal older adults with abnormal amyloid and tau pathology. These interactions were not detected in cognitively normal older adults with "neurotypical" levels of amyloid and tau. An age-related loss of cholinergic neuromodulation may remove key checks on microglial reactivity to amyloid and tau.

Social exclusion reliably engages the default network: A meta-analysis of Cyberball.

Social exclusion refers to the experience of being disregarded or rejected by others and has wide-ranging negative consequences for well-being and cognition. Cyberball, a game where a ball is virtually tossed between players, then leads to the exclusion of the research participant, is a common method used to examine the experience of social exclusion. The neural correlates of social exclusion remain a topic of debate, particularly with regards to the role of the dorsal anterior cingulate cortex (dACC) and the concept of social pain. Here we conducted a quantitative meta-analysis using activation likelihood estimation (ALE) to identify brain activity reliably engaged by social exclusion during Cyberball task performance (Studies = 53; total N = 1,817 participants). Results revealed consistent recruitment in ventral anterior cingulate and posterior cingulate cortex, inferior and superior frontal gyri, posterior insula, and occipital pole. No reliable activity was observed in dACC. Using a probabilistic atlas to define dACC, fewer than 15% of studies reported peak coordinates in dACC. Meta-analytic connectivity mapping suggests patterns of co-activation are consistent with the topography of the default network. Reverse inference for cognition associated with reliable Cyberball activity computed in Neurosynth revealed social exclusion to be associated with cognitive terms Social, Autobiographical, Mental States, and Theory of Mind. Taken together, these findings highlight the role of the default network in social exclusion and warns against interpretations of the dACC as a key region involved in the experience of social exclusion in humans.

Spatiotemporal functional interactivity among large-scale brain networks.

The macro-scale intrinsic functional network architecture of the human brain has been well characterized. Early studies revealed robust and enduring patterns of static connectivity, while more recent work has begun to explore the temporal dynamics of these large-scale brain networks. Little work to date has investigated directed connectivity within and between these networks, or the temporal patterns of afferent (input) and efferent (output) connections between network nodes. Leveraging a novel analytic approach, prediction correlation, we investigated the causal interactions within and between large-scale networks of the brain using resting state fMRI. This technique allows us to characterize information transfer between brain regions in both the spatial (direction) and temporal (duration) scales. Using data from the Human Connectome Project (N = 200) we applied prediction correlation techniques to four resting-state fMRI scans (each scan has TRs = 1200). Three central observations emerged. First, the strongest and longest duration connections were observed within the somatomotor, visual, and dorsal attention networks. Second, the short duration connections were observed for high-degree nodes in the visual and default networks, as well as in the hippocampus. Specifically, the connectivity profile of the highest-degree nodes was dominated by efferent connections to multiple cortical areas. Moderate high-degree nodes, particularly in hippocampal regions, showed an afferent connectivity profile. Finally, multimodal association nodes in lateral prefrontal brain regions demonstrated a short duration, bidirectional connectivity profile, consistent with this region's role in integrative and modulatory processing. These results provide novel insights into the spatiotemporal dynamics of human brain function.