Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8-minute consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic (MEG) recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.

People often form polarized beliefs, imbuing objects (e.g., themselves or others) with unambiguously positive or negative qualities. In clinical settings, this is referred to as dichotomous thinking or "splitting" and is a feature of several psychiatric disorders. Here, we introduce a Bayesian model of splitting that parameterizes a tendency to rigidly categorize objects as either entirely "Bad" or "Good," rather than to flexibly learn dispositions along a continuous scale. Distinct from the previous descriptive theories, the model makes quantitative predictions about how dichotomous beliefs emerge and are updated in light of new information. Specifically, the model addresses how splitting is context-dependent, yet exhibits stability across time. A key model feature is that phases of devaluation and/or idealization are consolidated by rationally attributing counter-evidence to external factors. For example, when another person is idealized, their less-than-perfect behavior is attributed to unfavorable external circumstances. However, sufficient counter-evidence can trigger switches of polarity, producing bistable dynamics. We show that the model can be fitted to empirical data, to measure individual susceptibility to relational instability. For example, we find that a latent categorical belief that others are "Good" accounts for less changeable, and more certain, character impressions of benevolent as opposed to malevolent others among healthy participants. By comparison, character impressions made by participants with borderline personality disorder reveal significantly higher and more symmetric splitting. The generative framework proposed invites applications for modeling oscillatory relational and affective dynamics in psychotherapeutic contexts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

We present a didactic introduction to spectral dynamic causal modeling (DCM), a Bayesian state-space modeling approach used to infer effective connectivity from noninvasive neuroimaging data. Spectral DCM is currently the most widely applied DCM variant for resting-state functional MRI analysis. Our aim is to explain its technical foundations to an audience with limited expertise in state-space modeling and spectral data analysis. Particular attention will be paid to cross-spectral density, which is the most distinctive feature of spectral DCM and is closely related to functional connectivity, as measured by (zero-lag) Pearson correlations. In fact, the model parameters estimated by spectral DCM are those that best reproduce the cross-correlations between all measurements-at all time lags-including the zero-lag correlations that are usually interpreted as functional connectivity. We derive the functional connectivity matrix from the model equations and show how changing a single effective connectivity parameter can affect all pairwise correlations. To complicate matters, the pairs of brain regions showing the largest changes in functional connectivity do not necessarily coincide with those presenting the largest changes in effective connectivity. We discuss the implications and conclude with a comprehensive summary of the assumptions and limitations of spectral DCM.

A pervasive challenge in neuroscience is testing whether neuronal connectivity changes over time due to specific causes, such as stimuli, events, or clinical interventions. Recent hardware innovations and falling data storage costs enable longer, more naturalistic neuronal recordings. The implicit opportunity for understanding the self-organised brain calls for new analysis methods that link temporal scales: from the order of milliseconds over which neuronal dynamics evolve, to the order of minutes, days, or even years over which experimental observations unfold. This review article demonstrates how hierarchical generative models and Bayesian inference help to characterise neuronal activity across different time scales. Crucially, these methods go beyond describing statistical associations among observations and enable inference about underlying mechanisms. We offer an overview of fundamental concepts in state-space modeling and suggest a taxonomy for these methods. Additionally, we introduce key mathematical principles that underscore a separation of temporal scales, such as the slaving principle, and review Bayesian methods that are being used to test hypotheses about the brain with multiscale data. We hope that this review will serve as a useful primer for experimental and computational neuroscientists on the state of the art and current directions of travel in the complex systems modelling literature.

The cerebral cortex underlies many of our unique strengths and vulnerabilities, but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are accessed through spatially dense neuroimaging maps, whereas microscale cellular and molecular features are typically measured with sparse postmortem sampling. Here, we integrate these distinct windows on brain organization by building upon existing postmortem data to impute, validate, and analyze a library of spatially dense neuroimaging-like maps of human cortical gene expression. These maps allow spatially unbiased discovery of cortical zones with extreme transcriptional profiles or unusually rapid transcriptional change which index distinct microstructure and predict neuroimaging measures of cortical folding and functional activation. Modules of spatially coexpressed genes define a family of canonical expression maps that integrate diverse spatial scales and temporal epochs of human brain organization - ranging from protein-protein interactions to large-scale systems for cognitive processing. These module maps also parse neuropsychiatric risk genes into subsets which tag distinct cyto-laminar features and differentially predict the location of altered cortical anatomy and gene expression in patients. Taken together, the methods, resources, and findings described here advance our understanding of human cortical organization and offer flexible bridges to connect scientific fields operating at different spatial scales of human brain research.

Prominent accounts of sentient behavior depict brains as generative models of organismic interaction with the world, evincing intriguing similarities with current advances in generative artificial intelligence (AI). However, because they contend with the control of purposive, life-sustaining sensorimotor interactions, the generative models of living organisms are inextricably anchored to the body and world. Unlike the passive models learned by generative AI systems, they must capture and control the sensory consequences of action. This allows embodied agents to intervene upon their worlds in ways that constantly put their best models to the test, thus providing a solid bedrock that is - we argue - essential to the development of genuine understanding. We review the resulting implications and consider future directions for generative AI.

Determining the psychological, computational, and neural bases of confidence and uncertainty holds promise for understanding foundational aspects of human metacognition. While a neuroscience of confidence has focused on the mechanisms underpinning subpersonal phenomena such as representations of uncertainty in the visual or motor system, metacognition research has been concerned with personal-level beliefs and knowledge about self-performance. I provide a road map for bridging this divide by focusing on a particular class of confidence computation: propositional confidence in one's own (hypothetical) decisions or actions. Propositional confidence is informed by the observer's models of the world and their cognitive system, which may be more or less accurate-thus explaining why metacognitive judgments are inferential and sometimes diverge from task performance. Disparate findings on the neural basis of uncertainty and performance monitoring are integrated into a common framework, and a new understanding of the locus of action of metacognitive interventions is developed.

Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to PD dementia, but quantitative susceptibility mapping (QSM), sensitive to brain tissue iron, shows potential for these purposes. The objective of the paper is to study, for the first time, the longitudinal relationship between cognition and QSM in PD in detail. We present a longitudinal study of clinical severity in PD using QSM, including 59 PD patients (without dementia at study onset), and 22 controls over 3 years. In PD, increased baseline susceptibility in the right temporal cortex, nucleus basalis of Meynert, and putamen was associated with greater cognitive severity after 3 years; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was associated with greater motor severity after 3 years. Increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, there were no consistent increases in susceptibility over 3 years. Our study suggests that QSM may predict changes in cognitive severity many months prior to overt cognitive involvement in PD. However, we did not find robust longitudinal changes in QSM over the course of the study. Additional tissue metrics may be required together with QSM for it to monitor progression in clinical practice and therapeutic trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort. CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated. Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri. Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain.

Private, subjective beliefs about uncertainty have been found to have idiosyncratic computational and neural substrates yet, humans share such beliefs seamlessly and cooperate successfully. Bringing together decision making under uncertainty and interpersonal alignment in communication, in a discovery plus pre-registered replication design, we examined the neuro-computational basis of the relationship between privately held and socially shared uncertainty. Examining confidence-speed-accuracy trade-off in uncertainty-ridden perceptual decisions under social vs isolated context, we found that shared (i.e. reported confidence) and subjective (inferred from pupillometry) uncertainty dynamically followed social information. An attractor neural network model incorporating social information as top-down additive input captured the observed behavior and demonstrated the emergence of social alignment in virtual dyadic simulations. Electroencephalography showed that social exchange of confidence modulated the neural signature of perceptual evidence accumulation in the central parietal cortex. Our findings offer a neural population model for interpersonal alignment of shared beliefs.