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PloS One 2022Theory of Mind (ToM), the ability to infer the mental states of others, is integral to facilitating healthy social interactions. People can reason about the mental...
Theory of Mind (ToM), the ability to infer the mental states of others, is integral to facilitating healthy social interactions. People can reason about the mental states of others even with limited or (sometimes) inconsistent information. However, little is known about how people make inferences about the mental states of others under uncertainty, and what features of information are important in aiding mental state reasoning. In the current study, we conducted three unique experiments that alter participant's uncertainty when engaging in ToM tests. In Experiment 1, we simultaneously manipulated both the amount and consistency of information available in social stimuli presented to 59 participants. In Experiments 2 and 3, we aimed to decipher which feature of social stimuli is more conducive to mental state reasoning. Experiment 2 manipulated only the amount of information available to 47 participants, while Experiment 3 manipulated only the consistency of information available to 46 participants. Using both frequentist and Bayesian statistics, results confirmed that manipulating the amount and consistency of information alters ToM performance. Exploratory analysis comparing the effects of the amount and consistency of information suggests that the effects of the consistency of information seem to be stronger than those of the amount of information. Taken together, all three experiments suggest that while both the amount and consistency of information are important features of social stimuli-the consistency of information available is more salient when inferring mental states of others. These findings are discussed in relation to information theory and have important implications for creating enriched social stimuli, which may enhance mental state reasoning in individuals with social deficits.
Topics: Humans; Uncertainty; Bayes Theorem; Theory of Mind; Problem Solving
PubMed: 36350920
DOI: 10.1371/journal.pone.0277356 -
Cell Reports Jun 2023Synaptic plasticity is hypothesized to underlie "replay" of salient experience during hippocampal sharp-wave/ripple (SWR)-based ensemble activity and to facilitate...
Synaptic plasticity is hypothesized to underlie "replay" of salient experience during hippocampal sharp-wave/ripple (SWR)-based ensemble activity and to facilitate systems-level memory consolidation coordinated by SWRs and cortical sleep spindles. It remains unclear how molecular changes at synapses contribute to experience-induced modification of network function. The synaptic protein KIBRA regulates plasticity and memory. To determine the impact of KIBRA-regulated plasticity on circuit dynamics, we recorded in vivo neural activity from wild-type (WT) mice and littermates lacking KIBRA and examined circuit function before, during, and after novel experience. In WT mice, experience altered population activity and oscillatory dynamics in a manner consistent with incorporation of new information content in replay and enhanced hippocampal-cortical communication. While baseline SWR features were normal in KIBRA conditional knockout (cKO) mice, experience-dependent alterations in SWRs were absent. Furthermore, intra-hippocampal and hippocampal-cortical communication during SWRs was disrupted following KIBRA deletion. These results indicate molecular mechanisms that underlie network-level adaptations to experience.
Topics: Animals; Mice; Hippocampus; Memory Consolidation; Sleep
PubMed: 37347662
DOI: 10.1016/j.celrep.2023.112662 -
Journal of the Endocrine Society Oct 2022Gestational diabetes mellitus (GDM) results in an increased risk of pre- and postpartum health complications for both mother and child. Metabolomics analysis can... (Review)
Review
Gestational diabetes mellitus (GDM) results in an increased risk of pre- and postpartum health complications for both mother and child. Metabolomics analysis can potentially identify predictive biomarkers and provide insight into metabolic alterations associated with GDM pathogenesis and progression, but few metabolomics studies investigate alterations observed across the first and third trimester. We hypothesize that metabolites altered in first-trimester GDM that remain altered in late pregnancy may best inform interventions. Metabolomic studies comparing plasma and serum metabolite alterations in GDM vs non-GDM pregnancies were retrieved by searching PubMed, Medline, and CINAHL Plus databases. The present scoping review summarizes the metabolites found to be consistently altered throughout the course of GDM and proposes mechanisms that explain how these metabolic perturbations relate to GDM development and progression. Metabolites involved in fatty acid metabolism, reductive carboxylation, branched-chain amino acid metabolism, cell membrane lipid metabolism, purine degradation, and the gut microbiome were found to be altered throughout GDM pregnancies, with many of these pathways showing mechanistic links to insulin resistance, inflammation, and impaired cell signaling. Future studies are required to investigate if normalization of these perturbed pathways can be the targets of interventions.
PubMed: 36320628
DOI: 10.1210/jendso/bvac134 -
Neuroscience and Biobehavioral Reviews Nov 2022Clinical empathy refers to the ability of healthcare providers (HP) to recognize and understand what patients feel. While neuroimaging investigations have identified a... (Meta-Analysis)
Meta-Analysis Review
Clinical empathy refers to the ability of healthcare providers (HP) to recognize and understand what patients feel. While neuroimaging investigations have identified a neural network of empathy, activation consistency of brain regions and their specific functions in clinical empathy remains unclear. Herein, we conducted meta-analyses of dispositional assessments using random-effects models and functional neuroimaging using Seed-based d Mapping with Permutation of Subject Images to ascertain the shared neural processes consistently identified as relevant to clinical empathy. The dispositional meta-analysis (n = 15) revealed that HP exhibited higher scores on empathic concern and perspective taking. The HP neuroimaging meta-analysis (n = 11) identified consistent activation of the anterior mid-cingulate cortex, anterior insula, and ventrolateral prefrontal cortex (vlPFC) while HP vs. controls comparison (n = 9) did not yield robust alterations. The vlPFC mediated positive and negative functional connectivity of the insula. We revisited the framework of emotion regulation in clinical empathy. The empathetic agent flexibly shifts between affective regulatory strategies to meet contextual demands, with vlPFC figuring as the key region where this neural mechanism takes place.
Topics: Humans; Empathy; Magnetic Resonance Imaging; Functional Neuroimaging; Emotions; Brain; Neuroimaging; Brain Mapping
PubMed: 36116577
DOI: 10.1016/j.neubiorev.2022.104874 -
Epilepsia Open Mar 2021Drug-resistant epileptic patients make up approximately one-third of the global epilepsy population. The pathophysiology of drug resistance has not been fully... (Review)
Review
Drug-resistant epileptic patients make up approximately one-third of the global epilepsy population. The pathophysiology of drug resistance has not been fully elucidated; however, current evidence suggests intestinal dysbiosis, as a possible etiopathogenic factor. Ketogenic diet, whose effect is considered to be mediated by alteration of gut microbiota synthesis, has long been administered in patients with medically refractory seizures, with positive outcomes. In this review, we present data derived from clinical studies regarding alterations of gut microbiome profile in drug-resistant epileptic patients. We further attempt to describe the mechanisms through which the gut microbiome modification methods (including ketogenic diet, pre- or probiotic administration) improve drug-resistant epilepsy, by reporting findings from preclinical and clinical studies. A comprehensive search of the published literature on the PubMed, Embase, and Web of science databases was performed. Overall, the role of gut microbiome in drug-resistant epilepsy is an area which shows promise for the development of targeted therapeutic interventions. More research is required to confirm the results from preliminary studies, as well as safety and effectiveness of altering gut bacterial composition, through the above-mentioned methods.
Topics: Diet, Ketogenic; Drug Resistant Epilepsy; Dysbiosis; Gastrointestinal Microbiome; Humans; Probiotics
PubMed: 33681645
DOI: 10.1002/epi4.12461 -
ELife Oct 2020Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly...
Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the 'precision-weighting of priors', thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.
Topics: Adult; Alpha Rhythm; Brain; Consciousness; Female; Hallucinogens; Humans; Male; Middle Aged; N,N-Dimethyltryptamine; Young Adult
PubMed: 33043883
DOI: 10.7554/eLife.59784 -
Frontiers in Synaptic Neuroscience 2023The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological... (Review)
Review
The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer's disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer's disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer's disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer's disease, and what we know from Alzheimer's disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer's disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer's disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer's disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer's disease. The synapse will certainly continue to be an important target within Alzheimer's disease for the foreseeable future.
PubMed: 36970154
DOI: 10.3389/fnsyn.2023.1129036 -
Scientific Reports Apr 2023In contrast to long-term relationships, far less is known about the temporal evolution of transient relationships, although these constitute a substantial fraction of...
In contrast to long-term relationships, far less is known about the temporal evolution of transient relationships, although these constitute a substantial fraction of people's communication networks. Previous literature suggests that ratings of relationship emotional intensity decay gradually until the relationship ends. Using mobile phone data from three countries (US, UK, and Italy), we demonstrate that the volume of communication between ego and its transient alters does not display such a systematic decay, instead showing a lack of any dominant trends. This means that the communication volume of egos to groups of similar transient alters is stable. We show that alters with longer lifetimes in ego's network receive more calls, with the lifetime of the relationship being predictable from call volume within the first few weeks of first contact. This is observed across all three countries, which include samples of egos at different life stages. The relation between early call volume and lifetime is consistent with the suggestion that individuals initially engage with a new alter so as to evaluate their potential as a tie in terms of homophily.
Topics: Humans; Social Support; Emotions; Ego; Cell Phone; Italy
PubMed: 37059731
DOI: 10.1038/s41598-023-32206-2 -
Personality Neuroscience 2020"Personality is an abstraction used to explain consistency and coherency in an individual's pattern of affects, cognitions, desires and behaviors [ABCDs]" (Revelle,... (Review)
Review
"Personality is an abstraction used to explain consistency and coherency in an individual's pattern of affects, cognitions, desires and behaviors [ABCDs]" (Revelle, 2007, p. 37). But personality research currently provides more a taxonomy of patterns than theories of fundamental causes. Psychiatric disorders can be viewed as involving extremes of personality but are diagnosed via symptom patterns not biological causes. Such surface-level taxonomic description is necessary for science, but consistent predictive explanation requires causal theory. Personality constructs, and especially their clinical extremes, should predict variation in ABCD patterns, with parsimony requiring the lowest effective causal level of explanation. But, even biologically inspired personality theories currently use an intuitive language-based approach for scale development that lacks biological anchors. I argue that teleonomic "purpose" explains the organisation and outputs of conserved brain emotion systems, where high activation is adaptive in specific situations but is otherwise maladaptive. Simple modulators of whole-system sensitivity evolved because the requisite adaptive level can vary across people and time. Sensitivity to a modulator is an abstract predictive personality factor that operates at the neural level but provides a causal explanation of both coherence and occasional apparent incoherence in ABCD variation. Neuromodulators impact all levels of the "personality hierarchy" from metatraits to aspects: stability appears altered by serotonergic drugs, neuroticism by ketamine and trait anxiety by simple anxiolytic drugs. Here, the tools of psychiatry transfer to personality research and imply both interaction between levels and oblique factor mappings to ABCD. On this view, much psychopathology reflects extremes of neural-level personality factors, and we can view much pharmacotherapy as temporarily altering personality. So, particularly for personality factors linked to basic emotions and their disorders, I think we should start with evolutionary biology and look directly at conserved neural-level modulators for our explanatory personality constructs and only invoke higher order, emergent, explanations when neural-level explanation fails.
PubMed: 32524065
DOI: 10.1017/pen.2020.5 -
Chinese Journal of Cancer Jan 2013Persistent infection with high-risk types of human papillomavirus(HPV) is known to cause cervical cancer; however, additional genetic and epigenetic alterations are... (Review)
Review
Persistent infection with high-risk types of human papillomavirus(HPV) is known to cause cervical cancer; however, additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer. DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis. In this review, we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications. Methylation of the HPV long control region (LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm. The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression. Moreover, promoters of tumor suppressor genes (TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers. Some are associated with squamous cell carcinomas, and others are associated with adenocarcinomas. Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV, atypical squamous cells of undetermined significance, or low grade squamous intraepithelial lesion (LSIL). However, consistent panels must be validated for this approach to be translated to the clinic. Furthermore, reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment, but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.
Topics: Apoptosis; Biomarkers, Tumor; Cell Adhesion; Cell Cycle; CpG Islands; DNA Methylation; Female; Genes, Tumor Suppressor; Genome, Viral; Humans; Papillomaviridae; Promoter Regions, Genetic; Signal Transduction; Uterine Cervical Neoplasms
PubMed: 22943599
DOI: 10.5732/cjc.012.10033