Neural Representations of Sensory Uncertainty and Confidence Are Associated with Perceptual Curiosity.

Humans are immensely curious and motivated to reduce uncertainty, but little is known about the neural mechanisms that generate curiosity. Curiosity is inversely associated with confidence, suggesting that it is triggered by states of low confidence (subjective uncertainty), but the neural mechanisms of this link, have been little investigated. Inspired by studies of sensory uncertainty, we hypothesized that visual areas provide multivariate representations of uncertainty, which are read out by higher-order structures to generate signals of confidence and, ultimately, curiosity. We scanned participants (17 female, 15 male) using fMRI while they performed a new task in which they rated their confidence in identifying distorted images of animals and objects and their curiosity to see the clear image. We measured the activity evoked by each image in the occipitotemporal cortex (OTC) and devised a new metric of "OTC Certainty" indicating the strength of evidence this activity conveys about the animal versus object categories. We show that, perceptual curiosity peaked at low confidence and OTC Certainty negatively correlated with curiosity, establishing a link between curiosity and a multivariate representation of sensory uncertainty. Moreover, univariate (average) activity in two frontal areas-vmPFC and ACC-correlated positively with confidence and negatively with curiosity, and the vmPFC mediated the relationship between OTC Certainty and curiosity. The results reveal novel mechanisms through which uncertainty about an event generates curiosity about that event.

Switching between External and Internal Attention in Hippocampal Networks.

Everyday experience requires processing external signals from the world around us and internal information retrieved from memory. To do both, the brain must fluctuate between states that are optimized for external versus internal attention. Here, we focus on the hippocampus as a region that may serve at the interface between these forms of attention and ask how it switches between prioritizing sensory signals from the external world versus internal signals related to memories and thoughts. Pharmacological, computational, and animal studies have identified input from the cholinergic basal forebrain as important for biasing the hippocampus toward processing external information, whereas complementary research suggests the dorsal attention network (DAN) may aid in allocating attentional resources toward accessing internal information. We therefore tested the hypothesis that the basal forebrain and DAN drive the hippocampus toward external and internal attention, respectively. We used data from 29 human participants (17 female) who completed two attention tasks during fMRI. One task (memory-guided) required proportionally more internal attention, and proportionally less external attention, than the other (explicitly instructed). We discovered that background functional connectivity between the basal forebrain and hippocampus was stronger during the explicitly instructed versus memory-guided task. In contrast, DAN-hippocampus background connectivity was stronger during the memory-guided versus explicitly instructed task. Finally, the strength of DAN-hippocampus background connectivity was correlated with performance on the memory-guided but not explicitly instructed task. Together, these results provide evidence that the basal forebrain and DAN may modulate the hippocampus to switch between external and internal attention.SIGNIFICANCE STATEMENT How does the brain balance the need to pay attention to internal thoughts and external sensations? We focused on the human hippocampus, a region that may serve at the interface between internal and external attention, and asked how its functional connectivity varies based on attentional states. The hippocampus was more strongly coupled with the cholinergic basal forebrain when attentional states were guided by the external world rather than retrieved memories. This pattern flipped for functional connectivity between the hippocampus and dorsal attention network, which was higher for attention tasks that were guided by memory rather than external cues. Together, these findings show that distinct networks in the brain may modulate the hippocampus to switch between external and internal attention.

Consolidation Enhances Sequential Multistep Anticipation but Diminishes Access to Perceptual Features.

Many experiences unfold predictably over time. Memory for these temporal regularities enables anticipation of events multiple steps into the future. Because temporally predictable events repeat over days, weeks, and years, we must maintain-and potentially transform-memories of temporal structure to support adaptive behavior. We explored how individuals build durable models of temporal regularities to guide multistep anticipation. Healthy young adults (Experiment 1: N = 99, age range = 18-40 years; Experiment 2: N = 204, age range = 19-40 years) learned sequences of scene images that were predictable at the category level and contained incidental perceptual details. Individuals then anticipated upcoming scene categories multiple steps into the future, immediately and at a delay. Consolidation increased the efficiency of anticipation, particularly for events further in the future, but diminished access to perceptual features. Further, maintaining a link-based model of the sequence after consolidation improved anticipation accuracy. Consolidation may therefore promote efficient and durable models of temporal structure, thus facilitating anticipation of future events.

Associative memory retrieval modulates upcoming perceptual decisions.

Expectations can inform fast, accurate decisions. But what informs expectations? Here we test the hypothesis that expectations are set by dynamic inference from memory. Participants performed a cue-guided perceptual decision task with independently-varying memory and sensory evidence. Cues established expectations by reminding participants of past stimulus-stimulus pairings, which predicted the likely target in a subsequent noisy image stream. Participant's responses used both memory and sensory information, in accordance to their relative reliability. Formal model comparison showed that the sensory inference was best explained when its parameters were set dynamically at each trial by evidence sampled from memory. Supporting this model, neural pattern analysis revealed that responses to the probe were modulated by the specific content and fidelity of memory reinstatement that occurred before the probe appeared. Together, these results suggest that perceptual decisions arise from the continuous sampling of memory and sensory evidence.

Effects of familiar music exposure on deliberate retrieval of remote episodic and semantic memories in healthy aging adults.

Familiar music facilitates memory retrieval in adults with dementia. However, mechanisms behind this effect, and its generality, are unclear because of a lack of parallel work in healthy aging. Exposure to familiar music enhances spontaneous recall of memories directly cued by the music, but it is unknown whether such effects extend to deliberate recall more generally - e.g., to memories not directly linked to the music being played. It is also unclear whether familiar music boosts recall of specific episodes versus more generalised semantic memories, or whether effects are driven by domain-general mechanisms (e.g., improved mood). In a registered report study, we examined effects of familiar music on deliberate recall in healthy adults ages 65-80 years (N = 75) by presenting familiar music from earlier in life, unfamiliar music, and non-musical audio clips across three sessions. After each clip, we assessed free recall of remote memories for pre-selected events. Contrary to our hypotheses, we found no effects of music exposure on recall of prompted events, though familiar music evoked spontaneous memories most often. These results suggest that effects of familiar music on recall may be limited to memories specifically evoked in response to the music (Preprint and registered report protocol at https://osf.io/kjnwd/).

Age-related change in task-evoked amygdala-prefrontal circuitry: A multiverse approach with an accelerated longitudinal cohort aged 4-22 years.

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed - perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala-mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years-old; N = 98; 183 scans; 1-3 scans/participant). Participants recruited from the greater Los Angeles area completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala-mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala-mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala-mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results.

A retrospective analysis of oral and maxillofacial pathological lesions in a group of Egyptian children over 21 years.

OBJECTIVES: The goal of the current study was to evaluate the relative frequency of oral and maxillofacial pathological lesions among Egyptian children. MATERIALS AND METHODS: Records of biopsies submitted to the department of oral and maxillofacial pathology from the year 1999 to 2019 were retrieved and reassessed for all cases under the age of 18 years. Information on age, sex, location of the lesion, and the histopathologic diagnosis was analyzed. RESULTS: Over the course of twenty-one years, 1108 specimens were analyzed where reactive soft tissue lesions, which accounted for 397 (35.8%) of all cases ranked the highest presented category, followed by inflammatory odontogenic cysts, which accounted for 213 cases (19.2%). With 208 cases, the inflammatory radicular cyst was on the top of the most common 20 lesions, followed by pyogenic granuloma (160 cases). Malignancy was found in 19 cases, with soft tissue tumors (10 cases) being the most common, followed by salivary gland (5 cases) and bone pathologies (4 cases). CONCLUSIONS: The frequency of oral and maxillofacial pathological lesions among Egyptian children increased over the years but remained consistent with global trends. CLINICAL RELEVANCE: This is the first study evaluating the relative frequency of oral and maxillofacial pathological lesions among Egyptian children and provides an insight into the most commonly encountered pediatric pathologies. This may aid in the understanding of the most prevalent oral lesions that impact the pediatric population, as well as providing the key to early detection of lesions.

The prescription pattern and awareness about antibiotic prophylaxis and resistance among a group of Egyptian pediatric and general dentists: a cross sectional study.

BACKGROUND: The use of antibiotics in dentistry as prophylaxis and treatment is frequent. Their misuse has led to a major public health problem globally known as antibiotic resistance. This study aimed to assess the pattern of antibiotic prescription and its prophylactic use for systemic conditions. Besides, this study evaluated the awareness and adherence to antibiotic prescription guidelines and antibiotic prophylaxis guidelines along with awareness of antibiotic resistance across pediatric and general dentists. METHODS: An overall of 378 pediatric and general dentists meeting the required eligibility criteria, fulfilled a pre-designed validated questionnaire. Data were collected, tabulated, and statistically analyzed. RESULTS: A significant statistical difference was found among the pediatric and general dentists regarding antibiotics prescription for most of the oral conditions where Amoxicillin with clavulanic acid was the most frequently prescribed antibiotic among the two groups (53% pediatric dentist and 52% general dentist). The majority of pediatric and general dentists, on the other hand, were aware of antibiotic resistance and prescribing recommendations. CONCLUSIONS: The present study showed a tendency to overprescribe and overuse antibiotics in certain dental conditions among the participants. The vast majority of dentists, especially general dentists do not have adherence to professional guidelines for antibiotics prescription in children despite their awareness of antibiotic resistance and prescription guidelines.

The Medial Temporal Lobe Is Critical for Spatial Relational Perception.

The medial temporal lobe (MTL) is traditionally considered to be a system that is specialized for long-term memory. Recent work has challenged this notion by demonstrating that this region can contribute to many domains of cognition beyond long-term memory, including perception and attention. One potential reason why the MTL (and hippocampus specifically) contributes broadly to cognition is that it contains relational representations-representations of multidimensional features of experience and their unique relationship to one another-that are useful in many different cognitive domains. Here, we explore the hypothesis that the hippocampus/MTL plays a critical role in attention and perception via relational representations. We compared human participants with MTL damage to healthy age- and education-matched individuals on attention tasks that varied in relational processing demands. On each trial, participants viewed two images (rooms with paintings). On "similar room" trials, they judged whether the rooms had the same spatial layout from a different perspective. On "similar art" trials, they judged whether the paintings could have been painted by the same artist. On "identical" trials, participants simply had to detect identical paintings or rooms. MTL lesion patients were significantly and selectively impaired on the similar room task. This work provides further evidence that the hippocampus/MTL plays a ubiquitous role in cognition by virtue of its relational and spatial representations and highlights its important contributions to rapid perceptual processes that benefit from attention.

Interpretable multimodal deep learning for real-time pan-tissue pan-disease pathology search on social media.

Pathologists are responsible for rapidly providing a diagnosis on critical health issues. Challenging cases benefit from additional opinions of pathologist colleagues. In addition to on-site colleagues, there is an active worldwide community of pathologists on social media for complementary opinions. Such access to pathologists worldwide has the capacity to improve diagnostic accuracy and generate broader consensus on next steps in patient care. From Twitter we curate 13,626 images from 6,351 tweets from 25 pathologists from 13 countries. We supplement the Twitter data with 113,161 images from 1,074,484 PubMed articles. We develop machine learning and deep learning models to (i) accurately identify histopathology stains, (ii) discriminate between tissues, and (iii) differentiate disease states. Area Under Receiver Operating Characteristic (AUROC) is 0.805-0.996 for these tasks. We repurpose the disease classifier to search for similar disease states given an image and clinical covariates. We report precision@k = 1 = 0.7618 ± 0.0018 (chance 0.397 ± 0.004, mean ±stdev ). The classifiers find that texture and tissue are important clinico-visual features of disease. Deep features trained only on natural images (e.g., cats and dogs) substantially improved search performance, while pathology-specific deep features and cell nuclei features further improved search to a lesser extent. We implement a social media bot (@pathobot on Twitter) to use the trained classifiers to aid pathologists in obtaining real-time feedback on challenging cases. If a social media post containing pathology text and images mentions the bot, the bot generates quantitative predictions of disease state (normal/artifact/infection/injury/nontumor, preneoplastic/benign/low-grade-malignant-potential, or malignant) and lists similar cases across social media and PubMed. Our project has become a globally distributed expert system that facilitates pathological diagnosis and brings expertise to underserved regions or hospitals with less expertise in a particular disease. This is the first pan-tissue pan-disease (i.e., from infection to malignancy) method for prediction and search on social media, and the first pathology study prospectively tested in public on social media. We will share data through http://pathobotology.org . We expect our project to cultivate a more connected world of physicians and improve patient care worldwide.

Focusing on what matters: Modulation of the human hippocampus by relational attention.

Hippocampal episodic memory is fundamentally relational, comprising links between events and the spatiotemporal contexts in which they occurred. Such relations are also important over shorter timescales, during online perception. For example, how do we assess the relative spatial positions of objects, their temporal order, or the relationship between their features? Here, we investigate the role of the hippocampus in online relational processing by manipulating attention to different kinds of relations. While undergoing fMRI, participants viewed two images in rapid succession on each trial and performed one of three relational tasks, judging the images' relative: spatial positions, temporal onsets, or sizes. Additionally, they sometimes judged whether one image was tilted, irrespective of the other. This served as a baseline item task with no demands on relational processing. The hippocampus showed reliable deactivation when participants attended to relational vs. item information. Attention to temporal relations was associated with the most robust deactivation. One interpretation of such deactivation is that it reflects hippocampal disengagement. If true, there should be reduced information content and noisier activity patterns for the temporal vs. other tasks. Instead, multivariate pattern analysis revealed more stable hippocampal representations in the temporal task. This increased pattern similarity was not simply a reflection of lower univariate activity. Thus, the hippocampus differentiates between relational and item processing even during online perception, and its representations of temporal relations are particularly robust. These findings suggest that the relational computations of the hippocampus extend beyond long-term memory, enabling rapid extraction of relational information in perception.

Correlating fragility and heterogeneous dynamics in polystyrene through single molecule studies.

Many macroscopic properties of polymers depend on their molecular weight, with one notable example being glass transition temperature: polymers with higher molecular weights typically have higher glass transition temperatures than their lower molecular weight polymeric and oligomeric counterparts. Polymeric systems close to their glass transition temperatures also exhibit interesting properties, showing both high (and molecular weight dependent) fragility and strong evidence of dynamic heterogeneity. While studies have detailed the correlations between molecular weight and fragility, studies clearly detailing correlations between molecular weight and degree of heterogeneous dynamics are lacking. In this study, we use single molecule rotational measurements to investigate the impact of molecular weight on polystyrene's degree of heterogeneity near its glass transition temperature. To this end, two types of fluorescent probes are embedded in films composed of polystyrene ranging from 0.6 to 1364.0 kg mol-1. We find correlation between polystyrene molecular weight, fragility, and degree of dynamic heterogeneity as reported by single molecule stretching exponents but do not find clear correlation between these quantities and time scales associated with dynamic exchange.

Attention promotes episodic encoding by stabilizing hippocampal representations.

Attention influences what is later remembered, but little is known about how this occurs in the brain. We hypothesized that behavioral goals modulate the attentional state of the hippocampus to prioritize goal-relevant aspects of experience for encoding. Participants viewed rooms with paintings, attending to room layouts or painting styles on different trials during high-resolution functional MRI. We identified template activity patterns in each hippocampal subfield that corresponded to the attentional state induced by each task. Participants then incidentally encoded new rooms with art while attending to the layout or painting style, and memory was subsequently tested. We found that when task-relevant information was better remembered, the hippocampus was more likely to have been in the correct attentional state during encoding. This effect was specific to the hippocampus, and not found in medial temporal lobe cortex, category-selective areas of the visual system, or elsewhere in the brain. These findings provide mechanistic insight into how attention transforms percepts into memories.

Clinical and radiographic evaluation of Biodentine and Mineral Trioxide Aggregate in revascularization of non-vital immature permanent anterior teeth (randomized clinical study).

OBJECTIVE: To asses clinically and radiographically the effect of using two types of coronal plug materials in revascularization of non-vital immature teeth. METHODS: A total of 26 necrotic immature permanent anterior teeth were enrolled for pulp revascularization using a double antibiotic mix for root canal disinfection. They were randomly divided into the following based on coronal plug materials used: Biodentine (Group I) and white Mineral Trioxide Aggregate (Group II; n = 13). Clinical and radiographic assessments were performed after 3, 6, 9, and 12 months. RESULTS: When comparing the overall clinical successes and percentage of increase in root length between the two groups, there was no statistically significant difference (P > 0.05). There was a significant difference in the distribution of discoloration between the two groups. One case was reported in Group I, and seven cases were reported in Group II (P = 0.01). CONCLUSIONS: Both Biodentine and Mineral Trioxide Aggregate were successful clinically regarding the resolution of signs and symptoms associated with the necrotic teeth.

Learning Naturalistic Temporal Structure in the Posterior Medial Network.

The posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on preexisting event schemas, but temporal structure can also arise de novo from learning. Here, we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the human posterior medial network. We tested whether, with repeated viewing, the network becomes engaged by scrambled movies with temporal structure. Replicating prior studies, activity in posterior medial regions was immediately locked to stimulus structure upon exposure to intact, but not scrambled, movies. However, for temporally structured scrambled movies, functional coupling within the network increased across stimulus repetitions, rising to the level of intact movies. Thus, temporal structure is a key determinant of network dynamics and function in the posterior medial network.

Attention Stabilizes Representations in the Human Hippocampus.

Attention and memory are intricately linked, but how attention modulates brain areas that subserve memory, such as the hippocampus, is unknown. We hypothesized that attention may stabilize patterns of activity in human hippocampus, resulting in distinct but reliable activity patterns for different attentional states. To test this prediction, we utilized high-resolution functional magnetic resonance imaging and a novel "art gallery" task. On each trial, participants viewed a room containing a painting, and searched a stream of rooms for a painting from the same artist (art state) or a room with the same layout (room state). Bottom-up stimulation was the same in both tasks, enabling the isolation of neural effects related to top-down attention. Multivariate analyses revealed greater pattern similarity in all hippocampal subfields for trials from the same, compared with different, attentional state. This stability was greater for the room than art state, was unrelated to univariate activity, and, in CA2/CA3/DG, was correlated with behavior. Attention therefore induces representational stability in the human hippocampus, resulting in distinct activity patterns for different attentional states. Modulation of hippocampal representational stability highlights the far-reaching influence of attention outside of sensory systems.

Neural correlates of state- and strength-based perception.

Perceptual judgments can be based on two kinds of information: state-based perception of specific, detailed visual information, or strength-based perception of global or relational information. State-based perception is discrete in the sense that it either occurs or fails, whereas strength-based perception is continuously graded from weak to strong. The functional characteristics of these types of perception have been examined in some detail, but whether state- and strength-based perception are supported by different brain regions has been largely unexplored. A consideration of empirical work and recent theoretical proposals suggests that parietal and occipito-temporal regions may be differentially associated with state- and strength-based signals, respectively. We tested this parietal/occipito-temporal state/strength hypothesis using fMRI and a visual perception task that allows separation of state- and strength-based perception. Participants made same/different judgments on pairs of faces and scenes using a 6-point confidence scale where "6" responses indicated a state of perceiving specific details that had changed, and "1" to "5" responses indicated judgments based on varying strength of relational match/mismatch. Regions in the lateral and medial posterior parietal cortex (supramarginal gyrus, posterior cingulate cortex, and precuneus) were sensitive to state-based perception and were not modulated by varying levels of strength-based perception. In contrast, bilateral fusiform gyrus activation was increased for strength-based "different" responses compared with misses and did not show state-based effects. Finally, the lateral occipital complex showed increased activation for state-based responses and additionally showed graded activation across levels of strength-based perception. These results offer support for a state/strength distinction between parietal and temporal regions, with the lateral occipital complex at the intersection of state- and strength-based processing.

Neurocomputational account of memory and perception: Thresholded and graded signals in the hippocampus.

Recent evidence suggests that the hippocampus, a region critical for long-term memory, also supports certain forms of high-level visual perception. A seemingly paradoxical finding is that, unlike the thresholded hippocampal signals associated with memory, the hippocampus produces graded, strength-based signals in perception. This article tests a neurocomputational model of the hippocampus, based on the complementary learning systems framework, to determine if the same model can account for both memory and perception, and whether it produces the appropriate thresholded and strength-based signals in these two types of tasks. The simulations showed that the hippocampus, and most prominently the CA1 subfield, produced graded signals when required to discriminate between highly similar stimuli in a perception task, but generated thresholded patterns of activity in recognition memory. A threshold was observed in recognition memory because pattern completion occurred for only some trials and completely failed to occur for others; conversely, in perception, pattern completion always occurred because of the high degree of item similarity. These results offer a neurocomputational account of the distinct hippocampal signals associated with perception and memory, and are broadly consistent with proposals that CA1 functions as a comparator of expected versus perceived events. We conclude that the hippocampal computations required for high-level perceptual discrimination are congruous with current neurocomputational models that account for recognition memory, and fit neatly into a broader description of the role of the hippocampus for the processing of complex relational information.

The brain hierarchically represents the past and future during multistep anticipation.

Memory for temporal structure enables both planning of future events and retrospection of past events. We investigated how the brain flexibly represents extended temporal sequences into the past and future during anticipation. Participants learned sequences of environments in immersive virtual reality. Pairs of sequences had the same environments in a different order, enabling context-specific learning. During fMRI, participants anticipated upcoming environments multiple steps into the future in a given sequence. Temporal structure was represented in the hippocampus and across higher-order visual regions (1) bidirectionally, with graded representations into the past and future and (2) hierarchically, with further events into the past and future represented in successively more anterior brain regions. In hippocampus, these bidirectional representations were context-specific, and suppression of far-away environments predicted response time costs in anticipation. Together, this work sheds light on how we flexibly represent sequential structure to enable planning over multiple timescales.