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Introduction: For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo. Methods: We examined the relationship between synaptic density measured by [11C]UCB‐J PET and neuropsychological test performance in 45 participants with early AD. Results: Global synaptic density showed a significant positive association with global cognition and performance on five individual cognitive domains in participants with early AD. Synaptic density was a stronger predictor of cognitive performance than gray matter volume. Conclusion: These results confirm neuropathologic studies demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD. [ABSTRACT FROM AUTHOR]

Background: Attempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration—at least in the dementia stage—as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau). Methods: We measured SV2A binding ([11C]UCB-J) and Aβ deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aβ deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches. Results: We observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = − 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = − 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus. Conclusions: Our findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers. [ABSTRACT FROM AUTHOR]

The effects of group membership on brain responses to social exclusion have been investigated in adults, revealing greater anterior cingulate responses to exclusion by members of one’s in-group (e.g., same-gender). However, social exclusion is a critical aspect of peer relations in youth and reaches heightened salience during adolescence, a time when social anxiety disorders are also emergent. While the behavioral and neural correlates of social exclusion in adolescence have been extensively explored, the effects of group membership on peer rejection are less clear. The current study used functional magnetic resonance imaging (fMRI) to investigate the differential neural correlates of being excluded by peers of one’s same- versus opposite-gender during an online ball-toss game. Participants were a group of typically developing children and adolescents (7–17 years). As predicted, anterior cingulate cortex showed a main effect of social exclusion versus fair play. However, unlike a previous adult study, this region did not show increased activation to same-gender exclusion. Instead, several regions differentiating same- versus opposite-gender exclusion were exclusively more sensitive to exclusion by one’s opposite gender. These results are discussed in the context of adolescent socio-emotional development. [ABSTRACT FROM AUTHOR]

Using fMRI we investigated the neural basis of audio-visual processing of speech and non-speech stimuli using physically similar auditory stimuli (speech and sinusoidal tones) and visual stimuli (animated circles and ellipses). Relative to uni-modal stimuli, the different multi-modal stimuli showed increased activation in largely non-overlapping areas. Ellipse-Speech, which most resembles naturalistic audio-visual speech, showed higher activation in the right inferior frontal gyrus, fusiform gyri, left posterior superior temporal sulcus, and lateral occipital cortex. Circle-Tone, an arbitrary audio-visual pairing with no speech association, activated middle temporal gyri and lateral occipital cortex. Circle-Speech showed activation in lateral occipital cortex, and Ellipse-Tone did not show increased activation relative to uni-modal stimuli. Further analysis revealed that middle temporal regions, although identified as multi-modal only in the Circle-Tone condition, were more strongly active to Ellipse-Speech or Circle-Speech, but regions that were identified as multi-modal for Ellipse-Speech were always strongest for Ellipse-Speech. Our results suggest that combinations of auditory and visual stimuli may together be processed by different cortical networks, depending on the extent to which multi-modal speech or non-speech percepts are evoked. [ABSTRACT FROM AUTHOR]

Introduction: For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo., Methods: We examined the relationship between synaptic density measured by [ 11 C]UCB-J PET and neuropsychological test performance in 45 participants with early AD., Results: Global synaptic density showed a significant positive association with global cognition and performance on five individual cognitive domains in participants with early AD. Synaptic density was a stronger predictor of cognitive performance than gray matter volume., Conclusion: These results confirm neuropathologic studies demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Attempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau)., Methods: We measured SV2A binding ([ 11 C]UCB-J) and Aβ deposition ([ 11 C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aβ deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches., Results: We observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus., Conclusions: Our findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.

Social exclusion elicits powerful feelings of negative affect associated with rejection. Additionally, experiencing social exclusion reliably recruits neural circuitry associated with emotion processing. Recent work has demonstrated abnormal neural responses to social exclusion in children and adolescents with autism spectrum disorders (ASD). However, it remains unknown to what extent these abnormalities are due to atypical social experiences versus genetic predispositions to atypical neural processing. To address this question, the current study investigated brain responses to social exclusion compared to a baseline condition of fair play in unaffected siblings of youth with ASD using functional magnetic resonance imaging. We identified common deviations between unaffected siblings and ASD probands that might represent trait-level abnormalities in processing Social Exclusion vs. Fair Play, specifically in the right anterior temporoparietal junction extending into posterior superior temporal sulcus. Thus, hypoactivation to Social Exclusion vs. Fair Play in this region may represent a shared genetic vulnerability to developing autism. In addition, we present evidence supporting the idea that one's status as an unaffected sibling moderates the relationship between IQ and neural activation to Social Exclusion vs. Fair Play in anterior cingulate cortex. These results are discussed in the context of previous literature on neural endophenotypes of autism., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We used functional magnetic resonance imaging (fMRI) and a naturalistic joint attention scenario to evaluate two, alternative hypotheses concerning the social brain. The first, Content Specific Attribution hypothesis, was that core regions previously identified as being involved in social cognition also participate in representing the contents of another mind. The second, Dual Role hypothesis, was that extrastriate, category-specific visual regions respond to a visible stimulus of a specific category and to the same stimulus occluded, but when it appears to be the focus of another person's visual attention. Participants viewed category-specific stimuli (Place and Body images) to localize the extrastriate body area (EBA) and parahippocampal place area (PPA). Then, they observed a computerized character viewing each stimulus category, occluded from the participant's view. In support of the Content Specific Attribution hypothesis, whole-brain analyses revealed that viewing someone else looking at an occluded picture of a body activated brain regions previously associated with components of social cognition more than viewing someone else looking at an occluded picture of a place. Counter to the Dual Role hypothesis, functional region of interest (ROI) analyses revealed that the EBA and PPA were not clearly involved in representing what the character was seeing., (Copyright 2010 Elsevier Inc. All rights reserved.)