In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

INTRODUCTION: Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density. METHODS: We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [11 C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio. RESULTS: We observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume. CONCLUSION: We were able to measure widespread synaptic loss due to AD using [11 C]UCB-J PET. Future studies will continue to evaluate the utility of SV2A PET for tracking AD progression and for monitoring potential therapies.

Action understanding in the superior temporal sulcus region.

The posterior superior temporal sulcus (STS) region plays an important role in the perception of social acts, although its full role has not been completely clarified. This functional magnetic resonance imaging experiment examined activity in the STS region as participants viewed actions that were congruent or incongruent with intentions established by a previous emotional context. Participants viewed an actress express either a positive or a negative emotion toward one of two objects and then subsequently pick up one of them. If the object that was picked up had received positive regard, or if the object that was not picked up had received negative regard, the action was congruent; otherwise, the action was incongruent. Activity in the right posterior STS region was sensitive to the congruency between the action and the actress's emotional expression (i.e., STS activity was greater on incongruent than on congruent trials). These findings suggest that the posterior STS represents not only biological motion, but also how another person's motion is related to his or her intentions.

Enhanced neural responses to rule violation in children with autism: a comparison to social exclusion.

The present study aimed to explore the neural correlates of two characteristic deficits in autism spectrum disorders (ASD); social impairment and restricted, repetitive behavior patterns. To this end, we used comparable experiences of social exclusion and rule violation to probe potentially atypical neural networks in ASD. In children and adolescents with and without ASD, we used the interactive ball-toss game (Cyberball) to elicit social exclusion and a comparable game (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic resonance imaging (fMRI), we identified group differences in brain responses to social exclusion and rule violation. Though both groups reported equal distress following exclusion, the right insula and ventral anterior cingulate cortex were hypoactive during exclusion in children with ASD. In rule violation, right insula and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a dissociation in activation; it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were modulated in each game, highlighting differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity. These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD.