Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects), and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning). Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas-areas active during the execution and the observation of an action-previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically.

The human visual pathways that are specialized for object recognition stretch from lateral occipital cortex (LO) to the ventral surface of the temporal lobe, including the fusiform gyrus. Plasticity in these pathways supports the acquisition of visual expertise, but precisely how training affects the different regions remains unclear. We used functional magnetic resonance imaging to measure neural activity in both LO and the fusiform gyrus in radiologists as they detected abnormalities in chest radiographs. Activity in the right fusiform face area (FFA) correlated with visual expertise, measured as behavioral performance during scanning. In contrast, activity in left LO correlated negatively with expertise, and the amount of LO that responded to radiographs was smaller in experts than in novices. Activity in the FFA and LO correlated negatively in experts, whereas in novices, the 2 regions showed no stable relationship. Together, these results suggest that the FFA becomes more engaged and left LO less engaged in interpreting radiographic images over the course of training. Achieving expert visual performance may involve suppressing existing neural representations while simultaneously developing others.

Reactivity to others' emotions not only can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants (N = 57) provided measures of EC, PD, prosocial behavior, and neural responses to emotional expressions at ages 10 and 13. Initial EC predicted subsequent prosocial behavior. Initial EC and PD predicted subsequent reactivity to emotions in the inferior frontal gyrus (IFG) and inferior parietal lobule, respectively. Activity in the IFG, a region linked to mirror neuron processes, as well as cognitive control and language, mediated the relation between initial EC and subsequent prosocial behavior.

Objective

Currently [18F]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [18F]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking amyloid-β deposits.

Methods

Fifteen patients with PSP received [18F]FDDNP PET scanning. [18F]FDDNP distribution volume ratios, in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson's disease with short disease duration, and age-matched control subjects without neurodegenerative disorders.

Results

[18F]FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain, and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [18F]FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [18F]FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with Parkinson's disease.

Conclusions

These results provide evidence that [18F]FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [18F]FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [18F]FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult.

Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, “shape preserving” and “shape standardizing”. aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to ρ 2, the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages.