Many social interactions rely upon mutual information exchange: one member of a pair changes in response to the other while at the same time producing actions that alter the behavior of the other. However, little is known about how such social processes are integrated in the brain. Here, we used a specially designed dualelectroencephalogram system and the conceptual framework of coordination dynamics to identify neural signatures of effective, real-time coordination between people and its breakdown or absence. High-resolution spectral analysis of electrical brain activity before and during visually mediated social coordination revealed a marked depression in occipital alpha and rolandic mu rhythms during social interaction that was independent of whether behavior was coordinated or not. In contrast, a pair of oscillatory components (phi 1 and phi2) located above right centroparietal cortex distinguished effective from ineffective coordination: increase of phi 1 favored independent behavior and increase of phi 2 favored coordinated behavior. The topography of the phi complex is consistent with neuroanatomical sources within the human mirror neuron system. A plausible mechanism is that the phi complex reflects the influence of the other on a person's ongoing behavior, with phi 1 expressing the inhibition of the human mirror neuron system and phi 2 its enhancement.brain oscillations ͉ electroencephalography ͉ mirror neuron system ͉ phi rhythm ͉ coordination dynamics T wo anatomically overlapping yet functionally distinct systems in the brain have been identified when we interact with others. The first, historically called the motor preparation system, consists of cortical circuitry that includes the premotor cortex, the supplementary motor area, and parts of the inferior parietal cortex (1). This system is deemed responsible for implementing the intention to realize one's own actions (2, 3). The second, the mirror-neuron system (4, 5), allows for the actions of others to be perceived (6), embodied (7), understood (8, 9), and appropriated (10) by our own motor system. Its main components are the inferior parietal sulcus, the premotor cortex (5,11,12), and the superior temporal sulcus (STS) (although the motor properties of STS neurons coactivated during observation and execution are presently the subject of some debate; see ref. 6). In evolutionary terms, the mirror-neuron system may facilitate important functions of skill learning, language acquisition, everyday joint action, and interpersonal coordination (13). A common viewpoint (5, 14) is that the mirror-neuron system is inactive most of the time but is activated upon request. Research on pathological imitation (15) suggests a further possibility, namely, that the mirror-neuron system is constantly available for use but is actively suppressed by inhibition (16).Neurophysiological studies of the influence of one person's actions on another have so far assessed the behavioral acts of pairs of individuals one at a time, i.e., one acts while the other observes; or o...

While emerging evidence suggests that neuroinflammation plays a crucial role in Alzheimer's disease, the impact of the microglia response in Alzheimer's disease remains a matter of debate. We aimed to study microglial activation in early Alzheimer's disease and its impact on clinical progression using a second-generation 18-kDa translocator protein positron emission tomography radiotracer together with amyloid imaging using Pittsburgh compound B positron emission tomography. We enrolled 96 subjects, 64 patients with Alzheimer's disease and 32 controls, from the IMABio3 study, who had both (11)C-Pittsburgh compound B and (18)F-DPA-714 positron emission tomography imaging. Patients with Alzheimer's disease were classified as prodromal Alzheimer's disease (n = 38) and Alzheimer's disease dementia (n = 26). Translocator protein-binding was measured using a simple ratio method with cerebellar grey matter as reference tissue, taking into account regional atrophy. Images were analysed at the regional (volume of interest) and at the voxel level. Translocator protein genotyping allowed the classification of all subjects in high, mixed and low affinity binders. Thirty high+mixed affinity binders patients with Alzheimer's disease were dichotomized into slow decliners (n = 10) or fast decliners (n = 20) after 2 years of follow-up. All patients with Alzheimer's disease had an amyloid positive Pittsburgh compound B positron emission tomography. Among controls, eight had positive amyloid scans (n = 6 high+mixed affinity binders), defined as amyloidosis controls, and were analysed separately. By both volumes of interest and voxel-wise comparison, 18-kDa translocator protein-binding was higher in high affinity binders, mixed affinity binders and high+mixed affinity binders Alzheimer's disease groups compared to controls, especially at the prodromal stage, involving the temporo-parietal cortex. Translocator protein-binding was positively correlated with Mini-Mental State Examination scores and grey matter volume, as well as with Pittsburgh compound B binding. Amyloidosis controls displayed higher translocator protein-binding than controls, especially in the frontal cortex. We found higher translocator protein-binding in slow decliners than fast decliners, with no difference in Pittsburgh compound B binding. Microglial activation appears at the prodromal and possibly at the preclinical stage of Alzheimer's disease, and seems to play a protective role in the clinical progression of the disease at these early stages. The extent of microglial activation appears to differ between patients, and could explain the overlap in translocator protein binding values between patients with Alzheimer's disease and amyloidosis controls.