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.

Spontaneous social coordination has been extensively described in natural settings but so far no controlled methodological approaches have been employed that systematically advance investigations into the possible self-organized nature of bond formation and dissolution between humans. We hypothesized that, under certain contexts, spontaneous synchrony -a well-described phenomenon in biological and physical settings-could emerge spontaneously between humans as a result of information exchange. Here, a new way to quantify interpersonal interactions in real time is proposed. In a simple experimental paradigm, pairs of participants facing each other were required to actively produce actions, while provided (or not) with the vision of similar actions being performed by someone else. New indices of interpersonal coordination, inspired by the theoretical framework of coordination dynamics (based on relative phase and frequency overlap between movements of individuals forming a pair) were developed and used. Results revealed that spontaneous phase synchrony (i.e., unintentional in-phase coordinated behavior) between two people emerges as soon as they exchange visual information, even if they are not explicitly instructed to coordinate with each other. Using the same tools, we also quantified the degree to which the behavior of each individual remained influenced by the social encounter even after information exchange had been removed, apparently a kind of social memory.

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ABSTRACT. The authors studied the interaction between rider and horse by measuring their ensemble motions in a trot sequence, comparing 1 expert and 1 novice rider. Whereas the novice's movements displayed transient departures from phase synchrony, the expert's motions were continuously phase-matched with those of the horse. The tight ensemble synchrony between the expert and the horse was accompanied by an increase in the temporal regularity of the oscillations of the trunk of the horse. Observed differences between expert and novice riders indicated that phase synchronization is by no means perfect but requires extended practice. Points of contact between horse and rider may haptically convey effective communication between them.

Our results indicate that the inflammatory properties of circulating neutrophils shift as the percentage of aged neutrophils expands in patients with AD-changes that may play an instrumental role in establishing systemic chronic inflammation. Most important, our data strongly suggest that the neutrophil phenotype may be associated with the rate of cognitive decline and may thus constitute an innovative and prognostic blood biomarker in patients with AD. Ann Neurol 2018;83:387-405.

The goal of the current study was to investigate whether a visual coupling between two people can produce spontaneous interpersonal postural coordination and change their intrapersonal postural coordination involved in the control of stance. We examined the front-to-back head displacements of participants and the angular motion of their hip and ankle during a visual tracking task performed alone and paired. Our results showed that visually paired participants exhibited spontaneous coordination between the movements of their head, hip, and ankle. Moreover, the visual coupling modified the spontaneous intrapersonal ankle-hip coordination dynamics of participants and their performance during visual tracking. Generally, our findings demonstrated reciprocal relations between intrapersonal and interpersonal coordination during social interaction.

Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up. Second, we analysed the longitudinal progression of 18F-DPA-714 binding in patients with Alzheimer's disease by comparison with controls, and assessed its influence on clinical progression. At baseline, all participants underwent a clinical assessment, brain MRI, 11C-PiB, 18F-DPA-714 PET imaging and TSPO genotyping. Participants were followed-up annually for 2 years. At the end of the study, subjects were asked to repeat a second 18F-DPA-714-PET imaging. Initial 18F-DPA-714 binding was higher in prodromal (n = 33) and in demented patients with Alzheimer's disease (n = 19) compared to controls (n = 17). After classifying patients into slow and fast decliners according to functional (Clinical Dementia Rating change) or cognitive (Mini-Mental State Examination score decline) outcomes, we found a higher initial 18F-DPA-714 binding in slow than fast decliners. Negative correlations were observed between initial 18F-DPA-714 binding and the Clinical Dementia Rating Sum of Boxes score increase, the MMSE score loss and the progression of hippocampal atrophy. This suggests that higher initial 18F-DPA-714 binding is associated with better clinical prognosis. Twenty-four patients with Alzheimer's disease and 15 control subjects performed a second DPA-PET. We observed an increase of 18F-DPA-714 in patients with Alzheimer's disease as compared with controls (mean 13.2% per year versus 4.2%) both at the prodromal (15.8%) and at the demented stages (8.3%). The positive correlations between change in 18F-DPA-714 binding over time and the three clinical outcome measures (Clinical Dementia Rating, Mini-Mental State Examination, hippocampal atrophy) suggested a detrimental effect on clinical Alzheimer's disease progression of increased neuroinflammation after the initial PET examination, without correlation with PiB-PET uptake at baseline. High initial 18F-DPA-714 binding was correlated with a low subsequent increase of microglial activation and favourable clinical evolution, whereas the opposite profile was observed when initial 18F-DPA-714 binding was low, independently of disease severity at baseline. Taken together, our results support a pathophysiological model involving two distinct profiles of microglial activation signatures with different dynamics, which differentially impact on disease progression and may vary depending on patients rather than disease stages.