Background: Ubiquitous digital technologies such as smartphone sensors promise to fundamentally change biomedical research and treatment monitoring in neurological diseases such as PD, creating a new domain of digital biomarkers. Objectives: The present study assessed the feasibility, reliability, and validity of smartphone‐based digital biomarkers of PD in a clinical trial setting. Methods: During a 6‐month, phase 1b clinical trial with 44 Parkinson participants, and an independent, 45‐day study in 35 age‐matched healthy controls, participants completed six daily motor active tests (sustained phonation, rest tremor, postural tremor, finger‐tapping, balance, and gait), then carried the smartphone during the day (passive monitoring), enabling assessment of, for example, time spent walking and sit‐to‐stand transitions by gyroscopic and accelerometer data. Results: Adherence was acceptable: Patients completed active testing on average 3.5 of 7 times/week. Sensor‐based features showed moderate‐to‐excellent test‐retest reliability (average intraclass correlation coefficient = 0.84). All active and passive features significantly differentiated PD from controls with P < 0.005. All active test features except sustained phonation were significantly related to corresponding International Parkinson and Movement Disorder Society–Sponsored UPRDS clinical severity ratings. On passive monitoring, time spent walking had a significant (P = 0.005) relationship with average postural instability and gait disturbance scores. Of note, for all smartphone active and passive features except postural tremor, the monitoring procedure detected abnormalities even in those Parkinson participants scored as having no signs in the corresponding International Parkinson and Movement Disorder Society–Sponsored UPRDS items at the site visit. Conclusions: These findings demonstrate the feasibility of smartphone‐based digital biomarkers and indicate that smartphone‐sensor technologies provide reliable, valid, clinically meaningful, and highly sensitive phenotypic data in Parkinson's disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Knowledge of objects in the world is stored in our brains as rich, multimodal representations. Because the neural pathways that process this diverse sensory information are largely anatomically distinct, a fundamental challenge to cognitive neuroscience is to explain how the brain binds the different sensory features that comprise an object to form meaningful, multimodal object representations. Studies with nonhuman primates suggest that a structure at the culmination of the object recognition system (the perirhinal cortex) performs this critical function. In contrast, human neuroimaging studies implicate the posterior superior temporal sulcus (pSTS). The results of the functional MRI study reported here resolve this apparent discrepancy by demonstrating that both pSTS and the perirhinal cortex contribute to crossmodal binding in humans, but in different ways. Significantly, only perirhinal cortex activity is modulated by meaning variables (e.g., semantic congruency and semantic category), suggesting that these two regions play complementary functional roles, with pSTS acting as a presemantic, heteromodal region for crossmodal perceptual features, and perirhinal cortex integrating these features into higher-level conceptual representations. This interpretation is supported by the results of our behavioral study: Patients with lesions, including the perirhinal cortex, but not patients with damage restricted to frontal cortex, were impaired on the same crossmodal integration task, and their performance was significantly influenced by the same semantic factors, mirroring the functional MRI findings. These results integrate nonhuman and human primate research by providing converging evidence that human perirhinal cortex is also critically involved in processing meaningful aspects of multimodal object representations.conceptual knowledge ͉ hierarchical object processing ͉ ventral stream A major outstanding question in the cognitive neurosciences is how different unimodal object features are integrated into coherent, multimodal object representations. Hierarchical models of object processing based on studies with nonhuman primates suggest that the perirhinal cortex, located at the culmination of the ventral occipitotemporal object-processing stream, performs this critical function. Within this stream, increasingly more complex combinations of visual object features are processed from posterior to anterior ventral temporal lobe sites (1-3), with perirhinal cortex of the anteromedial temporal lobe integrating the most complex combinations of features required for fine-grained visual discriminations between objects (4, 5). Recent functional MRI (fMRI) and lesion studies generally support this model in the human system. Lerner et al. (6) demonstrated that the sensitivity of ventral occipitotemporal regions to the scrambling of car images increased significantly from posterior (V1, V2, V3, V4͞V8) to more anteriorly situated sites (lateral occipital sulcus and posterior fusiform gyrus; lateral occipital complex), with scr...

Abstract■ Research on the spatio-temporal dynamics of visual object recognition suggests a recurrent, interactive model whereby an initial feedforward sweep through the ventral stream to prefrontal cortex is followed by recurrent interactions. However, critical questions remain regarding the factors that mediate the degree of recurrent interactions necessary for meaningful object recognition. The novel prediction we test here is that recurrent interactivity is driven by increasing semantic integration demands as defined by the complexity of semantic information required by the task and driven by the stimuli. To test this prediction, we recorded magnetoencephalography data while participants named living and nonliving objects during two naming tasks. We found that the spatio-temporal dynamics of neural activity were modulated by the level of semantic integration required. Specifically, source reconstructed time courses and phase synchronization measures showed increased recurrent interactions as a function of semantic integration demands. These findings demonstrate that the cortical dynamics of object processing are modulated by the complexity of semantic information required from the visual input. ■

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Conceptual representations are at the heart of our mental lives, involved in every aspect of cognitive functioning. Despite their centrality, a long-standing debate persists as to how the meanings of concepts are represented and processed. Many accounts agree that the meanings of concrete concepts are represented by their individual features, but disagree about the importance of different feature-based variables: some views stress the importance of the information carried by distinctive features in conceptual processing, others the features which are shared over many concepts, and still others the extent to which features co-occur. We suggest that previously disparate theoretical positions and experimental findings can be unified by an account which claims that task demands determine how concepts are processed in addition to the effects of feature distinctiveness and co-occurrence. We tested these predictions in a basic-level naming task which relies on distinctive feature information (Experiment 1) and a domain decision task which relies on shared feature information (Experiment 2). Both used large-scale regression designs with the same visual objects, and mixed-effects models incorporating participant, session, stimulusrelated and feature statistic variables to model the performance. We found that concepts with relatively more distinctive and more highly correlated distinctive relative to shared features facilitated basic-level naming latencies, while concepts with relatively more shared and more highly correlated shared relative to distinctive features speeded domain decisions. These findings demonstrate that the feature statistics of distinctiveness (shared vs. distinctive) and correlational strength, as well as the task demands, determine how concept meaning is processed in the conceptual system.