ABSTRACT
Alzheimer's Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.
ABSTRACT
INTRODUCTION: The application of digital monitoring biomarkers in health, wellness and disease management is reviewed. Harnessing the near limitless capacity of these approaches in the managed healthcare continuum will benefit from a systems-based architecture which presents data quality, quantity, and ease of capture within a decision-making dashboard. METHODS: A framework was developed which stratifies key components and advances the concept of contextualized biomarkers. The framework codifies how direct, indirect, composite, and contextualized composite data can drive innovation for the application of digital biomarkers in healthcare. RESULTS: The de novo framework implies consideration of physiological, behavioral, and environmental factors in the context of biomarker capture and analysis. Application in disease and wellness is highlighted, and incorporation in clinical feedback loops and closed-loop systems is illustrated. CONCLUSIONS: The study of contextualized biomarkers has the potential to offer rich and insightful data for clinical decision making. Moreover, advancement of the field will benefit from innovation at the intersection of medicine, engineering, and science. Technological developments in this dynamic field will thus fuel its logical evolution guided by inputs from patients, physicians, healthcare providers, end-payors, actuarists, medical device manufacturers, and drug companies.
ABSTRACT
Neuroprosthetics using intracortical microstimulation can potentially alleviate sensory deprivation due to injury or disease. However the information bandwidth of a single microstimulation channel remains largely unanswered. This paper presents three experiments that examine the importance of Peak Power/Charge and RMS Power/Charge for detection of acoustic and electrical Sinusoidal Amplitude Modulated stimuli by the auditory system. While the peripheral auditory system is sensitive to RMS power cues for the detection of acoustic stimuli, here we provide results that suggest that the auditory cortex is sensitive to peak charge cues for electrical stimuli. Varying the modulation frequency and depth do not change this effect for detection of modulated electrical stimuli.
Subject(s)
Auditory Perception/physiology , Electricity , Signal Processing, Computer-Assisted , Acoustic Stimulation , Acoustics , Animals , Auditory Cortex/physiology , Cues , Electric Stimulation , Male , Rats , Rats, Sprague-DawleyABSTRACT
In the development of sensory prosthetic devices based on intracortical microstimulation (ICMS) an important objective is to optimize the stimulus waveform. However, because of the large design space such optimization is an imposing challenge. This study highlights the ability of individual rats, trained using a conditioned avoidance paradigm and performing an adaptive task, to generate highly consistent and significant data. Three experiments on the effects of phase delay, stimulus pulse rate, and waveform asymmetry were completed and revealed detailed and significant results. These results, consisting of 244 individual thresholds, were generated by one rat in 19 days.
