IMPORTANCE Current Parkinson disease (PD) measures are subjective, rater-dependent, and assessed in clinic. Smartphones can measure PD features, yet no smartphone-derived rating score exists to assess motor symptom severity in real-world settings.OBJECTIVES To develop an objective measure of PD severity and test construct validity by evaluating the ability of the measure to capture intraday symptom fluctuations, correlate with current standard PD outcome measures, and respond to dopaminergic therapy. DESIGN, SETTING, AND PARTICIPANTSThis observational study assessed individuals with PD who remotely completed 5 tasks (voice, finger tapping, gait, balance, and reaction time) on the smartphone application. We used a novel machine-learning-based approach to generate a mobile Parkinson disease score (mPDS) that objectively weighs features derived from each smartphone activity (eg, stride length from the gait activity) and is scaled from 0 to 100 (where higher scores indicate greater severity). Individuals with and without PD additionally completed standard in-person assessments of PD with smartphone assessments during a period of 6 months. MAIN OUTCOMES AND MEASURESAbility of the mPDS to detect intraday symptom fluctuations, the correlation between the mPDS and standard measures, and the ability of the mPDS to respond to dopaminergic medication. RESULTSThe mPDS was derived from 6148 smartphone activity assessments from 129 individuals (mean [SD] age, 58.7 [8.6] years; 56 [43.4%] women). Gait features contributed most to the total mPDS (33.4%). In addition, 23 individuals with PD (mean [SD] age, 64.6 [11.5] years; 11 [48%] women) and 17 without PD (mean [SD] age 54.2 [16.5] years; 12 [71%] women) completed in-clinic assessments. The mPDS detected symptom fluctuations with a mean (SD) intraday change of 13.9 (10.3) points on a scale of 0 to 100. The measure correlated well with the Movement Disorder Society Unified Parkinson Disease's Rating Scale total (r = 0.81; P < .001) and part III only (r = 0.88; P < .001), the Timed Up and Go assessment (r = 0.72; P = .002), and the Hoehn and Yahr stage (r = 0.91; P < .001). The mPDS improved by a mean (SD) of 16.3 (5.6) points in response to dopaminergic therapy. CONCLUSIONS AND RELEVANCEUsing a novel machine-learning approach, we created and demonstrated construct validity of an objective PD severity score derived from smartphone assessments. This score complements standard PD measures by providing frequent, objective, real-world assessments that could enhance clinical care and evaluation of novel therapeutics.
Neurological disorders are the leading cause of global disability. However, for most people around the world, current neurological care is poor. In low-income countries, most individuals lack access to proper neurological care, and in high-income countries, distance and disability limit access. With the global proliferation of smartphones, teleneurology - the use of technology to provide neurological care and education remotely - has the potential to improve and increase access to care for billions of people. Telestroke has already fulfilled this promise, but teleneurology applications for chronic conditions are still in their infancy. Similarly, few studies have explored the capabilities of mobile technologies such as smartphones and wearable sensors, which can guide care by providing objective, frequent, real-world assessments of patients. In low-income settings, teleneurology can increase the capacity of local care systems through professional development, diagnostic support and consultative services. In high-income settings, teleneurology is likely to promote the expansion and migration of neurological care away from institutions, incorporate systems of asynchronous communication (such as e-mail), integrate clinicians with diverse skill sets and reach new populations. Inertia, outdated policies and social barriers - especially the digital divide - will slow this progress at considerable cost. However, a future increasingly will be possible in which neurological care can be accessed by anyone, anywhere. Here, we examine the emerging evidence regarding the benefits of teleneurology for chronic conditions, its role and risks in low-income countries and the promise of mobile technologies to measure disease status and deliver care. We conclude by discussing the future trends, barriers and timing for the adoption of teleneurology.
To explore theories of predictive coding, we presented mice with repeated sequences of images with novel images sparsely substituted. Under these conditions, mice could be rapidly trained to lick in response to a novel image, demonstrating a high level of performance on the first day of testing. Using 2-photon calcium imaging to record from layer 2/3 neurons in the primary visual cortex, we found that novel images evoked excess activity in the majority of neurons. When a new stimulus sequence was repeatedly presented, a majority of neurons had similarly elevated activity for the first few presentations, which then decayed to almost zero activity. The decay time of these transient responses was not fixed, but instead scaled with the length of the stimulus sequence. However, at the same time, we also found a small fraction of the neurons within the population (~2%) that continued to respond strongly and periodically to the repeated stimulus. Decoding analysis demonstrated that both the transient and sustained responses encoded information about stimulus identity. We conclude that the layer 2/3 population uses a two-channel predictive code: a dense transient code for novel stimuli and a sparse sustained code for familiar stimuli. These results extend and unify existing theories about the nature of predictive neural codes.
ObjectiveTo determine the frequency and relative importance of symptoms experienced by adults with Huntington disease (HD) and to identify factors associated with a higher disease burden.MethodsWe performed 40 qualitative interviews (n = 20 with HD, n = 20 caregivers) and analyzed 2,082 quotes regarding the symptomatic burden of HD. We subsequently performed a cross-sectional study with 389 participants (n = 156 with HD [60 of whom were prodromal], n = 233 caregivers) to assess the prevalence and relative importance (scale 0–4) of 216 symptoms and 15 symptomatic themes in HD. Cross-correlation analysis was performed based on sex, disease duration, age, number of CAG repeats, disease burden, Total Functional Capacity score, employment status, disease status, and ambulatory status.ResultsThe symptomatic themes with the highest prevalence in HD were emotional issues (83.0%), fatigue (82.5%), and difficulty thinking (77.0%). The symptomatic themes with the highest relative importance to participants were difficulty thinking (1.91), impaired sleep or daytime sleepiness (1.90), and emotional issues (1.81). High Total Functional Capacity scores, being employed, and having prodromal HD were associated with a lower prevalence of symptomatic themes. Despite reporting no clinical features of the disease, prodromal individuals demonstrated high rates of emotional issues (71.2%) and fatigue (69.5%). There was concordance between the prevalence of symptoms reported by manifest individuals and caregivers.ConclusionsMany symptomatic themes affect the lives of those with HD. These themes have a variable level of importance to the HD population and are identified both by those with HD and by their caregivers.
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