Toward meaningful digital measures: efficiency as a core concept of interest

Toward meaningful digital measures: efficiency as a core concept of interest Anoopum Gupta Massachusetts General Hospital Harvard Medical School The ingredients for progress in digital measures Cameras Microphones Wearable devices Motion sensors Touch sensors Deep Learning / Transformers Large Language Models Computer Vision Models Other Time Series Models Disease-modifying therapy development Ubiquitous devices to capture behavior in high resolution Informed, motivated, and organized patient community Powerful computational methods One approach to building digital measures that are meaningful and sensitive 1. Measure natural behaviors that are frequently performed at home (important) 2. Measure behaviors that are relevant across disease stages 3. Identify concepts of interest that are relevant across different behavioral domains and stages of disease Examples: 1. The individual’s choice of limb movements at home 2. Reading aloud Is there a unifying concept for how ataxias impact natural behavior? 1. Natural behaviors become less efficient. Definition of efficiency: • Minimize effort/energy expenditure (including cognitive load) and time • Maximize accuracy (and safety in some contexts) • Maintain flexibility to adapt to changing conditions 2. Efficiency is central to the function of the cerebellum • Cerebellum’s role in prediction and error-based learning • Role in making rapid adaptations to meet demands in diverse environments (Kim et al. 2024, Ann. Rev. Neuro.) 3. Is efficiency a meaningful concept in ataxias? Patients’ words reflect reduced efficiency across behaviors 1. I have to focus more on my daily activities to do them well (e.g., walking/talking/working on a computer). 2. By the end of the day, my speech is slightly slurred. 3. I can still knit, but it takes me longer. 4. I don’t feel comfortable walking without an assistive device outside the house or in a new environment. 5. Sometimes I have to repeat myself for others to understand me. My speech therapist tells me to slow down and concentrate on my breathing. 6. I no longer enjoy reading because I lose my place on the page and sometimes see double — it takes longer and more effort to read. 7. My handwriting is messy, I need a letter saying that my signature has changed due to my disease. 8. My bedroom is on the second floor and it is challenging to leave the house. 9. I don’t see my friends anymore because it is hard for them to understand me. Increasing the efficiency of natural, everyday behaviors, is inherently and objectively meaningful for ataxias Limb movement during natural behavior is less efficient in ataxias 1. Movements become slower, less accurate, and decomposed into smaller units 2. Reflected at the movement building block level (i.e., submovements) Analysis of natural behavior using wearable sensors Gupta et al. 2022, Cerebellum - ataxia telangiectasia Eklund et al. 2023, Brain Communications - SCAs and MSA-C Gupta et al. 2023, Nature Communications - ALS Manohar et al. 2025, Brain - SCAs and MSA-C Gupta and Patel. 2025, npj Parkinson’s disease - Parkinson’s Sensor outcomes in SCAs and MSA-C Manohar et al. 2025, Brain - SCAs and MSA-C Gupta et al. 2023, Nature Communications - ALS *ALS Model trained on data from individuals with ALS Top composite score features represent efficiency: 1. Submovement peak velocity 2. Submovement distance Longitudinal Analysis Extra Slides Efficiency is a generally meaningful concept 1. More efficient movement translates to: • “With the same amount of time and effort, I can do more things I care about” • “I can accomplish the same amount with less time and effort” 2. Human movement and speech/language have evolved under pressures favoring efficient performance. Bramble & Lieberman 2004; Lindblom 1990 3. Societies and industries have evolved to be more efficient.