What are the current options for monitoring the rapid cognitive and affective changes in epilepsy patients so as to assess the influence of time-dynamic factors, for example, DBS, seizures, pharmacological polytherapy, and its titration? The monitoring and treatment of epilepsy patients can be significantly improved by using digital biomarkers and cognitive proxies that are automatically recorded by smart devices such as smart watches, smart phones, and smart rings. These technologies enable continuous and discrete monitoring and provide important insights into patients’ motor and cognitive functioning.

Here, we list some examples of candidate digital biomarkers and proxies, some of which are already being used in smart devices. It is important to distinguish digital cognitive proxies from biomarkers. Biomarkers focus on measuring physical parameters associated with biological activity, such as movement or heart rate. By contrast, digital cognitive proxies infer mental capacity from the speed, results, and errors in cognitive tasks such as navigation, memory (codes, names, shortcuts), reading speed, and writing errors. A further distinction must be made between active and passive biomarkers and proxies. Active biomarkers and proxies act as tasks to be completed by the individual and have similarities to psychological performance tests. On the other hand, passive biomarkers, which are often more readily accepted by patients, collect information about the user’s cognitive and sensorimotor status through signals and parameters continuously derived from regular user behavior.

A.

Passive measurement strategies

1.

Seizure detection: Modern smartwatches and smartphones are equipped with accelerometers and gyroscopes that can detect motor seizures by identifying unusual or repetitive movement patterns. These devices also have the ability to record atypical vocalizations and heart rate patterns, providing a comprehensive approach to seizure monitoring.

2.

Heart rate variability, blood pressure, pulse oximetry: Smartwatches and, more recently, smart rings are capable of monitoring various cardiovascular biomarkers, providing valuable data on sudden changes that may signal the onset of certain seizure types, particularly autonomic seizures.

3.

Sleep pattern analysis: Given the prevalence of sleep disorders in individuals with epilepsy, smart devices play a critical role in monitoring sleep patterns. This technology can detect sleep irregularities that may indicate an increased risk of seizures or the occurrence of seizures during sleep.

4.

Macroscopic movement patterns: Analysis of topographic movement patterns, including changes in movement speed, unusual asymmetry, variations in the duration of bipedal support, and deviations from routine activities, can reveal potential epileptic events and the effects of treatment interventions such as DBS.

5.

Microscopic movement patterns: Examining subtle changes in tapping and swiping movements on smartphones can reveal cerebral dysfunction and tremors. These microscopic patterns of movement during smartphone interaction correlate with epileptiform activity as registered on EEG. They may also indicate side effects of ASM adjustments [8].

6.

Alterations in oral communication: This encompasses a range of speech and language disturbances, including variations in prosody, the presence of dysarthria, difficulties with word retrieval, changes in sentence construction, and changes in overall length and frequency of speech, providing parametric descriptions of symptom severity. Such symptoms may be associated with expressive language impairments involving both frontal and temporal lobes.

7.

Alterations in written communication: This includes a range of changes that affect the ability to communicate in written form, such as challenges with word retrieval, adherence to grammatical norms, sentence structure, and consistency in the length and frequency of written language. Other indicators include variations in reading and writing speed, increased incidence of spelling errors and overall fluency. Although fluctuations in attention play a role, these changes are especially symptomatic of expressive language disturbances affecting frontal and temporal regions.

8.

Smartphone camera detection of oculomotor abnormalities: Use of the smartphone camera to observe oculomotor irregularities during standardized interactions. Such abnormalities, including deviations in saccades, smooth pursuit movements, fixation stability, convergence ability, and the presence of nystagmus, may indicate underlying neural dysfunction. These may result from lesions, seizure activity, or adverse reactions to ASM. The ALTOIDA app is at the forefront of this application [9].

9.

Monitoring through smartphone games: Analyzing changes in playing frequency and performance in smartphone games such as Candy Crush or Chess (as assessed by ELO ratings) can serve as measures to assess cognitive and sensorimotor function. Significant changes in gaming behavior not only reflect potential impairments in these areas, but may also indicate shifts in an individual’s drive and motivation. This approach provides a noninvasive, engaging way to monitor through enjoyable everyday activities.

10.

Combined integrated measures: Modern smart devices are capable of capturing a wide range of digital biomarkers and cognitive proxies over different time scales. The key challenge is to distinguish clinically relevant biomarkers from those that are not. Achieving this distinction requires thorough validation studies to establish the reliability and relevance of each biomarker. At the same time, artificial intelligence (AI) plays a critical role in streamlining the vast data landscape to enable more efficient and accurate analysis. The Altoida app exemplifies this approach by using AI to evaluate over 800 biomarkers across 13 functional domains [9]. This integration of AI and digital biomarkers paves the way for potential breakthroughs in personalized medicine and diagnostic precision.

B.

Active measurement strategies

11.

Gamification of cognitive assessments via smart devices: Transform traditional cognitive tests by incorporating elements of gamification into smart device-based test tasks. This approach may target key cognitive areas on a daily or weekly basis such as memory and executive function, engaging users in a more interactive and enjoyable testing experience.

12.

Surveys on well-being and complaints to assess quality of life (QoL): Utilize comprehensive surveys delivered through smart devices on a daily, weekly, or monthly basis to gauge individual well-being and specific health complaints.

13.

Explicit sensorimotor tasks: Implement a variety of explicit sensorimotor tasks within smart device platforms on a daily to weekly basis to monitor individually defined sensorimotor domains.

The use of digital biomarkers and cognitive proxies, as outlined earlier, represents a promising avenue for personalized monitoring of neurocognitive and sensorimotor functions in patients with epilepsy. Although these cognitive proxies are not intended to replace comprehensive traditional neuropsychological assessment, they can significantly enhance neuropsychological diagnostics. They do so by providing insight into performance variability within specific functional domains that may be influenced by transient pathogenic events such as epileptic activity. However, the effective integration of these tools into clinical practice depends on rigorous longitudinal validation studies. These studies must include repeated administration of a full neuropsychological test battery to identify the most specific and sensitive cognitive proxies in the relevant functional domains.

A pioneering approach to comprehensive smartphone-based monitoring of cognitive and sensorimotor functions for diagnostic purposes is the development of the ALTOIDA app (altoida.com 80 M Street SE, Suite 100 Washington, DC 20003 USA). This application, designed to assess an individual’s risk of developing Alzheimer’s dementia, incorporates both active and passive biomarkers. Its effectiveness and reliability have been demonstrated in a longitudinal validation study conducted alongside standard neuropsychological tests. This highlights the potential of such technologies to revolutionize diagnostics in neurological disciplines.

However, the development and use of digital biomarkers and cognitive proxies requires strict adherence to national and international privacy standards. As the continuous monitoring of patient behavior through these technologies represents a significant intrusion into personal privacy, ensuring robust data protection measures is paramount. This is particularly critical in the expanding realm of global digital interactions, where the protection of patient privacy must be a priority. Such ethical considerations are integral to the responsible development and application of digital health monitoring tools in neurology and beyond.