ABSTRACT
Digital health can drive patient-centric innovation in neuromodulation by leveraging current tools to identify response predictors and digital biomarkers. Iterative technological evolution has led us to an ideal point to integrate digital health with neuromodulation. Here, we provide an overview of the digital health building-blocks, the status of advanced neuromodulation technologies, and future applications for neuromodulation with digital health integration.
ABSTRACT
Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome.
Subject(s)
Autistic Disorder/etiology , Epilepsy/etiology , Prenatal Exposure Delayed Effects/physiopathology , Stress, Psychological/physiopathology , Sympathomimetics/toxicity , Terbutaline/toxicity , Age Factors , Animals , Animals, Newborn , Disease Models, Animal , Female , Glial Fibrillary Acidic Protein/metabolism , Gliosis/pathology , Hippocampus/pathology , Pregnancy , Rats , Rats, Sprague-Dawley , Severity of Illness Index , Social Behavior , Vocalization, AnimalABSTRACT
Magnetoencephalography has long held the promise of providing a noninvasive tool for localizing epileptic seizures in humans because of its high spatial resolution compared with the scalp EEG. Yet, this promise has been elusive, not because of a lack of sensitivity or spatial resolution but because the large size and immobility of present cryogenic (superconducting) technology prevent long-term telemetry required to capture these very infrequent epileptiform events. To circumvent this limitation, we used Micro-Electro-Mechanical Systems technology to construct a noncryogenic (room temperature) microfabricated atomic magnetometer ("magnetrode") based on laser spectroscopy of rubidium vapor and similar in size and flexibility to scalp EEG electrodes. We tested the magnetrode by measuring the magnetic signature of epileptiform discharges in a rat model of epilepsy. We were able to measure neuronal currents of single epileptic discharges and more subtle spontaneous brain activity with a high signal-to-noise ratio approaching that of present superconducting sensors. These measurements are a promising step toward the goal of high-resolution noninvasive telemetry of epileptic events in humans with seizure disorders.
