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Adaptive deep brain stimulation (aDBS) is a promising concept for feedback-based neurostimulation, with the potential of clinical implementation with the sensing-enabled Percept neurostimulator. We aim to characterize chronic electrophysiological activity during stimulation and to validate beta-band activity as a biomarker for bradykinesia. Subthalamic activity was recorded during stepwise stimulation amplitude increase OFF medication in 10 Parkinson’s patients during rest and finger tapping. Offline analysis of wavelet-transformed beta-band activity and assessment of inter-variable relationships in linear mixed effects models were implemented. There was a stepwise suppression of low-beta activity with increasing stimulation intensity (p = 0.002). Low-beta power was negatively correlated with movement speed and predictive for velocity improvements (p p

BackgroundBeta band activity in the subthalamic local field potential (LFP) is correlated with Parkinson’s disease (PD) symptom severity, and is the therapeutic target and feedback signal for adaptive deep brain stimulation (aDBS). While clinically relevant beta fluctuations in PD patients are well characterised on shorter timescales and in the clinic, it is not known how beta activity evolves around the diurnal cycle, outside a clinical setting.ObjectiveTo characterise diurnal fluctuations in beta amplitude in PD patients receiving continuous, high frequency DBS.MethodsWe obtained chronic recordings (34±13 days) of subthalamic beta power in PD patients implanted with the Percept DBS device during high-frequency DBS, and analysed its diurnal properties. To investigate the influence of non-frequency-specific effects and artifacts, we compared beta to contralateral theta amplitude and recorded LFPs during various movements.ResultsBeta power had strong 24-hour periodicity, and time of day explained 41±9% of the variance in all long-term beta power recordings (pConclusionsDiurnal fluctuations in beta amplitude will need to be accommodated in aDBS to prevent suboptimal stimulation, particularly at night. Careful screening and/or mitigation of movement artifacts is needed to ensure that the signal is suitable for adaptive stimulation or neurophysiological investigation.

Evoked resonant neural activity (ERNA) is induced by subthalamic deep brain stimulation (DBS) and was recently suggested as a marker of lead placement and contact selection in Parkinson's disease. Yet, its underlying mechanisms and how it is modulated by stimulation parameters are unclear. Here, we recorded local field potentials from 27 Parkinson's disease patients, while leads were externalised to scrutinise the ERNA. First, we show that ERNA in the time series waveform and spectrogram likely represent the same activity, which was contested before. Second, our results show that the ERNA has fast and slow dynamics during stimulation, consistent with the synaptic failure hypothesis. Third, we show that ERNA parameters are modulated by different DBS frequencies, intensities, medication states and stimulation modes (continuous DBS vs. adaptive DBS). These results suggest the ERNA might prove useful as a predictor of the best DBS frequency and lowest effective intensity in addition to contact selection. Changes with levodopa and DBS mode suggest that the ERNA may indicate the state of the cortico-basal ganglia circuit making it a putative biomarker to track clinical state in adaptive DBS.

Epilepsy is one of the most common neurological disorders, and it affects almost 1% of the population worldwide. Many people living with epilepsy continue to have seizures despite anti-epileptic medication therapy, surgical treatments, and neuromodulation therapy. The unpredictability of seizures is one of the most disabling aspects of epilepsy. Furthermore, epilepsy is associated with sleep, cognitive, and psychiatric comorbidities, which significantly impact the quality of life. Seizure predictions could potentially be used to adjust neuromodulation therapy to prevent the onset of a seizure and empower patients to avoid sensitive activities during high-risk periods. Long-term objective data is needed to provide a clearer view of brain electrical activity and an objective measure of the efficacy of therapeutic measures for optimal epilepsy care. While neuromodulation devices offer the potential for acquiring long-term data, available devices provide very little information regarding brain activity and therapy effectiveness. Also, seizure diaries kept by patients or caregivers are subjective and have been shown to be unreliable, in particular for patients with memory-impairing seizures. This paper describes the design, architecture, and development of the Mayo Epilepsy Personal Assistant Device (EPAD). The EPAD has bi-directional connectivity to the implanted investigational Medtronic Summit RC+STM device to implement intracranial EEG and physiological monitoring, processing, and control of the overall system and wearable devices streaming physiological time-series signals. In order to mitigate risk and comply with regulatory requirements, we developed a Quality Management System (QMS) to define the development process of the EPAD system, including Risk Analysis, Verification, Validation, and protocol mitigations. Extensive verification and validation testing were performed on thirteen canines and benchtop systems. The system is now under a first-in-human trial as part of the US FDA Investigational Device Exemption given in 2018 to study modulated responsive and predictive stimulation using the Mayo EPAD system and investigational Medtronic Summit RC+STM in ten patients with non-resectable dominant or bilateral mesial temporal lobe epilepsy. The EPAD system coupled with an implanted device capable of EEG telemetry represents a next-generation solution to optimizing neuromodulation therapy.

There is growing interest in using adaptive neuro-modulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the, ‘Picostim DyNeuMo Mk-1’, (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient’s movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.

Collaborative efforts between basic scientists, engineers, and clinicians are enabling translational epileptology. In this article, we summarize the recent advances presented at the International Conference for Technology and Analysis of Seizures (ICTALS 2022): (1) novel developments of structural magnetic resonance imaging; (2) latest electroencephalography signal-processing applications; (3) big data for the development of clinical tools; (4) the emerging field of hyperdimensional computing; (5) the new generation of artificial intelligence (AI)-enabled neuroprostheses; and (6) the use of collaborative platforms to facilitate epilepsy research translation. We highlight the promise of AI reported in recent investigations and the need for multicenter data-sharing initiatives.