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Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of ‘network-guided neuromodulation’ for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key ‘propagation points’ in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points — including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients’ individual epileptogenic networks.

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.

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.

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.