WHAT'S NEW IN 2024 FROM THE DEEP BRAIN STIMULATION THINK TANK XII: UPDATES IN NEUROTECHNOLOGY AND NEUROMODULATION, VOLUME V

Alfonso Enrique Martinez-Nunez^1*Sarah-Anna Hescham²Adolfo Ramirez-Zamora¹Michael S Okun¹Joshua K Wong¹

• ¹Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Alabama, United States
• ²School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, Netherlands

Neuromodulation has been fully integrated into clinical practice since the FDA approved deep brain stimulation (DBS) for the treatment of tremor almost three decades ago. Using the concepts learned from DBS, like network-based targeting, biophysical modeling of neuronal stimulation, and electrical stimulation settings, other forms of neuromodulation have been developed and are rapidly expanding and transforming current therapies. Since 2012, the DBS Think Tank has held annual meetings that gather the leading experts in the field of neuromodulation to discuss future directions and collaborations to exploit novel technologies with an overarching goal to advance the methods and outcomes of neuromodulation. This year's XII Think Tank expanded its scope to discuss advances in DBS clinical applications for movement disorders, stroke, traumatic brain injury, sleep, epilepsy, and neuropsychiatric disorders. The discussions included current and upcoming devices for DBS, as well as novel techniques like MRI-guided focused ultrasound stimulation and nanomaterial magnetic stimulation. Finally, the ethical implications of chronic device implantation, abandonment and changes in agency and behavioral patterns were discussed. To reach a global audience of neuromodulation researchers, we publish the proceedings of the meeting each year (Martinez-Nunez et al., 2025) and the recordings of the discussions (Deep Brain Stimulation Think Tank, 2024) are made public (based on consent of lecturers).In this editorial we provide an overview of the articles included in the fifth volume of the Deep Brain Stimulation Think Tank collection. This collection is published every year with the support of the Frontiers Editorial Office and includes publications on the recent advances in neuromodulation. This volume will cover personalized stimulation for epilepsy, troubleshooting DBS for essential tremor, comparing intraoperative stimulation with the monopolar review, and computational models of temporal interference stimulation.Suresh et al describe a case of a patient with juvenile myoclonic epilepsy implanted with DBS in the centromedian nucleus of the thalamus (CM) (Suresh et al., 2024, p. 20). They studied sleep architecture using asleep electroencephalography (EEG) and compared high stimulation frequency (125 Hz) to low stimulation frequency (10 Hz) during sleep. They found a severely disrupted sleep architecture and a higher burden of seizures using high frequency stimulation. When switching to low frequency stimulation during sleep, they noted improvement in sleep architecture organization, better sleep quality, and lower seizure burden.The stimulation parameters used in DBS for epilepsy were derived from the SANTE trial for anterior nucleus of the thalamus stimulation (Fisher et al., 2010). This trial used a standardized stimulation frequency of 140 Hz, therefore most clinical programing is done at this high-frequency settings. The case presented by Suresh et al exemplifies how potentially engaging different brain network can lead to different side effects, such as sleep disruption, and this must be addressed on a case-by-case basis.Troubleshooting DBS for essential tremor.DBS in the ventral intermedius nucleus of the thalamus (Vim) for essential tremor has increased in efficacy and complexity since its FDA approval. With an increasing number of possibilities for DBS programming, we now have more strategies to maintain good clinical benefit despite gradual disease progression. Some of these strategies include changes in stimulation amplitude and pulse width, change in omnidirectional contacts, directional stimulation, bipolar stimulation, and interleaving stimulation.Martinez-Nunez et al wrote a review for this volume that covers the most common chronic stimulationinduced side effects from Vim-DBS, including dysarthria, dysphagia, ataxia, and gait impairment. The review is summarized with three figures that can be used for reference in the clinic and for teaching sessions.It is common to perform a monopolar review in the operating room after a DBS lead is placed to ensure adequate lead position, appropriate therapeutic window to facilitate effective stimulation without the unintended consequence of stimulation-induced side effects (Sammartino et al., 2020). To ensure that the stimulation ranges used in the operating room are comparable to the ones used in the clinic, the stimulation paradigm must closely resemble the chronic stimulation paradigm used by the implantable pulse generator (IPG) that is connected to the DBS lead.Mampre et al compared two different forms of charge balancing: active recharge, and passive recharge. Both are methods to ensure that there is no charge accumulation in nerve tissue that can potentially lead to damage. The authors uncovered the thresholds for stimulation-induced side effects using passive-recharge were most similar to the ones encountered in the clinic while stimulating from the IPG.Most importantly, they found that both methods of charge balancing resulted in a significant decrease in the stimulation amplitude required to elicit stimulation-induced side effects when compared to the monopolar review in the clinic. They found a mean decrease of 0.8 mA for passive-recharge, and 1.2 for active-recharge. This so-called "threshold contraction" is seen in clinical practice and it is often attributed to acute edema around the lead during the intraoperative stimulation testing. It usually resolves after several days following the implantation (Borellini et al., 2019). These numbers can serve as clear guidance to estimate use in clinical programing and in shared decision making; whether the expected therapeutic range is good enough, or if the lead should be intra-operatively repositioned.Non-invasive brain stimulation methods are becoming more effective and precise, and several studies have demonstrated significant clinical changes. It has become more important to determine precisely what structures are being stimulated with these techniques. Studies in humans have revealed changes in functional magnetic resonance imaging after transcranial temporal interference stimulation (tTIS), demonstrating modulation of neuronal tissue, although we must appreciate that its spatial resolution and the current intensity needed to effectively modulate brain circuitry remains unclear (Violante et al., 2023).To explore this phenomenon, Karimi et al compared the ability of tTIS and transcranial alternating current stimulation (tACS) to modulate a computational neuron model emulating excitatory and inhibitory neurons. Their modeling of tTIS revealed that superficial brain regions can be stimulated and entrained, and this includes the deep brain regions where the current from both stimulation sources overlap. They also uncovered that tTIS requires a significantly higher current intensity than tACS to entrain the neuronal model. Together these findings suggest that when considering a whole-brain model where the target is deep, tTIS has less spatial resolution and less stimulation efficacy than previously concluded, based on single-cell models.Advancements in neurotechnology continue to shape and develop clinical management to improve long term patient care and outcomes. Advances in DBS programing require a precise and personalized approach to lead implantation and programing. Non-invasive stimulation is becoming not only a potential treatment for neurological diseases, but also a powerful tool to study brain circuits.