closed-loop-neurostimulation-for-biomarker-driven-personalized

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major ...

University of California, San Francisco

Early studies of deep brain stimulation (DBS) for various neurological disorders involved a temporary trial period where implanted electrodes were externalized, in which the electrical contacts exiting the patient's brain are connected to external stimulation equipment, so that stimulation efficacy could be determined before permanent implant. As the optimal brain target sites for various diseases (i.e., Parkinson's disease, essential tremor) became better established, such trial periods have fallen out of favor. However, deep brain stimulation trial periods are experiencing a modern resurgence for at least two reasons: (1) studies of newer indications such as depression or chronic pain aim to identify new targets and (2) a growing interest in adaptive DBS tools necessitates neurophysiological recordings, which are often done in the peri-surgical period. In this review, we consider the possible approaches, benefits, and risks of such inpatient trial periods with a specific focus on developing new DBS therapies for chronic pain.

A Deep Brain Stimulation Trial Period for Treating Chronic Pain.

Rapid deployment of SARS-CoV-2 testing: The CLIAHUB.

The hippocampus is diversely interconnected with other brain systems along its axis. Cycles of theta-frequency activity are believed to propagate from the septal to temporal pole, yet it is unclear how this one-way route supports the flexible cognitive capacities of this structure. We leveraged novel thin-film microgrid arrays conformed to the human hippocampal surface to track neural activity two-dimensionally in vivo. All oscillation frequencies identified between 1-15 Hz propagated across the tissue. Moreover, they dynamically shifted between two roughly opposite directions oblique to the long axis. This predominant propagation axis was mirrored across participants, hemispheres, and consciousness states. Directionality was modulated in a participant who performed a behavioral task, and it could be predicted by wave amplitude topography over the hippocampal surface. Our results show that propagation directions may thus represent distinct meso-scale network computations, operating along versatile spatiotemporal processing routes across the hippocampal body.

Bidirectional propagation of low frequency oscillations over the human hippocampal surface.

Intracranial neural recordings and electrical stimulation are tools used in an increasing range of applications, including intraoperative clinical mapping and monitoring, therapeutic neuromodulation, and brain computer interface control and feedback. However, many of these applications suffer from a lack of spatial specificity and localization, both in terms of sensed neural signal and applied stimulation. This stems from limited manufacturing processes of commercial-off-the-shelf (COTS) arrays unable to accommodate increased channel density, higher channel count, and smaller contact size.Here, we describe a manufacturing and assembly approach using thin-film microfabrication for 32-channel high density subdural micro-electrocorticography (ECoG) surface arrays (contacts 1.2 mm diameter, 2 mm pitch) and intracranial electroencephalography (iEEG) depth arrays (contacts 0.5 mm × 1.5 mm, pitch 0.8 mm × 2.5 mm). Crucially, we tackle the translational hurdle and test these arrays during intraoperative studies conducted in four humans under regulatory approval.We demonstrate that the higher-density contacts provide additional unique information across the recording span compared to the density of COTS arrays which typically have electrode pitch of 8 mm or greater; 4 mm in case of specially ordered arrays. Our intracranial stimulation study results reveal that refined spatial targeting of stimulation elicits evoked potentials with differing spatial spread.Thin-film,ECoG and iEEG depth arrays offer a promising substrate for advancing a number of clinical and research applications reliant on high-resolution neural sensing and intracranial stimulation.

Article	Year
A Deep Brain Stimulation Trial Period for Treating Chronic Pain. Journal of clinical medicine\| PubMed ID: 33003443	2020
Rapid deployment of SARS-CoV-2 testing: The CLIAHUB. PLoS pathogens\| PubMed ID: 33112933	2020
Bidirectional propagation of low frequency oscillations over the human hippocampal surface. Nature communications\| PubMed ID: 33980852	2021
Thin-film microfabrication and intraoperative testing ofECoG and iEEG depth arrays for sense and stimulation. Journal of neural engineering\| PubMed ID: 34330113	2021
Changes in intracranial neurophysiology associated with acute COVID-19 infection. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 36791656	2023

Kristin K. Sellers

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