Invasive neurostimulation is a promising therapy for psychiatric disease, but with contemporary neurostimulation techniques, many patients in recent clinical trials have been nonresponders. For improved efficacy, invasive therapies in psychiatry may require a more advanced circuit-level understanding of these disorders, so as to target specific patterns of abnormal neural activity. In support of this concept, short term invasive recordings have revealed potential physiological biomarkers of specific psychiatric symptoms such as depression and anxiety. Signal discovery and circuit analysis will be further facilitated by newly available, chronically implantable, neural interfaces that can both deliver neurostimulation and wirelessly stream sensed electrical activity to external computers. These devices ? such as the responsive neurostimulaor (RNS, Neuropace) or Summit RC+S (Medtronic) have great potential for longitudinal correlations of psychiatric symptoms with neural activity. However, the permanently implantable cortical leads currently available to attach to these interfaces pose technical barriers to easy, safe surgical placement and signal discovery. Available cortical recording leads have a low channel count (4 contacts) low spatial resolution (1 cm), and are mechanically inflexible, precluding access to many cortical areas. Here, we address this problem by designing, fabricating, and testing cortical leads with mechanical properties favorable for the passage of leads through minimally invasive exposures. Testing will involve both benchtop tests and short term intraoperative human testing. Two lead designs will be fabricated and tested, one with lower channel count for multisite cortical recording, another with double the currently available channel count (8 contacts) and improved spatial resolution. These leads are designed to attach to Summit RC+S, under collaborative agreement with the neural interface manufacturer. The PIs bring complementary expertise to this project: electrical engineering with a specialty in brain lead fabrication; and neurosurgery/neurophysiology with a specialty in acute and chronic cortical recording (electrocorticography) for detection of physiological signatures of brain disorders. After this 2 year grant period, we expect to pursue biocompatibility testing and FDA approval for permanent implantation, and commercialization. The proposed work will facilitate the deployment of newly available neural interfaces, both for circuit analysis and for the development of ?adaptive stimuluation?, in which neural signals are used to autoregulate stimulation parameters, to respond to changing brain needs and reduce stimulation- induced adverse effects.

Public Health Relevance

Invasive recording (sensing) from the cortex of the brain is a promising method to detect signals related to psychiatric symptoms, a capability critical for the development of new neurostimulation therapies. While there are now implantable neurostimulators that incorporate a sensing capability, the available leads for cortical recording have too few channels and are mechanically difficult to insert through small skull openings. Here we develop new leads with greater channel count and more favorable mechanical properties for placement over the cortex through a single small surgical exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH120810-01
Application #
9828280
Study Section
Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section (BNVT)
Program Officer
Mcmullen, David
Project Start
2019-09-10
Project End
2021-06-30
Budget Start
2019-09-10
Budget End
2020-06-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118