The μDBS: Multiresolution, Directional Deep Brain Stimulation for Improved Targeting of Small Diameter Fibers

Abstract

Directional deep brain stimulation (DBS) leads have recently been approved and used in patients, and growing evidence suggests that directional contacts can increase the therapeutic window by redirecting stimulation to the target region while avoiding side-effect-inducing regions. We outline the design, fabrication, and testing of a novel directional DBS lead, the μDBS, which utilizes microscale contacts to increase the spatial resolution of stimulation steering and improve the selectivity in targeting small diameter fibers. We outline the steps of fabrication of the μDBS, from an integrated circuit design to post-processing and validation testing. We tested the onboard digital circuitry for programming fidelity, characterized impedance for a variety of electrode sizes, and demonstrated functionality in a saline bath. In a computational experiment, we determined that reduced electrode sizes focus the stimulation effect on small, nearby fibers. Smaller electrode sizes allow for a relative decrease in small-diameter axon thresholds compared to thresholds of large-diameter fibers, demonstrating a focusing of the stimulation effect within small, and possibly therapeutic, fibers. This principle of selectivity could be useful in further widening the window of therapy. The μDBS offers a unique, multiresolution design in which any combination of microscale contacts can be used together to function as electrodes of various shapes and sizes. Multiscale electrodes could be useful in selective neural targeting for established neurological targets and in exploring novel treatment targets for new neurological indications.

Keywords: computational modeling; deep brain stimulation; directional electrodes; electrode fabrication; neural targeting.

FIGURE 1

(A) Clinical deep brain stimulation electrode (left) with four contacts, and the μDBS (right) with hundreds of contacts. (B) The μDBS electrode is assembled from four total flat chips, with two flat chips paired back to back. The paired chips are assembled together to form a “+” shape when viewed from above.

FIGURE 2

Design and simulation of a single contact unit on the μDBS. (A) Single contact circuit diagram with three-bit digital logic for the gating of seven bus lines. (B) Simulation demonstrating programming of different bus lines on a single contact in Cadence ADE XL. With the example bit stream, 011101000, we demonstrate programming the flip flop states at the falling phase of the clock signal. (C) Integrated circuit layout design of a single contact used in the simulation (left), post-fabrication view of the VLSI design (middle), and view of contact after gold application in post-processing (right). Note that for any moment in time, at most 1 of the 7 bus lines can be connected to a contact (large, bright gold square at right) through one of its three subcontact conduits (small, dull white squares shown in the middle panel).

FIGURE 3

Design architecture for μDBS post-processing. Fabricated chips (0) undergo gold deposition (1) and are covered with AZ nLoF 2020 negative photoresist (2). Photoresist is exposed to UV light according to the desired contact layout through a photolithography mask and regions of photoresist not exposed to light are removed (3). Gold and titanium layers are etched away from regions not covered by photoresist to define the gold contacts (4). Remaining photoresist is washed off (5) and the chips are diced to the appropriate size (6). Connection pads are wirebonded to test PCBs (7) to enable device programming and functionality testing. Silicone was used to insulate non-contact regions from water exposure during the validation experiments.

FIGURE 4

μDBS experimental and computational setup. (A) Experimental setup for programming requires only input/output information from the μDBS chip interfaced with the Arduino and computer. (B) Impedance testing requires a potentiostat connected to one bus line of the μDBS, a Pt counter wire, and an Ag/AgCl reference wire in a saline bath. (C) Bath testing uses a CNC machine to move a voltage probe in the saline bath around the μDBS. Voltage recordings run through a peak detection circuit and on to the Arduino for recording. (D) A lead-in-the-box model was used to simulate the voltage spread; multicompartment models were used to measure the effects of contact size on activation for 2.0, 5.7, and 10.0 μm diameter axons.

FIGURE 5

Programming validation of μDBS chips. (A) Characterization of contact errors for 10 μDBS chips across 30 trials each, with incorrectly programmed contacts denoted as a dot (top), and as percentage distribution intervals (95/75/50/25/5) of contact errors (middle) and bit errors (bottom). Programming errors are largely chip-specific, with 3 chips (#’s 8–10) not displaying any programming errors. (B) Heatmaps of programming contact errors for each chip demonstrate that errors cluster on similar regions for each chip. (C) There was no significant trend that programming time affected programming error rate, indicating that chip-specific programming errors are independent of the clock rate.

FIGURE 6

Impedance and bath testing validation. (A) Magnitude and phase of impedance for 1 through 108 contacts activated. Impedance decreased at higher frequencies. (B) Impedance was inversely proportional to surface area. Average impedance for a single contact was 178.4 kΩ, with a trend toward increasing with the number of active contacts. (C) Bath testing demonstrates a directional shift in the normalized voltage field depending on the relative amplitudes of the electrode voltages.

FIGURE 7

(A) Multicompartment axon models were run with diameters of 2.0, 5,7, and 10.0 μm in response to stimulation from 1 to 36 contacts on the μDBS. (B) Maximum activation distance (mm) for each fiber size based on electrode size at –1 V (top) and –3 V (bottom). Large-diameter fibers can be activated at greater distances away from the electrode. For smaller diameter fibers, larger electrode sizes reduce activation spread. (C) Firing threshold was normalized to –1 V amplitude at 9 contacts on, which is approximately the height of classic DBS contact of 1.5 mm. A multi-resolution device may be useful to target different diameter fibers; as shown in the right panel, smaller contacts activate small diameter fibers at 65.75% efficiency over 5.7 μm fibers, and require about 113.1% additional voltage to activate the same 10.0 μm fibers. Larger contact sizes preferentially activate large diameter fibers, with about 50% lower thresholds relative to 5.7 μm fibers.