Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease

Abstract

OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation paradigms. Clinical trial registration no.: NCT01934296 (clinicaltrials.gov).

Keywords: DBS; DBS = deep brain stimulation; ECoG = electrocorticography; EKG = electrocardiogram; FDA = Food and Drug Administration; IPG = implanted pulse generator; LFP = local field potential; PD; PD = Parkinson's disease; PSD = power spectral density; Parkinson's disease; RMS = root mean square; STN = subthalamic nucleus; UPDRS = Unified Parkinson's Disease Rating Scale; basal ganglia; brain-machine interface; deep brain stimulation; electrophysiology; functional neurosurgery; motor cortex.

Figures

Figure 1

A. Schematic of the cranial hardware implantation (bilateral brain leads) as viewed from the top of the head. B. Lateral skull film showing cranial hardware and proximal lead extenders. This subject has unilateral DBS. C. Example lead locations (patient 4). Central sulcus indicated with the black arrow and DBS electrode location in the subthalamic nucleus indicated with the white dot. Electrode locations determined by merging the pre-operative MRI to a postoperative CT.

Figure 2

Example of motor cortex ECoG and STN LFP raw data (A) and their power spectra (B) from Activa PC+S versus an external recording system designed for intraoperative electrophysiology (Microguide, Alpha Omega). Both recordings were obtained on the same day, a few hours apart, from patient 5.

Figure 3

Signal quality and evolution over time. A. Example signals and their power spectra from patient 2, 10 day post-operative, for both STN (left panel) and motor cortex (right panel). On the STN PSD, the sharp peak at 32 Hz (arrow), on the right shoulder of the beta peak, is artifactual (further elaborated in Figure 6). B. Evolution of RMS voltage over time for all patients. Data for patient 1 at 1 day, 2 months, and 3 months is missing because the initial protocol did not include research visits at these time points. STN recordings which were contaminated by EKG artifact (see Figure 6) were also excluded.

Figure 4

Power and impedance change over time. A. Average log beta PSD over time for all subjects. B. Average log broadband gamma over time for all subjects. C. Average log beta peak height in STN over time for all subjects. Data for patient 1 at 1 day, 2 months, and 3 months is missing because the initial protocol did not include research visits at these time points. Also STN recordings contaminated by EKG artifact (see Figure 6) were excluded. D. Same as C, but motor cortex beta peak height. E. Average monopolor impedances across all electrode contacts for each region (motor cortex and STN). Impedances gradually increase over time. F. Example of an STN LFP power spectrum with (patient 4, 1 day after surgery) and without (patient 4, 10 days after surgery) the expected broad peak in the alpha-beta range. Note that the sharp peak at 32 Hz from the 10 day post-surgery recording is an artifact (described further in Results and Figure 6).

Figure 5

Detection of movement related changes in motor cortex ECoG potentials and their relationship to device noise floor. A, B: Movement related spectrograms (plotted on a log scale) aligned to movement onset (time 0) for a recording session that did (A, patient 2, 10 days postoperative) and did not (B, patient 3, 3 weeks postoperative) exhibit a movement-related gamma increase. Both examples have a beta decrease. D, C show the same plots on a non-log scale. E. PSD plots for recordings shown in A–D, as well as the maximum manufacturer-specified device noise floor. Note that gamma activity may be difficult to detect reliably in panels B and D because gamma activity in that recording is near the device noise floor.

Figure 6

Illustration of common Activa PC+S electrical artifacts. A. Example of DBS stimulation artifacts for constant current and constant voltage settings as well as off DBS in both motor cortex and STN in the same patient (patient 4). Stimulation parameters: c+1−, 160 Hz, 3 V, 60 microseconds pulse-width versus, c+2−, 130 Hz, 4.9 mA, 90 microseconds. Constant voltage recording is at 1 month postoperative, constant current and off stimulation recordings were at 1 year postoperative. Note that in all cases STN recordings were from bipolar contact pairs bordering stimulation to minimize artifact (0–1 for constant voltage recording and 1–3 for constant current and off stimulation). Motor cortex recordings were from contacts 9–11 in all recordings. B. Example of narrowband frequency artifacts associated with intrinsic firmware properties or clock configuration properties in Active PC+S. See Results for more information. C. Example of EKG artifact in STN. D. Example of baseline deflection artifact associated with filter start up transient. This occurred at the beginning of each recording for both electrode contacts. E. Example of transient baseline deflections of unknown etiology. These deflections can occur in motor cortex or STN.