Histological assessment of a chronically implanted cylindrically-shaped, polymer-based neural probe in the monkey.

Objective.Previous studies demonstrated the possibility to fabricate stereo-electroencephalography probes with high channel count and great design freedom, which incorporate macro-electrodes as well as micro-electrodes offering potential benefits for the pre-surgical evaluation of drug resistant epileptic patients. These new polyimide probes allowed to record local field potentials, multi- and single-unit activity (SUA) in the macaque monkey as early as 1 h after implantation, and yielded stable SUA for up to 26 d after implantation. The findings opened new perspectives for investigating mechanisms underlying focal epilepsy and its treatment, but before moving to possible human application, safety data are needed. In the present study we evaluate the tissue response of this new neural interface by assessing post-mortem the reaction of brain tissue along and around the probe implantation site.Approach.Three probes were implanted, independently, in the brain of one monkey (Macaca mulatta) at different times. We used specific immunostaining methods for visualizing neuronal cells and astrocytes, for measuring the extent of damage caused by the probe and for relating it with the implantation time.Main results.The size of the region where neurons cannot be detected did not exceed the size of the probe, indicating that a complete loss of neuronal cells is only present where the probe was physically positioned in the brain. Furthermore, around the probe shank, we observed a slightly reduced number of neurons within a radius of 50µm and a modest increase in the number of astrocytes within 100µm.Significance.In the light of previous electrophysiological findings, the present data suggest the potential usefulness and safety of this probe for human applications.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites.

OBJECTIVE: Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. APPROACH: Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 µm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. MAIN RESULTS: Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. SIGNIFICANCE: With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording.

This paper reports on the design, fabrication, and characterization of neural probes for stereoelectroencephalography (SEEG). The probe specifically targets focal epilepsy as key application. However, probes of this type can also be used for the diagnosis and treatment of other neural dysfunctions such as Parkinson's disease or tremor, typically requiring deep brain probes. The probe fabrication, of which most processes are parallel batch processes, relies on a novel fabrication concept for rolling and gluing thin film polyimide sheets with integrated electrodes into permanent cylindrical shapes with diameters down to 800 µm. The SEEG probes, comprise several macro-electrodes designed to record local field potentials, and micro-electrodes positioned in-between, dedicated to monitoring single unit activity, with a total channel count of 32, despite the small diameter. While platinum micro-electrodes with a diameter of 35 µm have impedances of about 255 kΩ at 1 kHz, impedance values down to about 1.5 kΩ have been measured for the macro-electrodes. The devices have shown good compatibility with magnetic resonance imaging in a 9.4 T magnet, enabling the precise post-operative probe localization within the brain.