A wireless transmission neural interface system for unconstrained non-human primates

Abstract

Objective: Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications.

Approach: To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation.

Main results: We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm.

Significance: We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

Figure 1

Configuration of a high-fidelity signal transmission wireless telemetry. (A) A multi electrode array (middle) is connected to a skull mounted pedestal (left). A removable wireless CerePlex radio transmitter (right) attaches to the pedestal and transmits neural signals to a radio receiver connected to a conventional multichannel recording system. (B) Utah array assembly. (C) The wireless transmission system that includes the transmitter pedestal was implemented to be carried by a monkey. (D) Schematics of the data acquisition system. (E) A detailed block diagram of the transmitter CerePlex digital wireless system.

Figure 2

Wireless transmissions are comparable to wired recordings. Performance of the data transmission system based on a Blackrock neural signal simulator and compares it to that recorded by our system after receiving it wirelessly. (A) Transmitted and received spike trains from an example channel. (B) Example of the transmitted and received local field potentials generated by the simulator. (C) Example of the recorded simulated signal using both wired and wireless setups and performed cluster analysis of spike waveforms. (D) The waveform shapes and (E) resulting principal component clusters from the transmitted and received signals. (F) Performance of the transmission based on the percentage of detected wave forms at 10 m distance between the receiver and transmitter.

Figure 3

Wireless recordings in anesthetized condition. Quality of the LFP signals acquired using our wireless system by recording LFP responses of visual cortical (area V4) neurons of one anesthetized monkey, and compared the wireless and wired recording. (A) Schematics of the drifting oriented gratings used as stimuli (see methods). (B) Broadband (1–250 Hz) LFP signals were recorded from 96 channels while moving luminance-contrast grating. (C) For both wired and wireless recordings, results showed strong responses to visual stimuli in both low- and high-frequency bands, and (D) a strong preference for the orientation and direction of the stimuli (see main text).

Figure 4

Wireless recordings in restrained (wired) and freely moving (wireless) conditions. Tests of our recording system for freely moving, non-human primates by recording single units and LFPs from 96 electrodes chronically implanted in the dlPFC in one animal. (A) The wired (left) and wireless (right) recording conditions. (B) Single units were extracted and sorted from the 96-channel uninterrupted raw data for both conditions. (C) Example of the identified single- and multi-unit spiking activity (using principal component analysis). (D) Examples of raster plots representing stable single-unit activity from 16 electrodes for a period of 5 s. (E) Waveforms were found to be very similar for both restrained and unrestrained recording conditions. (F) Plot showing that the spike waveforms of the neurons recorded wirelessly were remarkably stable even after 37 days.

Figure 5

Wireless monitoring of population activity during free exploration. Measure the cross-correlation between pairs of dlPFC neurons recorded from the same or different channels while the monkey was freely moving in its cage. (A) Most pairs (73.7%) showed peaks near zero lag (bottom) to indicate synchronized firing pairs. Correlation peaks displaced from the zero lag were observed less often (top). (B) Across all the recorded pairs, the correlation index was biased to positive values. (C) Correlation index as a function of the distance between the dlPFC neurons. Plots indicating a peak in the correlation index between dlPFC cell pairs from the same electrode, and a sharp decline in the mean correlation index between neurons separated by 400 μm or more (inset). (D) Correlations in LFP power by computing the Pearson correlation of band-limited LFP power between two electrodes as a function of electrode distance (in the 400–4400μm range). The LFP correlations decrease as a function of electrode distance (see main text).

Figure 6

Experiments examining changes in dlPFC responses in two conditions: (A) head-fixed and movement-restrained condition (top) and when the animal freely roamed in its cage (bottom). (B) The monkey performed 24 trials per reward type per session (five restrained and five freely moving sessions), and each reward type represented one trial. (C) Plot showing that as expected, the animal consumed the preferred reward more often than the non-preferred reward. (D) We quantified the movement of the animal by video recording the movements of the monkey in the freely moving condition then tracking the movements of the monkey’s head of offline by using the transmitter as the reference point (see section 4). (E) We did not observe a significant difference between the extent of movement associated with the preferred and non-preferred reward types during the reward presentation

Figure 7

Reward-dependent changes in neuronal correlations in the unrestrained condition. (A) Plots showing firing-rate histograms for one example neuron responding to both types of reward. (B) Results indicating that the population average firing rates for the two reward types (1000 ms following stimulus onset) were not significantly different from each other during the restrained and freely moving condition, and similar results were obtained when we extended the size of the window in which spikes were counted for the entire 10 s interval when the stimulus was presented. (C) Pearson correlation values associated with the two reward types as a function of expanding window size, starting from the time when the reward was first presented (see main text). (D) The mean correlation coefficient associated with the two types of reward was significantly different from each other (right). However, when the monkey was restrained, neuronal correlations associated with the preferred and non-preferred rewards were not statistically different (left).