NeuroGrid: recording action potentials from the surface of the brain

Abstract

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material–based, ultraconformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

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Figure 1: NeuroGrid structure and spike recordings in freely moving rats.
Figure 2: Neuron clustering and spike-waveform characterization.
Figure 3: Phase modulation of NeuroGrid spikes by brain oscillations.
Figure 4: Intraoperative NeuroGrid recording of LFP and spikes in epilepsy patients.

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Acknowledgements

This work was supported by US National Institutes of Health Grants (NS074015, MH54671, MH102840), the National Science Foundation, the Mathers Foundation and the James S. McDonnell Foundation. The device fabrication was performed at Microelectronic Centre of Provence and the Cornell NanoScale Facility (CNF), a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation (Grant ECCS-0335765). D.K. is supported through the Simons Foundation (junior fellow). J.G. is supported by the Pediatric Scientist Development Program through a grant from the March of Dimes Foundation. We thank M. Sessolo (University of Valencia), J. Rivnay and M. Ferro (Ecole des Mines), and A. Peyrache and G. Girardeau (NYU Langone Medical Center) for fruitful discussion. We thank M. Skvarla, R. Ilic and M. Metzler from the CNF for their technical support during device fabrication. We thank H. McKellar and A. Boomhaur for managing the institutional review board (IRB) protocol of intraoperative epilepsy patient recordings.

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Authors

Contributions

D.K., G.G.M. and G.B. conceived the project. D.K. designed, fabricated and characterized the devices. D.K. and J.N.G. did the rodent in vivo experiments. D.K. and J.N.G. analyzed neural data. D.K., J.N.G. and T.T. did the intraoperative patient recordings. W.D. was the attending neurosurgeon and supervised the intra-operative recordings. T.T. and O.D. supervised the epilepsy patient recordings and IRB approval process. D.K., J.N.G. and G.B. wrote the paper with input from the other authors.

Corresponding author

Correspondence to György Buzsáki.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Detailed NeuroGrid structure and electrical characteristics.

a) Optical micrograph of a 256-channel NeuroGrid (scale = 1 mm). Optical micrograph of PEDOT:PSS-based recording sites (inset; scale = 10 μm).b) Optical micrograph of 64-channel NeuroGrid conforming to a 100 μm diameter cylinder (scale = 200 μm).c) Current measurement by a single NeuroGrid electrode site in response to 0.5 V stimulation at 50 mHz is stable for over 9 hours. At shorter time scales (upper plots) waveforms are similar between widely separated time points (red boxes).d) Comparison of electrode impedance over a broad range of frequencies between the NeuroGrid (filled circles) and conventional Au-based electrodes (open circles). Impedance of NeuroGrid electrodes is consistent between different arrays (inset; blue circles) and more than an order of magnitude less than conventional implantable silicon probes (inset; red circles).

Supplementary Figure 2 Frequency characterization of the NeuroGrid and implantable probes.

a) Comparison of signal power over physiologically relevant frequencies for NeuroGrid (blue lines) and silicon probe (red lines) during REM sleep (upper traces) and post-mortem (lower traces).b) SNR of surface recording by the NeuroGrid and depth recording by a silicon probe.

Supplementary Figure 3 Extracellular action potential waveforms and recording stability in cortex.

a) Placement of a 64-channel NeuroGrid on rat somatosensory cortex (expanded version of Fig. 1b).b) Spike-triggered averages of multiple individual units recorded at each recording site overlaid on NeuroGrid geometry. Recording sites that were located over major blood vessels, as demonstrated in corresponding anatomical photograph (scale = 300 μm) of NeuroGrid placement, did not resolve any spikes (scale = 3 ms by 50 μV).c) Spatial extent and morphology of a sample subset of multiple individual trigger-averaged extracellular action potentials from (b) are consistent over 10 days of recording (scale = 3 ms by 50 μV).

Supplementary Figure 4 Extracellular action potential waveforms and recording stability in hippocampus.

a) Simultaneous implantation of a 64-channel NeuroGrid and a 4-shank silicon probe in rat hippocampus (scale = 300 μm).b) Spatial extent and morphology of a sample subset of multiple individual trigger-averaged extracellular action potentials on different NeuroGrid recording sites are consistent over 10 days of recording (scale = 3 ms, 100 μV).

Supplementary Figure 5 Simultaneous recording of ripples and units by the NeuroGrid (green) and a silicon probe (blue) in the hippocampus.

a) Raster plot of spike firing during ripples as recorded by the NeuroGrid on the hippocampal surface and a silicon probe inserted into CA1, immediately next to the NeuroGrid.b) Raw LFP showing a ripple recorded on multiple NeuroGrid electrodes and simultaneously captured by multiple sites of a linear silicon probe in CA1 (scale = 100 ms by 500 μV). Recording sites of the silicon probe are separated by 20 µm in the vertical direction. The tip of the probe is in the pyramidal layer.c) Band-pass filtered traces at ripple frequency (100 – 250 Hz) of the NeuroGrid and silicon probe recordings above (scale = 100 ms, 200 μV).d) High-pass filtered (fc = 500 Hz) time traces of the NeuroGrid and silicon probe LFP recordings above (scale = 100 ms, 100 μV).e) Autocorrelograms (in color) of a putative single unit’s spiking activity as recorded simultaneously by the NeuroGrid and a silicon probe. Cross-correlation (black) of spiking activity demonstrates co-occurrence of recorded spikes (bin size = 1 ms). Note the similar form of the autocorrelograms, though fewer spikes are recorded with the NeuroGrid.

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Khodagholy, D., Gelinas, J., Thesen, T. et al. NeuroGrid: recording action potentials from the surface of the brain. Nat Neurosci 18, 310–315 (2015). https://doi.org/10.1038/nn.3905

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