Phase relationship between micro-electrocorticography and cortical neurons.

OBJECTIVE: Electrocorticography (ECoG) is commonly used to map epileptic foci and to implement brain-computer interfaces. Understanding the spatiotemporal correspondence between potentials recorded from the brain's surface and the firing patterns of neurons within the cortex would inform the interpretation of ECoG signals and the design of (microfabricated) micro-ECoG electrode arrays. Based on the theory that synaptic potentials generated by neurons firing in synchrony superimpose to generate local field potentials (LFPs), we hypothesized that neurons in the cortex would fire at preferential phases of the micro-ECoG signal in a spatially dependent way. APPROACH: We custom fabricated micro-ECoG electrode arrays with a small opening for silicon arrays (NeuroNexus) to be inserted into the cortex. MAIN RESULTS: We found that the spectral coherence between micro-ECoG signals and intracortical LFPs decreased with distance and frequency, but the coherence with spiking units did not simply decrease over distance, likely due to the structure of the cortex. The majority of sorted units spiked during a preferred phase (usually downward) and frequency (usually below 20 Hz) of the micro-ECoG signal. Their preferred frequency decreased with administration of dexmeditomidine, a sedative commonly used for cortical mapping in patients with epilepsy prior to surgical resection. Dexmedetomidine concomitantly shifted the micro-ECoG spectral density towards lower frequencies. Therefore, the phase relationship between micro-ECoG signals and cortical spiking depends on the state of the brain, and spectrum shifts towards lower frequencies in the electrocorticography signal are a signature of increased spike-phase coupling. However, spike-phase coupling is not a static property since visual stimuli were found to modulate the magnitude of phase coupling at gamma frequency ranges (30-80 Hz), providing empirical evidence that neurons transiently phase-lock. SIGNIFICANCE: The phase relationship between intracortical spikes and micro-ECoG signals depends on brain state, site separation, cortical structure, and external stimuli.

Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics.

Transparent graphene-based neural electrode arrays provide unique opportunities for simultaneous investigation of electrophysiology, various neural imaging modalities, and optogenetics. Graphene electrodes have previously demonstrated greater broad-wavelength transmittance (∼90%) than other transparent materials such as indium tin oxide (∼80%) and ultrathin metals (∼60%). This protocol describes how to fabricate and implant a graphene-based microelectrocorticography (µECoG) electrode array and subsequently use this alongside electrophysiology, fluorescence microscopy, optical coherence tomography (OCT), and optogenetics. Further applications, such as transparent penetrating electrode arrays, multi-electrode electroretinography, and electromyography, are also viable with this technology. The procedures described herein, from the material characterization methods to the optogenetic experiments, can be completed within 3-4 weeks by an experienced graduate student. These protocols should help to expand the boundaries of neurophysiological experimentation, enabling analytical methods that were previously unachievable using opaque metal-based electrode arrays.