Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and ...

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Nanotools for Neuroscience and Brain Activity Mapping

Neural probes designed for extracellular recording of brain electrical activity are traditionally implanted with an insertion speed between 1 µm/s and 1 mm/s into the brain tissue. Although the physical effects of insertion speed on the tissue are well studied, there is a lack of research investigating how the quality of the acquired electrophysiological signal depends on the speed of probe insertion. In this study, we used four different insertion speeds (0.002 mm/s, 0.02 mm/s, 0.1 mm/s, 1 mm/s) to implant high-density silicon probes into deep layers of the somatosensory cortex of ketamine/xylazine anesthetized rats. After implantation, various qualitative and quantitative properties of the recorded cortical activity were compared across different speeds in an acute manner. Our results demonstrate that after the slowest insertion both the signal-to-noise ratio and the number of separable single units were significantly higher compared with those measured after inserting probes at faster speeds. Furthermore, the amplitude of recorded spikes as well as the quality of single unit clusters showed similar speed-dependent differences. Post hoc quantification of the neuronal density around the probe track showed a significantly higher number of NeuN-labelled cells after the slowest insertion compared with the fastest insertion. Our findings suggest that advancing rigid probes slowly (~1 µm/s) into the brain tissue might result in less tissue damage, and thus in neuronal recordings of improved quality compared with measurements obtained after inserting probes with higher speeds.

Slow insertion of silicon probes improves the quality of acute neuronal recordings

Extracellular recordings from the brain are the basis for the fundamental understanding of the complex interaction of electrical signals in neural information transfer. Going beyond wire electrodes and bundles of electrode wires such as tetrodes, multielectrode arrays based on silicon technologies are receiving growing attention, since they enable a pronounced increase in the number of recording sites per probe shaft. In this paper, recent innovations contributed by the authors to the development of probe arrays based on microelectromechanical system (MEMS) technologies within the EU-funded research project NeuroProbes are described. The resulting structures include passive electrode arrays based on single-shaft and four-shaft probes comprising nine planar electrodes per shaft with lengths of up to 8 mm. Further, active probe arrays with complementary metal–oxide–semiconductor (CMOS) circuitry integrated on the probe shaft, enabling the arrangement of 188 electrodes in two columns along a 4-mm-long probe shaft with an electrode pitch of only 40 µm, are described. These active probes were developed for an electronic depth control. Further, the paper reports assembly technologies for combining the probe arrays with highly flexible ribbon cables. Applications of the probes in in vivo experiments are summarized. © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/tee.20566

Recent Progress in Neural Probes Using Silicon MEMS Technology

A complementary-metal-oxide-semiconductor-compatible fabrication technique for ultrathin silicon chips of arbitrary shape is reported. It combines deep reactive ion etching and wafer grinding to define the in-plane geometry and thickness of the chips, respectively. Neural probes with shaft lengths up to 12 mm and thicknesses down to 25 μm were fabricated.

Ultrathin Silicon Chips of Arbitrary Shape by Etching Before Grinding

A silicon-based neural probe with densely-packed low-impedance titanium nitride microelectrodes for ultrahigh-resolution in vivo recordings

This paper reports on a novel CMOS-based silicon microprobe for high-density intracortical stress mapping. In contrast to existing systems, square p-type field effect transistors (FET) with four source/drain contacts (piezo-FETs) are integrated on the slender, needle-like probe shaft. In total, 345 stress sensors are arranged in five columns (x/y-pitch of 51.4/26.6 µm) along the 180-µm-wide shaft. Measuring in-plane normal stress in silicon neural probes is envisioned to avoid probe fracture during insertion and to evaluate the probe deflection caused by brain motion after insertion. The combination with switchable electrodes will enable the simultaneous neural recording of brain activity. The paper presents the probe concept, the post-CMOS fabrication process, the piezo-FET characterization, and measurements demonstrating stress mapping in a brain model.

CMOS-based high-density silicon microprobe for stress mapping in intracortical applications

This paper presents the NeuroSelect software for managing the electronic depth control of cerebral CMOS-based microprobes for extracellular in vivo recordings. These microprobes contain up to 500 electronically switchable electrodes which can be appropriately selected with regard to specific neuron locations in the course of a recording experiment. NeuroSelect makes it possible to scan the electrodes electronically and to (re)select those electrodes of best signal quality resulting in a closed-loop design of a neural acquisition system. The signal quality is calculated by the relative power of the spikes compared with the background noise. The spikes are detected by an adaptive threshold using a robust estimator of the standard deviation. Electrodes can be selected in a manual or semi-automatic mode based on the signal quality. This electronic depth control constitutes a significant improvement for multielectrode probes, given that so far the only alternative has been the fine positioning by mechanical probe translation. In addition to managing communication with the hardware controller of the probe array, the software also controls acquisition, processing, display and storage of the neural signals for further analysis.

Control and data acquisition software for high-density CMOS-based microprobe arrays implementing electronic depth control.

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CMOS-based high-density silicon microprobe for stress mapping in intracortical applications

Control and data acquisition software for high-density CMOS-based microprobe arrays implementing electronic depth control.