Three-dimensional brain reconstruction of in vivo electrode tracks for neuroscience and neural prosthetic applications

Abstract

The brain is a densely interconnected network that relies on populations of neurons within and across multiple nuclei to code for features leading to perception and action. However, the neurophysiology field is still dominated by the characterization of individual neurons, rather than simultaneous recordings across multiple regions, without consistent spatial reconstruction of their locations for comparisons across studies. There are sophisticated histological and imaging techniques for performing brain reconstructions. However, what is needed is a method that is relatively easy and inexpensive to implement in a typical neurophysiology lab and provides consistent identification of electrode locations to make it widely used for pooling data across studies and research groups. This paper presents our initial development of such an approach for reconstructing electrode tracks and site locations within the guinea pig inferior colliculus (IC) to identify its functional organization for frequency coding relevant for a new auditory midbrain implant (AMI). Encouragingly, the spatial error associated with different individuals reconstructing electrode tracks for the same midbrain was less than 65 μm, corresponding to an error of ~1.5% relative to the entire IC structure (~4–5 mm diameter sphere). Furthermore, the reconstructed frequency laminae of the IC were consistently aligned across three sampled midbrains, demonstrating the ability to use our method to combine location data across animals. Hopefully, through further improvements in our reconstruction method, it can be used as a standard protocol across neurophysiology labs to characterize neural data not only within the IC but also within other brain regions to help bridge the gap between cellular activity and network function. Clinically, correlating function with location within and across multiple brain regions can guide optimal placement of electrodes for the growing field of neural prosthetics.

A new concept for noninvasive tinnitus treatment utilizing multimodal pathways

“…Basic surgical and analysis procedures have been described in detail in previous work [26,27] and are only briefly described in this paper.…”

“…An additional 32-site array was sometimes inserted into the right primary auditory cortex (A1) depending on the experiment. All recording electrode placements were posthumously verified through histological examination of electrode tracts and three-dimensional computer reconstructions [26]. Subcutaneous needle electrodes were inserted into specific somatic stimulation sites including the neck, shoulders, back, and rear thighs of the animal.…”

Descending and tonotopic projection patterns from the auditory cortex to the inferior colliculus

“…This reference point is consistent across animals and serves as a critical landmark for normalizing and aligning the different brains with each other (for further details and images, see (Markovitz et al, 2012)). Isofrequency laminae were approximated by creating a plane orthogonal to the average insertion angle of all best fit lines of each array placement.…”

“…Isofrequency laminae were approximated by creating a plane orthogonal to the average insertion angle of all best fit lines of each array placement. The depth of each lamina was determined by calculating the distance from the surface of the IC, where neurons do not respond to broadband noise, to locations where neurons respond with specific BFs (Markovitz et al, 2012). This distance was The FSL of antidromic activity at threshold was found and compared to orthodromic activity at threshold.…”

“…Detailed description of the histological procedure, midbrain reconstruction, normalization, and approximation of frequency laminae is provided in a previous publication (Markovitz et al, 2012). Briefly, the midbrain was fixed with 3.7% paraformaldehyde and cryosliced into sagittal sections of 60-lm widths using a sliding microtome (Leica, Buffalo Grove, IL, USA).…”