Accessibility and Manipulation of Brain Signals for Neuroprosthetic Applications.

The field of Neural Engineering spawned in response to the perpetual problem of neurology: injured central nervous system neurons do not regenerate or repair, and stem cell/molecular genetic solutions, while the ideal intervention, are far away from clinical utilization. A current solution is to substitute computers and electrodes for neurons, as either transducers (cochlear implants, retinal implants, and visual cortex ECoG implants for sensory replacement), regulators (deep brain stimulations for Parkinson's disease), and output signal readers (motor cortex neuroprosthetics). I have focused on improving the technology of motor neuroprosthetics, and in this dissertation I investigated three sub-systems of this relatively new technology in a rat model. In my first experiment, I demonstrated that the cingulate cortex, part of the prefrontal cortex, can be used as an additional control signal for a motor neuroprosthetic device in the event that upper motor neurons of the motor cortex are degenerated by neurodegenerative diseases. In my second experiment, I examined whether electrocorticograms (ECoGs) and local field potentials (LFPs) are independent from the spiking activity of motor neurons and could be thus used as additional control channels. I showed these signals are not necessarily independent, specifically, the spikes phase-lock to the field potentials at defined frequencies, and careful algorithms will have to be developed to combine spikes, LFPs, and ECoGs as different control channels for a neuroprosthetic device. In my third experiment, I investigated the use of feedback in a neuroprosthetic model. I combined intracortical microstimulation (ICMS) of the visual cortex with simultaneous motor cortex ensemble recordings in real time to demonstrate the feasibility of a closed-loop neuroprosthesis. I showed that though sensory cortex ICMS can be combined with motor cortex recording in real-time in a viable preparation, increased technological development in simultaneous decoding with brain stimulation needs to occur before feasible clinical implementation can become a reality. By reading and manipulating brain signals via microelectrodes, a basic level of neural control and neural replacement can be achieved. Until the day that physicians have access to technology that allows spinal cords to regrow and limbs to regenerate, current technology allows us to achieve....Ph.D.NeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61629/4/tmarzull_2.pd

Use of a Bayesian maximum-likelihood classifier to generate training data for brain–machine interfaces

Brain–machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technological limitations, there is a need for decoding algorithms which (a) are not dependent upon a large number of neurons for control, (b) are adaptable to alternative sources of neuronal input such as local field potentials (LFPs), and (c) require only marginal training data for daily calibrations. Moreover, practical algorithms must recognize when the user is not intending to generate a control output and eliminate poor training data. In this paper, we introduce and evaluate a Bayesian maximum-likelihood estimation strategy to address the issues of isolating quality training data and self-paced control. Six animal subjects demonstrate that a multiple state classification task, loosely based on the standard center-out task, can be accomplished with fewer than five engaged neurons while requiring less than ten trials for algorithm training. In addition, untrained animals quickly obtained accurate device control, utilizing LFPs as well as neurons in cingulate cortex, two non-traditional neural inputs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90824/1/1741-2552_8_4_046009.pd

Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation

While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine–xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation method estimates it within ±69.3 µm. We propose that these methods can be used to estimate the in situ location of laminar electrodes implanted in the rat motor cortex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90825/1/1741-2552_8_4_046018.pd

Reduction of neurovascular damage resulting from microelectrode insertion into the cerebral cortex using

Penetrating neural probe technologies allow investigators to record electrical signals in the brain. The implantation of probes causes acute tissue damage, partially due to vasculature disruption during probe implantation. This trauma can cause abnormal electrophysiological responses and temporary increases in neurotransmitter levels, and perpetuate chronic immune responses. A significant challenge for investigators is to examine neurovascular features below the surface of the brain in vivo. The objective of this study was to investigate localized bleeding resulting from inserting microscale neural probes into the cortex using two-photon microscopy (TPM) and to explore an approach to minimize blood vessel disruption through insertion methods and probe design. 3D TPM images of cortical neurovasculature were obtained from mice and used to select preferred insertion positions for probe insertion to reduce neurovasculature damage. There was an 82.8 ± 14.3% reduction in neurovascular damage for probes inserted in regions devoid of major (>5 µm) sub-surface vessels. Also, the deviation of surface vessels from the vector normal to the surface as a function of depth and vessel diameter was measured and characterized. 68% of the major vessels were found to deviate less than 49 µm from their surface origin up to a depth of 500 µm. Inserting probes more than 49 µm from major surface vessels can reduce the chances of severing major sub-surface neurovasculature without using TPM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85401/1/7_4_046011.pd

Open labware: 3-D printing your own lab equipment

The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current “maker movement,” which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one’s own garage—a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the “little things” that help a lab get up and running much faster and easier than ever before

The SpikerBox: A Low Cost, Open-Source BioAmplifier for Increasing Public Participation in Neuroscience Inquiry

Although people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed) the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience

Raw Cockroach New Molt Photos

All Cockroach Photos taken during the study. File Names are Day#-A#, Day#-S#, and Day#-U#. Day = Day of Observation post leg removal. A = autotomy groups. U = unsterilized coxa-cut group. S = sterilized coxa-cut group. Number after letter is to identify different cockroaches. Note Day03, Day10, and Day20 have rulers in the photos for calibration. After Day 20, the microscope was improved and all photos have a built-in calibration mark that measures 10 mm by 1 mm

Leg Neurophysiology Recordings

Raw data of 8 legs recorded. The left, metathoracic leg from 8 cockroaches was removed via a transverse coxa cut. One stainless steel “map pin” electrode was inserted into the coxa, the other map-pin electrode in the tibia/tarsus joint, and the electrodes were plugged into a “SpikerBox” Neural Amplifier. 10 seconds of spontaneous activity were recorded, followed by 10 seconds of lightly tapping the prominente barbs on the tibia of the cockroach leg with a plastic probe. After this measurement, the electrode that was in the coxa was then inserted into the center of the femur, and the same recording procedure repeated (10 seconds of spontaneous activity followed by 10 seconds of light touch). Finally, the coxa was then removed with forceps, the electrodes left in place, and the recording procedure repeated once more. The three electrode conditions are separated by periods of silence in the .wav files