Bradley Greger

Cognitive control signals for neural prosthetics

Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external devices. In this study, higher level signals related to the goals of movements were decoded from three monkeys and used to position cursors on a computer screen without the animals emitting any behavior. Their performance in this task improved over a period of weeks. Expected value signals related to fluid preference, the expected magnitude, or probability of reward were decoded simultaneously with the intended goal. For neural prosthetic applications, the goal signals can be used to operate computers, robots, and vehicles, whereas the expected value signals can be used to continuously monitor a paralyzed patients preferences and motivation.

Wireless Neural Recording With Single Low-Power Integrated Circuit

We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6- mum 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902-928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor.

Human neocortical electrical activity recorded on nonpenetrating microwire arrays: applicability for neuroprostheses.

OBJECT The goal of this study was to determine whether a nonpenetrating, high-density microwire array could provide sufficient information to serve as the interface for decoding motor cortical signals. METHODS Arrays of nonpenetrating microwires were implanted over the human motor cortex in 2 patients. The patients performed directed stereotypical reaching movements in 2 directions. The resulting data were used to determine whether the reach direction could be distinguished through a frequency power analysis. RESULTS Correlation analysis revealed decreasing signal correlation with distance. The gamma-band power during motor planning allowed binary classification of gross directionality in the reaching movements. The degree of power change was correlated to the underlying gyral pattern. CONCLUSIONS The nonpenetrating microwire platform showed good potential for allowing differentiated signals to be recorded with high spatial fidelity without cortical penetration.

Avalanche Analysis from Multielectrode Ensemble Recordings in Cat, Monkey, and Human Cerebral Cortex during Wakefulness and Sleep

Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep, and REM sleep, using high density electrode arrays in cat motor cortex (96 electrodes), monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes) in epileptic patients. In neuronal avalanches defined from units (up to 160 single units), the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs) and in particular LFP negative peaks (nLFPs) among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and premotor cortices). In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP) peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF) and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey, and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man.

Multiple factors may influence the performance of a visual prosthesis based on intracortical microstimulation: nonhuman primate behavioural experimentation

We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts.

Continuous Detection and Decoding of Dexterous Finger Flexions With Implantable MyoElectric Sensors

A rhesus monkey was trained to perform individuated and combined finger flexions of the thumb, index, and middle finger. Nine implantable myoelectric sensors (IMES) were then surgically implanted into the finger muscles of the monkeys forearm, without any adverse effects over two years postimplantation. Using an inductive link, EMG was wirelessly recorded from the IMES as the monkey performed a finger flexion task. The EMG from the different IMES implants showed very little cross correlation. An offline parallel linear discriminant analysis (LDA) based algorithm was used to decode finger activity based on features extracted from continuously presented frames of recorded EMG. The offline parallel LDA was run on intraday sessions as well as on sessions where the algorithm was trained on one day and tested on following days. The performance of the algorithm was evaluated continuously by comparing classification output by the algorithm to the current state of the finger switches. The algorithm detected and classified seven different finger movements, including individual and combined finger flexions, and a no-movement state (chance performance = 12.5%) . When the algorithm was trained and tested on data collected the same day, the average performance was 43.8±3.6% n=10. When the training-testing separation period was five months, the average performance of the algorithm was 46.5±3.4% n=8. These results demonstrated that using EMG recorded and wirelessly transmitted by IMES offers a promising approach for providing intuitive, dexterous control of artificial limbs where human patients have sufficient, functional residual muscle following amputation.

A Simple Quantitative Method for Analyzing Electrographic Status Epilepticus in Rats

Electrographic status epilepticus (ESE) is a medical emergency consisting of repetitive seizures and may result in death or severe brain damage. Epilepsy can develop following ESE. The properties of ESE (e.g., duration and intensity) are variable, as are the effects of putative therapeutic treatments. Therefore a straightforward method to quantify different components of ESE would be beneficial for both researchers and clinicians. A frequency range close to the gamma band was selected for extraction of seizure-related activity from the EEG. This filtering strategy reduced motion artifacts and other noise sources in the electrophysiological recordings, thus increasing the signal-to-noise ratio of the EEG spike activity. EEG spiking was quantified using an energy operator and modeled by an eighth-order polynomial. In a benzodiazepine-resistant rat model of pilocarpine-induced ESE, the efficacy of various pharmaceutical agents at suppressing ESE was analyzed with this and other methods on data collected for < or =24 h after ESE induction. This approach allows for the objective, quantitative, and rapid assessment of the effects of both short- and long-lasting pharmacological manipulations on ESE and other forms of prolonged repetitive electrical activity.

Recording advances for neural prosthetics

An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications.

The functional consequences of chronic, physiologically effective intracortical microstimulation.

Many studies have demonstrated the ability of chronically implanted multielectrode arrays (MEAs) to extract information from the motor cortex of both humans and nonhuman primates. Similarly, many studies have shown the ability of intracortical microstimulation to impart information to the brain via a single or a few electrodes acutely implanted in sensory cortex of nonhuman primates, but relatively few microstimulation studies characterizing chronically implanted MEAs have been performed. Additionally, device and tissue damage have been reported at the levels of microstimulation used in these studies. Whether the damage resulting from microstimulation impairs the ability of MEAs to chronically produce physiological effects, however, has not been directly tested. In this study, we examined the functional consequences of multiple months of periodic microstimulation via chronically implanted MEAs at levels capable of evoking physiological responses, that is, electromyogram (EMG) activity. The functionality of the MEA and neural tissue was determined by measuring impedances, the ability of microstimulation to evoke EMG responses, and the recording of action potentials. We found that impedances and the number of recorded action potentials followed the previously reported trend of decreasing over time in both animals that received microstimulation and those which did not receive microstimulation. Despite these trends, the ability to evoke EMG responses and record action potentials was retained throughout the study. The results of this study suggest that intracortical microstimulation via MEAs did not cause functional failure, suggesting that MEA-based microstimulation is ready to transition into subchronic (< 30 days) human trials to determine whether complex spatiotemporal sensory percepts can be evoked by patterned microstimulation.

Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns). However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.