Bradley Greger

Action potentials (AP) from subthalamic nucleus (STN) neurons were significantly related to local field potentials in STN and motor cortex. Functional connectivity between STN neuron APs and cortical local field potentials was topographically organized on a sub-centimeter scale. This spatial specificity of functional connectivity was different for different subthalamic neurons, including neighboring subthalamic neurons.

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a… Show more

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area. Show less

An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high… Show more

An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject's phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback. Show less

Objective. In order to move forward with the development of a cortical vision prosthesis, the critical issues in the field must be identified. Approach. To begin this process, we performed a brief review of several different cortical and retinal stimulation techniques that can be used to restore vision. Main results. Intracortical microelectrodes and epicortical macroelectrodes have been evaluated as the basis of a vision prosthesis. We concluded that an important knowledge gap necessitates an… Show more

Objective. In order to move forward with the development of a cortical vision prosthesis, the critical issues in the field must be identified. Approach. To begin this process, we performed a brief review of several different cortical and retinal stimulation techniques that can be used to restore vision. Main results. Intracortical microelectrodes and epicortical macroelectrodes have been evaluated as the basis of a vision prosthesis. We concluded that an important knowledge gap necessitates an experimental in vivo performance evaluation of microelectrodes placed on the surface of the visual cortex. A comparison of the level of vision restored by intracortical versus epicortical microstimulation is necessary. Because foveal representation in the primary visual cortex involves more cortical columns per degree of visual field than does peripheral vision, restoration of foveal vision may require a large number of closely spaced microelectrodes. Based on previous studies of epicortical macrostimulation, it is possible that stimulation via surface microelectrodes could produce a lower spatial resolution, making them better suited for restoring peripheral vision. Significance. The validation of epicortical microstimulation in addition to the comparison of epicortical and intracortical approaches for vision restoration will fill an important knowledge gap and may have important implications for surgical strategies and device longevity. It is possible that the best approach to vision restoration will utilize both epicortical and intracortical microstimulation approaches, applying them appropriately to different visual representations in the primary visual cortex. Show less

OBJECTIVE: Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses.

METHODS: This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes:… Show more

OBJECTIVE: Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses.

METHODS: This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes: electrocorticographic (ECoG) electrodes, non-penetrating micro-ECoG (μECoG) electrodes that use microelectrodes and have tighter interelectrode spacing; and penetrating microelectrodes (MEA) that penetrate the cortex to record single- or multiunit activity (SUA or MUA) and local field potentials (LFP).

RESULTS: While the finest spatial scales are found in LFPs recorded intracortically, we found that LFP recorded from μECoG electrodes demonstrate scales of linear similarity (i.e., correlation, coherence, and phase) closer to the intracortical electrodes than the clinical ECoG electrodes.

CONCLUSIONS: We conclude that LFPs can be recorded intracortically and epicortically at finer scales than clinical ECoG electrodes are capable of capturing.

SIGNIFICANCE: Recorded with appropriately scaled electrodes and grids, field potentials expose a more detailed representation of cortical network activity, enabling advanced analyses of cortical pathology and demanding applications such as brain-computer interfaces. Show less

In interpersonal communication, the listener can often see as well as hear the speaker. Visual stimuli can subtly change a listener’s auditory perception, as in the McGurk illusion, in which perception of a phoneme’s auditory identity is changed by a concurrent video of a mouth articulating a different phoneme. Studies have yet to link visual influences on the neural representation of language with subjective language perception. Here we show that vision influences the electrophysiological… Show more

In interpersonal communication, the listener can often see as well as hear the speaker. Visual stimuli can subtly change a listener’s auditory perception, as in the McGurk illusion, in which perception of a phoneme’s auditory identity is changed by a concurrent video of a mouth articulating a different phoneme. Studies have yet to link visual influences on the neural representation of language with subjective language perception. Here we show that vision influences the electrophysiological representation of phonemes in human auditory cortex prior to the presentation of the auditory stimulus. We used the McGurk effect to dissociate the subjective perception of phonemes from the auditory stimuli. With this paradigm we demonstrate that neural representations in auditory cortex are more closely correlated with the visual stimuli of mouth articulation, which drive the illusory subjective auditory perception, than the actual auditory stimuli. Additionally, information about visual and auditory stimuli transfer in the caudal–rostral direction along the superior temporal gyrus during phoneme perception as would be expected of visual information flowing from the occipital cortex into the ventral auditory processing stream. These results show that visual stimuli influence the neural representation in auditory cortex early in sensory processing and may override the subjective auditory perceptions normally generated by auditory stimuli. These findings depict a marked influence of vision on the neural processing of audition in tertiary auditory cortex and suggest a mechanistic underpinning for the McGurk effect. Show less

Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs) to investigate the effects of propofol anesthesia on action potentials (APs) and local field potentials (LFPs). UEAs were implanted into the neocortex of two… Show more

Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs) to investigate the effects of propofol anesthesia on action potentials (APs) and local field potentials (LFPs). UEAs were implanted into the neocortex of two humans and three felines. The two human patients and one feline received propofol by bolus injection, while the other two felines received target-controlled infusions. We examined the changes in LFP power spectra and AP firing at different levels of anesthesia. Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, and the generation of large-amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol. The probability that an AP would fire at this local minimum of the LFP increased with propofol administration. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased and the AP–LFP relationship became more predictable firing rate encoding capacity is impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness. Show less

A Kalman filter was used to decode hand trajectories from micro-electrocorticography recorded over motor cortex in human patients. In two cases, signals were recorded during stereotyped tasks, and the trajectories were decoded offline, with maximum correlation coefficients between actual and predicted trajectories of 0.51 (x-direction position) and 0.54 (y-direction position). In a third setting, a human patient with full neural control of a computer cursor acquired onscreen targets within 6.24… Show more

A Kalman filter was used to decode hand trajectories from micro-electrocorticography recorded over motor cortex in human patients. In two cases, signals were recorded during stereotyped tasks, and the trajectories were decoded offline, with maximum correlation coefficients between actual and predicted trajectories of 0.51 (x-direction position) and 0.54 (y-direction position). In a third setting, a human patient with full neural control of a computer cursor acquired onscreen targets within 6.24 sec on average, with no algorithmic constraints on the output trajectory. These practical results illustrate the potential utility of signals recorded at the cortical surface with high spatial resolution, demonstrating that surface potentials contain relevant and sufficient information to drive sophisticated brain-computer interface systems. Show less

Dexterous finger movements can be decoded from neuronal action potentials acquired from a non-human primate using a chronically implanted Utah Electrode Array. We have developed an algorithm that can, after training, detect and classify individual and combined finger movements without any a priori knowledge of the data, task, or behavior. The algorithm is based on changes in the firing rates of individual neurons that are tuned for one or more finger movement types. Nine different movement… Show more

Dexterous finger movements can be decoded from neuronal action potentials acquired from a non-human primate using a chronically implanted Utah Electrode Array. We have developed an algorithm that can, after training, detect and classify individual and combined finger movements without any a priori knowledge of the data, task, or behavior. The algorithm is based on changes in the firing rates of individual neurons that are tuned for one or more finger movement types. Nine different movement types, which consisted of individual flexions, individual extensions, and combined flexions of the thumb, index finger, and middle finger, were decoded. The algorithm performed reliably on data recorded continuously during movement tasks, including a no-movement state, with an overall average sensitivity and specificity that were both >92%. These results demonstrate a viable algorithm for decoding dexterous finger movements under conditions similar to those required for a real-world neural prosthetic application. Show less

The ability to detect and classify individual and combined finger movements from neural data is rapidly advancing. The work that has been done has demonstrated the feasibility of decoding finger movements from acutely recorded neurons. There is a need for a recording model that meets the chronic requirements of a neuroprosthetic application and to address this need we have developed an algorithm that can detect and classify individual and combined finger movements using neuronal data acquired… Show more

The ability to detect and classify individual and combined finger movements from neural data is rapidly advancing. The work that has been done has demonstrated the feasibility of decoding finger movements from acutely recorded neurons. There is a need for a recording model that meets the chronic requirements of a neuroprosthetic application and to address this need we have developed an algorithm that can detect and classify individual and combined finger movements using neuronal data acquired from a chronically implanted Utah Electrode Array (UEA). The algorithm utilized the firing rates of individual neurons and performed with an average sensitivity and an average specificity that were both greater than 92% across all movement types. These results lend further support that a chronically implanted UEA is suitable for acquiring and decoding neuronal data and also demonstrate a decoding method that can detect and classify finger movements without any a priori knowledge of the data, task, or behavior. Show less

Pathological conditions such as amyotrophic lateral sclerosis or damage to the brainstem can leave patients severely paralyzed but fully aware, in a condition known as 'locked-in syndrome'. Communication in this state is often reduced to selecting individual letters or words by arduous residual movements. More intuitive and rapid communication may be restored by directly interfacing with language areas of the cerebral cortex. We used a grid of closely spaced, nonpenetrating micro-electrodes to… Show more

Pathological conditions such as amyotrophic lateral sclerosis or damage to the brainstem can leave patients severely paralyzed but fully aware, in a condition known as 'locked-in syndrome'. Communication in this state is often reduced to selecting individual letters or words by arduous residual movements. More intuitive and rapid communication may be restored by directly interfacing with language areas of the cerebral cortex. We used a grid of closely spaced, nonpenetrating micro-electrodes to record local field potentials (LFPs) from the surface of face motor cortex and Wernicke's area. From these LFPs we were successful in classifying a small set of words on a trial-by-trial basis at levels well above chance. We found that the pattern of electrodes with the highest accuracy changed for each word, which supports the idea that closely spaced micro-electrodes are capable of capturing neural signals from independent neural processing assemblies. These results further support using cortical surface potentials (electrocorticography) in brain–computer interfaces. These results also show that LFPs recorded from the cortical surface (micro-electrocorticography) of language areas can be used to classify speech-related cortical rhythms and potentially restore communication to locked-in patients. Show less

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… Show more

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.
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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… Show more

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 patient's preferences and motivation. Show less