Dynamical constraints on neural population activity.

The manner in which neural activity unfolds over time is thought to be central to sensory, motor, and cognitive functions in the brain. Network models have long posited that the brain's computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate. We leveraged a brain-computer interface (BCI) to challenge monkeys to violate the naturally-occurring time courses of neural population activity that we observed in motor cortex. This included challenging animals to traverse the natural time course of neural activity in a time-reversed manner. Animals were unable to violate the natural time courses of neural activity when directly challenged to do so. These results provide empirical support for the view that activity time courses observed in the brain indeed reflect the underlying network-level computational mechanisms that they are believed to implement.

Monkeys exhibit a paradoxical decrease in performance in high-stakes scenarios.

In high-stakes situations, people sometimes exhibit a frustrating phenomenon known as "choking under pressure." Usually, we perform better when the potential payoff is larger. However, once potential rewards get too high, performance paradoxically decreases-we "choke." Why do we choke under pressure? An animal model of choking would facilitate the investigation of its neural basis. However, it could be that choking is a uniquely human occurrence. To determine whether animals also choke, we trained three rhesus monkeys to perform a difficult reaching task in which they knew in advance the amount of reward to be given upon successful completion. Like humans, monkeys performed worse when potential rewards were exceptionally valuable. Failures that occurred at the highest level of reward were due to overly cautious reaching, in line with the psychological theory that explicit monitoring of behavior leads to choking. Our results demonstrate that choking under pressure is not unique to humans, and thus, its neural basis might be conserved across species.

Stabilization of a brain-computer interface via the alignment of low-dimensional spaces of neural activity.

The instability of neural recordings can render clinical brain-computer interfaces (BCIs) uncontrollable. Here, we show that the alignment of low-dimensional neural manifolds (low-dimensional spaces that describe specific correlation patterns between neurons) can be used to stabilize neural activity, thereby maintaining BCI performance in the presence of recording instabilities. We evaluated the stabilizer with non-human primates during online cursor control via intracortical BCIs in the presence of severe and abrupt recording instabilities. The stabilized BCIs recovered proficient control under different instability conditions and across multiple days. The stabilizer does not require knowledge of user intent and can outperform supervised recalibration. It stabilized BCIs even when neural activity contained little information about the direction of cursor movement. The stabilizer may be applicable to other neural interfaces and may improve the clinical viability of BCIs.

New neural activity patterns emerge with long-term learning.

Learning has been associated with changes in the brain at every level of organization. However, it remains difficult to establish a causal link between specific changes in the brain and new behavioral abilities. We establish that new neural activity patterns emerge with learning. We demonstrate that these new neural activity patterns cause the new behavior. Thus, the formation of new patterns of neural population activity can underlie the learning of new skills.

Remapping cortical modulation for electrocorticographic brain-computer interfaces: a somatotopy-based approach in individuals with upper-limb paralysis.

OBJECTIVE: Brain-computer interface (BCI) technology aims to provide individuals with paralysis a means to restore function. Electrocorticography (ECoG) uses disc electrodes placed on either the surface of the dura or the cortex to record field potential activity. ECoG has been proposed as a viable neural recording modality for BCI systems, potentially providing stable, long-term recordings of cortical activity with high spatial and temporal resolution. Previously we have demonstrated that a subject with spinal cord injury (SCI) could control an ECoG-based BCI system with up to three degrees of freedom (Wang et al 2013 PLoS One). Here, we expand upon these findings by including brain-control results from two additional subjects with upper-limb paralysis due to amyotrophic lateral sclerosis and brachial plexus injury, and investigate the potential of motor and somatosensory cortical areas to enable BCI control. APPROACH: Individuals were implanted with high-density ECoG electrode grids over sensorimotor cortical areas for less than 30 d. Subjects were trained to control a BCI by employing a somatotopic control strategy where high-gamma activity from attempted arm and hand movements drove the velocity of a cursor. MAIN RESULTS: Participants were capable of generating robust cortical modulation that was differentiable across attempted arm and hand movements of their paralyzed limb. Furthermore, all subjects were capable of voluntarily modulating this activity to control movement of a computer cursor with up to three degrees of freedom using the somatotopic control strategy. Additionally, for those subjects with electrode coverage of somatosensory cortex, we found that somatosensory cortex was capable of supporting ECoG-based BCI control. SIGNIFICANCE: These results demonstrate the feasibility of ECoG-based BCI systems for individuals with paralysis as well as highlight some of the key challenges that must be overcome before such systems are translated to the clinical realm. ClinicalTrials.gov Identifier: NCT01393444.

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate.

OBJECTIVE: Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. APPROACH: We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. MAIN RESULTS: Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. SIGNIFICANCE: These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

Motor-related brain activity during action observation: a neural substrate for electrocorticographic brain-computer interfaces after spinal cord injury.

After spinal cord injury (SCI), motor commands from the brain are unable to reach peripheral nerves and muscles below the level of the lesion. Action observation (AO), in which a person observes someone else performing an action, has been used to augment traditional rehabilitation paradigms. Similarly, AO can be used to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface (BCI) even when the user cannot generate overt movements. BCIs use brain signals to control external devices to replace functions that have been lost due to SCI or other motor impairment. Previous studies have reported congruent motor cortical activity during observed and overt movements using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). Recent single-unit studies using intracortical microelectrodes also demonstrated that a large number of motor cortical neurons had similar firing rate patterns between overt and observed movements. Given the increasing interest in electrocorticography (ECoG)-based BCIs, our goal was to identify whether action observation-related cortical activity could be recorded using ECoG during grasping tasks. Specifically, we aimed to identify congruent neural activity during observed and executed movements in both the sensorimotor rhythm (10-40 Hz) and the high-gamma band (65-115 Hz) which contains significant movement-related information. We observed significant motor-related high-gamma band activity during AO in both able-bodied individuals and one participant with a complete C4 SCI. Furthermore, in able-bodied participants, both the low and high frequency bands demonstrated congruent activity between action execution and observation. Our results suggest that AO could be an effective and critical procedure for deriving the mapping from ECoG signals to intended movement for an ECoG-based BCI system for individuals with paralysis.

Collaborative approach in the development of high-performance brain-computer interfaces for a neuroprosthetic arm: translation from animal models to human control.

Our research group recently demonstrated that a person with tetraplegia could use a brain-computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able-bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short-term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real-world clinical situations.

An electrocorticographic brain interface in an individual with tetraplegia.

Brain-computer interface (BCI) technology aims to help individuals with disability to control assistive devices and reanimate paralyzed limbs. Our study investigated the feasibility of an electrocorticography (ECoG)-based BCI system in an individual with tetraplegia caused by C4 level spinal cord injury. ECoG signals were recorded with a high-density 32-electrode grid over the hand and arm area of the left sensorimotor cortex. The participant was able to voluntarily activate his sensorimotor cortex using attempted movements, with distinct cortical activity patterns for different segments of the upper limb. Using only brain activity, the participant achieved robust control of 3D cursor movement. The ECoG grid was explanted 28 days post-implantation with no adverse effect. This study demonstrates that ECoG signals recorded from the sensorimotor cortex can be used for real-time device control in paralyzed individuals.

Stable online control of an electrocorticographic brain-computer interface using a static decoder.

A brain computer interface (BCI) system was implemented by recording electrocorticographic signals (ECoG) from the motor cortex of a Rhesus macaque. These signals were used to control two-dimensional cursor movements in a standard center-out task, utilizing an optimal linear estimation (OLE) method. We examined the time course over which a monkey could acquire accurate control when operating in a co-adaptive training scheme. Accurate and maintained control was achieved after 4-5 days. We then held the decode parameters constant and observed stable control over the next 28 days. We also investigated the underlying neural strategy employed for control, asking whether neural features that were correlated with a given kinematic output (e.g. velocity in a certain direction) were clustered anatomically, and whether the features were coordinated or conflicting in their contributions to the control signal.

Sparse linear regression with elastic net regularization for brain-computer interfaces.

This paper demonstrates the feasibility of decoding neuronal population signals using a sparse linear regression model with an elastic net penalty. In offline analysis of real electrocorticographic (ECoG) neural data the elastic net achieved a timepoint decoding accuracy of 95% for classifying hand grasps vs. rest, and 82% for moving a cursor in 1-D space towards a target. These results were superior to those obtained using ℓ(2)-penalized and unpenalized linear regression, and marginally better than ℓ(1)-penalized regression. Elastic net and the ℓ(1)-penalty also produced sparse feature sets, but the elastic net did not eliminate correlated features, which could result in a more stable decoder for brain-computer interfaces.

Craniux: a LabVIEW-based modular software framework for brain-machine interface research.

This paper presents "Craniux," an open-access, open-source software framework for brain-machine interface (BMI) research. Developed in LabVIEW, a high-level graphical programming environment, Craniux offers both out-of-the-box functionality and a modular BMI software framework that is easily extendable. Specifically, it allows researchers to take advantage of multiple features inherent to the LabVIEW environment for on-the-fly data visualization, parallel processing, multithreading, and data saving. This paper introduces the basic features and system architecture of Craniux and describes the validation of the system under real-time BMI operation using simulated and real electrocorticographic (ECoG) signals. Our results indicate that Craniux is able to operate consistently in real time, enabling a seamless work flow to achieve brain control of cursor movement. The Craniux software framework is made available to the scientific research community to provide a LabVIEW-based BMI software platform for future BMI research and development.

Toward synergy-based brain-machine interfaces.

This paper demonstrates a synergy-based brain-machine interface that uses low-dimensional command signals to control a high dimensional virtual hand. First, temporal postural synergies were extracted from the angular velocities of finger joints of five healthy subjects when they performed hand movements that were similar to activities of daily living. Two synergies inspired from the extracted synergies, namely, two-finger pinch and whole-hand grasp, were used in real-time brain control, where a virtual hand with 10 degrees of freedom was controlled to grasp or pinch virtual objects. These two synergies were controlled by electrocorticographic (ECoG) signals recorded from two electrodes of an electrode array that spanned motor and speech areas of an individual with intractable epilepsy, thus demonstrating closed loop control of a synergy-based brain-machine interface.

Decoding semantic information from human electrocorticographic (ECoG) signals.

This study examined the feasibility of decoding semantic information from human cortical activity. Four human subjects undergoing presurgical brain mapping and seizure foci localization participated in this study. Electrocorticographic (ECoG) signals were recorded while the subjects performed simple language tasks involving semantic information processing, such as a picture naming task where subjects named pictures of objects belonging to different semantic categories. Robust high-gamma band (60-120 Hz) activation was observed at the left inferior frontal gyrus (LIFG) and the posterior portion of the superior temporal gyrus (pSTG) with a temporal sequence corresponding to speech production and perception. Furthermore, Gaussian Naïve Bayes and Support Vector Machine classifiers, two commonly used machine learning algorithms for pattern recognition, were able to predict the semantic category of an object using cortical activity captured by ECoG electrodes covering the frontal, temporal and parietal cortices. These findings have implications for both basic neuroscience research and development of semantic-based brain-computer interface systems (BCI) that can help individuals with severe motor or communication disorders to express their intention and thoughts.

Frequency tracking and variable bandwidth for line noise filtering without a reference.

This paper presents a method for filtering line noise using an adaptive noise canceling (ANC) technique. This method effectively eliminates the sinusoidal contamination while achieving a narrower bandwidth than typical notch filters and without relying on the availability of a noise reference signal as ANC methods normally do. A sinusoidal reference is instead digitally generated and the filter efficiently tracks the power line frequency, which drifts around a known value. The filter's learning rate is also automatically adjusted to achieve faster and more accurate convergence and to control the filter's bandwidth. In this paper the focus of the discussion and the data will be electrocorticographic (ECoG) neural signals, but the presented technique is applicable to other recordings.

The impact of electrode characteristics on electrocorticography (ECoG).

Used clinically since Penfield and Jasper's pioneering work in the 1950's, electrocorticography (ECoG) has recently been investigated as a promising technology for brain-computer interfacing. Many researchers have attempted to analyze the properties of ECoG recordings, including prediction of optimal electrode spacing and the improved resolution expected with smaller electrodes. This work applies an analytic model of the volume conductor to investigate the sensitivity field of electrodes of various sizes. The benefit to spatial resolution was minimal for electrodes smaller than ~1mm, while smaller electrodes caused a dramatic decrease in signal-to-noise ratio. The temporal correlation between electrode pairs is predicted over a range of spacings and compared to correlation values from a series of recordings in subjects undergoing monitoring for intractable epilepsy. The observed correlations are found to be much higher than predicted by the analytic model and suggest a more detailed model of cortical activity is needed to identify appropriate ECoG grid spacing.

Classification of hand posture from electrocorticographic signals recorded during varying force conditions.

In the presented work, standard and high-density electrocorticographic (ECoG) electrodes were used to record cortical field potentials in three human subjects during a hand posture task requiring the application of specific levels of force during grasping. We show two-class classification accuracies of up to 80% are obtained when classifying between two-finger pinch and whole-hand grasp hand postures despite differences in applied force levels across trials. Furthermore, we show that a four-class classification accuracy of 50% is achieved when predicting both hand posture and force level during a two-force, two-hand-posture grasping task, with hand posture most reliably predicted during high-force trials. These results suggest that the application of force plays a significant role in ECoG signal modulation observed during motor tasks, emphasizing the potential for electrocorticography to serve as a source of control signals for dexterous neuroprosthetic devices.

Decoding and cortical source localization for intended movement direction with MEG.

Magnetoencephalography (MEG) enables a noninvasive interface with the brain that is potentially capable of providing movement-related information similar to that obtained using more invasive neural recording techniques. Previous studies have shown that movement direction can be decoded from multichannel MEG signals recorded in humans performing wrist movements. We studied whether this information can be extracted without overt movement of the subject, because the targeted users of brain-controlled interface (BCI) technology are those with severe motor disabilities. The objectives of this study were twofold: 1) to decode intended movement direction from MEG signals recorded during the planning period before movement onset and during imagined movement and 2) to localize cortical sources modulated by intended movement direction. Ten able-bodied subjects performed both overt and imagined wrist movement while their cortical activities were recorded using a whole head MEG system. The intended movement direction was decoded using linear discriminant analysis and a Bayesian classifier. Minimum current estimation (MCE) in combination with a bootstrapping procedure enabled source-space statistical analysis, which showed that the contralateral motor cortical area was significantly modulated by intended movement direction, and this modulation was the strongest ∼100 ms before the onset of overt movement. These results suggest that it is possible to study cortical representation of specific movement information using MEG, and such studies may aid in presurgical localization of optimal sites for implanting electrodes for BCI systems.