Intracortical brain-computer interfaces in primates: a review and outlook.

Brain-computer interfaces (BCI) translate brain signals into artificial output to restore or replace natural central nervous system (CNS) functions. Multiple processes, including sensorimotor integration, decision-making, motor planning, execution, and updating, are involved in any movement. For example, a BCI may be better able to restore naturalistic motor behaviors if it uses signals from multiple brain areas and decodes natural behaviors' cognitive and motor aspects. This review provides an overview of the preliminary information necessary to plan a BCI project focusing on intracortical implants in primates. Since the brain structure and areas of non-human primates (NHP) are similar to humans, exploring the result of NHP studies will eventually benefit human BCI studies. The different types of BCI systems based on the target cortical area, types of signals, and decoding methods will be discussed. In addition, various successful state-of-the-art cases will be reviewed in more detail, focusing on the general algorithm followed in the real-time system. Finally, an outlook for improving the current BCI research studies will be debated.

Volitional control of beta activities in Parkinson's disease patients.

Patients diagnosed with Parkinson's disease (PD) have difficulty initiating and executing movements due to an acquired imbalance of the basal ganglia thalamocortical circuit secondary to loss of dopaminergic input into the striatum. The unbalanced circuit is hyper-synchronized, presenting as larger and longer bursts of beta-band (13-30 Hz) oscillations in the subthalamic nucleus (STN). As a first step toward a novel PD therapy that aims to improve symptoms through beta desynchronization, we sought to determine if individuals with PD could acquire volitional control of STN beta power in a neurofeedback task. We found a significant difference in STN beta power between task conditions, and relevant brain signal features could be detected and decoded in real time. This demonstration of volitional control of STN beta motivates development of a neurofeedback therapy to modulate PD symptom severity.

Ensembles code for associative learning in the primate lateral prefrontal cortex.

The lateral prefrontal cortex (LPFC) of primates is thought to play a role in associative learning. However, it remains unclear how LPFC neuronal ensembles dynamically encode and store memories for arbitrary stimulus-response associations. We recorded the activity of neurons in LPFC of two macaques during an associative learning task using multielectrode arrays. During task trials, the color of a symbolic cue indicated the location of one of two possible targets for a saccade. During a trial block, multiple randomly chosen associations were learned by the subjects. A state-space analysis indicated that LPFC neuronal ensembles rapidly learn new stimulus-response associations mirroring the animals' learning. Multiple associations acquired during training are stored in a neuronal subspace and can be retrieved hours after learning. Finally, knowledge of old associations facilitates learning new, similar associations. These results indicate that neuronal ensembles in the primate LPFC provide a flexible and dynamic substrate for associative learning.

Proprioceptive Feedback Facilitates Motor Imagery-Related Operant Learning of Sensorimotor ß-Band Modulation.

Motor imagery (MI) activates the sensorimotor system independent of actual movements and might be facilitated by neurofeedback. Knowledge on the interaction between feedback modality and the involved frequency bands during MI-related brain self-regulation is still scarce. Previous studies compared the cortical activity during the MI task with concurrent feedback (MI with feedback condition) to cortical activity during the relaxation task where no feedback was provided (relaxation without feedback condition). The observed differences might, therefore, be related to either the task or the feedback. A proper comparison would necessitate studying a relaxation condition with feedback and a MI task condition without feedback as well. Right-handed healthy subjects performed two tasks, i.e., MI and relaxation, in alternating order. Each of the tasks (MI vs. relaxation) was studied with and without feedback. The respective event-driven oscillatory activity, i.e., sensorimotor desynchronization (during MI) or synchronization (during relaxation), was rewarded with contingent feedback. Importantly, feedback onset was delayed to study the task-related cortical activity in the absence of feedback provision during the delay period. The reward modality was alternated every 15 trials between proprioceptive and visual feedback. Proprioceptive input was superior to visual input to increase the range of task-related spectral perturbations in the α- and ß-band, and was necessary to consistently achieve MI-related sensorimotor desynchronization (ERD) significantly below baseline. These effects occurred in task periods without feedback as well. The increased accuracy and duration of learned brain self-regulation achieved in the proprioceptive condition was specific to the ß-band. MI-related operant learning of brain self-regulation is facilitated by proprioceptive feedback and mediated in the sensorimotor ß-band.

Single-trial decoding of intended eye movement goals from lateral prefrontal cortex neural ensembles.

Neurons in the lateral prefrontal cortex (LPFC) encode sensory and cognitive signals, as well as commands for goal-directed actions. Therefore, the LPFC might be a good signal source for a goal-selection brain-computer interface (BCI) that decodes the intended goal of a motor action previous to its execution. As a first step in the development of a goal-selection BCI, we set out to determine if we could decode simple behavioral intentions to direct gaze to eight different locations in space from single-trial LPFC neural activity. We recorded neuronal spiking activity from microelectrode arrays implanted in area 8A of the LPFC of two adult macaques while they made visually guided saccades to one of eight targets in a center-out task. Neuronal activity encoded target location immediately after target presentation, during a delay epoch, during the execution of the saccade, and every combination thereof. Many (40%) of the neurons that encoded target location during multiple epochs preferred different locations during different epochs. Despite heterogeneous and dynamic responses, the neuronal feature set that best predicted target location was the averaged firing rates from the entire trial and it was best classified using linear discriminant analysis (63.6-96.9% in 12 sessions, mean 80.3%; information transfer rate: 21-59, mean 32.8 bits/min). Our results demonstrate that it is possible to decode intended saccade target location from single-trial LPFC activity and suggest that the LPFC is a suitable signal source for a goal-selection cognitive BCI.

Electrocorticographic activity over sensorimotor cortex and motor function in awake behaving rats.

Sensorimotor cortex exerts both short-term and long-term control over the spinal reflex pathways that serve motor behaviors. Better understanding of this control could offer new possibilities for restoring function after central nervous system trauma or disease. We examined the impact of ongoing sensorimotor cortex (SMC) activity on the largely monosynaptic pathway of the H-reflex, the electrical analog of the spinal stretch reflex. In 41 awake adult rats, we measured soleus electromyographic (EMG) activity, the soleus H-reflex, and electrocorticographic activity over the contralateral SMC while rats were producing steady-state soleus EMG activity. Principal component analysis of electrocorticographic frequency spectra before H-reflex elicitation consistently revealed three frequency bands: µß (5-30 Hz), low γ (γ1; 40-85 Hz), and high γ (γ2; 100-200 Hz). Ongoing (i.e., background) soleus EMG amplitude correlated negatively with µß power and positively with γ1 power. In contrast, H-reflex size correlated positively with µß power and negatively with γ1 power, but only when background soleus EMG amplitude was included in the linear model. These results support the hypothesis that increased SMC activation (indicated by decrease in µß power and/or increase in γ1 power) simultaneously potentiates the H-reflex by exciting spinal motoneurons and suppresses it by decreasing the efficacy of the afferent input. They may help guide the development of new rehabilitation methods and of brain-computer interfaces that use SMC activity as a substitute for lost or impaired motor outputs.