Prefrontal-subthalamic theta signaling mediates delayed responses during conflict processing.

While medial frontal cortex (MFC) and subthalamic nucleus (STN) have been implicated in conflict monitoring and action inhibition, respectively, an integrated understanding of the spatiotemporal and spectral interaction of these nodes and how they interact with motor cortex (M1) to definitively modify motor behavior during conflict is lacking. We recorded neural signals intracranially across presupplementary motor area (preSMA), M1, STN, and globus pallidus internus (GPi), during a flanker task in 20 patients undergoing deep brain stimulation implantation surgery for Parkinson disease or dystonia. Conflict is associated with sequential and causal increases in local theta power from preSMA to STN to M1 with movement delays directly correlated with increased STN theta power, indicating preSMA is the MFC locus that monitors conflict and signals STN to implement a 'break.' Transmission of theta from STN-to-M1 subsequently results in a transient increase in M1-to-GPi beta flow immediately prior to movement, modulating the motor network to actuate the conflict-related action inhibition (i.e., delayed response). Action regulation during conflict relies on two distinct circuits, the conflict-related theta and movement-related beta networks, that are separated spatially, spectrally, and temporally, but which interact dynamically to mediate motor performance, highlighting complex parallel yet interacting networks regulating movement.

Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing.

Objective.The study aims to characterize movements with different sensory goals, by contrasting the neural activity involved in processing proprioceptive and visuo-motor information. To accomplish this, we have developed a new methodology that utilizes the irregularity of the instantaneous gamma frequency parameter for characterization.Approach.In this study, eight essential tremor patients undergoing an awake deep brain stimulation implantation surgery repetitively touched the clinician's finger (forward visually-guided/FV movement) and then one's own chin (backward proprioceptively-guided/BP movement). Neural electrocorticographic recordings from the motor (M1), somatosensory (S1), and posterior parietal cortex (PPC) were obtained and band-pass filtered in the gamma range (30-80 Hz). The irregularity of the inter-event intervals (IEI; inverse of instantaneous gamma frequency) were examined as: (1) auto-information of the IEI time series and (2) correlation between the amplitude and its proceeding IEI. We further explored the network connectivity after segmenting the FV and BP movements by periods of accelerating and decelerating forces, and applying the IEI parameter to transfer entropy methods.Main results.Conceptualizing that the irregularity in IEI reflects active new information processing, we found the highest irregularity in M1 during BP movement, highest in PPC during FV movement, and the lowest during rest at all sites. Also, connectivity was the strongest from S1 to M1 and from S1 to PPC during FV movement with accelerating force and weakest during rest.Significance. We introduce a novel methodology that utilize the instantaneous gamma frequency (i.e. IEI) parameter in characterizing goal-oriented movements with different sensory goals, and demonstrate its use to inform the directional connectivity within the motor cortical network. This method successfully characterizes different movement types, while providing interpretations to the sensory-motor integration processes.

Sequence of visual cortex stimulation affects phosphene brightness in blind subjects.

BACKGROUND: Visual cortical prostheses (VCP) could potentially benefit a majority of the blind population. Feasibility testing of these VCP opens new avenues to characterize stimulation of visual cortex in blind subjects. OBJECTIVE/HYPOTHESIS: To determine if sequential stimulation of visual cortex produces a perception bias in phosphene brightness. METHODS: We stimulated three blind subjects implanted with the Orion array with sequences of two and three electrodes and asked them to determine the brighter phosphene, using interval forced-choice paradigms. We selected a set of reference electrodes as the constant stimuli across sequences and compared across three different amplitude levels keeping all other stimulation parameters fixed across electrodes. RESULTS: For two subjects, we measured a significant increase in the probability of perceiving a lower-level amplitude just as bright or brighter than a higher-level amplitude when stimulated later in the sequence (p < 0.001, Wilcoxon rank sum test). The probability of reference electrodes selected as brighter was also higher during the second phase, across most amplitude comparisons. For the third subject, there were measurable but not significant changes, where the first stimuli were perceived as brighter. The effects were consistent within subjects in the three-electrode sequences, where the probability of the reference electrode selected as brighter was correlated to when it was presented in the sequence. CONCLUSIONS: We showed evidence of temporal interactions in non-overlapping sequences of electrodes, where the direction of the effect was subject specific but consistent across a variety of electrode locations and current amplitude levels.

Multi-electrode stimulation evokes consistent spatial patterns of phosphenes and improves phosphene mapping in blind subjects.

BACKGROUND: Visual cortical prostheses (VCPs) have the potential to restore visual function to patients with acquired blindness. Successful implementation of VCPs requires the ability to reliably map the location of the phosphene produced by stimulation of each implanted electrode. OBJECTIVE: To evaluate the efficacy of different approaches to phosphene mapping and propose simple improvements to mapping strategy. METHODS: We stimulated electrodes implanted in the visual cortex of five blind and fifteen sighted patients. We tested two fixation strategies, unimanual fixation, where subjects placed a single index finger on a tactile fixation point and bimanual fixation, where subjects overlaid their right index finger over their left on the tactile point. In addition, we compared absolute mapping in which a single electrode was stimulated on each trial, and relative mapping with sequences containing stimulation of three to five phosphenes on each trial. Trial-to-trial variability present in relative mapping sequences was quantified. RESULTS: Phosphene mapping was less precise in blind subjects than in sighted subjects (2DRMS, 16 ± 2.9° vs. 1.9 ± 0.93°; t (18) = 18, p = <0.001). Within blind subjects, bimanual fixation resulted in more consistent phosphene localization than unimanual fixation (BS1: 4.0 ± 2.6° vs. 19 ± 4.7°, t (79) = 24, p < 0.001; BS2 4.1 ± 2.0° vs. 12 ± 2.7°, t (65) = 19, p < 0.001). Multi-point relative mapping had similar baseline precision to absolute mapping (BS1: 4.7 ± 2.6° vs. 3.9 ± 2.0°; BS2: 4.1 ± 2.0° vs. 3.2 ± 1.1°) but improved significantly when trial-to-trial translational variability was removed. Although multi-point mapping methods did reveal more of the functional organization expected in early visual cortex, subjects tended to artificially regularize the spacing between phosphenes. We attempt to address this issue by fitting a standard logarithmic map to relative multi-point sequences. CONCLUSIONS: Relative mapping methods, combined with bimanual fixation, resulted in the most precise estimates of phosphene organization. These techniques, combined with use of a standard logarithmic model of visual cortex, may provide a practical way to improve the implementation of a VCP.

Eye movements and the perceived location of phosphenes generated by intracranial primary visual cortex stimulation in the blind.

BACKGROUND: Restoring sight for the blind using electrical stimulation of the visual pathways is feasible but demands an understanding of the spatial mapping of the visual world at the site of targeted stimulation, whether in the retina, thalamus, or cortex. While a visual cortex stimulator can bypass the eye and create visual percepts, there is an inherent dissociation between this stimulation and eye movements. It is unknown whether and how robustly the brain maintains the oculomotor circuitry in patients with bare- or no-light perception. OBJECTIVE: To critically and quantitatively evaluate the effect of eye movements have on phosphene locations elicited by cortical stimulation that bypasses the eyes in order to restore sight in blind subjects. METHODS: The NeuroPace Responsive Neurostimulator (RNS) and the Orion visual cortical prosthesis devices were used to electrically stimulate the visual cortex of blind subjects with bare or no light perception. Eye positions were recorded synchronized with stimulation and the location of the percepts were measured using a handheld marker. RESULTS: The locations of cortical stimulation-evoked percepts are shifted based on the eye position at the time of stimulation. Measured responses can be remapped based on measured eye positions to determine the retinotopic locations associated with the implanted electrodes, with remapped responses having variance limited by pointing error. CONCLUSIONS: Eye movements dominate the perceived location of cortical stimulation-evoked phosphenes, even after years of blindness. By accounting for eye positions, we can mimic retinal mapping as in natural sight.

Dynamic Stimulation of Visual Cortex Produces Form Vision in Sighted and Blind Humans.

A visual cortical prosthesis (VCP) has long been proposed as a strategy for restoring useful vision to the blind, under the assumption that visual percepts of small spots of light produced with electrical stimulation of visual cortex (phosphenes) will combine into coherent percepts of visual forms, like pixels on a video screen. We tested an alternative strategy in which shapes were traced on the surface of visual cortex by stimulating electrodes in dynamic sequence. In both sighted and blind participants, dynamic stimulation enabled accurate recognition of letter shapes predicted by the brain's spatial map of the visual world. Forms were presented and recognized rapidly by blind participants, up to 86 forms per minute. These findings demonstrate that a brain prosthetic can produce coherent percepts of visual forms.

Phosphene perceptions and safety of chronic visual cortex stimulation in a blind subject.

Stimulation of primary visual cortices has the potential to restore some degree of vision to blind individuals. Developing safe and reliable visual cortical prostheses requires assessment of the long-term stability, feasibility, and safety of generating stimulation-evoked perceptions.A NeuroPace responsive neurostimulation system was implanted in a blind individual with an 8-year history of bare light perception, and stimulation-evoked phosphenes were evaluated over 19 months (41 test sessions). Electrical stimulation was delivered via two four-contact subdural electrode strips implanted over the right medial occipital cortex. Current and charge thresholds for eliciting visual perception (phosphenes) were measured, as were the shape, size, location, and intensity of the phosphenes. Adverse events were also assessed.Stimulation of all contacts resulted in phosphene perception. Phosphenes appeared completely or partially in the left hemifield. Stimulation of the electrodes below the calcarine sulcus elicited phosphenes in the superior hemifield and vice versa. Changing the stimulation parameters of frequency, pulse width, and burst duration affected current thresholds for eliciting phosphenes, and increasing the amplitude or frequency of stimulation resulted in brighter perceptions. While stimulation thresholds decreased between an average of 5% and 12% after 19 months, spatial mapping of phosphenes remained consistent over time. Although no serious adverse events were observed, the subject experienced mild headaches and dizziness in three instances, symptoms that did not persist for more than a few hours and for which no clinical intervention was required.Using an off-the-shelf neurostimulator, the authors were able to reliably generate phosphenes in different areas of the visual field over 19 months with no serious adverse events, providing preliminary proof of feasibility and safety to proceed with visual epicortical prosthetic clinical trials. Moreover, they systematically explored the relationship between stimulation parameters and phosphene thresholds and discovered the direct relation of perception thresholds based on primary visual cortex (V1) neuronal population excitation thresholds.

Brain Machine Interfaces for Vision Restoration: The Current State of Cortical Visual Prosthetics.

Loss of vision alters the day to day life of blind individuals and may impose a significant burden on their family and the economy. Cortical visual prosthetics have been shown to have the potential of restoring a useful degree of vision via stimulation of primary visual cortex. Due to current advances in electrode design and wireless power and data transmission, development of these prosthetics has gained momentum in the past few years and multiple sites around the world are currently developing and testing their designs. In this review, we briefly outline the visual prosthetic approaches and describe the history of cortical visual prosthetics. Next, we focus on the state of the art of cortical visual prosthesis by briefly explaining the design of current devices that are either under development or in the clinical testing phase. Lastly, we shed light on the challenges of each design and provide some potential solutions.

Motor Task Detection From Human STN Using Interhemispheric Connectivity.

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders, such as Parkinson's disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient's behavior. Subthalamic nucleus (STN) local field potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. In this paper, we introduce a behavior detection method capable of asynchronously detecting the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from the STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity for detecting finger movement. Our experimental results, using the recordings from 11 patients with PD, demonstrate that this approach is applicable for behavior detection in the majority of subjects (average area under curve of 70±12%).

Motor task event detection using Subthalamic Nucleus Local Field Potentials.

Deep Brain Stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson's disease. Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and DBS side effects. In such systems, DBS parameters are adjusted based on patient's behavior, which means that behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local Field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. A practical behavior detection method should be able to detect behaviors asynchronously meaning that it should not use any prior knowledge of behavior onsets. In this paper, we introduce a behavior detection method that is able to asynchronously detect the finger movements of Parkinson patients. As a result of this study, we learned that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We used non-linear regression method to measure this connectivity and use it to detect the finger movements. Performance of this method is evaluated using Receiver Operating Characteristic (ROC).

Single trial behavioral task classification using subthalamic nucleus local field potential signals.

Deep Brain Stimulation (DBS) has been a successful technique for alleviating Parkinson's disease (PD) symptoms especially for whom drug therapy is no longer efficient. Existing DBS therapy is open-loop, providing a time invariant stimulation pulse train that is not customized to the patient's current behavioral task. By customizing this pulse train to the patient's current task the side effects may be suppressed. This paper introduces a method for single trial recognition of the patient's current task using the local field potential (LFP) signals. This method utilizes wavelet coefficients as features and support vector machine (SVM) as the classifier for recognition of a selection of behaviors: speech, motor, and random. The proposed method is 82.4% accurate for the binary classification and 73.2% for classifying three tasks. These algorithms will be applied in a closed loop feedback control system to optimize DBS parameters to the patient's real time behavioral goals.