Highlights d Visual cortical prosthetic stimulation paradigms were examined d Letters or other shapes were traced on the surface of cortex with electrical current d Static stimulation was unable to produce letter percepts in participants d Dynamic current steering evoked percepts of letter forms by blind and sighted participants

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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) ¼ 18, p ¼ <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) ¼ 24, p < 0.001; BS2 4.1 ± 2.0 vs. 12 ± 2.7 , t (65) ¼ 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.

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SUMMARY Advances in therapeutic neuromodulation devices have enabled concurrent stimulation and electrophysiology in the central nervous system. However, stimulation artifacts often obscure the sensed underlying neural activity. Here, we develop a method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five unique in vivo paradigms across animal and human studies, and an obscured movement biomarker are used for validation. Performance is found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: (1) it is superior in signal recovery; (2) it is easily adaptable to several neurostimulation paradigms; and (3) it has low complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies.

Objective. Brain-Machine Interfaces (BMIs) hold great promises for advancing neuroprosthetics, robotics, and for providing treatment options for severe neurological diseases. The objective of this work is the development and in vivo evaluation of electrodes for BMIs that meet the needs to record brain activity at sub-millimeter resolution over a large area of the cortex while being soft and electromechanically robust (i.e. stretchable). Approach. Current electrodes require a trade-off between high spatiotemporal resolution and cortical coverage area. To address the needs for simultaneous high resolution and large cortical coverage, the prototype electrode array developed in this study employs a novel bilayer routing of soft and stretchable lead wires from the recording sites on the surface of the brain (electrocorticography, ECoG) to the data acquisition system. Main results. To validate the recording characteristics, the array was implanted in healthy felines for up to 5 months. Neural signals recorded from both layers of the device showed elevated mid-frequency structures typical of local field potential (LFP) signals that were stable in amplitude over implant duration, and also exhibited consistent frequency-dependent modulation after anesthesia induction by Telazol. Significance. The successful development of a soft and stretchable large-area, high resolution micro ECoG electrode array (lahrμECoG) is an important step to meet the neurotechnological needs of advanced BMI applications.

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