Dinal Andreasen

A Wireless Brain-Machine Interface for Real-Time Speech Synthesis

Background Brain-machine interfaces (BMIs) involving electrodes implanted into the human cerebral cortex have recently been developed in an attempt to restore function to profoundly paralyzed individuals. Current BMIs for restoring communication can provide important capabilities via a typing process, but unfortunately they are only capable of slow communication rates. In the current study we use a novel approach to speech restoration in which we decode continuous auditory parameters for a real-time speech synthesizer from neuronal activity in motor cortex during attempted speech. Methodology/Principal Findings Neural signals recorded by a Neurotrophic Electrode implanted in a speech-related region of the left precentral gyrus of a human volunteer suffering from locked-in syndrome, characterized by near-total paralysis with spared cognition, were transmitted wirelessly across the scalp and used to drive a speech synthesizer. A Kalman filter-based decoder translated the neural signals generated during attempted speech into continuous parameters for controlling a synthesizer that provided immediate (within 50 ms) auditory feedback of the decoded sound. Accuracy of the volunteers vowel productions with the synthesizer improved quickly with practice, with a 25% improvement in average hit rate (from 45% to 70%) and 46% decrease in average endpoint error from the first to the last block of a three-vowel task. Conclusions/Significance Our results support the feasibility of neural prostheses that may have the potential to provide near-conversational synthetic speech output for individuals with severely impaired speech motor control. They also provide an initial glimpse into the functional properties of neurons in speech motor cortical areas.

Using human extra-cortical local field potentials to control a switch

Individuals with profound paralysis and mutism require a communication channel. Traditional assistive technology devices eventually fail, especially in the case of amyotrophic lateral sclerosis (ALS) subjects who gradually become totally locked-in. A direct brain-to-computer interface that provides switch functions can provide a direct communication channel to the external world. Electroencephalographic (EEG) signals recorded from scalp electrodes are significantly degraded due to skull and scalp attenuation and ambient noise. The present system using conductive skull screws allows more reliable access to cortical local field potentials (LFPs) without entering the brain itself. We describe an almost locked-in human subject with ALS who activated a switch using online time domain detection techniques. Frequency domain analysis of his LFP activity demonstrates this to be an alternative method of detecting switch activation intentions. With this brain communicator system it is reasonable to expect that locked-in, but cognitively intact, humans will always be able to communicate.

Neurotrophic electrode: Method of assembly and implantation into human motor speech cortex

The neurotrophic electrode (NE) is designed for longevity and stability of recorded signals. To achieve this aim it induces neurites to grow through its glass tip, thus anchoring it in neuropil. The glass tip contains insulated gold wires for recording the activity of the myelinated neurites that grow into the tip. Neural signals inside the tip are electrically insulated from surrounding neural activity by the glass. The most recent version of the electrode has four wires inside its tip to maximize the number of discriminable signals recorded from ingrown neurites, and has a miniature connector. Flexible coiled, insulated gold wires connect to electronics on the skull that remain subcutaneous. The implanted electronics consist of differential amplifiers, FM transmitters, and a sine wave at power up for tuning and calibration. Inclusion criteria for selecting locked-in subjects include medical stability, normal cognition, and strong caregiver support. The implant target is localized via an fMRI-naming task. Final localization at surgery is achieved by 3D stereotaxic localization. During recording, implanted electronics are powered by magnetic induction across an air gap. Coiled antennas placed on the scalp over the implanted transmitters receive the amplified FM transmitter outputs. Data is processed as described elsewhere where stability and longevity issues are addressed. Five subjects have been successfully implanted with the NE. Recorded signals persisted for over 4 years in two subjects who died from underlying illnesses, and continue for over 3 years in our present subject.

Classification of intended phoneme production from chronic intracortical microelectrode recordings in speech-motor cortex

We conducted a neurophysiological study of attempted speech production in a paralyzed human volunteer using chronic microelectrode recordings. The volunteer suffers from locked-in syndrome leaving him in a state of near-total paralysis, though he maintains good cognition and sensation. In this study, we investigated the feasibility of supervised classification techniques for prediction of intended phoneme production in the absence of any overt movements including speech. Such classification or decoding ability has the potential to greatly improve the quality-of-life of many people who are otherwise unable to speak by providing a direct communicative link to the general community. We examined the performance of three classifiers on a multi-class discrimination problem in which the items were 38 American English phonemes including monophthong and diphthong vowels and consonants. The three classifiers differed in performance, but averaged between 16 and 21% overall accuracy (chance-level is 1/38 or 2.6%). Further, the distribution of phonemes classified statistically above chance was non-uniform though 20 of 38 phonemes were classified with statistical significance for all three classifiers. These preliminary results suggest supervised classification techniques are capable of performing large scale multi-class discrimination for attempted speech production and may provide the basis for future communication prostheses.

Regenerative Scaffold Electrodes for Peripheral Nerve Interfacing

Advances in neural interfacing technology are required to enable natural, thought-driven control of a prosthetic limb. Here, we describe a regenerative electrode design in which a polymer-based thin-film electrode array is integrated within a thin-film sheet of aligned nanofibers, such that axons regenerating from a transected peripheral nerve are topographically guided across the electrode recording sites. Cultures of dorsal root ganglia were used to explore design parameters leading to cellular migration and neurite extension across the nanofiber/electrode array boundary. Regenerative scaffold electrodes (RSEs) were subsequently fabricated and implanted across rat tibial nerve gaps to evaluate device recording capabilities and influence on nerve regeneration. In 20 of these animals, regeneration was compared between a conventional nerve gap model and an amputation model. Characteristic shaping of regenerated nerve morphology around the embedded electrode array was observed in both groups, and regenerated axon profile counts were similar at the eight week end point. Implanted RSEs recorded evoked neural activity in all of these cases, and also in separate implantations lasting up to five months. These results demonstrate that nanofiber-based topographic cues within a regenerative electrode can influence nerve regeneration, to the potential benefit of a peripheral nerve interface suitable for limb amputees.

Making the lifetime connection between brain and machine for restoring and enhancing function.

A reliable neural interface that lasts a lifetime will lead to the development of neural prosthetic devices as well as the possibility that brain function can be enhanced. Our data demonstrate that a reliable neural interface is best achieved when the surrounding neuropil grows into the electrode tip where it is held securely, allowing myelinated axons to be recorded using implanted amplifiers. Stable single and multiunits were recorded from three implanted subjects and classified according to amplitudes and firing rates. In one paralyzed and mute subject implanted for over 5 years with a double electrode in the speech motor cortex, the single units allowed recognition of over half the 39 English language phonemes detected using a variety of decoding methods. These single units were used by the subject in a speech task where vowel phonemes were recognized and fed back to the subject using audio output. Weeks of training resulted in an 80% success rate in producing four vowels in an adaptation of the classic center-out task used in motor control studies. The importance of using single units was shown in a different task using pure tones that the same subject heard and then sung or hummed in his head. Feedback was associated with smoothly coordinated unit firings. The plasticity of the unit firings was demonstrated over several sessions first without, and then with, feedback. These data suggest that units can be reliably recorded over years, that there is an inverse relationship between single unit firing rate and amplitude, that pattern recognition decoding paradigms can allow phoneme recognition, that single units appear more important than multiunits when precision is important, and that units are plastic in their functional relationships. These characteristics of a reliable neural interface are essential for the development of neural prostheses and also for the future enhancement of human brain function.

A regenerative electrode scaffold for peripheral nerve interfacing

Novel approaches to peripheral nerve interfacing are required to establish the stable, high-resolution connections demanded by the emerging generation of advanced neuroprosthetic devices. Here we propose a nanofiber scaffold-based design for a regenerative electrode capable of establishing significant numbers of stable and selective electrical connections with subsets of peripheral nerve. The design features one or more polyimide thin-film electrode arrays integrated within a layered nanofiber scaffold such that regenerating axons from a transected nerve are directed across the embedded electrodes. In-vitro and in-vivo experiments with a rat peripheral nerve model were performed to validate and optimize the ability of our regenerative electrode scaffold (RES) to direct axonal regeneration across an implanted electrode array. Immunostaining of cultured dorsal root ganglia revealed that migrating Schwann cells and extending neurites can be directed along oriented nanofibers and across an overlaid polyimide electrode in-vitro. RESs were then fabricated and implanted between the stumps of transected rat tibial nerves (n=10). After 3-6 weeks the scaffolds were explanted and stained to characterize regeneration through the RESs. Staining revealed robust axonal regeneration through the scaffolds. This regeneration was directed as close as several microns to the surfaces of the integrated electrode arrays. Staining also revealed minimal inflammatory response at the electrode array site. Additionally, the same results were obtained in the absence of an intact distal stump. In conclusion, our results suggest the feasibility of this design for use in interfacing an amputated nerve stump. Electrophysiological capabilities of the interface and facilitation of long term trophic support for the nerve will be examined in future experiments.

Distance Controlled and Electrically Driven Photoluminescence Quench From Quantum Dot-Au Complexes

Quantum Dots (QDs) bound to gold nanoparticles have shown photoluminescence (PL) quenching dependent on distance between the two particles. The incident light from the QD couples to plasmon excitation of the metal when the frequencies of the light and the surface plasmon resonance (SPR) coincide, leading to a reduction in emitted PL in the system. The quenching effect of gold nanoparticles on QDs was used to study protein-protein interactions with the potential for drug screening applications. CdTe and CdHgTe QDs with emission wavelengths from 500˜900nm were synthesized and gold nanospheres and nanorods with controlled absorption in the visible and near-infrared (NIR) wavelength regions were prepared. The PL quenching of QD-Protein-Protein-Au complexes was studied as a function of Au concentration, QD size and protein type. A quenching efficiency of up to 90% was observed. The QD-Au complexes were also studied for electric potential sensing. The surface of the QDs was negatively charged due to thiol ligands capping. By applying a positive potential on the gold or gold nanoparticle attached substrate, the local electric field between the substrate and the statically charged QDs would pull the QDs closer to the gold surface and quench the QD PL. PL quenching of QD with Au was studied as a function of electric signal and QD type. In this methodology, electric signals were effectively converted to optical signals.