Recruitment and Differential Firing Patterns of Single Units During Conditioning to a Tone in a Mute Locked-In Human.

Single units that are not related to the desired task can become related to the task by conditioning their firing rates. We theorized that, during conditioning of firing rates to a tone, (a) unrelated single units would be recruited to the task; (b) the recruitment would depend on the phase of the task; (c) tones of different frequencies would produce different patterns of single unit recruitment. In our mute locked-in participant, we conditioned single units using tones of different frequencies emitted from a tone generator. The conditioning task had three phases: Listen to the tone for 20 s, then silently sing the tone for 10 s, with a prior control period of resting for 10 s. Twenty single units were recorded simultaneously while feedback of one of the twenty single units was made audible to the mute locked-in participant. The results indicate that (a) some of the non-audible single units were recruited during conditioning, (b) some were recruited differentially depending on the phase of the paradigm (listen, rest, or silent sing), and (c) single unit firing patterns were specific for different tone frequencies such that the tone could be recognized from the pattern of single unit firings. These data are important when conditioning single unit firings in brain-computer interfacing tasks because they provide evidence that increased numbers of previously unrelated single units can be incorporated into the task. This incorporation expands the bandwidth of the recorded single unit population and thus enhances the brain-computer interface. This is the first report of conditioning of single unit firings in a human participant with a brain to computer implant.

Slow Firing Single Units Are Essential for Optimal Decoding of Silent Speech.

The motivation of someone who is locked-in, that is, paralyzed and mute, is to find relief for their loss of function. The data presented in this report is part of an attempt to restore one of those lost functions, namely, speech. An essential feature of the development of a speech prosthesis is optimal decoding of patterns of recorded neural signals during silent or covert speech, that is, speaking "inside the head" with output that is inaudible due to the paralysis of the articulators. The aim of this paper is to illustrate the importance of both fast and slow single unit firings recorded from an individual with locked-in syndrome and from an intact participant speaking silently. Long duration electrodes were implanted in the motor speech cortex for up to 13 years in the locked-in participant. The data herein provide evidence that slow firing single units are essential for optimal decoding accuracy. Additional evidence indicates that slow firing single units can be conditioned in the locked-in participant 5 years after implantation, further supporting their role in decoding.

Performance Characteristics of a Novel 3D-Printed Bubble Intermittent Mandatory Ventilator (B-IMV) for Adult Pulmonary Support.

The COVID-19 pandemic has brought attention to the need for developing effective respiratory support that can be rapidly implemented during critical surge capacity scenarios in healthcare settings. Lung support with bubble continuous positive airway pressure (B-CPAP) is a well-established therapeutic approach for supporting neonatal patients. However, the effectiveness of B-CPAP in larger pediatric and adult patients has not been addressed. Using similar principles of B-CPAP pressure generation, application of intermittent positive pressure inflations above CPAP could support gas exchange and high work of breathing levels in larger patients experiencing more severe forms of respiratory failure. This report describes the design and performance characteristics of the BubbleVent, a novel 3D-printed valve system that combined with commonly found tubes, hoses, and connectors can provide intermittent mandatory ventilation (IMV) suitable for adult mechanical ventilation without direct electrification. Testing of the BubbleVent was performed on a passive adult test lung model and compared with a critical care ventilator commonly used in tertiary care centers. The BubbleVent was shown to deliver stable PIP and PEEP levels, as well as timing control of breath delivery that was comparable with a critical care ventilator.

Emphysematous cholecystitis following routine colonoscopy.

Cholecystitis is a rare sequela of colonoscopy, the relationship between which has not yet been defined. This case study reviews a rural elderly patient who developed right upper quadrant pain following routine colonoscopy. He developed emphysematous cholecystitis, which required laparoscopy with conversion to open via Kocher's incision and underwent a subtotal cholecystectomy due to the severity of necrosis and inflammation. He had an uncomplicated recovery. Colonoscopy is an important diagnostic procedure, the most common complications of which are haemorrhage and perforation. There are less than 10 cases of associated cholecystitis and no reports of emphysematous cholecystitis. The hypothesized pathogenesis is dehydration and lithogenesis associated with traumatic translocation of organisms, however, no definitive correlation has been determined. Due to the potential health impact, cholecystitis cannot be excluded regarding post-colonoscopy abdominal pain, however, the correlation between procedure and pathology remains unclear.

Histological Confirmation of Myelinated Neural Filaments Within the Tip of the Neurotrophic Electrode After a Decade of Neural Recordings.

AIM: Electrodes that provide brain to machine or computer interfacing must survive the lifetime of the person to be considered an acceptable prosthetic. The electrodes may be external such as with electroencephalographic (EEG), internal extracortical such as electrocorticographic (ECoG) or intracortical. METHODS: Most intracortical electrodes are placed close to the neuropil being recorded and do not survive years of recording. However, the Neurotrophic Electrode is placed within the cortex and the neuropil grows inside and through the hollow tip of the electrode and is thus trapped inside. Highly flexible coiled lead wires minimize the strain on the electrode tip. Histological analysis includes immunohistochemical detection of neurofilaments and the absence of gliosis. RESULTS: This configuration led to a decade long recording in this locked-in person. At year nine, the neural activity underwent conditioning experiments indicating that the neural activity was functional and not noise. This paper presents data on the histological analysis of the tissue inside the electrode tip after 13 years of implantation. CONCLUSION: This paper is a singular example of histological analysis after a decade of recording. The histological analysis laid out herein is strong evidence that the brain can grow neurites into the electrode tip and record for a decade. This is profoundly important in the field of brain to machine or computer interfacing by implying that long term electrodes should incorporate some means of growing the neuropil into the electrode rather than placing the electrode into the neuropil.

Detecting Silent Vocalizations in a Locked-In Subject.

Problem Addressed. Decoding of silent vocalization would be enhanced by detecting vocalization onset. This is necessary in order to improve decoding of neural firings and thus synthesize near conversational speech in locked-in subjects implanted with brain computer interfacing devices. Methodology. Cortical recordings were obtained during attempts at inner speech in a mute and paralyzed subject (ER) implanted with a recording electrode to detect and analyze lower beta band peaks meeting the criterion of a minimum 0.2% increase in the power spectrum density (PSD). To provide supporting data, three speaking subjects were used in a similar testing paradigm using EEG signals recorded over the speech area. Results. Conspicuous lower beta band peaks were identified around the time of assumed speech onset. The correlations between single unit firings, recorded at the same time as the continuous neural signals, were found to increase after the lower beta band peaks as compared to before the peaks. Studies in the nonparalyzed control individuals suggested that the lower beta band peaks were related to the movement of the articulators of speech (tongue, jaw, and lips), not to higher order speech processes. Significance and Potential Impact. The results indicate that the onset of silent and overt speech is associated with a sharp peak in lower beta band activity-an important step in the development of a speech prosthesis. This raises the possibility of using these peaks in online applications to assist decoding paradigms being developed to decode speech from neural signal recordings in mute humans.

Changes in emotional state modulate neuronal firing rates of human speech motor cortex: a case study in long-term recording.

In many brain areas, modulations in neuronal firing rates are thought to code information. However, in electrophysiological recording experiments, especially recordings in human patients, the type of information that is coded by a neuron's discharge patterns is often not known, or difficult to determine. From our long experience with chronic recordings in humans, we have come to suspect that such unexplained modulations in firing rates are often due to state changes in the subject. We here present two case studies, with extensive data in one subject to illustrate the point that a change in the subject's emotions, such as sudden fear, surprise, or happiness, may trigger substantial changes in firing rates.

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.

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.

Brain-Computer Interfaces for Speech Communication.

This paper briefly reviews current silent speech methodologies for normal and disabled individuals. Current techniques utilizing electromyographic (EMG) recordings of vocal tract movements are useful for physically healthy individuals but fail for tetraplegic individuals who do not have accurate voluntary control over the speech articulators. Alternative methods utilizing EMG from other body parts (e.g., hand, arm, or facial muscles) or electroencephalography (EEG) can provide capable silent communication to severely paralyzed users, though current interfaces are extremely slow relative to normal conversation rates and require constant attention to a computer screen that provides visual feedback and/or cueing. We present a novel approach to the problem of silent speech via an intracortical microelectrode brain computer interface (BCI) to predict intended speech information directly from the activity of neurons involved in speech production. The predicted speech is synthesized and acoustically fed back to the user with a delay under 50 ms. We demonstrate that the Neurotrophic Electrode used in the BCI is capable of providing useful neural recordings for over 4 years, a necessary property for BCIs that need to remain viable over the lifespan of the user. Other design considerations include neural decoding techniques based on previous research involving BCIs for computer cursor or robotic arm control via prediction of intended movement kinematics from motor cortical signals in monkeys and humans. Initial results from a study of continuous speech production with instantaneous acoustic feedback show the BCI user was able to improve his control over an artificial speech synthesizer both within and across recording sessions. The success of this initial trial validates the potential of the intracortical microelectrode-based approach for providing a speech prosthesis that can allow much more rapid communication rates.

Conditional same-different discrimination by pigeons: acquisition and generalization to novel and few-item displays.

The authors explored whether pigeons can learn to discriminate simultaneously presented arrays of 16 identical (Same) visual items from arrays of 16 nonidentical (Different) visual items, when the correct choice was conditional on the presence of another cue: the color of the background. In one experiment, pigeons rapidly learned this task and, after training with arrays created from a 72-icon set, they exhibited nearly perfect transfer to novel testing arrays. In a second experiment, pigeons' accuracy to 24-, 20-, 12-, and 8-icon arrays during later testing remained as high as accuracy to training arrays; although accuracy declined with 4- and 2-icon arrays, it was still significantly above chance. In both experiments, pigeons' choice reaction time scores nicely complemented their choice accuracy scores. These results suggest that the conditional discrimination procedure is well suited to disclose same-different discrimination in pigeons and to elucidate the interaction between perception and abstraction in conceptual learning.

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 volunteer's 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.

Subphrenic abscess secondary to Actinomycosis meyeri and Klebsiella ozaenae following laparoscopic cholecystectomy.

A case is reported of a subphrenic abscess 12 months post-laparoscopic cholecystectomy in a 72-year-old male with identification of Actinomyces meyeri and the oropharyngeal commensal Klebsiella ozaenae. The first organism is exceptionally rare following laparoscopic cholecystectomy and is presumed to be a result of inadvertent gallstone spillage. The second organism has not previously been reported in a subphrenic abscess. The etiopathogenesis and management of this condition are presented.

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.

Computer control using human intracortical local field potentials.

We describe the use of human cortical control signals to operate two assistive technology tools--a virtual keyboard speller and a computer-simulated digit. The cortical signals used for control are local field potentials recorded through an implanted neurotrophic electrode. In this system, the patients' cortical signals are transmitted wirelessly to a receiver and translated by computer software into either a computer cursor movement (for the virtual keyboard) or flexion of a cyber digit on a virtual hand. This report focuses on the progress of two subjects toward effective use of their "virtual" neuro-prosthetic devices to meet their assistive technology needs.

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.