Preliminary Results of Branch Level, Brachial Plexus Peripheral Nerve Stimulation on a Non-Human Primate.

Restoring functional hand control is a priority for those suffering from neurological impairments. Functional electrical stimulation (FES) is commonly applied to assist with rehabilitation. However, FES applied intramuscularly typically results in complex surgeries requiring many implants. This paper presents the preliminary findings from a feasibility study focused on evaluating the potential to access the upper extremity peripheral nerves through a single surgical approach (axillary approach). A single Japanese macaque (macaca fuscata) monkey was used to validate the feasibility of this study. Four of the five peripheral nerves which control the upper extremity were exposed, and had multi-contact epineural cuffs implanted: median, radial, ulnar and musculocutaneous. The axillary nerve was not accessible for epineural cuff placement with the current surgical approach used in this study. Electrical stimuli were used to produce movement contraction patterns of muscles relevant to the innervated peripheral nerves. In addition, to assist in quantifying the outcome, evoked potentials were simultaneously recorded from five extrinsic forearm flexors during median nerve stimulation. This feasibility study demonstrated that the axillary approach enables electrode placement to four of the five peripheral nerves required for upper extremity control through a single skin incision.Clinical relevance- This study demonstrated that the electrode placement to most of the peripheral nerves that control the arm and hand can be done by a single surgical approach: axillary approach.

Chronic subdural electrocorticography in nonhuman primates by an implantable wireless device for brain-machine interfaces.

Background: Subdural electrocorticography (ECoG) signals have been proposed as a stable, good-quality source for brain-machine interfaces (BMIs), with a higher spatial and temporal resolution than electroencephalography (EEG). However, long-term implantation may lead to chronic inflammatory reactions and connective tissue encapsulation, resulting in a decline in signal recording quality. However, no study has reported the effects of the surrounding tissue on signal recording and device functionality thus far. Methods: In this study, we implanted a wireless recording device with a customized 32-electrode-ECoG array subdurally in two nonhuman primates for 15 months. We evaluated the neural activities recorded from and wirelessly transmitted to the devices and the chronic tissue reactions around the electrodes. In addition, we measured the gain factor of the newly formed ventral fibrous tissue in vivo. Results: Time-frequency analyses of the acute and chronic phases showed similar signal features. The average root mean square voltage and power spectral density showed relatively stable signal quality after chronic implantation. Histological examination revealed thickening of the reactive tissue around the electrode array; however, no evident inflammation in the cortex. From gain factor analysis, we found that tissue proliferation under electrodes reduced the amplitude power of signals. Conclusion: This study suggests that subdural ECoG may provide chronic signal recordings for future clinical applications and neuroscience research. This study also highlights the need to reduce proliferation of reactive tissue ventral to the electrodes to enhance long-term stability.

Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.

Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.

Clinical Factors Related to Outcomes in Pediatric Epilepsy Surgery: Insight into Predictors of Poor Surgical Outcome.

Successful surgery for drug-resistant pediatric epilepsy can facilitate motor and cognitive development and improve quality of life by resolution or reduction of epileptic seizures. Therefore, surgery should be considered early in the disease course. However, in some cases, the estimated surgical outcomes are not achieved, and additional surgical treatments are considered. In this study, we investigated the clinical factors related with such unsatisfactory outcomes.We reviewed the clinical data of 92 patients who underwent 112 surgical procedures (69 resection and 53 palliation procedures). Surgical outcomes were assessed according to the postoperative disease status, which was classified as good, controlled, and poor. The following clinical factors were analyzed in relation to surgical outcome: sex, age at onset, etiology (malformation of cortical development, tumor, temporal lobe epilepsy, scar, inflammation, and non-lesional epilepsy), presence of genetic cause, and history of developmental epileptic encephalopathy. At a median of 59 (30-81.25) months after the initial surgery, the disease status was good in 38 (41%), controlled in 39 (42%), and poor in 15 (16%) patients. Among the evaluated factors, etiology exhibited the strongest correlation with surgical outcomes. Tumor-induced and temporal lobe epilepsy were correlated with good, whereas malformation of cortical development, early seizure onset, and presence of genetic cause were correlated with poor disease status. Although epilepsy surgery for the patients who present with the latter factors is challenging, these patients demonstrate a greater need for surgical treatment. Hence, development of more effective surgical options is warranted, including palliative procedures.

Intracranial EEG Recordings of High-Frequency Activity From a Wireless Implantable BMI Device in Awake Nonhuman Primates.

OBJECTIVE: Wireless implantable brain machine interfaces (BMIs) are a promising tool to restore communication and motor functions for individuals with severe motor disability. Prior to clinical application, recording performance must be sufficiently confirmed by animal experiments. In this paper, we aimed to evaluate the performance of a novel BMI wireless device for recording brain activity in two nonhuman primates. METHOD: We customized a wireless device for implantable BMIs for clinical application. We used a battery instead of a wireless power charging system. Thirty-two electrodes were subdurally implanted over the left temporoparietal cortex. We evaluated the recording performance of the wireless device by auditory steady-state responses (ASSRs) and ketamine-induced responses. RESULT: The devices successfully recorded broadband oscillatory activities up to the high-frequency band from the temporal cortex in two awake macaque monkeys. Spectral analysis of raw signals demonstrated that the devices detected characteristic results of a 40-Hz ASSR and prominent high-frequency band activity induced by ketamine injection. CONCLUSION: We confirmed the functionality of the wireless device in recording and transmitting electrocorticography (ECoG) signals with both millisecond precision and recording stability. SIGNIFICANCE: These results provide confidence that this wireless device can be a translational tool for other fundamental neuroscientific studies in free-moving models.

Dual-MEG interbrain synchronization during turn-taking verbal interactions between mothers and children.

Verbal interaction and imitation are essential for language learning and development in young children. However, it is unclear how mother-child dyads synchronize oscillatory neural activity at the cortical level in turn-based speech interactions. Our study investigated interbrain synchrony in mother-child pairs during a turn-taking paradigm of verbal imitation. A dual-MEG (magnetoencephalography) setup was used to measure brain activity from interactive mother-child pairs simultaneously. Interpersonal neural synchronization was compared between socially interactive and noninteractive tasks (passive listening to pure tones). Interbrain networks showed increased synchronization during the socially interactive compared to noninteractive conditions in the theta and alpha bands. Enhanced interpersonal brain synchrony was observed in the right angular gyrus, right triangular, and left opercular parts of the inferior frontal gyrus. Moreover, these parietal and frontal regions appear to be the cortical hubs exhibiting a high number of interbrain connections. These cortical areas could serve as a neural marker for the interactive component in verbal social communication. The present study is the first to investigate mother-child interbrain neural synchronization during verbal social interactions using a dual-MEG setup. Our results advance our understanding of turn-taking during verbal interaction between mother-child dyads and suggest a role for social "gating" in language learning.

Neurophysiological Basis of Deep Brain Stimulation and Botulinum Neurotoxin Injection for Treating Oromandibular Dystonia.

Oromandibular dystonia (OMD) induces severe motor impairments, such as masticatory disturbances, dysphagia, and dysarthria, resulting in a serious decline in quality of life. Non-invasive brain-imaging techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) are powerful approaches that can elucidate human cortical activity with high temporal resolution. Previous studies with EEG and MEG have revealed that movements in the stomatognathic system are regulated by the bilateral central cortex. Recently, in addition to the standard therapy of botulinum neurotoxin (BoNT) injection into the affected muscles, bilateral deep brain stimulation (DBS) has been applied for the treatment of OMD. However, some patients' OMD symptoms do not improve sufficiently after DBS, and they require additional BoNT therapy. In this review, we provide an overview of the unique central spatiotemporal processing mechanisms in these regions in the bilateral cortex using EEG and MEG, as they relate to the sensorimotor functions of the stomatognathic system. Increased knowledge regarding the neurophysiological underpinnings of the stomatognathic system will improve our understanding of OMD and other movement disorders, as well as aid the development of potential novel approaches such as combination treatment with BoNT injection and DBS or non-invasive cortical current stimulation therapies.

Development and evaluation of a new assistive device for low back load reduction in caregivers: an experimental study.

Low back pain among healthcare professionals is associated with the manual handling of patients. Some bed features for turning and repositioning have been developed; however, the load during patient care remains heavy. We developed a device to reduce low back load in caregivers during patient bedside care and evaluated it objectively and subjectively from a caregiver's perspective using a randomised crossover study. Overall, 28 clinical nurses and care workers were randomly assigned to two interventional groups: administering care with (Device method) and without (Manual method) the device in an experimental room. We measured the caregiver's trunk flexion angle using inertial measurement units and video recording during care and then defined a trunk flexion angle of > 45° as the threshold; the variables were analysed using linear mixed models. Subsequently, participants responded to a survey regarding the usability of the device. Trunk flexion time and percentage of time were 26.5 s (95% confidence interval: 14.1 s, 38.9 s) (p < 0.001) and 23.0% (95% confidence interval: 16.4%, 29.6%) (p < 0.001) lower, respectively, in the Device group than in the Manual group. Furthermore, caregivers evaluated the care they could administer with the device as being better than that associated with manual care.

Fully-Automated Spike Detection and Dipole Analysis of Epileptic MEG Using Deep Learning.

Magnetoencephalography (MEG) is a useful tool for clinically evaluating the localization of interictal spikes. Neurophysiologists visually identify spikes from the MEG waveforms and estimate the equivalent current dipoles (ECD). However, presently, these analyses are manually performed by neurophysiologists and are time-consuming. Another problem is that spike identification from MEG waveforms largely depends on neurophysiologists' skills and experiences. These problems cause poor cost-effectiveness in clinical MEG examination. To overcome these problems, we fully automated spike identification and ECD estimation using a deep learning approach fully automated AI-based MEG interictal epileptiform discharge identification and ECD estimation (FAMED). We applied a semantic segmentation method, which is an image processing technique, to identify the appropriate times between spike onset and peak and to select appropriate sensors for ECD estimation. FAMED was trained and evaluated using clinical MEG data acquired from 375 patients. FAMED training was performed in two stages: in the first stage, a classification network was learned, and in the second stage, a segmentation network that extended the classification network was learned. The classification network had a mean AUC of 0.9868 (10-fold patient-wise cross-validation); the sensitivity and specificity were 0.7952 and 0.9971, respectively. The median distance between the ECDs estimated by the neurophysiologists and those using FAMED was 0.63 cm. Thus, the performance of FAMED is comparable to that of neurophysiologists, and it can contribute to the efficiency and consistency of MEG ECD analysis.

Frequency band coupling with high-frequency activities in tonic-clonic seizures shifts from θ to δ band.

OBJECTIVE: To clarify variations in the relationship between high-frequency activities (HFAs) and low-frequency bands from the tonic to the clonic phase in focal to bilateral tonic-clonic seizures (FBTCS), using phase-amplitude coupling. METHODS: This retrospective study enrolled six patients with drug-resistant focal epilepsy who underwent intracranial electrode placement at Osaka University Hospital (July 2018-July 2019). We recorded 11 FBTCS. The synchronization index (SI) and receiver-operating characteristic (ROC) analysis were used to analyze the coupling between HFA amplitude (80-250 Hz) and lower frequencies phase. RESULTS: In the tonic phase, the θ (4-8 Hz)-HFA coupling peaked, and the HFA power occurred at baseline (0 µV) of θ oscillations. In contrast, in the clonic phase, the δ (2-4 Hz)-HFA coupling peaked, and the HFA power occurred at the trough of δ oscillations. ROC analysis indicated that the δ-HFA SI discriminated well the clonic from the tonic phase. CONCLUSIONS: The main low-frequency band modulating the HFA shifted from the θ band in the tonic phase to the δ band in the clonic phase. SIGNIFICANCE: Neurophysiological key frequency bands were implied to be the θ band and δ band in tonic and clonic seizures, respectively, which improves our understanding of FBTCS.

Electrocorticographic effects of acute ketamine on non-human primate brains.

Objective. Acute blockade of glutamate N-methyl-D-aspartate receptors by ketamine induces symptoms and electrophysiological changes similar to schizophrenia. Previous studies have shown that ketamine elicits aberrant gamma oscillations in several cortical areas and impairs coupling strength between the low-frequency phase and fast frequency amplitude, which plays an important role in integrating functional information.Approach. This study utilized a customized wireless electrocorticography (ECoG) recording device to collect subdural signals from the somatosensory and primary auditory cortices in two monkeys. Ketamine was administered at a dose of 3 mg kg-1(intramuscular) or 0.56 mg kg-1(intravenous) to elicit brain oscillation reactions. We analyzed the raw data using methods such as power spectral density, time-frequency spectra, and phase-amplitude coupling (PAC).Main results. Acute ketamine triggered broadband gamma and high gamma oscillation power and decreased lower frequencies. The effect was stronger in the primary auditory cortex than in the somatosensory area. The coupling strength between the low phase of theta and the faster amplitude of gamma/high gamma bands was increased by a lower dose (0.56 mg kg-1iv) and decreased with a higher dose (3 mg kg-1im) ketamine.Significance. Our results showed that lower and higher doses of ketamine elicited differential effects on theta-gamma PAC. These findings support the utility of ECoG models as a translational platform for pharmacodynamic research in future research.

Singing Experience Influences RSST Scores.

It has recently been shown that the aging population is refractory to the maintenance of swallowing function, which can seriously affect quality of life. Singing and vocal training contribute to mastication, swallowing and respiratory function. Previous studies have shown that singers have better vocal cord health. No consensus has been reached as to how vocal training affects swallowing ability. Our study was designed to establish evidence that singers are statistically superior at inducing the swallowing reflex. To test our hypothesis, we undertook a clinical trial on 55 singers and 141 non-singers (mean age: 60.1 ± 11.7 years). This cross-sectional study with propensity score matching resulted in significant differences in a repetitive saliva swallowing test among singers: 7.1 ± 2.4, n = 53 vs. non-singers: 5.9 ± 1.9, n = 53, p < 0.05. We conclude that singing can serve an important role in stabilizing the impact of voluntary swallowing on speech.

Masked diabetes insipidus in pituitary metastasis from breast cancer after thalamic biopsy: a case report.

BACKGROUND: Symptomatic pituitary metastasis is rare; furthermore, it can result in diabetes insipidus and panhypopituitarism. Since diabetes insipidus is masked by concurrent panhypopituitarism, it can impede the diagnosis of pituitary dysfunction. CASE PRESENTATION: A 68-year-old Japanese female suffering from pituitary and thalamic metastases caused by untreated breast cancer, underwent a biopsy targeting the thalamus, not the pituitary. She lacked prebiopsy pituitary dysfunction symptoms; however, these symptoms unexpectedly occurred after biopsy. Diabetes insipidus was masked by corticosteroid insufficiency, and she showed normal urinary output and plasma sodium levels. Upon commencement of glucocorticoid replacement therapy, the symptoms of diabetes insipidus appeared. CONCLUSIONS: In this case, thalamic biopsy, as opposed to pituitary biopsy, was performed to preserve pituitary function. However, pituitary dysfunction could not be avoided. Caution is necessary for asymptomatic patients with pituitary metastases as invasive interventions, such as surgery, may induce pituitary dysfunction. Moreover, with respect to masked diabetes insipidus, there is a need to carefully consider pituitary dysfunction to avoid misdiagnosis and delayed treatment.

Functional cortical localization of tongue movements using corticokinematic coherence with a deep learning-assisted motion capture system.

Corticokinematic coherence (CKC) between magnetoencephalographic and movement signals using an accelerometer is useful for the functional localization of the primary sensorimotor cortex (SM1). However, it is difficult to determine the tongue CKC because an accelerometer yields excessive magnetic artifacts. Here, we introduce a novel approach for measuring the tongue CKC using a deep learning-assisted motion capture system with videography, and compare it with an accelerometer in a control task measuring finger movement. Twelve healthy volunteers performed rhythmical side-to-side tongue movements in the whole-head magnetoencephalographic system, which were simultaneously recorded using a video camera and examined using a deep learning-assisted motion capture system. In the control task, right finger CKC measurements were simultaneously evaluated via motion capture and an accelerometer. The right finger CKC with motion capture was significant at the movement frequency peaks or its harmonics over the contralateral hemisphere; the motion-captured CKC was 84.9% similar to that with the accelerometer. The tongue CKC was significant at the movement frequency peaks or its harmonics over both hemispheres. The CKC sources of the tongue were considerably lateral and inferior to those of the finger. Thus, the CKC with deep learning-assisted motion capture can evaluate the functional localization of the tongue SM1.

Phase-amplitude coupling between infraslow and high-frequency activities well discriminates between the preictal and interictal states.

Infraslow activity (ISA) and high-frequency activity (HFA) are key biomarkers for studying epileptic seizures. We aimed to elucidate the relationship between ISA and HFA around seizure onset. We enrolled seven patients with drug-resistant focal epilepsy who underwent intracranial electrode placement. We comparatively analyzed the ISA, HFA, and ISA-HFA phase-amplitude coupling (PAC) in the seizure onset zone (SOZ) or non-SOZ (nSOZ) in the interictal, preictal, and ictal states. We recorded 15 seizures. HFA and ISA were larger in the ictal states than in the interictal or preictal state. During seizures, the HFA and ISA of the SOZ were larger and occurred earlier than those of nSOZ. In the preictal state, the ISA-HFA PAC of the SOZ was larger than that of the interictal state, and it began increasing at approximately 87 s before the seizure onset. The receiver-operating characteristic curve revealed that the ISA-HFA PAC of the SOZ showed the highest discrimination performance in the preictal and interictal states, with an area under the curve of 0.926. This study demonstrated the novel insight that ISA-HFA PAC increases before the onset of seizures. Our findings indicate that ISA-HFA PAC could be a useful biomarker for discriminating between the preictal and interictal states.

Motor and sensory cortical processing of neural oscillatory activities revealed by human swallowing using intracranial electrodes.

Swallowing is attributed to the orchestration of motor output and sensory input. We hypothesized that swallowing can illustrate differences between motor and sensory neural processing. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus. Mouth opening and swallowing were treated as motor tasks, whereas water injection was treated as a sensory task. Phase-amplitude coupling between lower-frequency and high γ (HG) bands (75-150 Hz) was investigated. An α (10-16 Hz)-HG coupling appeared before motor-related HG power increases (burst), and a θ (5-9 Hz)-HG coupling appeared during sensory-related HG bursts. The peaks of motor-related coupling were 0.6-0.7 s earlier than that of HG power. The motor-related HG was modulated at the trough of the α oscillation, and the sensory-related HG amplitude was modulated at the peak of the θ oscillation. These contrasting results can help to elucidate the brain's sensory motor functions.

Effects of familiarity on child brain networks when listening to a storybook reading: A magneto-encephalographic study.

Parent-child book reading is important for fostering the development of various lifelong cognitive and social abilities in young children. Despite numerous reports describing the effects of familiarity on shared reading for children, the exact neural basis of the functional network architecture remains unclear. We conducted Magnet-Encephalographic (MEG) experiments using graph theory to elucidate the role of familiarity in shared reading in a child's brain network and to measure the connectivity dynamics of a child while Listening to Storybook Reading (LSBR), which represents the daily activity of shared book reading between the child and caregiver. The LSBR task was performed with normally developing preschool- and school-age children (N = 15) under two conditions: reading by their own mother (familiar condition) vs. an experimenter (unfamiliar condition). We used the phase lag index (PLI), which captures synchronization of MEG signals, to estimate functional connectivity. For the whole brain network topology, an undirected weighted graph was produced using 68 brain regions as nodes and interregional PLI values as edges for five frequency bands. Behavioral data (i.e., the degree of attention and facial expressions) were evaluated from video images of the child's face during the two conditions. Our results showed enhanced widespread functional connectivity in the alpha band during the mother condition. In the mother condition, the whole brain network in the alpha band exhibited topographically high local segregation with high global integration, indicating an increased small-world property. Results of the behavioral analysis revealed that children were more attentive and showed more positive facial expressions in the mother condition than in the experimenter condition. Behavioral data were significantly correlated with graph metrics in the mother condition but not in the experimenter condition. In this study, we identified the neural correlates of a familiarity effect in children's brain connectivity dynamics during LSBR. Furthermore, these familiarity-related brain dynamics were closely linked to the child's behavior. Graph theory applied to MEG data may provide useful insight into the familiarity-related child brain response in a naturalistic setting and its relevance to child attitudes.

Relationship between the Surface Roughness of Material and Bone Cement: An Increased "Polished" Stem May Result in the Excessive Taper-Slip.

Although some reports suggest that taper-slip cemented stems may be associated with a higher periprosthetic femoral fractures rate than composite-beam cemented stems, few studies have focused on the biomaterial effect of the polished material on the stem-cement interface. The purpose of this study was to investigate the relationship between surface roughness of materials and bone cement. Four types of metal discs-cobalt-chromium-molybdenum alloy (CoCr), stainless steel alloy 316 (SUS), and two titanium alloys (Ti-6Al-4V and Ti-15Mo-5Zr-3Al)-were prepared. Five discs of each material were produced with varying degrees of surface roughness. In order to evaluate surface wettability, the contact angle was measured using the sessile drop method. A pin was made using two bone cements and the frictional coefficient was assessed with a pin-on-disc test. The contact angle of each metal increased with decreasing surface roughness and the surface wettability of metal decreased with higher degrees of polishing. With a surface roughness of Ra = 0.06 µm and moderate viscosity bone cement, the frictional coefficient was significantly lower in CoCr than in SUS (p = 0.0073). In CoCr, the low adhesion effect with low frictional coefficient may result in excessive taper-slip, especially with the use of moderate viscosity bone cement.

Swallowing-related neural oscillation: an intracranial EEG study.

OBJECTIVE: Swallowing is a unique movement due to the indispensable orchestration of voluntary and involuntary movements. The transition from voluntary to involuntary swallowing is executed within milliseconds. We hypothesized that the underlying neural mechanism of swallowing would be revealed by high-frequency cortical activities. METHODS: Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus and cortical oscillatory changes, including the high γ band (75-150 Hz) and ß band (13-30 Hz), were investigated at the time of mouth opening, water injection, and swallowing. RESULTS: Increases in high γ power associated with mouth opening were observed in the ventrolateral prefrontal cortex (VLPFC) with water injection in the lateral central sulcus and with swallowing in the region along the Sylvian fissure. Mouth opening induced a decrease in ß power, which continued until the completion of swallowing. The high γ burst of activity was focal and specific to swallowing; however, the ß activities were extensive and not specific to swallowing. In the interim between voluntary and involuntary swallowing, swallowing-related high γ power achieved its peak, and subsequently, the power decreased. INTERPRETATION: We demonstrated three distinct activities related to mouth opening, water injection, and swallowing induced at different timings using high γ activities. The peak of high γ power related to swallowing suggests that during voluntary swallowing phases, the cortex is the main driving force for swallowing as opposed to the brain stem.