Differential contribution of sensorimotor cortex and subthalamic nucleus to unimanual and bimanual hand movements.

Why does unilateral deep brain stimulation improve motor function bilaterally? To address this clinical observation, we collected parallel neural recordings from sensorimotor cortex (SMC) and the subthalamic nucleus (STN) during repetitive ipsilateral, contralateral, and bilateral hand movements in patients with Parkinson's disease. We used a cross-validated electrode-wise encoding model to map electromyography data to the neural signals. Electrodes in the STN encoded movement at a comparable level for both hands, whereas SMC electrodes displayed a strong contralateral bias. To examine representational overlap across the two hands, we trained the model with data from one condition (contralateral hand) and used the trained weights to predict neural activity for movements produced with the other hand (ipsilateral hand). Overall, between-hand generalization was poor, and this limitation was evident in both regions. A similar method was used to probe representational overlap across different task contexts (unimanual vs. bimanual). Task context was more important for the STN compared to the SMC indicating that neural activity in the STN showed greater divergence between the unimanual and bimanual conditions. These results indicate that SMC activity is strongly lateralized and relatively context-free, whereas the STN integrates contextual information with the ongoing behavior.

Effects of deep brain stimulation on quantitative sleep electroencephalogram during non-rapid eye movement in Parkinson's disease.

Introduction: Sleep dysfunction is frequently experienced by people with Parkinson's disease (PD) and negatively influences quality of life. Although subthalamic nucleus (STN) deep brain stimulation (DBS) can improve sleep in PD, sleep microstructural features such as sleep spindles provide additional insights about healthy sleep. For example, sleep spindles are important for better cognitive performance and for sleep consolidation in healthy adults. We hypothesized that conventional STN DBS settings would yield a greater enhancement in spindle density compared to OFF and low frequency DBS. Methods: In a previous within-subject, cross-sectional study, we evaluated effects of low (60 Hz) and conventional high (≥130 Hz) frequency STN DBS settings on sleep macroarchitectural features in individuals with PD. In this post hoc, exploratory analysis, we conducted polysomnography (PSG)-derived quantitative electroencephalography (qEEG) assessments in a cohort of 15 individuals with PD who had undergone STN DBS treatment a median 13.5 months prior to study participation. Fourteen participants had unilateral DBS and 1 had bilateral DBS. During three nonconsecutive nights of PSG, the participants were assessed under three different DBS conditions: DBS OFF, DBS LOW frequency (60 Hz), and DBS HIGH frequency (≥130 Hz). The primary objective of this study was to investigate the changes in sleep spindle density across the three DBS conditions using repeated-measures analysis of variance. Additionally, we examined various secondary outcomes related to sleep qEEG features. For all participants, PSG-derived EEG data underwent meticulous manual inspection, with the exclusion of any segments affected by movement artifact. Following artifact rejection, sleep qEEG analysis was conducted on frontal and central leads. The measures included slow wave (SW) and spindle density and morphological characteristics, SW-spindle phase-amplitude coupling, and spectral power analysis during non-rapid eye movement (NREM) sleep. Results: The analysis revealed that spindle density was significantly higher in the DBS HIGH condition compared to the DBS LOW condition. Surprisingly, we found that SW amplitude during NREM was significantly higher in the DBS LOW condition compared to DBS OFF and DBS HIGH conditions. However, no significant differences were observed in the other sleep qEEG features during sleep at different DBS conditions. Conclusion: This study presents preliminary evidence suggesting that conventional HIGH frequency DBS settings enhance sleep spindle density in PD. Conversely, LOW frequency settings may have beneficial effects on increasing slow wave amplitude during sleep. These findings may inform mechanisms underlying subjective improvements in sleep quality reported in association with DBS. Moreover, this work supports the need for additional research on the influence of surgical interventions on sleep disorders, which are prevalent and debilitating non-motor symptoms in PD.

Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia.

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Accuracy of Point-of-Care Ultrasound in Follow Up Abdominal Aortic Aneurysm Imaging.

BACKGROUND: Point-of-care ultrasound (POCUS) has been reported as a valuable tool for bedside diagnoses of abdominal Aortic Aneurysms (AAA). However, no data exist regarding POCUS in measuring follow-up AAA diameter studies in patients with existing AAAs. The purpose of this study was to determine the variability of aortic measurements performed by a non-physician using POCUS vs standard of care (SOC) measurements by a registered vascular technologist or an abdominal/pelvic CT scan. METHODS: A prospective observational ultrasound study was performed from 1/1/2019 to 3/31/2021 on patients with a diagnosis of an AAA (≥3.0 cm). A research coordinator (non-physician) underwent a 3-hour training session in ultrasound operation and basic human anatomy to measure AAA diameter. The maximum aortic diameter was documented and compared to measurements obtained by SOC ultrasonography or CT scan. The POCUS and SOC ultrasounds were separated by no more than 90 days. Clinical risk factors including age, race, body mass index, coronary artery disease, hypertension, peripheral vascular disease, cerebrovascular disease, diabetes, and current smoking were also collected. RESULTS: Eighty-one patients (mean age: 73.6 ± 5.8 years, body mass index: 29.5 ± 6.2 kg/m2) were being followed in a vascular clinic and underwent both a POCUS and SOC ultrasounds. One indeterminant study was reported in identifying an AAA diagnosis, due to an overlying colostomy. The average follow-up time from initial screening aortic diameter to POCUS was 4.4 ± 3.7 years. Overall average aortic diameter measurements obtained were 4.1 ± .9 cm for POCUS and 4.0 ± .9 cm for SOC (P = NS). Average difference in aortic measurement for POCUS and SOC was -.1 ± .3 cm. CONCLUSIONS: POCUS is an accurate method to follow AAA diameter in patients. POCUS could improve patient follow up with AAA diameter measurements, streamline care and reduce overall burden for both patients and Radiology Departments in assessing follow up AAA diameters.

Costs of abdominal aortic aneurysm care at a regional Veterans Affairs medical center with the implementation of an abdominal aortic aneurysm screening program.

BACKGROUND: Abdominal aortic aneurysm (AAA) screening has demonstrated to be cost-effective in reducing AAA-related morbidity and all-cause mortality. However, the downstream care costs of an implemented AAA screening in clinical practice have not been reported. The purpose of this study is to determine direct regional Department of Veterans Affairs (VA) costs in implementing and sustaining an AAA screening program over a 10-year period. METHODS: A cost data analysis (adjusted to 2021 U.S. dollars) of an AAA screening program was conducted from 2007 to 2016, where 19,649 veteran patients aged 65-75 with a smoking history were screened at a regional VA medical center. A decision support system tracked direct and indirect encounter costs from Medicare billing codes associated with AAA care. Costs from a patient's initial screening, follow-up imaging, to AAA repair or at the end of the analysis period, March 31, 2021, were recorded. Costs for AAA repairs outside the VA system were also tracked. RESULTS: A total of 1,183 patients screened were identified with an AAA ≥3.0 cm without history of repair. Estimated screening costs were $2.8 million or $280,000 annually ($143/screening) in the care of 19,649 screened patients. There were 221 patients who required repair (143 repairs in VA, 78 repairs outside VA). The average cost of elective endovascular repair was $43,021 and that of open repair was $49,871. The total costs for all elective repairs were $9,692,591. Screening, implementation, maintenance, and surgical repair cost involved in the management of patients with AAA disease was $13.7 million, with $10,686 per life-year lived after repair (5.8 ± 3.5 mean life-years) and $490 per life-year lived after screening (6.9 ± 3.5 mean life-years) for all patients screened. There were 13 deaths of unknown causes and one patient with a ruptured AAA that required emergency repair at a cost of $124,392. CONCLUSIONS: Despite known limitations, the implementation of an AAA ultrasound screening program is feasible, cost-effective, and a worthwhile endeavor.

Subcortical short-term plasticity elicited by deep brain stimulation.

OBJECTIVE: To investigate local short-term neuroplasticity elicited by subthalamic, thalamic, and pallidal deep brain stimulation (DBS) for movement disorders. METHODS: During DBS surgery, we delivered pairs of stimulus pulses with both circular and directional leads across 90 interstimulus intervals in 17 participants and recorded local field potentials from unused contacts on the implanted electrode array. We removed the stimulus artifact, validated the neural origin of the underlying signals, and examined short-term plasticity as a function of interstimulus interval and DBS target, using linear mixed effects models. RESULTS: DBS evokes short latency local field potentials that are readily detected with both circular and directional leads at all stimulation targets (0.31 ± 0.10 msec peak latency, mean ± SD). Peak amplitude, area, and latency are modified strongly by interstimulus interval (P < 0.001) and display absolute and relative refractory periods (0.56 ± 0.08 and 2.94 ± 1.05 msec, respectively). We also identified later oscillatory activity in the subthalamic-pallidal circuit (4.50 ± 1.11 msec peak latency) that displays paired pulse facilitation (present in 5/8 subthalamic, 4/5 pallidal, and 0/6 thalamic trajectories, P = 0.018, Fisher's exact test), and correlates with resting beta frequency power (P < 0.001), therapeutic DBS frequencies, and stimulation sites chosen later for therapy in the ambulatory setting (P = 0.031). INTERPRETATION: Paired DBS pulses synchronize local circuit electrophysiology and elicit short-term neuroplasticity in the subthalamic-pallidal circuit. Collectively, these responses likely represent the earliest detectable interaction between the DBS pulse and local neuronal tissue in humans. Evoked subcortical field potentials could serve as a predictive biomarker to guide the implementation of next-generation directional and adaptive stimulation devices.

Latency of subthalamic nucleus deep brain stimulation-evoked cortical activity as a potential biomarker for postoperative motor side effects.

OBJECTIVE: Here, we investigate whether cortical activation predicts motor side effects of deep brain stimulation (DBS) and whether these potential biomarkers have utility under general anesthesia. METHODS: We recorded scalp potentials elicited by DBS during surgery (n = 11), both awake and under general anesthesia, and in an independent ambulatory cohort (n = 8). Across a range of stimulus configurations, we measured the amplitude and timing of short- and long-latency response components and linked them to motor side effects. RESULTS: Regardless of anesthesia state, in both cohorts, DBS settings with capsular side effects elicited early responses with peak latencies clustering at <1 ms. This early response was preserved under anesthesia in all participants (11/11). In contrast, the long-latency components were suppressed completely in 6/11 participants. Finally, the latency of the earliest response could predict the presence of postoperative motor side effects both awake and under general anesthesia (84.8% and 75.8% accuracy, awake and under anesthesia, respectively). CONCLUSION: DBS elicits short-latency cortical activation, both awake and under general anesthesia, which appears to reveal interactions between the stimulus and the corticospinal tract. SIGNIFICANCE: Short-latency evoked cortical activity can potentially be used to aid both DBS lead placement and post-operative programming.

A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees.

Peripheral nerves provide a promising source of motor control signals for neuroprosthetic devices. Unfortunately, the clinical utility of current peripheral nerve interfaces is limited by signal amplitude and stability. Here, we showed that the regenerative peripheral nerve interface (RPNI) serves as a biologically stable bioamplifier of efferent motor action potentials with long-term stability in upper limb amputees. Ultrasound assessments of RPNIs revealed prominent contractions during phantom finger flexion, confirming functional reinnervation of the RPNIs in two patients. The RPNIs in two additional patients produced electromyography signals with large signal-to-noise ratios. Using these RPNI signals, subjects successfully controlled a hand prosthesis in real-time up to 300 days without control algorithm recalibration. RPNIs show potential in enhancing prosthesis control for people with upper limb loss.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

INTRODUCTION: Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. METHODS: We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). RESULTS: Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. CONCLUSION: Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Risk of developing an abdominal aortic aneurysm after ectatic aorta detection from initial screening.

OBJECTIVE: Current abdominal aortic aneurysm (AAA) surveillance guidelines lack any follow-up recommendations after initial abdominal aortic screening diameter of less than 3.0 cm. Some reports have demonstrated patients with late AAA formation and late ruptures after initial ultrasound screening detection of patients with an aortic diameter of 2.5 to 2.9 cm (ectatic aorta). The purpose of this study was to determine ectatic aorta prevalence, AAA development, rupture risk, and risk factor profile in patients with detected ectatic aortas in a AAA screening program. METHODS: A retrospective chart review of all patients screened for AAA from January 1, 2007, to December 31, 2016, within a regional health care system was conducted. Screening criteria were men 65 to 75 years of age that smoked a minimum of 100 cigarettes in their lifetime. An ectatic aorta was defined as a maximum aortic diameter from 2.5 to 2.9 cm. An AAA was defined as an aortic diameter of 3 cm or greater. Patients screened with ectatic aortas who had subsequent follow-up imaging of the aorta with a minimum of 1-year follow-up were analyzed for associated clinical and cardiovascular risk factors. All data were collected through December 3,/2018. A logistic regression of statistically significant variables from univariate and χ2 analyses were performed to identify risks associated with the development of AAA from an initially diagnosed ectatic aorta. A Cox proportional hazard model was used to assess survival data. A P value of less than .05 was considered statistically significant. RESULTS: From a screening pool of 19,649 patients, 3205 (16.3%) with a mean age of 72.1 ± 5.3 years were identified to have an ectatic aorta from January 1, 2007, to December 31, 2016. The average screening ectatic aortic diameter was 2.6 ± 0.1 cm. There were 672 patients (21.0%) with a mean age of 73.0 ± 5.7 years who received subsequent imaging for other clinical indications and 193 of these patients (28.7%) with ectatic aortas developed an AAA from the last follow-up scan (4.2 ± 2.5 years). The average observation length of all patients was 6.4 ± 2.9 years. No ruptures were reported, but 27.8% of deaths were of unknown cause. One patient had aortic growth to 5.5 cm or greater (0.15%). Larger initial screening diameter (P < .01), presence of chronic obstructive pulmonary disease (P < .01), and active smoking (P = .01) were associated with AAA development. CONCLUSIONS: Patients with diagnosed ectatic aortas from screening who are active smokers or have chronic obstructive pulmonary disease are likely to develop an AAA.

The 10-year outcomes of a regional abdominal aortic aneurysm screening program.

OBJECTIVE: In 2007, Medicare established ultrasound screening guidelines to identify patients at risk for abdominal aortic aneurysm (AAA). The purpose of this study was to evaluate AAA diagnosis rates and compliance with screening during 10 years (2007-2016) of the Screen for Abdominal Aortic Aneurysms Very Efficiently Act implementation within a regional health care system. METHODS: A retrospective chart review of all patients screened for AAA from 2007 to 2016 within a regional Veterans Affairs health care system was conducted. Screening criteria were men 65 to 75 years of age who smoked a minimum of 100 cigarettes in their lifetime. An AAA was defined as a maximum aortic diameter ≥3 cm. A comparison was made of the AAA diagnosis rate and clinical adherence rate of screening criteria between the first 5 years and total years evaluated. AAA-related mortality was identified by using terminal diagnosis notes or autopsy reports. All data were recorded by August 31, 2017. RESULTS: A total of 19,649 patients (70.7 ± 4.8 years of age, mean ± standard deviation) were screened from January 1, 2007, to December 31, 2016. There were 9916 new patients screened from 2012 to 2016. A total of 1232 aneurysms (6.3% total patients) were identified during the 10-year period. The overall AAA diagnosis rate has declined from 7.2% in the first 5 years to 6.3% in 10 years (13.5% decrease; P < .01). There were 66 patients found with AAA ≥5.5 cm (5.3% of AAAs), and 54 of these patients received successful elective repair. A total of 2321 patients died (11.8%) and 6 deaths were suspected AAA ruptures (0.03%) within the analysis period. A total of 3680 patients screened (18.7%) did not meet screening criteria: 593 patients were <65 years of age, 3087 patients were >75 years of age, and 59 patients were women. This rate has declined from 28.2% within the first 5 years to 18.7% overall in 10 years (33.7% decrease; P < .01). The compliance of screened patients using screening criteria improved significantly from 61.7% in 2007 to 92.4% in 2016 (P < .01). The overall compliance rate since implementation of the screening program during the past 10 years is 81.3%. CONCLUSIONS: The overall 10-year rate of AAA diagnosis is 6.3%. There are more smaller aneurysms (3.0-4.4 cm) detected and fewer large AAAs ≥5.5 cm in the last 5 years compared with the first 5 years of the screening program. The overall AAA-related mortality rate of all screened patients is 0.03%. There were 54 patients with AAA ≥5.5 cm who underwent successful elective repair resulting from the AAA screening program. The overall compliance of screened patients using screening criteria improved significantly from 61.7% in 2007 to 81.3% since implementation of the screening program during the past 10 years.

Design and testing of a 96-channel neural interface module for the Networked Neuroprosthesis system.

BACKGROUND: The loss of motor functions resulting from spinal cord injury can have devastating implications on the quality of one's life. Functional electrical stimulation has been used to help restore mobility, however, current functional electrical stimulation (FES) systems require residual movements to control stimulation patterns, which may be unintuitive and not useful for individuals with higher level cervical injuries. Brain machine interfaces (BMI) offer a promising approach for controlling such systems; however, they currently still require transcutaneous leads connecting indwelling electrodes to external recording devices. While several wireless BMI systems have been designed, high signal bandwidth requirements limit clinical translation. Case Western Reserve University has developed an implantable, modular FES system, the Networked Neuroprosthesis (NNP), to perform combinations of myoelectric recording and neural stimulation for controlling motor functions. However, currently the existing module capabilities are not sufficient for intracortical recordings. METHODS: Here we designed and tested a 1 × 4 cm, 96-channel neural recording module prototype to fit within the specifications to mate with the NNP. The neural recording module extracts power between 0.3-1 kHz, instead of transmitting the raw, high bandwidth neural data to decrease power requirements. RESULTS: The module consumed 33.6 mW while sampling 96 channels at approximately 2 kSps. We also investigated the relationship between average spiking band power and neural spike rate, which produced a maximum correlation of R = 0.8656 (Monkey N) and R = 0.8023 (Monkey W). CONCLUSION: Our experimental results show that we can record and transmit 96 channels at 2ksps within the power restrictions of the NNP system and successfully communicate over the NNP network. We believe this device can be used as an extension to the NNP to produce a clinically viable, fully implantable, intracortically-controlled FES system and advance the field of bioelectronic medicine.

Cortical Decoding of Individual Finger Group Motions Using ReFIT Kalman Filter.

Objective: To date, many brain-machine interface (BMI) studies have developed decoding algorithms for neuroprostheses that provide users with precise control of upper arm reaches with some limited grasping capabilities. However, comparatively few have focused on quantifying the performance of precise finger control. Here we expand upon this work by investigating online control of individual finger groups. Approach: We have developed a novel training manipulandum for non-human primate (NHP) studies to isolate the movements of two specific finger groups: index and middle-ring-pinkie (MRP) fingers. We use this device in combination with the ReFIT (Recalibrated Feedback Intention-Trained) Kalman filter to decode the position of each finger group during a single degree of freedom task in two rhesus macaques with Utah arrays in motor cortex. The ReFIT Kalman filter uses a two-stage training approach that improves online control of upper arm tasks with substantial reductions in orbiting time, thus making it a logical first choice for precise finger control. Results: Both animals were able to reliably acquire fingertip targets with both index and MRP fingers, which they did in blocks of finger group specific trials. Decoding from motor signals online, the ReFIT Kalman filter reliably outperformed the standard Kalman filter, measured by bit rate, across all tested finger groups and movements by 31.0 and 35.2%. These decoders were robust when the manipulandum was removed during online control. While index finger movements and middle-ring-pinkie finger movements could be differentiated from each other with 81.7% accuracy across both subjects, the linear Kalman filter was not sufficient for decoding both finger groups together due to significant unwanted movement in the stationary finger, potentially due to co-contraction. Significance: To our knowledge, this is the first systematic and biomimetic separation of digits for continuous online decoding in a NHP as well as the first demonstration of the ReFIT Kalman filter improving the performance of precise finger decoding. These results suggest that novel nonlinear approaches, apparently not necessary for center out reaches or gross hand motions, may be necessary to achieve independent and precise control of individual fingers.

Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings.

The rate of interictal high frequency oscillations (HFOs) is a promising biomarker of the seizure onset zone, though little is known about its consistency over hours to days. Here we test whether the highest HFO-rate channels are consistent across different 10-min segments of EEG during sleep. An automated HFO detector and blind source separation are applied to nearly 3000 total hours of data from 121 subjects, including 12 control subjects without epilepsy. Although interictal HFOs are significantly correlated with the seizure onset zone, the precise localization is consistent in only 22% of patients. The remaining patients either have one intermittent source (16%), different sources varying over time (45%), or insufficient HFOs (17%). Multiple HFO networks are found in patients with both one and multiple seizure foci. These results indicate that robust HFO interpretation requires prolonged analysis in context with other clinical data, rather than isolated review of short data segments.

Closed-Loop Continuous Hand Control via Chronic Recording of Regenerative Peripheral Nerve Interfaces.

Loss of the upper limb imposes a devastating interruption to everyday life. Full restoration of natural arm control requires the ability to simultaneously control multiple degrees of freedom of the prosthetic arm and maintain that control over an extended period of time. Current clinically available myoelectric prostheses do not provide simultaneous control or consistency for transradial amputees. To address this issue, we have implemented a standard Kalman filter for continuous hand control using intramuscular electromyography (EMG) from both regenerative peripheral nerve interfaces (RPNI) and an intact muscle within non-human primates. Seven RPNIs and one intact muscle were implanted with indwelling bipolar intramuscular electrodes in two rhesus macaques. Following recuperations, function-specific EMG signals were recorded and then fed through the Kalman filter during a hand-movement behavioral task to continuously predict the monkey's finger position. We were able to reconstruct continuous finger movement offline with an average correlation of and a root mean squared error (RMSE) of 0.12 between actual and predicted position from two macaques. This finger movement prediction was also performed in real time to enable closed-loop neural control of a virtual hand. Compared with physical hand control, neural control performance was slightly slower but maintained an average target hit success rate of 96.70%. Recalibration longevity measurements maintained consistent average correlation over time but had a significant change in RMSE ( ). Additionally, extracted single units varied in amplitude by a factor of +18.65% and -25.85% compared with its mean. This is the first demonstration of chronic indwelling electrodes being used for continuous position control via the Kalman filter. Combining these analyses with our novel peripheral nerve interface, we believe that this demonstrates an important step in providing patients with more naturalistic control of their prosthetic limbs.

Robust tactile sensory responses in finger area of primate motor cortex relevant to prosthetic control.

OBJECTIVE: Challenges in improving the performance of dexterous upper-limb brain-machine interfaces (BMIs) have prompted renewed interest in quantifying the amount and type of sensory information naturally encoded in the primary motor cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to tactile stimulation, as well as passive and active movement of the limbs. However, recent work in this area has focused primarily on proprioception. Here we examined instead how tactile somatosensation of the hand and fingers is represented in M1. APPROACH: We recorded multi- and single units and thresholded neural activity from macaque M1 while gently brushing individual finger pads at 2 Hz. We also recorded broadband neural activity from electrocorticogram (ECoG) grids placed on human motor cortex, while applying the same tactile stimulus. MAIN RESULTS: Units displaying significant differences in firing rates between individual fingers (p < 0.05) represented up to 76.7% of sorted multiunits across four monkeys. After normalizing by the number of channels with significant motor finger responses, the percentage of electrodes with significant tactile responses was 74.9% ± 24.7%. No somatotopic organization of finger preference was obvious across cortex, but many units exhibited cosine-like tuning across multiple digits. Sufficient sensory information was present in M1 to correctly decode stimulus position from multiunit activity above chance levels in all monkeys, and also from ECoG gamma power in two human subjects. SIGNIFICANCE: These results provide some explanation for difficulties experienced by motor decoders in clinical trials of cortically controlled prosthetic hands, as well as the general problem of disentangling motor and sensory signals in primate motor cortex during dextrous tasks. Additionally, examination of unit tuning during tactile and proprioceptive inputs indicates cells are often tuned differently in different contexts, reinforcing the need for continued refinement of BMI training and decoding approaches to closed-loop BMI systems for dexterous grasping.

Effect of sampling rate and filter settings on High Frequency Oscillation detections.

OBJECTIVE: High Frequency Oscillations (HFOs) are being studied as a biomarker of epilepsy, yet it is unknown how various acquisition parameters at different centers affect detection and analysis of HFOs. This paper specifically quantifies effects of sampling rate (FS) and anti-aliasing filter (AAF) positions on automated HFO detection. METHODS: HFOs were detected on intracranial EEG recordings (17 patients) with 5kHz FS. HFO detection was repeated on downsampled and/or filtered copies of the EEG data, mimicking sampling rates and low-pass filter settings of various acquisition equipment. For each setting, we compared the HFO detection sensitivity, HFO features, and ability to identify the ictal onset zone. RESULTS: The relative sensitivity remained above 80% for either FS ⩾2kHz or AAF ⩾500Hz. HFO feature distributions were consistent (AUROC<0.7) down to 1kHz FS or 200Hz AAF. HFO rate successfully identified ictal onset zone over most settings. HFO peak frequency was highly variable under most parameters (Spearman correlation<0.5). CONCLUSIONS: We recommend at least FS ⩾2kHz and AAF ⩾500Hz to detect HFOs. Additionally, HFO peak frequency is not robust at any setting: the same HFO event can be variably classified either as a ripple (<200Hz) or fast ripple (>250Hz) under different acquisition settings. SIGNIFICANCE: These results inform clinical centers on requirements to analyze HFO rates and features.

Disruption of corticocortical information transfer during ketamine anesthesia in the primate brain.

The neural mechanisms of anesthetic-induced unconsciousness have yet to be fully elucidated, in part because of the diverse molecular targets of anesthetic agents. We demonstrate, using intracortical recordings in macaque monkeys, that information transfer between structurally connected cortical regions is disrupted during ketamine anesthesia, despite preserved primary sensory representation. Furthermore, transfer entropy, an information-theoretic measure of directed connectivity, decreases significantly between neuronal units in the anesthetized state. This is the first direct demonstration of a general anesthetic disrupting corticocortical information transfer in the primate brain. Given past studies showing that more commonly used GABAergic drugs inhibit surrogate measures of cortical communication, this finding suggests the potential for a common network-level mechanism of anesthetic-induced unconsciousness.

Enabling Low-Power, Multi-Modal Neural Interfaces Through a Common, Low-Bandwidth Feature Space.

Brain-Machine Interfaces (BMIs) have shown great potential for generating prosthetic control signals. Translating BMIs into the clinic requires fully implantable, wireless systems; however, current solutions have high power requirements which limit their usability. Lowering this power consumption typically limits the system to a single neural modality, or signal type, and thus to a relatively small clinical market. Here, we address both of these issues by investigating the use of signal power in a single narrow frequency band as a decoding feature for extracting information from electrocorticographic (ECoG), electromyographic (EMG), and intracortical neural data. We have designed and tested the Multi-modal Implantable Neural Interface (MINI), a wireless recording system which extracts and transmits signal power in a single, configurable frequency band. In prerecorded datasets, we used the MINI to explore low frequency signal features and any resulting tradeoff between power savings and decoding performance losses. When processing intracortical data, the MINI achieved a power consumption 89.7% less than a more typical system designed to extract action potential waveforms. When processing ECoG and EMG data, the MINI achieved similar power reductions of 62.7% and 78.8%. At the same time, using the single signal feature extracted by the MINI, we were able to decode all three modalities with less than a 9% drop in accuracy relative to using high-bandwidth, modality-specific signal features. We believe this system architecture can be used to produce a viable, cost-effective, clinical BMI.