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Objective. Current intracortical brain-computer interfaces (iBCIs) rely predominantly on threshold crossings ('spikes') for decoding neural activity into a control signal for an external device. Spiking data can yield high accuracy online control during complex behaviors; however, its dependence on high-sampling-rate data collection can pose challenges. An alternative signal for iBCI decoding is the local field potential (LFP), a continuous-valued signal that can be acquired simultaneously with spiking activity. However, LFPs are seldom used alone for online iBCI control as their decoding performance has yet to achieve parity with spikes. Approach. Here, we present a strategy to improve the performance of LFP-based decoders by first training a neural dynamics model to use LFPs to reconstruct the firing rates underlying spiking data, and then decoding from the estimated rates. We test these models on previously-collected macaque data during center-out and random-target reaching tasks as well as data collected from a human iBCI participant during attempted speech. Main results. In all cases, training models from LFPs enables firing rate reconstruction with accuracy comparable to spiking-based dynamics models. In addition, LFP-based dynamics models enable decoding performance exceeding that of LFPs alone and approaching that of spiking-based models. In all applications except speech, LFP-based dynamics models also facilitate decoding accuracy exceeding that of direct decoding from spikes. Significance. Because LFP-based dynamics models operate on lower bandwidth and with lower sampling rate than spiking models, our findings indicate that iBCI devices can be designed to operate with lower power requirements than devices dependent on recorded spiking activity, without sacrificing high-accuracy decoding., (Creative Commons Attribution license.)

Understanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the "motor homunculus"). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map. Here, we revisit the motor homunculus using microelectrode array recordings from 20 arrays that broadly sample PCG across 8 individuals, creating a comprehensive map of human motor cortex at single neuron resolution. We found whole-body representations throughout all sampled points of PCG, contradicting traditional leg/arm/face boundaries. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them, previously unaccounted for by the homunculus. Throughout PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (e.g., toe curl and hand close) having correlated representations. Our findings indicate that, while the classic homunculus aligns with each area's preferred body region at a coarse level, at a finer scale, PCG may be better described as a mosaic of functional zones, each with its own whole-body representation.

A novel transverse velocity spectral estimation method is proposed to estimate the velocity component in the direction transverse to the beam axis for ultrafast imaging. The transverse oscillation was introduced by filtering the envelope data after the axial oscillation was removed. The complex transverse oscillated signal was then used to estimate the transverse velocity spectrum and mean velocity. In simulations, both steady flow with a parabolic flow profile and temporally varying flow were simulated to investigate the performance of the proposed method. Next, the proposed approach was used to estimate the flow velocity in a phantom with pulsatile flow, and finally, this method was applied in vivo in a small animal model. Results of the simulation study indicate that the proposed method provided an accurate velocity spectrogram for beam-to-flow angles from 45° to 90°, without significant performance degradation as the angle decreased. For the simulation of temporally varying flow, the proposed method had a reduced bias ( % versus 73.3%) and higher peak-to-background ratio (PBR) (>15.6 versus 10.5 dB) compared to previous methods. Results in a vessel phantom show that the temporally varying flow velocity can be estimated in the transverse direction obtained using the spectrogram produced by the proposed method operating on the envelope data. Finally, the proposed method was used to map the microvascular blood flow velocity in the mouse spinal cord, demonstrating the estimation of pulsatile blood flow in both the axial and transverse directions in vivo over several cardiac cycles.

The regional brain networks and the underlying neurophysiological mechanisms subserving the cognition of visual narrative in humans have largely been studied with non-invasive brain recording. In this study, we specifically investigated how regional and cross-regional cortical activities support visual narrative interpretation using intracranial stereotactic electroencephalograms recordings from thirteen human subjects (6 females, and 7 males). Widely distributed recording sites across the brain were sampled while subjects were explicitly instructed to observe images from fables presented in "sequential" order, and a set of images drawn from multiple fables presented in "scrambled" order. Broadband activity mainly within the frontal and temporal lobes were found to encode if a presented image is part of a visual narrative (sequential) or random image set (scrambled). Moreover, the temporal lobe exhibits strong activation in response to visual narratives while the frontal lobe is more engaged when contextually novel stimuli are presented. We also investigated the dynamics of interregional interactions between visual narratives and contextually novel series of images. Interestingly, the interregional connectivity is also altered between sequential and scrambled sequences. Together, these results suggest that both changes in regional neuronal activity and cross-regional interactions subserve visual narrative and contextual novelty processing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sabra, Alawieh, Bonilha, Naselaris and AuYong.)

Objective: Facial pain refractory to medical treatments may benefit from neurosurgical interventions. Only a few studies have reported on the efficacy of peripheral trigeminal stimulation and more specifically supraorbital nerve (SON) and infraorbital nerve (ION) stimulation for the treatment of facial pain., Patients and Methods: In the present study, we identified all patients at our institution who underwent SON and/or ION stimulation for treatment of facial pain due to post-herpetic, traumatic or idiopathic etiology. Relevant pre and post-operative outcomes were analyzed., Results: We identified 15 patients who underwent SON and/or ION stimulation. Among them, 12 (80 %) endorsed >50 % pain relief during the trial stimulation period. After a median follow-up of 5.8 months with permanent implantation, 1 patient (8.3 %) was diagnosed with lead erosion and IPG migration, two patients had lead infections (16.7 %) and one (8.3 %) had wound dehiscence. No lead migrations were identified during the long-term follow-up. The VAS score showed a statistically significant reduction from a median pre-operative score of 7 to a post-operative score of 1.8 (p = 0.011), which corresponded to a 74.3 % average pain reduction., Conclusion: SON and/or ION stimulation can be an effective treatment for intractable facial pain due to post-herpetic, traumatic or idiopathic etiology; however the complication rate is relatively high. Future prospective studies with longer follow-up periods are warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

β hypersynchrony within the basal ganglia-thalamocortical (BGTC) network has been suggested as a hallmark of Parkinson disease (PD) pathophysiology. Subthalamic nucleus (STN)-DBS has been shown to alter cortical-subcortical synchronization. It is unclear whether this is a generalizable phenomenon of therapeutic stimulation across targets., Objectives: We aimed to evaluate whether DBS of the globus pallidus internus (GPi) results in cortical-subcortical desynchronization, despite the lack of monosynaptic connections between GPi and sensorimotor cortex., Approach: We recorded local field potentials from the GPi and electrocorticographic signals from the ipsilateral sensorimotor cortex, off medications in nine PD patients, undergoing DBS implantation. We analyzed both local oscillatory power and functional connectivity (coherence and debiased weighted phase lag index (dWPLI)) with and without stimulation while subjects were resting with eyes open., Main Results: DBS significantly suppressed low β power within the GPi (-26.98%  ±  15.14%), p  <  0.05) without modulation of sensorimotor cortical β power (low or high). In contrast, stimulation suppressed pallidocortical high β coherence (-38.89%  ±  6.19%, p  =  0.02) and dWPLI (-61.40%  ±  8.75%, p  =  0.02). Changes in cortical-subcortical functional connectivity were spatially specific to the motor cortex., Significance: We highlight the role of DBS in desynchronizing network activity, particularly in the high β band. The current study of GPi-DBS suggests these network-level effects are not necessarily dependent and potentially may be independent of the hyperdirect pathway. Importantly, these results draw a sharp distinction between the potential significance of low β oscillations locally within the basal ganglia and high β oscillations across the BGTC motor circuit.

There is converging evidence that bilateral basal ganglia motor networks jointly support normal movement behaviors including unilateral movements. The extent and manner in which these networks interact during lateralized movement remains unclear. In this study, simultaneously recorded bilateral Globus Pallidus interna (GPi) local field potentials (LFP) were examined from 19 subjects with idiopathic Parkinson disease (PD), while undergoing awake deep brain stimulation (DBS) implantation. Recordings were carried out during two behavioral states; rest and cued left hand movement (finger tapping). The state-dependent effects on α- β oscillatory power and β phase-encoded phase amplitude coupling (PAC), including symmetrical and assymetrical changes between hemispheres, were identified. Unilateral hand movement resulted in symmetrical oscillatory power suppression within bilateral GPi at α (8-12 Hz) and high β (21-35 Hz) and increase in power of high frequency oscillations (HFO, 200-300 Hz) frequency bands. Asymmetrical attenuation was also observed at both low β (13-20 Hz) and low γ (40-80 Hz) bands within the contralateral GPi ( P = 0.009). In addition, unilateral movement effects on PAC were confined to the contralateral GPi with attenuation of both low β-low γ and β-HFO PAC ( P < 0.05). Further analysis showed that the lateralized attenuation of low β and low γ power did not correlate with low β-low γ PAC changes. The overall coherence between bilateral GPi was not significantly altered with unilateral movement, however the preferred phase difference in the high β range increased from 0.23 (±1.31) radians during rest to 1.99 (±0.78) radians during movement execution. Together, the present results suggest that unilateral motor control involves bilateral basal ganglia networks with movement features differentially encoded by distinct frequency bands. The lateralization of low β and low γ attenuation with movement suggests that these frequency bands are specific to the motor act whereas symmetrical expression of α, high β, and HFO oscillations best correspond to motor state. The restriction of movement-related PAC modulation to the contralateral GPi indicates that cross-frequency interactions appear to be associated with lateralized movements. Despite no significant movement-related changes in the interhemispheric coherence, the increase in phase difference suggests that the communication between bilateral GPi is altered with unilateral movement.

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are equally efficacious in the management of Parkinson disease (PD). Studies of STN-DBS have revealed a therapeutic reduction in excessive cortical β-γ phase-amplitude coupling (PAC). It is unclear whether this is specific to STN-DBS and potentially mediated by modulation of the hyperdirect pathway or if it is a generalizable mechanism seen with DBS of other targets. Moreover, it remains unclear how cortical signals are differentially modulated by movement versus therapy. To clarify, the effects of GPi-DBS and movement on cortical β power and β-γ PAC were examined., Methods: Right sensorimotor electrocorticographic signals were recorded in 10 PD patients undergoing GPi-DBS implantation surgery. We evaluated cortical β power and β-γ PAC during blocks of rest and contralateral hand movement (finger tapping) with GPi-DBS off and on., Results: Movement suppressed cortical low β power (P = 0.008) and high β-γ PAC (P = 0.028). Linear mixed effect modeling (LMEM) showed that power in low and high β bands are differentially modulated by movement (P = 0.022). GPi-DBS also results in a significant suppression of high β-γ PAC but without power modulation in either β sub-band (P = 0.008). Cortical high β-γ PAC is significantly correlated with severity of bradykinesia (Rho = 0.59, P = 0.045) and changes proportionally with therapeutic improvement (Rho = 0.61, P = 0.04)., Conclusions: Similar to STN-DBS, GPi-DBS reduces motor cortical β-γ PAC, like that also reported with dopaminergic mediations, suggesting it is a generalizable symptom biomarker in PD, independent of therapeutic target or proximity to the hyperdirect pathway., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Anesthetics are believed to alter functional connectivity across brain regions. However, network-level analyses of anesthesia, particularly in humans, are sparse. The authors hypothesized that propofol-induced loss of consciousness results in functional disconnection of human sensorimotor cortices underlying the loss of volitional motor responses., Methods: The authors recorded local field potentials from sensorimotor cortices in patients with Parkinson disease (N = 12) and essential tremor (N = 7) undergoing deep brain stimulation surgery, before and after propofol-induced loss of consciousness. Local spectral power and interregional connectivity (coherence and imaginary coherence) were evaluated separately across conditions for the two populations., Results: Propofol anesthesia caused power increases for frequencies between 2 and 100 Hz across the sensorimotor cortices and a shift of the dominant spectral peak in α and β frequencies toward lower frequencies (median ± SD peak frequency: 24.5 ± 2.6 Hz to 12.8 ± 2.3 Hz in Parkinson disease; 13.8 ± 2.1 Hz to 12.1 ± 1.0 Hz in essential tremor). Despite local increases in power, sensorimotor cortical coherence was suppressed with propofol in both cohorts, specifically in β frequencies (18 to 29 Hz) for Parkinson disease and α and β (10 to 48 Hz) in essential tremor., Conclusions: The decrease in functional connectivity between sensory and motor cortices, despite an increase in local spectral power, suggests that propofol causes a functional disconnection of cortices with increases in autonomous activity within cortical regions. This pattern occurs across diseases evaluated, suggesting that these may be generalizable effects of propofol in patients with movement disorders and beyond. Sensorimotor network disruption may underlie anesthetic-induced loss of volitional control.

Background/aims: There are reports that microelectrode recording (MER) can be performed under certain anesthetized conditions for functional confirmation of the optimal deep brain stimulation (DBS) target. However, it is generally accepted that anesthesia affects MER. Due to a potential role of local field potentials (LFPs) in DBS functional mapping, we characterized the effect of propofol on globus pallidus interna (GPi) and externa (GPe) LFPs in Parkinson disease (PD) patients., Methods: We collected LFPs in 12 awake and anesthetized PD patients undergoing DBS implantation. Spectral power of β (13-35 Hz) and high-frequency oscillations (HFOs: 200-300 Hz) was compared across the pallidum., Results: Propofol suppressed GPi power by > 20 Hz while increasing power at lower frequencies. A similar power shift was observed in GPe; however, power in the high β range (20-35 Hz) increased with propofol. Before anesthesia both β and HFO activity were significantly greater at the GPi (χ2 = 20.63 and χ2 = 48.81, p < 0.0001). However, during anesthesia, we found no significant difference across the pallidum (χ2 = 0.47, p = 0.79, and χ2 = 4.11, p = 0.12)., Conclusion: GPi and GPe are distinguishable using LFP spectral profiles in the awake condition. Propofol obliterates this spectral differentiation. Therefore, LFP spectra cannot be relied upon in the propofol-anesthetized state for functional mapping during DBS implantation., (© 2018 S. Karger AG, Basel.)

Objective: Recent discoveries suggest that it is most likely the coupling of β oscillations (13-30Hz) and not merely their power that relates to Parkinson disease (PD) pathophysiology., Methods: We analyzed power and phase amplitude coupling (PAC) in local field potentials (LFP) recorded from Pallidum after placement of deep brain stimulation (DBS) leads in nineteen PD patients and three patients with dystonia., Results: Within GPi, we identified PAC between phase of β and amplitude of high frequency oscillations (200-300Hz) and distinct β-low γ (40-80Hz) PAC both modulated by contralateral movement. Resting β-low γ PAC, also present in dystonia patients, inversely correlated with severity of rigidity and bradykinesia (R=-0.44, P=0.028). These findings were specific to the low β band, suggesting a differential role for the two β sub-bands., Conclusions: PAC is present across distinct frequency bands within the GPi. Given the presence of low β-low γ PAC in dystonia and the inverse correlation with symptom severity, we propose that this PAC may be a normal pallidal signal., Significance: This study provides new evidence on the pathophysiological contribution of local pallidal coupling and suggests similar and distinct patterns of coupling within GPi and STN in PD., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual's daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less "automatic" than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury., Objective: Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function., Methods and Results: Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3-fold) and volitional hand control in the presence of epidural stimulation., Conclusions: The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention., (© The Author(s) 2016.)

The lumbar spinal cord contains the necessary circuitry to independently drive locomotor behaviors. This function is retained following spinal cord injury (SCI) and is amenable to rehabilitation. Although the effectiveness of task-specific training and pharmacologic modulation has been repeatedly demonstrated in animal studies, results from human studies are less striking. Recently, lumbar epidural stimulation (EDS) along with locomotor training was shown to restore weight-bearing function and lower-extremity voluntary control in a chronic, motor-complete human SCI subject. Related animal studies incorporating EDS as part of the therapeutic regiment are also encouraging. EDS is emerging as a promising neuromodulatory tool for SCI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The lumbar spinal cord circuitry can autonomously generate locomotion, but it remains to be determined which types of neurons constitute the locomotor generator and how their population activity is organized spatially in the mammalian spinal cord. In this study, we investigated the spatiotemporal dynamics of the spinal interneuronal population activity in the intermediate zone of the adult mammalian cord. Segmental interneuronal population activity was examined via multiunit activity (MUA) during air-stepping initiated by perineal stimulation in subchronic spinal cats. In contrast to single-unit activity, MUA provides a continuous measure of neuronal activity within a ∼100-μm volume around the recording electrode. MUA was recorded during air-stepping, along with hindlimb muscle activity, from segments L3 to L7 with two multichannel electrode arrays placed into the left and right hemicord intermediate zones (lamina V-VII). The phasic modulation and spatial organization of MUA dynamics were examined in relation to the locomotor cycle. Our results show that segmental population activity is modulated with respect to the ipsilateral step cycle during air-stepping, with maximal activity occurring near the ipsilateral swing to stance transition period. The phase difference between the population activity within the left and right hemicords was also found to correlate to the left-right alternation of the step cycle. Furthermore, examination of MUA throughout the rostrocaudal extent showed no differences in population dynamics between segmental levels, suggesting that the spinal interneurons targeted in this study may operate as part of a distributed "clock" mechanism rather than a rostrocaudal oscillation as seen with motoneuronal activity.

Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher prevalence of early switching to the flexion phase was observed at higher stimulation levels and if stimulation was applied in the late stance phase. All flexor muscles were activated by the stimulation. These results suggest that electrical stimulation of the sural nerve may be used to increase the magnitude of the swing phase and control the timing of its onset after spinal cord injury and locomotor training.

Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as stepping, scratching, and swimming. Based on an observed rostrocaudal wave of activity in the motoneuronal firing during locomotor tasks, the traveling-wave hypothesis proposes that spinal interneuronal firing follows a similar rostrocaudal pattern of activation, suggesting the presence of spatially organized interneuronal modules within the spinal motor system. In this study, we examined if the spatial organization of the lumbar interneuronal activity patterns during locomotor activity in the adult mammalian spinal cord was consistent with a traveling-wave organizational scheme. The activity of spinal interneurons within the lumbar intermediate zone was examined during air-stepping in subchronic spinal cats. The preferred phase of interneuronal activity during a step cycle was determined using circular statistics. We found that the preferred phases of lumbar interneurons from both sides of the cord were evenly distributed over the entire step cycle with no indication of functional groupings. However, when units were subcategorized according to spinal hemicords, the preferred phases of units on each side largely fell around the period of extensor muscle activity on each side. In addition, there was no correlation between the preferred phases of units and their rostrocaudal locations along the spinal cord with preferred phases corresponding to both flexion and extension phases of the step cycle found at every rostrocaudal level of the cord. These results are consistent with the hypothesis that interneurons operate as part of a longitudinally distributed network rather than a rostrocaudally organized traveling-wave network.

Jefferson fractures of the immature spine have received little attention in the study of pediatric spinal trauma. Fractures through synchondroses are a possibility in the immature spine, in addition to fractures through osseous portions of the vertebral ring, and they create opportunities for misinterpretation of diagnostic imaging. The authors describe 3 examples of Jefferson fractures in young children. All 3 cases featured fractures through an anterior synchondrosis in association with persistence of the posterior synchondrosis or a fracture of the posterior arch. The possibility of a Jefferson fracture should be considered for any child presenting with neck pain, cervical muscle spasm, or torticollis following a head injury, despite a seemingly normal cervical spine study. Jefferson fractures in young children are probably much more common than previously recognized.