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Objective. Traditionally known for its involvement in emotional processing, the amygdala's involvement in motor control remains relatively unexplored, with sparse investigations into the neural mechanisms governing amygdaloid motor movement and inhibition. This study aimed to characterize the amygdaloid beta-band (13-30 Hz) power between 'Go' and 'No-go' trials of an arm-reaching task.Approach. Ten participants with drug-resistant epilepsy implanted with stereoelectroencephalographic (SEEG) electrodes in the amygdala were enrolled in this study. SEEG data was recorded throughout discrete phases of a direct reach Go/No-go task, during which participants reached a touchscreen monitor or withheld movement based on a colored cue. Multitaper power analysis along with Wilcoxon signed-rank and Yates-correctedZtests were used to assess significant modulations of beta power between the Response and fixation (baseline) phases in the 'Go' and 'No-go' conditions.Main results. In the 'Go' condition, nine out of the ten participants showed a significant decrease in relative beta-band power during the Response phase (p⩽ 0.0499). In the 'No-go' condition, eight out of the ten participants presented a statistically significant increase in relative beta-band power during the response phase (p⩽ 0.0494). Four out of the eight participants with electrodes in the contralateral hemisphere and seven out of the eight participants with electrodes in the ipsilateral hemisphere presented significant modulation in beta-band power in both the 'Go' and 'No-go' conditions. At the group level, no significant differences were found between the contralateral and ipsilateral sides or between genders.Significance.This study reports beta-band power modulation in the human amygdala during voluntary movement in the setting of motor execution and inhibition. This finding supplements prior research in various brain regions associating beta-band power with motor control. The distinct beta-power modulation observed between these response conditions suggests involvement of amygdaloid oscillations in differentiating between motor inhibition and execution.
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Amígdala del Cerebelo , Brazo , Ritmo beta , Desempeño Psicomotor , Humanos , Amígdala del Cerebelo/fisiología , Masculino , Femenino , Adulto , Ritmo beta/fisiología , Desempeño Psicomotor/fisiología , Brazo/fisiología , Adulto Joven , Movimiento/fisiología , Persona de Mediana Edad , Epilepsia Refractaria/fisiopatología , Electroencefalografía/métodosRESUMEN
Objective.Can we classify movement execution and inhibition from hippocampal oscillations during arm-reaching tasks? Traditionally associated with memory encoding, spatial navigation, and motor sequence consolidation, the hippocampus has come under scrutiny for its potential role in movement processing. Stereotactic electroencephalography (SEEG) has provided a unique opportunity to study the neurophysiology of the human hippocampus during motor tasks. In this study, we assess the accuracy of discriminant functions, in combination with principal component analysis (PCA), in classifying between 'Go' and 'No-go' trials in a Go/No-go arm-reaching task.Approach.Our approach centers on capturing the modulation of beta-band (13-30 Hz) power from multiple SEEG contacts in the hippocampus and minimizing the dimensional complexity of channels and frequency bins. This study utilizes SEEG data from the human hippocampus of 10 participants diagnosed with epilepsy. Spectral power was computed during a 'center-out' Go/No-go arm-reaching task, where participants reached or withheld their hand based on a colored cue. PCA was used to reduce data dimension and isolate the highest-variance components within the beta band. The Silhouette score was employed to measure the quality of clustering between 'Go' and 'No-go' trials. The accuracy of five different discriminant functions was evaluated using cross-validation.Main results.The Diagonal-Quadratic model performed best of the 5 classification models, exhibiting the lowest error rate in all participants (median: 9.91%, average: 14.67%). PCA showed that the first two principal components collectively accounted for 54.83% of the total variance explained on average across all participants, ranging from 36.92% to 81.25% among participants.Significance.This study shows that PCA paired with a Diagonal-Quadratic model can be an effective method for classifying between Go/No-go trials from beta-band power in the hippocampus during arm-reaching responses. This emphasizes the significance of hippocampal beta-power modulation in motor control, unveiling its potential implications for brain-computer interface applications.
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Brazo , Ritmo beta , Hipocampo , Humanos , Hipocampo/fisiología , Femenino , Ritmo beta/fisiología , Masculino , Adulto , Brazo/fisiología , Desempeño Psicomotor/fisiología , Movimiento/fisiología , Electroencefalografía/métodos , Electroencefalografía/clasificación , Análisis de Componente Principal , Adulto Joven , Reproducibilidad de los Resultados , Persona de Mediana EdadRESUMEN
The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing. The figures presented are reprinted from our prior publications and key publications referenced in the manuscript. We summarize all studies to date that employ invasive intracranial recordings in humans during performance of conflict-inducing tasks. For our own studies, we analyzed local field potentials (LFPs) from patients with implanted stereotactic electroencephalography (SEEG) electrodes, and we observed intracortical oscillation patterns as well as intercortical temporal relationships in the hippocampus, amygdala, and orbitofrontal cortex (OFC) during the cue-processing phase of a modified Stroop Task. Our findings suggest that non-emotional human conflict processing involves modulation across multiple frequency bands within and between brain structures.
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Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of comorbid conditions, with nutritional rehabilitation reserved for severe cases of anorexia nervosa. Unfortunately, many patients often fail to respond, leaving a concerning treatment gap between the current and requisite treatments for eating disorders. To better understand the neurobiology underlying these eating disorders, investigations have been undertaken to characterize the activity of various neural networks, primarily those activated during tasks of executive inhibition, reward processing, and self-reference. Various neuromodulatory techniques have been proposed to stimulate these networks with the goal of improving patients' BMI and mental health. The aim of this review is to compile a comprehensive summarization of the current literature regarding the underlying neural connectivity of anorexia nervosa, bulimia nervosa, and binge eating disorder as well as the numerous neuromodulatory modalities that have been investigated. Importantly, we aimed to summarize the most significant clinical trials to date as well as to provide an updated assessment of the role of deep brain stimulation, summarizing numerous recently published clinical studies that have greatly contributed to the literature. In this review, we found therapeutic evidence for transcranial magnetic stimulation and transcranial direct current stimulation in treating individuals suffering from anorexia nervosa, bulimia nervosa, and binge eating disorder. We also found significant evidence for the role of deep brain stimulation, particularly as an escalatory therapy option for the those who failed standard therapy. Finally, we hope to provide promising directions for future clinical investigations.
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AIM: To investigate the relationship between planned drill approach angle and angular deviation of the stereotactically placed intracranial electrode tips. MATERIAL AND METHODS: Stereotactic electrode implantation was performed in 13 patients with drug resistant epilepsy. A total of 136 electrodes were included in our analysis. Stereotactic targets were planned on pre-operative magnetic resonance imaging (MRI) scans and implantation was carried out using a Cosman-Roberts-Wells stereotactic frame with the Ad-Tech drill guide and electrodes. Post implant electrode angles in the axial, coronal, and sagittal planes were determined from post-operative computerized tomography (CT) scans and compared with planned angles using Bland-Altman plots and linear regression. RESULTS: Qualitative assessment of correlation plots between planned and actual angles demonstrated a linear relationship for axial, coronal, and sagittal planes, with no overt angular deflection for any magnitude of the planned angle. CONCLUSION: The accuracy of CRW frame-based electrode placement using the Ad-Tech drill guide and electrodes is not significantly affected by the magnitude of the planning angle. Based on our results, oblique electrode insertion is a safe and accurate procedure.
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Epilepsia Refractaria , Técnicas Estereotáxicas , Humanos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Imagenología Tridimensional , Electrodos Implantados , Imagen por Resonancia MagnéticaRESUMEN
Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex.
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Interfaces Cerebro-Computador , Corteza Somatosensorial , Humanos , Mapeo Encefálico/métodos , Corteza Somatosensorial/fisiologíaRESUMEN
PURPOSE: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers. MATERIALS AND METHODS: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary. RESULTS: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters. CONCLUSIONS: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.
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Síntomas del Sistema Urinario Inferior , Estimulación de la Médula Espinal , Accidente Cerebrovascular , Humanos , Micción/fisiología , Proyectos Piloto , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/terapia , Síntomas del Sistema Urinario Inferior/diagnóstico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Encéfalo/diagnóstico por imagen , OxígenoRESUMEN
BACKGROUND AND OBJECTIVES: Neurological manifestations may occur in more than 80% of patients hospitalized with COVID-19 infection, including severe disruptions of the central nervous system (CNS), such as strokes, encephalitis, or seizures. Although the primary pathophysiological mechanism for the effects of COVID-19 in CNS remains unknown, evidence exists for both direct injury from neuroinvasion and indirect effects from disruptions in systemic inflammatory and coagulation pathways. In this study, we analyzed CNS tissue from living patients to better understand these processes. METHODS: With institutional review board approval and patient consent, samples that would be otherwise discarded from patients with active or recent (within 6 days of surgery) COVID-19 infection undergoing neurosurgical intervention were collected and tested for the presence of SARS-CoV-2 using immunohistochemistry, in situ hybridization, electron microscopy, and reverse transcription polymerase chain reaction. RESULTS: Five patients with perioperative mild-to-moderate COVID-19 infection met inclusion criteria (2 male, 3 female; mean age 38.8 ± 13.5 years). Neurosurgical diagnoses included a glioblastoma, a ruptured arteriovenous malformation, a ruptured posterior inferior cerebellar artery aneurysm, a middle cerebral artery occlusion, and a hemorrhagic pontine cavernous malformation. Samples analyzed included the frontal lobe cortex, olfactory nerve, arteriovenous malformation/temporal lobe parenchyma, middle cerebral artery, cerebellum, and cavernous malformation/brainstem parenchyma. Testing for the presence of SARS-CoV-2 was negative in all samples. CONCLUSION: The CNS is likely not a significant viral reservoir during mild-to-moderate COVID-19 infection, although direct neuroinvasion is not definitively excluded. Additional testing to help elucidate the relative contributions of direct and indirect pathways for CNS injury from COVID is warranted.
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Malformaciones Arteriovenosas , COVID-19 , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , SARS-CoV-2 , Sistema Nervioso Central , Tronco EncefálicoRESUMEN
Background: Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods: We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results: In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion: We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.
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Enfermedades Desmielinizantes , Traumatismos de la Médula Espinal , Ratones , Animales , FN-kappa B/metabolismo , Traumatismos de la Médula Espinal/patología , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Minerales/uso terapéutico , Zinc/metabolismo , Enfermedades Desmielinizantes/metabolismoRESUMEN
The aim of this study is to estimate the maximum power consumption that guarantees the thermal safety of a skull unit (SU). The SU is part of a fully-implantable bi-directional brain computer-interface (BD-BCI) system that aims to restore walking and leg sensation to those with spinal cord injury (SCI). To estimate the SU power budget, we created a bio-heat model using the finite element method (FEM) implemented in COMSOL. To ensure that our predictions were robust against the natural variation of the model's parameters, we also performed a sensitivity analysis. Based on our simulations, we estimated that the SU can nominally consume up to 70 mW of power without raising the surrounding tissues' temperature above the thermal safety threshold of 1°C. When considering the natural variation of the model's parameters, we estimated that the power budget could range between 47 and 81 mW. This power budget should be sufficient to power the basic operations of the SU, including amplification, serialization and A/D conversion of the neural signals, as well as control of cortical stimulation. Determining the power budget is an important specification for the design of the SU and, in turn, the design of a fully-implantable BD-BCI system.
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Interfaces Cerebro-Computador , Humanos , Calor , Cráneo , Cabeza , Prótesis e ImplantesRESUMEN
Objective.Invasive brain-computer interfaces (BCIs) have shown promise in restoring motor function to those paralyzed by neurological injuries. These systems also have the ability to restore sensation via cortical electrostimulation. Cortical stimulation produces strong artifacts that can obscure neural signals or saturate recording amplifiers. While front-end hardware techniques can alleviate this problem, residual artifacts generally persist and must be suppressed by back-end methods.Approach.We have developed a technique based on pre-whitening and null projection (PWNP) and tested its ability to suppress stimulation artifacts in electroencephalogram (EEG), electrocorticogram (ECoG) and microelectrode array (MEA) signals from five human subjects.Main results.In EEG signals contaminated by narrow-band stimulation artifacts, the PWNP method achieved average artifact suppression between 32 and 34 dB, as measured by an increase in signal-to-interference ratio. In ECoG and MEA signals contaminated by broadband stimulation artifacts, our method suppressed artifacts by 78%-80% and 85%, respectively, as measured by a reduction in interference index. When compared to independent component analysis, which is considered the state-of-the-art technique for artifact suppression, our method achieved superior results, while being significantly easier to implement.Significance.PWNP can potentially act as an efficient method of artifact suppression to enable simultaneous stimulation and recording in bi-directional BCIs to biomimetically restore motor function.
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Artefactos , Terapia por Estimulación Eléctrica , Humanos , Electrocorticografía , Electroencefalografía , Amplificadores ElectrónicosRESUMEN
BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training-related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil. METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial). The sham coil appearance mimicked the active coil but without the weak electric field in the NICHE trial sham coil. Outcomes measured 1 week, and 1, 3, and 6 months after the end of treatment included the following: upper extremity Fugl-Meyer (primary, 6 months after end of treatment), Action Research Arm Test, National Institutes of Health Stroke Scale, quality of life (EQ-5D), and safety. RESULTS: Of 60 participants randomized, 58 completed treatment and were included for analysis. Bayesian analysis of combined data from the E-FIT and the NICHE trials indicated that active treatment was not superior to sham at the primary end point (posterior mean odds ratio of 1.94 [96% credible interval of 0.61-4.80]). For the E-FIT intent-to-treat population, upper extremity Fugl-Meyer improvement ≥5 pts occurred in 60% (18/30) active group and 50% (14/28) sham group. Participants enrolled 3 to 6 months following stroke had a 67% (31%-91% CI) response rate in the active group at the 6-month end point versus 50% in the sham group (21.5%-78.5% CI). There were significant improvements from baseline to 6 months for both active and sham groups in upper extremity Fugl-Meyer, Action Research Arm Test, and EQ-5D (P<0.05). Improvement in National Institutes of Health Stroke Scale was observed only in the active group (P=0.004). Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P=0.72). CONCLUSIONS: Intensive motor rehabilitation 3 to 12 months after stroke improved clinical impairment, function, and quality of life; however, 1 Hz-repetitive transcranial magnetic stimulation was not an effective treatment adjuvant in the present sample population with mixed lesion location and extent. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03010462.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Calidad de Vida , Teorema de Bayes , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Estimulación Magnética Transcraneal/métodos , Resultado del Tratamiento , Extremidad Superior , Recuperación de la FunciónRESUMEN
Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.
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Estimulación Encefálica Profunda , Enfermedades del Sistema Nervioso , Enfermedad de Parkinson , Humanos , Estimulación Encefálica Profunda/efectos adversos , Electrodos , NeurofisiologíaRESUMEN
Objective.Transcranial magnetic stimulation (TMS) is a non-invasive technique widely used for neuromodulation. Animal models are essential for investigating the underlying mechanisms of TMS. However, the lack of miniaturized coils hinders the TMS studies in small animals, since most commercial coils are designed for humans and thus incapable of focal stimulation in small animals. Furthermore, it is difficult to perform electrophysiological recordings at the TMS focal point using conventional coils.Approach.We designed, fabricated, and tested a novel miniaturized TMS coil (4-by-7 mm) that consisted of a C-shaped iron powder core and insulated copper wires (30 turns). The resulting magnetic and electric fields were characterized with experimental measurements and finite element modeling. The efficacy of this coil in neuromodulation was validated with electrophysiological recordings of single-unit activities (SUAs), somatosensory evoked potentials (SSEPs), and motor evoked potentials (MEPs) in rats (n= 32) following repetitive TMS (rTMS; 3 min, 10 Hz).Main results.This coil could generate a maximum magnetic field of 460 mT and an electric field of 7.2 V m-1in the rat brain according to our simulations. With subthreshold rTMS focally delivered over the sensorimotor cortex, mean firing rates of primary somatosensory and motor cortical neurons significantly increased (154±5% and 160±9% from the baseline level, respectively); MEP and SSEP amplitude significantly increased (136±9%) and decreased (74±4%), respectively.Significance.This miniaturized C-shaped coil enabled focal TMS and concurrent electrophysiological recording/stimulation at the TMS focal point. It provided a useful tool to investigate the neural responses and underlying mechanisms of TMS in small animal models. Using this paradigm, we for the first time observed distinct modulatory effects on SUAs, SSEPs, and MEPs with the same rTMS protocol in anesthetized rats. These results suggested that multiple neurobiological mechanisms in the sensorimotor pathways were differentially modulated by rTMS.
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Corteza Motora , Estimulación Magnética Transcraneal , Humanos , Ratas , Animales , Estimulación Magnética Transcraneal/métodos , Roedores , Corteza Motora/fisiología , Potenciales Evocados Motores/fisiología , Potenciales Evocados SomatosensorialesRESUMEN
BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke. OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury. METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment. FINDINGS: The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P = .001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups. CONCLUSION: The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment.
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Accidente Cerebrovascular Isquémico , Trastornos Motores , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación del Nervio Vago , Humanos , Persona de Mediana Edad , Trastornos Motores/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Extremidad Superior , Recuperación de la Función , Resultado del TratamientoRESUMEN
Cranioplasties are common procedures in plastic surgery. The use of tissue expansion (TE) in staged cranioplasties is less common. We present two cases of cranioplasties with TE and systematically review literature describing the use of TE in staged cranioplasties and postoperative outcomes. A systematic review was performed by querying multiple databases. Eligible articles include published case series, retrospective reviews, and systematic reviews that described use of TE for staged bony cranioplasty. Data regarding study size, patient demographics, preoperative characteristics, staged procedure characteristics, and postoperative outcomes were collected. Of 755 identified publications, 26 met inclusion criteria. 85 patients underwent a staged cranioplasty with TE. Average defect size was 122 cm 2 , and 30.9% of patients received a previous reconstruction. Average expansion period was 14.2 weeks. The most common soft tissue closures were performed with skin expansion only (75.3%), free/pedicled flap (20.1%), and skin graft (4.7%). The mean postoperative follow-up time was 23.9 months. Overall infection and local complication rates were 3.53 and 9.41%, respectively. The most common complications were cerebrospinal fluid leak (7.1%), hematoma (7.1%), implant exposure (3.5%), and infection (3.5%). Factors associated with higher complication rates include the following: use of alloplastic calvarial implants and defects of congenital etiology ( p = 0.023 and 0.035, respectively). This is the first comprehensive review to describe current practices and outcomes in staged cranioplasty with TE. Adequate soft tissue coverage contributes to successful cranioplasties and TE can play a safe and effective role in selected cases.
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Cortical oscillations within or across brain regions play fundamental roles in sensory, motor, and memory functions. It can be altered by neuromodulations such as repetitive transcranial magnetic stimulation (rTMS) and pharmacological manipulations such as ketamine. However, the neurobiological basis of the effects of rTMS and ketamine, as well as their interactions, on cortical oscillations is not understood. In this study, we developed and applied a rodent model that enabled simultaneous rTMS treatment, pharmacological manipulations, and invasive electrophysiological recordings, which is difficult in humans. Specifically, a miniaturized C-shaped coil was designed and fabricated to deliver focal subthreshold rTMS above the primary somatosensory (S1) and motor (M1) cortex in rats. Multi-electrode arrays (MEA) were implanted to record local field potentials (LFPs) and single unit activities. A novel form of synchronized activities, poly population spikes (PPS), was discovered as the biomarker of ketamine in LFPs. Brief subthreshold rTMS effectively and reversibly suppressed PPS while increasing the firing rates of single unit activities. These results suggest that ketamine and rTMS have convergent but opposing effects on cortical oscillations and circuits. This highly robust phenomenon has important implications to understanding the neurobiological mechanisms of rTMS and ketamine as well as developing new therapeutic strategies involving both neuromodulation and pharmacological agents.
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Cortical stimulation via electrocorticography (ECoG) may be an effective method for inducing artificial sensation in bi-directional brain-computer interfaces (BD-BCIs). However, strong electrical artifacts caused by electrostimulation may significantly degrade or obscure neural information. A detailed understanding of stimulation artifact propagation through relevant tissues may improve existing artifact suppression techniques or inspire the development of novel artifact mitigation strategies. Our work thus seeks to comprehensively characterize and model the propagation of artifacts in subdural ECoG stimulation. To this end, we collected and analyzed data from eloquent cortex mapping procedures of four subjects with epilepsy who were implanted with subdural ECoG electrodes. From this data, we observed that artifacts exhibited phase-locking and ratcheting characteristics in the time domain across all subjects. In the frequency domain, stimulation caused broadband power increases, as well as power bursts at the fundamental stimulation frequency and its super-harmonics. The spatial distribution of artifacts followed the potential distribution of an electric dipole with a median goodness-of-fit of R 2 = 0.80 across all subjects and stimulation channels. Artifacts as large as ±1,100 µV appeared anywhere from 4.43 to 38.34 mm from the stimulation channel. These temporal, spectral and spatial characteristics can be utilized to improve existing artifact suppression techniques, inspire new strategies for artifact mitigation, and aid in the development of novel cortical stimulation protocols. Taken together, these findings deepen our understanding of cortical electrostimulation and provide critical design specifications for future BD-BCI systems.
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OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.