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Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.
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Encéfalo , Electroencefalografía , Animales , Encéfalo/fisiología , Electroencefalografía/métodos , Porcinos , Ratas , Neuronas/fisiología , Mapeo Encefálico/métodos , Ratas Sprague-Dawley , Electrocorticografía/métodos , MasculinoRESUMEN
Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.
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Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.
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Encéfalo , Neuronas , Humanos , Encéfalo/fisiología , Electrodos , Potenciales de Acción/fisiología , Neuronas/fisiología , Electrodos ImplantadosRESUMEN
OBJECTIVE: The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs). METHODS: A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction. RESULTS: Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031). CONCLUSIONS: High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.
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Sistemas de Computación , Craneotomía , Humanos , Microelectrodos , Lenguaje , PeróxidosRESUMEN
OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.
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Epilepsia Refractaria , Estado Epiléptico , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Estado Epiléptico/terapia , Estado Epiléptico/etiología , Resultado del Tratamiento , Epilepsia Refractaria/terapiaRESUMEN
Brain surgeries are among the most delicate clinical procedures and must be performed with the most technologically robust and advanced tools. When such surgical procedures are performed in functionally critical regions of the brain, functional mapping is applied as a standard practice that involves direct coordinated interactions between the neurosurgeon and the clinical neurology electrophysiology team. However, information flow during these interactions is commonly verbal as well as time consuming which in turn increases the duration and cost of the surgery, possibly compromising the patient outcomes. Additionally, the grids that measure brain activity and identify the boundaries of pathological versus functional brain regions suffer from low resolution (3-10 mm contact to contact spacing) with limited conformity to the brain surface. Here, we introduce a brain intracranial electroencephalogram microdisplay (Brain-iEEG-microdisplay) which conforms to the brain to measure the brain activity and display changes in near real-time (40 Hz refresh rate) on the surface of the brain in the surgical field. We used scalable engineered gallium nitride (GaN) substrates with 6" diameter to fabricate, encapsulate, and release free-standing arrays of up to 2048 GaN light emitting diodes (µLEDs) in polyimide substrates. We then laminated the µLED arrays on the back of micro-electrocorticography (µECoG) platinum nanorod grids (PtNRGrids) and developed hardware and software to perform near real-time intracranial EEG analysis and activation of light patterns that correspond to specific cortical activities. Using the Brain-iEEG-microdisplay, we precisely ideFSntified and displayed important cortical landmarks and pharmacologically induced pathological activities. In the rat model, we identified and displayed individual cortical columns corresponding to individual whiskers and the near real-time evolution of epileptic discharges. In the pig animal model, we demonstrated near real-time mapping and display of cortical functional boundaries using somatosensory evoked potentials (SSEP) and display of responses to direct electrical stimulation (DES) from the surface or within the brain tissue. Using a dual-color Brain-iEEG-microdisplay, we demonstrated co-registration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The Brain-iEEG-microdisplay holds the promise of increasing the efficiency of diagnosis and possibly surgical treatment, thereby reducing the cost and improving patient outcomes which would mark a major advancement in neurosurgery. These advances can also be translated to broader applications in neuro-oncology and neurophysiology.
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OBJECTIVE: The impact of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes has not been extensively evaluated outside of the original clinical trials and post-approval studies. The goal of this study was to ascertain the potential real-world effects of RNS on cognitive, psychiatric, and quality of life (QOL) outcomes in relation to seizure outcomes by examining 50 patients undergoing RNS implantation for drug-resistant epilepsy (DRE). METHODS: We performed a retrospective review of all patients treated at our institution with RNS for DRE with at least 12 months of follow-up. In addition to baseline demographic and disease-related characteristics, we collected cognitive (Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning Index), psychiatric (Beck Depression and Anxiety Inventory Scores), and QOL (QOLIE-31) outcomes at 6 and 12 months after RNS implantation and correlated them with seizure outcomes. RESULTS: Fifty patients (median age 39.5 years, 64% female) were treated with RNS for DRE in our institution from 2005 to 2020. Of the 37 of them who had well-documented pre and post-implantation seizure diaries, the 6-month median seizure frequency reduction was 88%, the response rate (50% or greater seizure frequency reduction) was 78%, and 32% of patients were free of disabling seizures in this timeframe. There was no statistically significant difference at a group level in any of the evaluated cognitive, psychiatric, and QOL outcomes at 6 and 12 months post-implantation compared to the pre-implantation baseline, irrespective of seizure outcomes, although a subset of patients experienced a decline in mood or cognitive variables. SIGNIFICANCE: Responsive neurostimulation does not appear to have a statistically significant negative or positive impact on neuropsychiatric and psychosocial status at the group level. We observed significant variability in outcome, with a minority of patients experiencing worse behavioral outcomes, which seemed related to RNS implantation. Careful outcome monitoring is required to identify the subset of patients experiencing a poor response and to make appropriate adjustments in care.
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Epilepsia Refractaria , Calidad de Vida , Humanos , Femenino , Adulto , Masculino , Epilepsia Refractaria/terapia , Estudios Retrospectivos , Convulsiones , Resultado del TratamientoRESUMEN
OBJECTIVE: Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used increasingly in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication for either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare the seizure benefits and adverse effects associated with these therapies in this patient population. We, therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE at our center. METHODS: We performed a retrospective review of patients who were treated with either ANT-DBS or TL-RNS for drug-resistant TLE with at least 12 months of follow-up. Along with the clinical characteristics of each patient's epilepsy, seizure frequency was recorded throughout each patient's postoperative clinical course. RESULTS: Twenty-six patients underwent ANT-DBS implantation and 32 patients underwent TL-RNS for drug-resistant TLE. The epilepsy characteristics of both groups were similar. Patients who underwent ANT-DBS demonstrated a median seizure reduction of 58% at 12-15 months, compared to a median seizure reduction of 70% at 12-15 months in patients treated with TL-RNS (p > .05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT-DBS and 56% for TL-RNS (p > .05). The incidence of complications and stimulation-related side effects did not significantly differ between therapies. SIGNIFICANCE: We demonstrate in our single-center experience that patients with drug-resistant TLE benefit similarly from either ANT-DBS or TL-RNS. Selection of either ANT-DBS or TL-RNS may, therefore, depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another.
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Núcleos Talámicos Anteriores , Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Epilepsia , Estimulación Encefálica Profunda/métodos , Epilepsia Refractaria/terapia , Epilepsia/terapia , Epilepsia del Lóbulo Temporal/terapia , Humanos , Convulsiones/terapia , Lóbulo Temporal , Resultado del TratamientoRESUMEN
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Despite improvements in survival, treatments that improve functional outcome remain lacking. There is, therefore, a pressing need to develop novel treatments to improve functional recovery. Here, we investigated task-matched deep-brain stimulation of the nucleus accumbens (NAc) to augment reinforcement learning in a rodent model of TBI. We demonstrate that task-matched deep brain stimulation (DBS) of the NAc can enhance learning following TBI. We further demonstrate that animals receiving DBS exhibited greater behavioral improvement and enhanced neural proliferation. Treated animals recovered to an uninjured behavioral baseline and showed retention of improved performance even after stimulation was stopped. These results provide encouraging early evidence for the potential of NAc DBS to improve functional outcomes following TBI and that its effects may be broad, with alterations in neurogenesis and synaptogenesis.
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OBJECTIVE: Neuromodulation of the centromedian nucleus of the thalamus (CM) has unclear effectiveness in the treatment of drug-resistant epilepsy. Prior reports suggest that it may be more effective in the generalized epilepsies such as Lennox-Gastaut syndrome (LGS). The objective of this study was to determine the outcome of CM deep brain stimulation (DBS) at the authors' institution. METHODS: Retrospective chart review was performed for all patients who underwent CM DBS at Emory University, which occurred between December 2018 and May 2021. CM DBS electrodes were implanted using three different surgical methods, including frame-based, robot-assisted, and direct MRI-guided. Seizure frequency, stimulation parameters, and adverse events were recorded from subsequent clinical follow-up visits. RESULTS: Fourteen patients underwent CM DBS: 9 had symptomatic generalized epilepsy (including 5 with LGS), 3 had primary or idiopathic generalized epilepsy, and 2 had bifrontal focal epilepsy. At last follow-up (mean [± SEM] 19 ± 5 months, range 4.1-33 months, ≥ 6 months in 11 patients), the median seizure frequency reduction was 91%. Twelve patients (86%) were considered responders (≥ 50% decrease in seizure frequency), including 10 of 12 with generalized epilepsy and both patients with bifrontal epilepsy. Surgical adverse events were rare and included 1 patient with hardware breakage, 1 with a postoperative aspiration event, and 1 with a nonclinically significant intracranial hemorrhage. CONCLUSIONS: CM DBS was an effective treatment for drug-resistant generalized and bifrontal epilepsies. Additional studies and analyses may investigate whether CM DBS is best suited for specific epilepsy types, and the relationship of lead location to outcome in different epilepsies.
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Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia , Núcleos Talámicos Intralaminares , Humanos , Estimulación Encefálica Profunda/métodos , Estudios Retrospectivos , Epilepsia Refractaria/terapia , Núcleos Talámicos Intralaminares/cirugía , Resultado del Tratamiento , Convulsiones/terapiaRESUMEN
Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 µm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.
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Mapeo Encefálico , Epilepsia , Animales , Encéfalo/fisiología , Estimulación Eléctrica , Humanos , Ratas , VigiliaRESUMEN
OBJECTIVE: Interictal discharges (IIDs) and high frequency oscillations (HFOs) are established neurophysiologic biomarkers of epilepsy, while microseizures are less well studied. We used custom poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand these markers' microscale spatial dynamics. METHODS: Electrodes with spatial resolution down to 50 µm were used to record intraoperatively in 30 subjects. IIDs' degree of spread and spatiotemporal paths were generated by peak-tracking followed by clustering. Repeating HFO patterns were delineated by clustering similar time windows. Multi-unit activity (MUA) was analyzed in relation to IID and HFO timing. RESULTS: We detected IIDs encompassing the entire array in 93% of subjects, while localized IIDs, observed across < 50% of channels, were seen in 53%. IIDs traveled along specific paths. HFOs appeared in small, repeated spatiotemporal patterns. Finally, we identified microseizure events that spanned 50-100 µm. HFOs covaried with MUA, but not with IIDs. CONCLUSIONS: Overall, these data suggest that irritable cortex micro-domains may form part of an underlying pathologic architecture which could contribute to the seizure network. SIGNIFICANCE: These results, supporting the possibility that epileptogenic cortex comprises a mosaic of irritable domains, suggests that microscale approaches might be an important perspective in devising novel seizure control therapies.
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Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Electroencefalografía/métodos , Epilepsia/fisiopatología , Monitorización Neurofisiológica Intraoperatoria/métodos , Microelectrodos , Adulto , Encéfalo/cirugía , Electroencefalografía/instrumentación , Epilepsia/diagnóstico , Epilepsia/cirugía , Femenino , Humanos , Monitorización Neurofisiológica Intraoperatoria/instrumentación , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
No clear evidence-based treatment paradigm currently exists for refractory and super-refractory status epilepticus, which can result in significant mortality and morbidity. While patients are typically treated with antiepileptic drugs and anesthetics, neurosurgical neuromodulation techniques can also be considered. We present a novel case in which responsive neurostimulation was used to effectively treat a patient who had developed super-refractory status epilepticus, later consistent with epilepsia partialis continua, that was refractory to antiepileptic drugs, immunomodulatory therapies, and transcranial magnetic stimulation. This case demonstrates how regional therapy provided by responsive neurostimulation can be effective in treating super-refractory status epilepticus through neuromodulation of seizure networks.
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Epilepsia Refractaria/terapia , Terapia por Estimulación Eléctrica , Neuroestimuladores Implantables , Estado Epiléptico/terapia , Adulto , Electrocorticografía , Epilepsia Parcial Continua/terapia , Femenino , Humanos , Imagen por Resonancia Magnética , Adulto JovenRESUMEN
Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.
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Corteza Cerebral/fisiología , Neuronas/fisiología , Estimulación Acústica , Adulto , Animales , Estimulación Eléctrica , Electroencefalografía , Fenómenos Electrofisiológicos , Epilepsia/fisiopatología , Espacio Extracelular/fisiología , Femenino , Humanos , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Microelectrodos , Persona de Mediana Edad , Corteza Somatosensorial/fisiología , Análisis de Ondículas , Adulto JovenRESUMEN
BACKGROUND: Subcortical mapping of the corticospinal tract has been extensively used during craniotomies under general anesthesia to achieve maximal resection while avoiding postoperative motor deficits. To our knowledge, similar methods to map the thalamocortical tract (TCT) have not yet been developed. OBJECTIVE: To describe a neurophysiologic technique for TCT identification in 2 patients who underwent resection of frontoparietal lesions. METHODS: The central sulcus (CS) was identified using the somatosensory evoked potentials (SSEP) phase reversal technique. Furthermore, monitoring of the cortical postcentral N20 and precentral P22 potentials was performed during resection. Subcortical electrical stimulation in the resection cavity was done using the multipulse train (case #1) and Penfield (case #2) techniques. RESULTS: Subcortical stimulation within the postcentral gyrus (case #1) and in depth of the CS (case #2), resulted in a sudden drop in amplitudes in N20 (case #1) and P22 (case #2), respectively. In both patients, the potentials promptly recovered once the stimulation was stopped. These results led to redirection of the surgical plane with avoidance of damage of thalamocortical input to the primary somatosensory (case #1) and motor regions (case #2). At the end of the resection, there were no significant changes in the median SSEP. Both patients had no new long-term postoperative sensory or motor deficit. CONCLUSION: This method allows identification of TCT in craniotomies under general anesthesia. Such input is essential not only for preservation of sensory function but also for feedback modulation of motor activity.
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Potenciales Evocados Motores , Monitoreo Intraoperatorio , Mapeo Encefálico , Craneotomía , Potenciales Evocados Somatosensoriales , HumanosRESUMEN
OBJECTIVE: Electrical stimulation via microelectrodes implanted in cortex has been suggested as a potential treatment for a wide range of neurological disorders. Despite some success however, the effectiveness of conventional electrodes remains limited, in part due to an inability to create specific patterns of neural activity around each electrode and in part due to challenges with maintaining a stable interface. The use of implantable micro-coils to magnetically stimulate the cortex has the potential to overcome these limitations because the asymmetric fields from coils can be harnessed to selectively activate some neurons, e.g. vertically-oriented pyramidal neurons while avoiding others, e.g. horizontally-oriented passing axons. In vitro experiments have shown that activation is indeed confined with micro-coils but their effectiveness in the intact brain of living animals has not been evaluated. APPROACH: To assess the efficacy of stimulation, a 128-channel custom recording microelectrode array was positioned on the surface of the visual cortex (ECoG) in anesthetized mice and responses to magnetic and electric stimulation were compared. Stimulation was delivered from electrodes or micro-coils implanted through a hole in the center of the recording array at a rate of 200 pulses per second for 100 ms. MAIN RESULTS: Both electric and magnetic stimulation reliably elicited cortical responses, although activation from electric stimulation was spatially expansive, often extending more than 1 mm from the stimulation site, while activation from magnetic stimulation was typically confined to a â¼300 µm diameter region around the stimulation site. Results were consistent for stimulation of both cortical layer 2/3 and layer 5 as well as across a range of stimulus strengths. SIGNIFICANCE: The improved focality with magnetic stimulation suggests that the effectiveness of cortical stimulation can be improved. Improved focality may be particularly attractive for cortical prostheses that require high spatial resolution, e.g. devices that target sensory cortex, as it may lead to improved acuity.
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Corteza Visual , Animales , Estimulación Eléctrica , Electrodos Implantados , Fenómenos Magnéticos , Ratones , Microelectrodos , NeuronasRESUMEN
The enhanced electrochemical activity of nanostructured materials is readily exploited in energy devices, but their utility in scalable and human-compatible implantable neural interfaces can significantly advance the performance of clinical and research electrodes. We utilize low-temperature selective dealloying to develop scalable and biocompatible one-dimensional platinum nanorod (PtNR) arrays that exhibit superb electrochemical properties at various length scales, stability, and biocompatibility for high performance neurotechnologies. PtNR arrays record brain activity with cellular resolution from the cortical surfaces in birds and nonhuman primates. Significantly, strong modulation of surface recorded single unit activity by auditory stimuli is demonstrated in European Starling birds as well as the modulation of local field potentials in the visual cortex by light stimuli in a nonhuman primate and responses to electrical stimulation in mice. PtNRs record behaviorally and physiologically relevant neuronal dynamics from the surface of the brain with high spatiotemporal resolution, which paves the way for less invasive brain-machine interfaces.
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Potenciales de Acción , Materiales Biocompatibles , Interfaces Cerebro-Computador , Nanotubos , Neuronas/metabolismo , Platino (Metal) , Corteza Visual/fisiología , Animales , Estimulación Eléctrica , Electrodos , Macaca mulatta , Masculino , Ratones , Pájaros CantoresRESUMEN
OBJECTIVE: Intraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication. METHODS: The authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken. RESULTS: Overall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38-0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26-0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22-24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05). CONCLUSIONS: This study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.
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BACKGROUND AND IMPORTANCE: Myopericytoma is an emerging class of neoplasm originating from the perivascular myoid cellular environment, previously classified as a variant of hemangiopericytoma. Most reported myopericytomas are found in soft tissues of the extremities; however, infrequent cases are described involving the central nervous system. Intracranial myopericytoma remains rare. Here, we describe the first report of myopericytoma occurring at the cervicomedullary junction in close proximity to the vertebral artery, mimicking a vascular lesion. CLINICAL PRESENTATION: A 64-yr-old woman presented with radiating neck pain. Magnetic resonance imaging revealed a well-circumscribed enhancing lesion adjacent to the vertebral artery-accessory nerve complex. She underwent a far lateral craniotomy and cervical laminectomy to obtain proximal vertebral artery control and adequate exposure of the lesion, which appeared most consistent with neoplasm at surgery. Histopathology revealed a grade I myopericytoma. A gross total resection was achieved, and the patient has no evidence of recurrence 3 yr after surgery. CONCLUSION: Tumors of perivascular origin include hemangiopericytoma, glomus tumor, myofibroma, and myopericytoma and are uncommon lesions intracranially. Consideration of and distinction among these perivascular tumors is critically important, as they each have distinct clinical behaviors and management. Myopericytoma can mimic other neoplastic and cerebrovascular pathologies, but it most commonly has a benign course and can be surgically cured if a gross total resection can be achieved. Rarer myopericytoma variants that adopt a more malignant course have been described, and ongoing molecular studies may identify mutations or activated signaling pathways that can be targeted to offer chemotherapeutic options in the future.