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1.
PLoS Biol ; 22(9): e3002774, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39241107

ABSTRACT

Modular organization at approximately 1 mm scale could be fundamental to cortical processing, but its presence in human association cortex is unknown. Using custom-built, high-density electrode arrays placed on the cortical surface of 7 patients undergoing awake craniotomy for tumor excision, we investigated receptive speech processing in the left (dominant) human posterior superior temporal gyrus. Responses to consonant-vowel syllables and noise-vocoded controls recorded with 1,024 channel micro-grids at 200 µm pitch demonstrated roughly circular domains approximately 1.7 mm in diameter, with sharp boundaries observed in 128 channel linear arrays at 50 µm pitch, possibly consistent with a columnar organization. Peak latencies to syllables in different modules were bimodally distributed centered at 252 and 386 ms. Adjacent modules were sharply delineated from each other by their distinct time courses and stimulus selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.


Subject(s)
Speech Perception , Temporal Lobe , Humans , Temporal Lobe/physiology , Speech Perception/physiology , Adult , Male , Female , Middle Aged , Brain Mapping/methods , Language , Acoustic Stimulation
2.
Neurosurg Focus ; 57(3): E8, 2024 09 01.
Article in English | MEDLINE | ID: mdl-39217636

ABSTRACT

OBJECTIVE: Advancements in MRI-guided focused ultrasound (MRgFUS) technology have led to the successful treatment of select movement disorders. Based on the comparative success between ablation and deep brain stimulation, interest arises in focused ultrasound (FUS) as a promising treatment modality for psychiatric illnesses. In this systematic review, the authors examined current applications of FUS for psychiatric conditions and explored its potential opportunities and challenges. METHODS: The authors performed a comprehensive review using the PRISMA guidelines of studies investigating psychiatric applications for FUS. Articles indexed on PubMed between 2014 to 2024 were included. The authors synthesized the psychiatric conditions treated, neural targets, outcomes, study design, and sonication parameters, and they reviewed important considerations for the treatment of psychiatric disorders with FUS. They also discussed active clinical trials in this research domain. RESULTS: Of 250 articles, 10 met the inclusion criteria. Eight articles investigated the clinical, safety, and imaging correlates of MRgFUS in obsessive-compulsive disorder (OCD), whereas 3 examined treatment-resistant depression. Bilateral anterior capsulotomy resulted in a full responder rate of 67% (≥ 35% reduction in the Yale-Brown Obsessive-Compulsive Scale score) and 33% (≥ 50% reduction in the score on the Hamilton Rating Scale for Depression) in OCD and treatment-resistant depression, respectively. Sonications ranged from 8 to 36 with targeted lesional temperatures of 51°C-56°C. Lesions in the anterodorsal aspect of the anterior limb of the internal capsule (ALIC) and increased functional connectivity to the left dorsolateral prefrontal cortex and dorsal anterior cingulate cortex significantly predicted reduction in symptoms among patients with OCD, with decreases in beta-band activity in the frontocentral and temporal regions associated with reductions in depression and anxiety. Treatment of the nucleus accumbens with low-intensity FUS (LIFU) in patients with opioid-use disorders resulted in significant reductions in cue-reactive cravings, lasting up to 90 days. No serious adverse events were reported, including cognitive decline. Side effects were generally mild and transient, consisting of headaches, pin-site swelling, and nausea. Fourteen active clinical trials were identified, primarily targeting depression with LIFU. CONCLUSIONS: Currently, FUS for psychiatric conditions is centered on OCD, with early pilot studies demonstrating promising safety and efficacy. Further research expanding on defining optimal patient selection, study design, intensity, and sonication parameters is warranted, particularly as FUS expands to other psychiatric illnesses and incorporates LIFU paradigms. Ethical considerations such as patient consent and equitable access also remain paramount.


Subject(s)
Mental Disorders , Humans , Mental Disorders/therapy , Mental Disorders/diagnostic imaging , Obsessive-Compulsive Disorder/therapy , Obsessive-Compulsive Disorder/diagnostic imaging
3.
Neuromodulation ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878055

ABSTRACT

OBJECTIVE: Advancements in deep brain stimulation (DBS) devices provide a unique opportunity to record local field potentials longitudinally to improve the efficacy of treatment for intractable facial pain. We aimed to identify potential electrophysiological biomarkers of pain in the ventral posteromedial nucleus (VPM) of the thalamus and periaqueductal gray (PAG) using a long-term sensing DBS system. MATERIALS AND METHODS: We analyzed power spectra of ambulatory pain-related events from one patient implanted with a long-term sensing generator, representing different pain intensities (pain >7, pain >9) and pain qualities (no pain, burning, stabbing, and shocking pain). Power spectra were parametrized to separate oscillatory and aperiodic features and compared across the different pain states. RESULTS: Overall, 96 events were marked during a 16-month follow-up. Parameterization of spectra revealed a total of 62 oscillatory peaks with most in the VPM (77.4%). The pain-free condition did not show any oscillations. In contrast, ß peaks were observed in the VPM during all episodes (100%) associated with pain >9, 56% of episodes with pain >7, and 50% of burning pain events (center frequencies: 28.4 Hz, 17.8 Hz, and 20.7 Hz, respectively). Episodes of pain >9 indicated the highest relative ß band power in the VPM and decreased aperiodic exponents (denoting the slope of the power spectra) in both the VPM and PAG. CONCLUSIONS: For this patient, an increase in ß band activity in the sensory thalamus was associated with severe facial pain, opening the possibility for closed-loop DBS in facial pain.

4.
Sci Transl Med ; 16(744): eadj7257, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38657026

ABSTRACT

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.


Subject(s)
Brain , Electroencephalography , Animals , Brain/physiology , Electroencephalography/methods , Swine , Rats , Neurons/physiology , Brain Mapping/methods , Rats, Sprague-Dawley , Electrocorticography/methods , Male
5.
Nat Commun ; 15(1): 218, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233418

ABSTRACT

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.


Subject(s)
Brain , Neurons , Humans , Brain/physiology , Electrodes , Action Potentials/physiology , Neurons/physiology , Electrodes, Implanted
6.
bioRxiv ; 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38293030

ABSTRACT

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.

7.
J Neurosurg ; 140(3): 665-676, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37874692

ABSTRACT

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.


Subject(s)
Computer Systems , Craniotomy , Humans , Microelectrodes , Language , Peroxides
8.
J Craniofac Surg ; 34(7): e682-e684, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37639663

ABSTRACT

Syndrome of the Trephined (SoT) is a frequently misunderstood and underdiagnosed outcome of decompressive craniectomy, especially in cases of trauma. The pressure gradient between atmospheric pressure and the sub-atmospheric intracranial pressure results in a sinking of the scalp overlying the craniectomy site. This gradually compresses the underlying brain parenchyma. This parenchymal compression can disrupt normal autoregulation and subsequent metabolism, yielding symptoms ranging from headaches, dizziness, altered behavior to changes in sensation, and difficulty with ambulation, coordination, and activities of daily living. We present a case of SoT treated with a 3D-printed custom polycarbonate external cranial orthotic that allowed us to re-establish this pressure gradient by returning the cranium to a closed system. The patient demonstrated subjective improvement in quality of life and his symptoms. This was consistent with the re-expanded brain parenchyma on CT imaging.


Subject(s)
Decompressive Craniectomy , Trephining , Humans , Activities of Daily Living , Quality of Life , Skull/diagnostic imaging , Skull/surgery , Printing, Three-Dimensional
9.
bioRxiv ; 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37503216

ABSTRACT

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.

10.
MRS Bull ; 48(5): 531-546, 2023 May.
Article in English | MEDLINE | ID: mdl-37476355

ABSTRACT

Electrophysiological recording and stimulation are the gold standard for functional mapping during surgical and therapeutic interventions as well as capturing cellular activity in the intact human brain. A critical component probing human brain activity is the interface material at the electrode contact that electrochemically transduces brain signals to and from free charge carriers in the measurement system. Here, we summarize state-of-the-art electrode array systems in the context of translation for use in recording and stimulating human brain activity. We leverage parametric studies with multiple electrode materials to shed light on the varied levels of suitability to enable high signal-to-noise electrophysiological recordings as well as safe electrophysiological stimulation delivery. We discuss the effects of electrode scaling for recording and stimulation in pursuit of high spatial resolution, channel count electrode interfaces, delineating the electrode-tissue circuit components that dictate the electrode performance. Finally, we summarize recent efforts in the connectorization and packaging for high channel count electrode arrays and provide a brief account of efforts toward wireless neuronal monitoring systems.

11.
Neurosurg Focus ; 54(2): E4, 2023 02.
Article in English | MEDLINE | ID: mdl-36724521

ABSTRACT

OBJECTIVE: Stereotactic electroencephalography (sEEG) is an increasingly utilized method for identifying electrophysiological processes underlying sensorimotor, cognitive, and emotional behaviors. In this review, the authors outline current research using sEEG to investigate the neural activity underlying emotional and psychiatric behaviors. Understanding the current structure of intracranial research using sEEG will inform future studies of psychiatric disease and therapeutics for effective neuromodulation. METHODS: The authors conducted a comprehensive systematic review of studies according to PRISMA guidelines to investigate behaviors related to psychiatric conditions in patients with epilepsy undergoing monitoring with sEEG. Articles indexed on PubMed between 2010 and 2022 were included if they studied emotions or affective behaviors or met the National Institute of Mental Health Research Domain Criteria positive and negative valence domains. Data extracted from articles included study sample size, paradigms and behavioral tasks employed, cortical and subcortical targets, EEG analysis methods, and identified electrophysiological activity underlying the studied behavior. The Newcastle-Ottawa Scale was used to assess bias risk. RESULTS: Thirty-two primary articles met inclusion criteria. Study populations ranged from 3 to 39 patients. The most common structures investigated were the amygdala, insula, orbitofrontal cortex (OFC), hippocampus, and anterior cingulate cortex (ACC). Paradigms, stimuli, and behavioral tasks widely varied. Time-frequency analyses were the most common, followed by connectivity analyses. Multiple oscillations encoded a variety of behaviors related to emotional and psychiatric conditions. High gamma activity was observed in the amygdala and anterior insula in response to aversive audiovisual stimuli and in the OFC in response to reward processing. ACC beta band power increases and hippocampal-amygdala beta coherence variations were predictive of worsening mood states. Insular and amygdalar theta oscillations encoded social pain and fear learning, respectively. Most studies performed passing recordings, allowing for the decoding of affective states and depression symptoms, while other studies utilized direct stimulation, such as in the OFC to improve mood symptoms. CONCLUSIONS: Stereotactic EEG in epilepsy has identified multiple corticolimbic structures with specific oscillatory and synchronization activity underlying a diverse range of behaviors related to emotions and affective conditions. Given the heterogeneity of psychiatric conditions, sEEG provides an opportunity to study these neural correlates to develop personalized effective neuromodulatory treatments. Future studies should focus on optimizing paradigms and tasks to investigate a broad range of behavioral phenotypes that overlap across psychiatric conditions.


Subject(s)
Emotions , Epilepsy , Humans , Emotions/physiology , Electroencephalography/methods , Epilepsy/surgery , Prefrontal Cortex , Fear
12.
World Neurosurg ; 170: e716-e723, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36442775

ABSTRACT

OBJECTIVE: To evaluate the efficacy of intraoperative bupivacaine hydrochloride wound infiltration as an adjunct means of pain relief following noninstrumented posterior spine surgery. METHODS: A retrospective cohort analysis was performed of all patients who underwent posterior spinal decompression surgery at the University of California, San Diego, and at the San Diego VA Medical Center between June 2020 and July 2021, following a change in practice to including bupivacaine infiltration at the end of the surgery. Patients were stratified into groups based on whether they received intrawound bupivacaine during surgery. Demographic and clinical data were extracted from the electronic health record. Postoperative opioid use, visual analog pain scores, heart rate, and blood pressure were compared. RESULTS: The analysis included 43 patients; 21 received bupivacaine infiltration, and 22 did not. No complications were encountered in the perioperative period. Patients who received bupivacaine consumed significantly less opioids over the 72 hours following surgery, had slightly lower pain scores, and experienced slightly lower heart rates. No significant difference was found between groups with respect to systolic blood pressure, operative time, or length of hospital stay. CONCLUSIONS: Intraoperative infiltration of the exposed paraspinous musculature and peri-incisional subdermal layer with bupivacaine significantly reduced postoperative opioid consumption for 72 hours after surgery and slightly reduced pain ratings and conferred superior heart rate control. This low-cost intervention produced significant patient benefit with minimal risk and no significant increase in surgical time or hospital stay.


Subject(s)
Bupivacaine , Opioid-Related Disorders , Humans , Analgesics, Opioid/therapeutic use , Anesthetics, Local/therapeutic use , Retrospective Studies , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control
13.
Oper Neurosurg (Hagerstown) ; 24(1): 80-87, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36519881

ABSTRACT

BACKGROUND: Systematic use of neurosurgical training simulators across institutions is significantly hindered by logistical and financial constraints. OBJECTIVE: To evaluate feasibility of large-scale implementation of an intraoperative catastrophe simulation, we introduced a highly portable and low-cost immersive neurosurgical simulator into a nationwide curriculum for neurosurgery residents, during years 2016 to 2019. METHODS: The simulator was deployed at 9 Society of Neurological Surgeons junior resident courses and a Congress of Neurological Surgeons education course for a cohort of 526 residents. Heart rate was tracked to monitor physiological responses to simulated stress. Experiential survey data were collected to evaluate simulator fidelity and resident attitudes toward simulation. RESULTS: Residents rated the simulator positively with a statistically significant increase in satisfaction over time accompanying refinements in the simulator model and clinical scenario. The simulated complications induced stress-related tachycardia in most participants (n = 249); however, a cohort of participants was identified that experienced significant bradycardia (n = 24) in response to simulated stress. CONCLUSION: Incorporation of immersive neurosurgical simulation into the US national curriculum is logistically feasible and cost-effective for neurosurgical learners. Participant surveys and physiological data suggest that the simulation model recreates the situational physiological stress experienced during practice in the live clinical environment. Simulation may provide an opportunity to identify trainees with maladaptive responses to operative stress who could benefit from additional simulated exposure to mitigate stress impacts on performance.


Subject(s)
Internship and Residency , Neurosurgery , Humans , Neurosurgery/education , Curriculum , Educational Measurement , Personal Satisfaction
14.
Adv Funct Mater ; 32(25)2022 Jun 17.
Article in English | MEDLINE | ID: mdl-36381629

ABSTRACT

The Utah array powers cutting-edge projects for restoration of neurological function, such as BrainGate, but the underlying electrode technology has itself advanced little in the last three decades. Here, advanced dual-side lithographic microfabrication processes is exploited to demonstrate a 1024-channel penetrating silicon microneedle array (SiMNA) that is scalable in its recording capabilities and cortical coverage and is suitable for clinical translation. The SiMNA is the first penetrating microneedle array with a flexible backing that affords compliancy to brain movements. In addition, the SiMNA is optically transparent permitting simultaneous optical and electrophysiological interrogation of neuronal activity. The SiMNA is used to demonstrate reliable recordings of spontaneous and evoked field potentials and of single unit activity in chronically implanted mice for up to 196 days in response to optogenetic and to whisker air-puff stimuli. Significantly, the 1024-channel SiMNA establishes detailed spatiotemporal mapping of broadband brain activity in rats. This novel scalable and biocompatible SiMNA with its multimodal capability and sensitivity to broadband brain activity will accelerate the progress in fundamental neurophysiological investigations and establishes a new milestone for penetrating and large area coverage microelectrode arrays for brain-machine interfaces.

15.
Sci Transl Med ; 14(664): eabq4744, 2022 09 28.
Article in English | MEDLINE | ID: mdl-36170445

ABSTRACT

Intraoperative neuromonitoring (IONM) is a widely used practice in spine surgery for early detection and minimization of neurological injury. IONM is most commonly conducted by indirectly recording motor and somatosensory evoked potentials from either muscles or the scalp, which requires large-amplitude electrical stimulation and provides limited spatiotemporal information. IONM may inform of inadvertent events during neurosurgery after they occur, but it does not guide safe surgical procedures when the anatomy of the diseased spinal cord is distorted. To overcome these limitations and to increase our understanding of human spinal cord neurophysiology, we applied a microelectrode array with hundreds of channels to the exposed spinal cord during surgery and resolved spatiotemporal dynamics with high definition. We used this method to construct two-dimensional maps of responsive channels and define with submillimeter precision the electrophysiological midline of the spinal cord. The high sensitivity of our microelectrode array allowed us to record both epidural and subdural responses at stimulation currents that are well below those used clinically and to resolve postoperative evoked potentials when IONM could not. Together, these advances highlight the potential of our microelectrode arrays to capture previously unexplored spinal cord neural activity and its spatiotemporal dynamics at high resolution, offering better electrophysiological markers that can transform IONM.


Subject(s)
Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Evoked Potentials, Motor/physiology , Evoked Potentials, Somatosensory/physiology , Humans , Microelectrodes , Neurosurgical Procedures/methods , Retrospective Studies , Spinal Cord
16.
Sci Transl Med ; 14(628): eabj1441, 2022 01 19.
Article in English | MEDLINE | ID: mdl-35044788

ABSTRACT

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.


Subject(s)
Brain Mapping , Epilepsy , Animals , Brain/physiology , Electric Stimulation , Humans , Rats , Wakefulness
17.
Cereb Cortex ; 31(8): 3678-3700, 2021 07 05.
Article in English | MEDLINE | ID: mdl-33749727

ABSTRACT

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.


Subject(s)
Cerebral Cortex/physiology , Neurons/physiology , Acoustic Stimulation , Adult , Animals , Electric Stimulation , Electroencephalography , Electrophysiological Phenomena , Epilepsy/physiopathology , Extracellular Space/physiology , Female , Humans , Macaca mulatta , Magnetic Resonance Imaging , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Microelectrodes , Middle Aged , Somatosensory Cortex/physiology , Wavelet Analysis , Young Adult
18.
Stereotact Funct Neurosurg ; 97(4): 249-254, 2019.
Article in English | MEDLINE | ID: mdl-31661697

ABSTRACT

Trigeminal neuralgia (TN) is a debilitating but treatable disease. Classic TN has referable vascular compression of the trigeminal nerve, but rarely secondary sources of anatomic compression will present, including vascular malformations, aneurysms, or tumors. Understanding the etiology of the patients' symptoms leads to targeted treatment. Three patients presented with symptoms consistent with TN: shooting, paroxysmal pains in the distribution of the trigeminal nerve. However, imaging revealed no vascular conflict at the root entry zone of the trigeminal nerve. Instead, on the affected side Meckel's cave was absent. No other compressive mass lesion was identified. In all three cases, patients were offered both Gamma Knife Radiosurgery and surgical decompression of Meckel's cave. All 3 patients elected to proceed with stereotactic radiation and reported improvement in pain. Many cases of classic TN can be explained by neurovascular conflict at the trigeminal root entry zone, but secondary sources of compression or restriction along the nerve can result in similar symptomology. In this case series, an absent or hypoplastic ipsilateral Meckel's cave may have produced symptoms consistent with TN. Imaging with fine cuts through Meckel's cave is an important diagnostic tool.


Subject(s)
Cranial Fossa, Middle/abnormalities , Cranial Fossa, Middle/diagnostic imaging , Trigeminal Nerve/diagnostic imaging , Trigeminal Neuralgia/diagnostic imaging , Adult , Cranial Fossa, Middle/surgery , Decompression, Surgical/methods , Female , Humans , Middle Aged , Radiosurgery/methods , Trigeminal Nerve/surgery , Trigeminal Neuralgia/surgery
19.
Nano Lett ; 19(9): 6244-6254, 2019 09 11.
Article in English | MEDLINE | ID: mdl-31369283

ABSTRACT

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.


Subject(s)
Action Potentials , Biocompatible Materials , Brain-Computer Interfaces , Nanotubes , Neurons/metabolism , Platinum , Visual Cortex/physiology , Animals , Electric Stimulation , Electrodes , Macaca mulatta , Male , Mice , Songbirds
20.
Neurosurg Focus ; 46(3): E9, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30835678

ABSTRACT

Spinal cord injury (SCI) has been associated with a dismal prognosis-recovery is not expected, and the most standard interventions have been temporizing measures that do little to mitigate the extent of damage. While advances in surgical and medical techniques have certainly improved this outlook, limitations in functional recovery continue to impede clinically significant improvements. These limitations are dependent on evolving immunological mechanisms that shape the cellular environment at the site of SCI. In this review, we examine these mechanisms, identify relevant cellular components, and discuss emerging treatments in stem cell grafts and adjuvant immunosuppressants that target these pathways. As the field advances, we expect that stem cell grafts and these adjuvant treatments will significantly shift therapeutic approaches to acute SCI with the potential for more promising outcomes.


Subject(s)
Graft Rejection/prevention & control , Graft vs Host Disease/prevention & control , Immunosuppressive Agents/therapeutic use , Induced Pluripotent Stem Cells/transplantation , Oligodendrocyte Precursor Cells/transplantation , Spinal Cord Injuries/therapy , Adjuvants, Immunologic , Allografts , Animals , Basiliximab/therapeutic use , Cells, Cultured , Clinical Trials as Topic , Cyclosporine/therapeutic use , Female , Graft Survival/immunology , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/immunology , Humans , Induced Pluripotent Stem Cells/immunology , Male , Mice , Mycophenolic Acid/therapeutic use , Oligodendrocyte Precursor Cells/immunology , Rats , Tacrolimus/therapeutic use , Transplantation, Autologous
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