The evolution of neuromodulation for chronic stroke: From neuroplasticity mechanisms to brain-computer interfaces.

Stroke is one of the most common and debilitating neurological conditions worldwide. Those who survive experience motor, sensory, speech, vision, and/or cognitive deficits that severely limit remaining quality of life. While rehabilitation programs can help improve patients' symptoms, recovery is often limited, and patients frequently continue to experience impairments in functional status. In this review, invasive neuromodulation techniques to augment the effects of conventional rehabilitation methods are described, including vagus nerve stimulation (VNS), deep brain stimulation (DBS) and brain-computer interfaces (BCIs). In addition, the evidence base for each of these techniques, pivotal trials, and future directions are explored. Finally, emerging technologies such as functional near-infrared spectroscopy (fNIRS) and the shift to artificial intelligence-enabled implants and wearables are examined. While the field of implantable devices for chronic stroke recovery is still in a nascent stage, the data reviewed are suggestive of immense potential for reducing the impact and impairment from this globally prevalent disorder.

Subthalamic functional connectivity associated with freezing of gait dopa-response.

INTRODUCTION: Freezing of gait (FOG) is a prevalent and debilitating feature of Parkinson's Disease (PD). The subthalamic nucleus (STN) is a center for controlled locomotion and a common DBS target. The objective of this study was to identify STN circuitry associated with FOG response to dopaminergic medication. In this study, we compare BOLD functional connectivity of the subthalamic nucleus (STN) in participants with and without dopa-responsive FOG. METHODS: 55 PD participants either with FOG (n = 38) or without FOG (n = 17) were recruited. Among FOG participants 22 were dopa-responsive and 16 were dopa-unresponsive. STN whole-brain connectivity was performed using CONN toolbox. The relationship between the degree of self-reported FOG dopa-response and STN connectivity was evaluated using partial correlations corrected for age, disease duration, and levodopa equivalent daily dose. RESULTS: Right STN connectivity with the cerebellar locomotor region and the temporal/occipital cortex was greater in the dopa-responsive FOG group (voxel threshold p < 0.01, FWE corrected p < 0.05). Left STN connectivity with the occipital cortex was greater in the dopa-responsive FOG group and connectivity with the postcentral gyrus was greater in the dopa-unresponsive FOG group. Strength of connectivity to these regions correlated with l-dopa induced improvement in UPDRS Item-14 (FOG), but not UPDRS Part-III (overall motor score). DISCUSSION: We demonstrate that dopa-unresponsive FOG is associated with changes in BOLD functional connectivity between the STN and locomotor as well as sensory processing regions. This finding supports the conceptual framework that effective treatment for freezing of gait likely requires the engagement of both locomotor and sensory brain regions.

Protracted respiratory failure in a case of global spinal syringomyelia and Chiari malformation following administration of diazepam: illustrative case.

BACKGROUND: Syringomyelia is defined as dilation of the spinal cord's central canal and is often precipitated by skull base herniation disorders. Although respiratory failure (RF) can be associated with skull base abnormalities due to brainstem compression, most cases occur in pediatric patients and quickly resolve. The authors report the case of an adult patient with global spinal syringomyelia and Chiari malformation who developed refractory RF after routine administration of diazepam. OBSERVATIONS: A 31-year-old female presented with malnutrition, a 1-month history of right-sided weakness, and normal respiratory dynamics. After administration of diazepam prior to magnetic resonance imaging (MRI), she suddenly developed hypercapnic RF followed MRI and required intubation. MRI disclosed a Chiari malformation type I and syrinx extending from C1 to the conus medullaris. After decompressive surgery, her respiratory function progressively returned to baseline status, although 22 months after initial benzodiazepine administration, the patient continues to require nocturnal ventilation. LESSONS: Administration of central nervous system depressants should be closely monitored in patients with extensive syrinx formation given the potential to exacerbate diminished central respiratory drive. Early identification of syrinx in the context of Chiari malformation and hemiplegia should prompt clinical suspicion of underlying respiratory compromise and early involvement of intensive care consultants.

Deep brain stimulation for essential tremor versus essential tremor plus: should we target the same spot in the thalamus?

Background: Although ET is a phenomenologically heterogeneous condition, thalamic DBS appears to be equally effective across subtypes. We hypothesized stimulation sites optimized for individuals with essential tremor (ET) would differ from individuals with essential tremor plus syndrome (ET-plus). We examined group differences in optimal stimulation sites within the ventral thalamus and their overlap of with relevant white matter tracts. By capturing these differences, we sought to determine whether ET subtypes are associated with anatomically distinct neural pathways. Methods: A retrospective chart review was conducted on ET patients undergoing VIM DBS at MUSC between 01/2012 and 02/2022. Clinical, demographic, neuroimaging, and DBS stimulation parameter data were collected. Clinical characteristics and pre-DBS videos were reviewed to classify ET and ET-plus cohorts. Patients in ET-plus cohorts were further divided into ET with dystonia, ET with ataxia, and ET with others. DBS leads were reconstructed using Lead-DBS and the volume of tissue activated (VTA) overlap was performed using normative connectomes. Tremor improvement was measured by reduction in a subscore of tremor rating scale (TRS) post-DBS lateralized to the more affected limb. Results: Sixty-eight ET patients were enrolled after initial screening, of these 10 ET and 24 ET-plus patients were included in the final analyses. ET group had an earlier age at onset (p = 0.185) and underwent surgery at a younger age (p = 0.096). Both groups achieved effective tremor control. No significant differences were found in lead placement or VTA overlap within ventral thalamus. The VTA center of gravity (COG) in the ET-plus cohort was located dorsal to that of the ET cohort. No significant differences were found in VTA overlap with the dentato-rubral-thalamic (DRTT) tracts or the ansa lenticularis. Dystonia was more prevalent than ataxia in the ET-plus subgroups (n = 18 and n = 5, respectively). ET-plus with dystonia subgroup had a more medial COG compared to ET-plus with ataxia. Conclusion: VIM DBS therapy is efficacious in patients with ET and ET-plus. There were no significant differences in optimal stimulation site or VTA overlap with white-matter tracts between ET, ET-plus and ET-plus subgroups.

Racial disparities in access to DBS: results of a real-world U.S. claims data analysis.

Introduction: Deep brain stimulation (DBS) is an effective and standard-of-care therapy for Parkinson's Disease and other movement disorders when symptoms are inadequately controlled with conventional medications. It requires expert care for patient selection, surgical targeting, and therapy titration. Despite the known benefits, racial/ethnic disparities in access have been reported. Technological advancements with smartphone-enabled devices may influence racial disparities. Real-world evidence investigations can shed further light on barriers to access and demographic disparities for DBS patients. Methods: A retrospective cross-sectional study was performed using Medicare claims linked with manufacturer patient data tracking to analyze 3,869 patients who received DBS. Patients were divided into two categories: traditional omnidirectional DBS systems with dedicated proprietary controllers ("traditional"; n = 3,256) and directional DBS systems with smart controllers ("smartphone-enabled"; n = 613). Demographics including age, sex, and self-identified race/ethnicity were compared. Categorical demographics, including race/ethnicity and distance from implanting facility, were analyzed for the entire population. Results: A significant disparity in DBS utilization was evident. White individuals comprised 91.4 and 89.9% of traditional and smartphone-enabled DBS groups, respectively. Non-White patients were significantly more likely to live closer to implanting facilities compared with White patients. Conclusion: There is great racial disparity in utilization of DBS therapy. Smartphone-enabled systems did not significantly impact racial disparities in receiving DBS. Minoritized patients were more likely to live closer to their implanting facility than White patients. Further research is warranted to identify barriers to access for minoritized patients to receive DBS. Technological advancements should consider the racial discrepancy of DBS utilization in future developments.

Investigation of neurophysiologic and functional connectivity changes following glioma resection using magnetoencephalography.

Background: In patients with glioma, clinical manifestations of neural network disruption include behavioral changes, cognitive decline, and seizures. However, the extent of network recovery following surgery remains unclear. The aim of this study was to characterize the neurophysiologic and functional connectivity changes following glioma surgery using magnetoencephalography (MEG). Methods: Ten patients with newly diagnosed intra-axial brain tumors undergoing surgical resection were enrolled in the study and completed at least two MEG recordings (pre-operative and immediate post-operative). An additional post-operative recording 6-8 weeks following surgery was obtained for six patients. Resting-state MEG recordings from 28 healthy controls were used for network-based comparisons. MEG data processing involved artifact suppression, high-pass filtering, and source localization. Functional connectivity between parcellated brain regions was estimated using coherence values from 116 virtual channels. Statistical analysis involved standard parametric tests. Results: Distinct alterations in spectral power following tumor resection were observed, with at least three frequency bands affected across all study subjects. Tumor location-related changes were observed in specific frequency bands unique to each patient. Recovery of regional functional connectivity occurred following glioma resection, as determined by local coherence normalization. Changes in inter-regional functional connectivity were mapped across the brain, with comparable changes in low to mid gamma-associated functional connectivity noted in four patients. Conclusion: Our findings provide a framework for future studies to examine other network changes in glioma patients. We demonstrate an intrinsic capacity for neural network regeneration in the post-operative setting. Further work should be aimed at correlating neurophysiologic changes with individual patients' clinical outcomes.

Vasospasm secondary to responsive neurostimulator placement: a previously unreported complication. Illustrative case.

BACKGROUND: The Responsive Neurostimulation (RNS) system is an implantable device for patients with drug-resistant epilepsy who are not candidates for resection of a seizure focus. As a relatively new therapeutic, the full spectrum of adverse effects has yet to be determined. A literature review revealed no previous reports of cerebral vasospasm following RNS implantation. OBSERVATIONS: A 35-year-old man developed severe angiographic and clinical vasospasm following bilateral mesial temporal lobe RNS implantation. He initially presented with concerns for status epilepticus 8 days after implantation. On hospital day 3, a decline in his clinical examination prompted imaging studies that revealed a left middle cerebral artery (MCA) stroke with angiographic evidence of severe vasospasm of the left internal carotid artery (ICA), MCA, anterior cerebral artery (ACA), and right ICA and ACA. Despite improvements in angiographic vasospasm after appropriate treatment, a thrombus developed in the posterior M2 branch, requiring mechanical thrombectomy. Ultimately, the patient was stabilized and discharged to a rehabilitation facility with residual cognitive and motor deficits. LESSONS: Cerebral vasospasm as a cause of ischemic stroke after uneventful RNS implantation is exceedingly rare, yet demands particular attention given the potential for severe consequences and the growing number of patients receiving RNS devices.

Transcranial Direct Current Stimulation for Chronic Stroke: Is Neuroimaging the Answer to the Next Leap Forward?

During rehabilitation, a large proportion of stroke patients either plateau or begin to lose motor skills. By priming the motor system, transcranial direct current stimulation (tDCS) is a promising clinical adjunct that could augment the gains acquired during therapy sessions. However, the extent to which patients show improvements following tDCS is highly variable. This variability may be due to heterogeneity in regions of cortical infarct, descending motor tract injury, and/or connectivity changes, all factors that require neuroimaging for precise quantification and that affect the actual amount and location of current delivery. If the relationship between these factors and tDCS efficacy were clarified, recovery from stroke using tDCS might be become more predictable. This review provides a comprehensive summary and timeline of the development of tDCS for stroke from the viewpoint of neuroimaging. Both animal and human studies that have explored detailed aspects of anatomy, connectivity, and brain activation dynamics relevant to tDCS are discussed. Selected computational works are also included to demonstrate how sophisticated strategies for reducing variable effects of tDCS, including electric field modeling, are moving the field ever closer towards the goal of personalizing tDCS for each individual. Finally, larger and more comprehensive randomized controlled trials involving tDCS for chronic stroke recovery are underway that likely will shed light on how specific tDCS parameters, such as dose, affect stroke outcomes. The success of these collective efforts will determine whether tDCS for chronic stroke gains regulatory approval and becomes clinical practice in the future.

Neuromodulation for treatment-resistant depression: Functional network targets contributing to antidepressive outcomes.

Non-invasive brain stimulation is designed to target accessible brain regions that underlie many psychiatric disorders. One such method, transcranial magnetic stimulation (TMS), is commonly used in patients with treatment-resistant depression (TRD). However, for non-responders, the choice of an alternative therapy is unclear and often decided empirically without detailed knowledge of precise circuit dysfunction. This is also true of invasive therapies, such as deep brain stimulation (DBS), in which responses in TRD patients are linked to circuit activity that varies in each individual. If the functional networks affected by these approaches were better understood, a theoretical basis for selection of interventions could be developed to guide psychiatric treatment pathways. The mechanistic understanding of TMS is that it promotes long-term potentiation of cortical targets, such as dorsolateral prefrontal cortex (DLPFC), which are attenuated in depression. DLPFC is highly interconnected with other networks related to mood and cognition, thus TMS likely alters activity remote from DLPFC, such as in the central executive, salience and default mode networks. When deeper structures such as subcallosal cingulate cortex (SCC) are targeted using DBS for TRD, response efficacy has depended on proximity to white matter pathways that similarly engage emotion regulation and reward. Many have begun to question whether these networks, targeted by different modalities, overlap or are, in fact, the same. A major goal of current functional and structural imaging in patients with TRD is to elucidate neuromodulatory effects on the aforementioned networks so that treatment of intractable psychiatric conditions may become more predictable and targeted using the optimal technique with fewer iterations. Here, we describe several therapeutic approaches to TRD and review clinical studies of functional imaging and tractography that identify the diverse loci of modulation. We discuss differentiating factors associated with responders and non-responders to these stimulation modalities, with a focus on mechanisms of action for non-invasive and intracranial stimulation modalities. We advance the hypothesis that non-invasive and invasive neuromodulation approaches for TRD are likely impacting shared networks and critical nodes important for alleviating symptoms associated with this disorder. We close by describing a therapeutic framework that leverages personalized connectome-guided target identification for a stepwise neuromodulation paradigm.

Neurosurgery for psychiatric disorders: reviewing the past and charting the future.

Surgical techniques targeting behavioral disorders date back thousands of years. In this review, the authors discuss the history of neurosurgery for psychiatric disorders, starting with trephination in the Stone Age, progressing through the fraught practice of prefrontal lobotomy, and ending with modern neurosurgical techniques for treating psychiatric conditions, including ablative procedures, conventional deep brain stimulation, and closed-loop neurostimulation. Despite a tumultuous past, psychiatric neurosurgery is on the cusp of becoming a transformative therapy for patients with psychiatric dysfunction, with an ever-increasing evidence base suggesting reproducible and ethical therapeutic benefit.

Functional MRI-Guided Motor Cortex and Deep Brain Stimulation for Intractable Facial Pain: A Novel, Personalized Approach in 1 Patient.

BACKGROUND: Facial neuropathic pain syndromes such as trigeminal neuralgia are debilitating disorders commonly managed by medications, vascular decompression, and/or ablative procedures. In trigeminal neuralgia cases unresponsive to these interventions, trigeminal deafferentation pain syndrome (TDPS) can emerge and remain refractory to any further attempts at these conventional therapies. Deep brain stimulation (DBS) and motor cortex stimulation are 2 neuromodulatory treatments that have demonstrated efficacy in small case series of TDPS yet remain largely underutilized. In addition, functional MRI (fMRI) is a tool that can help localize central processing of evoked stimuli such as mechanically triggered facial pain. In this study, we present a case report and operative technique in a patient with TDPS who underwent fMRI to guide the operative management and placement of dual targets in the sensory thalamus and motor cortex. OBJECTIVE: To evaluate the safety, efficacy, and outcome of a novel surgical approach for TDPS in a single patient. METHODS: The fMRI and operative technique of unilateral DBS targeting the ventroposteromedial nucleus of the thalamus and facial motor cortex stimulator placement through a single burr hole is illustrated as well as the patient's clinical outcome. RESULTS: In less than 1 year, the patient had near complete resolution of his facial pain with no postoperative complications. CONCLUSION: We present the first published case of successful treatment of TDPS using simultaneous DBS of the ventroposteromedial and motor cortex stimulation. fMRI can be used as an effective imaging modality to guide neuromodulation in this complex disorder.

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex.

INTRODUCTION: There is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects. OBJECTIVE: The aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity. METHODS: An 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated. RESULTS: tbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence. CONCLUSION: The findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.

Trigeminal Neuralgia Secondary to Meckel's Cave Meningoencephaloceles: A Systematic Review and Illustrative Case.

Background: The culprit of trigeminal neuralgia (TGN) may occur at any point between the nerve's root entry zone (REZ) and Meckel's cave. Meckel's cave meningoencephaloceles are rare middle cranial fossa defects that usually remain asymptomatic but may contain prolapsed trigeminal nerve rootlets and result in TGN. Their management and surgical outcomes remain poorly understood. Objectives: To perform a systematic review of clinical presentation and surgical outcomes of middle fossa defects presenting with trigeminal nerve-related symptoms. Materials and Methods: A systematic review was conducted in accordance with the PRISMA guidelines for all reports of middle cranial fossa defects causing trigeminal nerve-related symptoms. The pathophysiology, presentation, surgical management, and outcomes are discussed and illustrated with a case. Results: Initial search from inception to March 2021 identified 33 articles for screening. After applying inclusion and exclusion criteria, 6 articles were included representing a total of 8 cases in addition to our case (n = 9). All 9 patients were females and 33.3% (n = 3) presented with classic trigeminal neuralgia. "Empty sella" syndrome and radiologic signs of intracranial hypertension were present in 40%-62%. No patient presented with cerebrospinal fluid leak. The preferred treatment modality was surgical with subtemporal extradural repairs using combinations of autologous fat and muscle grafts and synthetic dura. Postoperative outcomes were only available in 55.5% (n = 5) of the cases, and nearly all reported complete symptom resolution, except for one case in which the meningoencephalocele wall was incised, along with trigeminal rootlets adhered to it. Our patient had immediate and durable symptom relief after a 4-year follow-up. Conclusions: MEC containing prolapsed trigeminal nerve rootlets can cause typical trigeminal neuralgia from chronic pulsatile stress. This supports the hypothesis that the compressive or demyelinating culprit can locate more ventrally on the course of the trigeminal nerve. Subtemporal extradural surgical repairs can be safe, effective, and durable. Incising the MEC wall should be avoided as it may have trigeminal rootlets adhered to it.

Case report: Awake craniotomy during pregnancy for resection of glioblastoma.

Few cases have been reported of the diagnosis and treatment of glioblastoma (GB) during pregnancy. Subsequently, surgical, medical, and obstetrical management of complicated primary central nervous system malignancy in antepartum and postpartum patients remains under-investigated. The authors report the case of a 24-year-old female patient who developed generalized tonic-clonic seizures and focal neurologic deficits. MRI imaging (3T Skyra, Siemens, Erlangen, Germany) revealed an intracranial mass suspicious for malignant tumor and surgical resection under awake sedation was scheduled. The patient was incidentally found to be in her first trimester of pregnancy. Using neuronavigation, neurophysiologic monitoring, and conscious sedation the tumor was debulked successfully and histopathologic analysis confirmed giant cell glioblastoma, WHO Grade IV, 1p/19q intact, IDH wild-type, with NF1 p.Y2285fs and RB1 p.S318fs somatic mutations. Post-surgical oncologic management continued with fractioned radiotherapy and use of the Optune® device. The patient underwent uncomplicated cesarean section at 34-weeks gestation, the child remains healthy and the patient remains disease-disease free at 1-year. Thus, this case presents an approach to management of complicated GBM during first trimester pregnancy.

Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition.

BACKGROUND: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. OBJECTIVES: The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. METHODS: We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. RESULTS: NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low- and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05). CONCLUSIONS: Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement. © 2021 International Parkinson and Movement Disorder Society.

Patterns of seizure spread in temporal lobe epilepsy are associated with distinct white matter tracts.

OBJECTIVE: It is commonly hypothesized that seizure spread patterns in patients with focal epilepsy are associated with structural brain pathways. However, this relationship is poorly understood and has not been fully demonstrated in patients with temporal lobe epilepsy. Here, we sought to determine whether directionality of seizure spread (DSS) is associated with specific cerebral white matter tracts in patients with temporal lobe epilepsy. METHODS: Thirty-three adult patients with temporal lobe epilepsy who underwent stereoelectroencephalography (sEEG) and magnetic resonance diffusion tensor imaging (MR-DTI) as part of their standard-of-care clinical evaluation were included in the study. DSS was defined as anterior-posterior (AP) or medial-lateral (ML) spread based upon sEEG evaluation by two independent specialists who demonstrated excellent inter-rater agreement (Cohen's kappa = .92). DTI connectometry was used to assess differences between seizure spread pattern groups along major fiber pathways regarding fractional anisotropy (FA). RESULTS: Twenty-four participants showed seizures with AP spread and nine participants showed seizures with ML spread. There were no significant differences between the groups on their demographic and clinical profile. Patients with ML seizures had higher FA along the corpus callosum and, to a lesser degree, some portions of the bilateral cingulate tracts. In contrast, patients with AP seizures had higher FA along several anterior-posterior white matter projections bundles, including the cingulate fasciculus and the inferior longitudinal, with significantly less involvement of the corpus callosum compared with ML seizures. SIGNIFICANCE: This study confirms the hypothesis that the anatomical pattern of electrophysiological ictal propagation is associated with the structural reinforcement of supporting pathways in temporal lobe epilepsy. This observation can help elucidate mechanisms of ictal propagation and may guide future translational approaches to curtail seizure spread.

Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. OBJECTIVE: We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. METHODS: Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. RESULTS: Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. CONCLUSIONS: Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.

Characterizing the effects of deep brain stimulation with magnetoencephalography: A review.

BACKGROUND: Deep brain stimulation (DBS) is an important form of neuromodulation that is being applied to patients with motor, mood, or cognitive circuit disorders. Despite the efficacy and widespread use of DBS, the precise mechanisms by which it works remain unknown. Over the last decade, magnetoencephalography (MEG) has become an important functional neuroimaging technique used to study DBS. OBJECTIVE: This review summarizes the literature related to the use of MEG to characterize the effects of DBS. METHODS: Peer reviewed literature on DBS-MEG was obtained by searching the publicly accessible literature databases available on PubMed. The abstracts of all reports were scanned and publications which combined DBS-MEG in human subjects were selected for review. RESULTS: A total of 32 publications met the selection criteria, and included studies which applied DBS for Parkinson's disease, dystonia, chronic pain, phantom limb pain, cluster headache, and epilepsy. DBS-MEG studies provided valuable insights into network connectivity, pathological coupling, and the modulatory effects of DBS. CONCLUSIONS: As DBS-MEG research continues to develop, we can expect to gain a better understanding of diverse pathophysiological networks and their response to DBS. This knowledge will improve treatment efficacy, reduce side-effects, reveal optimal surgical targets, and advance the development of closed-loop neuromodulation.

Airway Management With a Stereotactic Headframe In Situ-A Mannequin Study.

BACKGROUND: Stereotactic headframe-based imaging is often needed for target localization during surgery for insertion of deep brain stimulators. A major concern during this surgery is the need for emergency airway management while an awake or sedated patient is in the stereotactic headframe. The aim of our study was to determine the ease of emergency airway management with a stereotactic headframe in situ. MATERIALS AND METHODS: We conducted an observational study using a mannequin. A Leksell stereotactic headframe was placed on a mannequin in the operating room and the frame was fixed to the operating room table. Anesthesia personnel were asked to insert a #4 laryngeal mask and then to intubate the mannequin, using both direct (DL) and video laryngoscopy (VL). In addition, participants were asked to perform the same airway techniques in the mannequin without the headframe. Data were analyzed for time taken for airway management using different devices with and without the headframe. In addition, we compared the time taken to secure the airway between different participant groups. RESULTS: Thirty anesthesia personnel (7 residents, 12 fellows, and 11 consultants) participated in the study. With the headframe in situ, 97% of participants were able to insert a laryngeal mask on their first attempt; 93% and 97% of participants were able to intubate the mannequin using DL and VL respectively on their first attempt. Without the stereotactic headframe, all participants were able to insert the laryngeal mask and intubate on the first attempt. The average time taken to insert a laryngeal mask and intubate the mannequin using DL and VL with the headframe in situ was 39.3, 58.6, and 54.8 seconds, respectively. CONCLUSIONS: Our study showed that both laryngeal mask insertion and tracheal intubation can be performed with a stereotactic headframe in situ. A laryngeal mask is the quickest airway device to insert and can be inserted while the mannequin is in the standard surgical position. Further study is needed to validate the results in patients.