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.

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.

Advances in surgery for movement disorders.

Movement disorder surgery has evolved throughout history as our knowledge of motor circuits and ways in which to manipulate them have expanded. Today, the positive impact on patient quality of life for a growing number of movement disorders such as Parkinson's disease is now well accepted and confirmed through several decades of randomized, controlled trials. Nevertheless, residual motor symptoms after movement disorder surgery such as deep brain stimulation and lack of a definitive cure for these conditions demand that advances continue to push the boundaries of the field and maximize its therapeutic potential. Similarly, advances in related fields - wireless technology, artificial intelligence, stem cell and gene therapy, neuroimaging, nanoscience, and minimally invasive surgery - mean that movement disorder surgery stands at a crossroads to benefit from unique combinations of all these developments. In this minireview, we outline some of these developments as well as evidence supporting topics of recent discussion and controversy in our field. Moving forward, expectations remain high that these improvements will come to encompass an even broader range of patients who might benefit from this therapy and decrease the burden of disease associated with these conditions. © 2016 International Parkinson and Movement Disorder Society.

Comparison of General and Local Anesthesia for Deep Brain Stimulator Insertion: A Systematic Review.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) has become a standard treatment for many patients with Parkinson's disease (PD). The reported clinical outcome measures for procedures done under general anesthesia (GA) compared to traditional local anesthetic (LA) technique are quite heterogeneous and difficult to compare. The aim of this systematic review and metaanalysis was to determine whether the clinical outcome after STN-DBS insertion under GA is comparable to that under LA in patients with Parkinson's disease. METHODS: The databases of Medline Embase, Cochrane library and Pubmed were searched for eligible studies (human trials, English language, published between 1946 and January of 2016). The primary outcome of this study was to assess the postoperative improvement in the symptoms, evaluated using either Unified Parkinson's Disease Rating Scale (UPDRS) scores or levodopa equivalent dosage (LEDD) requirement. RESULTS: The literature searches yielded 395 citations and six retrospective cohort studies with a sample size of 455 (194 in GA and 261 in LA) were included in the analysis. Regarding the clinical outcomes, there were no significant differences in the postoperative Unified Parkinson's disease rating scale and levodopa equivalent drug dosage between the GA and the LA groups. Similarly, the adverse events and target accuracy were also comparable between the groups. CONCLUSIONS: This systematic review and meta-analysis shows that currently there is no good quality data to suggest equivalence of GA to LA during STN-DBS insertion in patients with PD, with some factors trending towards LA. There is a need for a prospective randomized control trial to validate our results.

Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.

Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain.

Etiology, prognosis, and management of secondary pituitary abscesses forming in underlying pituitary adenomas.

Pituitary abscesses occurring in pre-existing pituitary pathology like Rathke's cleft cyst or adenomas (secondary pituitary abscesses) are rare and of unclear etiology. While surgery and antibiotics have been effective in some cases reported to date, leading to the suggestion that secondary pituitary abscesses are mostly indolent, we investigated the hypothesis that infected adenomas, given their propensity to invade the paranasal sinuses and subarachnoid space, could carry a worse prognosis than uninfected adenomas or secondary abscesses forming in other pituitary pathologies. We identified infected adenomas from our center through retrospective review. Given the rarity of this diagnosis at any single center, we also reviewed published cases of secondary pituitary abscesses occurring in pituitary adenomas to look for common features. Twenty-three cases (19 from the literature and four from our center) of infected adenomas were identified. The mean age at presentation was 46 years, with 65 % male. The most common presenting symptoms were visual disturbances (83 %) and headache (65 %), followed by infectious signs like fever (39 %) and meningitis (26 %). The sphenoidal sinus was the most common site of extrasellar invasion. While good outcome occurred in 74 % of patients, and most achieved vision improvement, the mortality was 26 %. Patients with infected pituitary adenomas commonly present with visual disturbances and headache, with symptoms of infection also occurring. Surgery and antibiotics are indicated for these lesions. While the infection is more indolent than other intracranial abscesses, it is associated with high mortality even after prompt operation and antibiotic treatment.

Three-dimensional accuracy of ECOG strip electrode localization using coregistration of preoperative MRI and intraoperative fluoroscopy.

BACKGROUND/AIMS: Algorithms that estimate implanted cortical strip electrode coordinates using postoperative skull X-ray coregistration with preoperative magnetic resonance imaging (MRI) have been proposed. However, when cortical strip electrodes are inserted for temporary use and removed prior to closure, intraoperative imaging - either fluoroscopy or computed tomography (CT) - must be substituted. OBJECTIVES: To measure the accuracy of temporarily inserted subdural strip electrode coordinates using intraoperative fluoroscopic coregistration with preoperative MRI compared to intraoperative CT coregistration with preoperative MRI. METHODS: In 5 patients undergoing movement disorder surgery, preoperative MRI was used to generate a three-dimensional cortical surface manually scaled to fit an intraoperative skull fluorogram with an in situ six-contact subdural electrode strip. Individual contact coordinates were estimated using subjacent gyral and sulcal patterns. Estimated coordinates were compared to reference coordinates obtained by preoperative MRI coregistration with intraoperative CT in the same patients. RESULTS: Mean electrode coordinate distances between estimated and reference locations were 6.0 ± 0.8 (x-axis, mediolateral), 3.3 ± 0.5 (y-axis, anterior-posterior) and 4.0 ± 0.5 mm (z-axis, superior-inferior; n = 30). CONCLUSIONS: Localization of temporarily inserted subdural electrodes can be accomplished using preoperative MRI and intraoperative fluoroscopy. The accuracy of this approach is verified by preoperative MRI and intraoperative CT coregistration in the same patients.

Noninvasive brain stimulation during EEG improves machine learning classification in chronic stroke.

Background: In individuals with chronic stroke and hemiparesis, noninvasive brain stimulation (NIBS) may be used as an adjunct to therapy for improving motor recovery. Specific states of movement during motor recovery are more responsive to brain stimulation than others, thus a system that could auto-detect movement state would be useful in correctly identifying the most effective stimulation periods. The aim of this study was to compare the performance of different machine learning models in classifying movement periods during EEG recordings of hemiparetic individuals receiving noninvasive brain stimulation. We hypothesized that transcranial direct current stimulation, a form of NIBS, would modulate brain recordings correlating with movement state and improve classification accuracies above those receiving sham stimulation. Methods: Electroencephalogram data were obtained from 10 participants with chronic stroke and 11 healthy individuals performing a motor task while undergoing transcranial direct current stimulation. Eight traditional machine learning algorithms and five ensemble methods were used to classify two movement states (a hold posture and an arm reaching movement) before, during and after stimulation. To minimize compute times, preprocessing and feature extraction were limited to z-score normalization and power binning into five frequency bands (delta through gamma). Results: Classification of disease state produced significantly higher accuracies in the stimulation (versus sham) group at 78.9% (versus 55.6%, p < 0.000002). We observed significantly higher accuracies when classifying stimulation state in the chronic stroke group (77.6%) relative to healthy controls (64.1%, p < 0.0095). In the chronic stroke cohort, classification of hold versus reach was highest during the stimulation period (75.2%) as opposed to the pre- and post-stimulation periods. Linear discriminant analysis, logistic regression, and decision tree algorithms classified movement state most accurately in participants with chronic stroke during the stimulation period (76.1%). For the ensemble methods, the highest classification accuracy for hold versus reach was achieved using low gamma frequency (30-50 Hz) as a feature (74.5%), although this result did not achieve statistical significance. Conclusions: Machine learning algorithms demonstrated sufficiently high movement state classification accuracy in participants with chronic stroke performing functional tasks during noninvasive brain stimulation. tDCS improved disease state and movement state classification in participants with chronic stroke.

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.

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.

Concurrent tDCS-fMRI after stroke reveals link between attention network organization and motor improvement.

Restoring motor function after stroke necessitates involvement of numerous cognitive systems. However, the impact of damage to motor and cognitive network organization on recovery is not well understood. To discover correlates of successful recovery, we explored imaging characteristics in chronic stroke subjects by combining noninvasive brain stimulation and fMRI. Twenty stroke survivors (6 months or more after stroke) were randomly assigned to a single session of transcranial direct current stimulation (tDCS) or sham during image acquisition. Twenty healthy subjects were included as controls. tDCS was limited to 10 min at 2 mA to serve as a mode of network modulation rather than therapeutic delivery. Fugl-Meyer Assessments (FMA) revealed significant motor improvement in the chronic stroke group receiving active stimulation (p = 0.0005). Motor changes in this group were correlated in a data-driven fashion with imaging features, including functional connectivity (FC), surface-based morphometry, electric field modeling and network topology, focusing on relevant regions of interest. We observed stimulation-related changes in FC in supplementary motor (p = 0.0029), inferior frontal gyrus (p = 0.0058), and temporo-occipital (p = 0.0095) areas, though these were not directly related to motor improvement. The feature most strongly associated with FMA improvement in the chronic stroke cohort was graph topology of the dorsal attention network (DAN), one of the regions surveyed and one with direct connections to each of the areas with FC changes. Chronic stroke subjects with a greater degree of motor improvement had lower signal transmission cost through the DAN (p = 0.029). While the study was limited by a small stroke cohort with moderate severity and variable lesion location, these results nevertheless suggest a top-down role for higher order areas such as attention in helping to orchestrate the stroke recovery process.

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.

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.

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.

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.

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.

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.

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.