Trigeminal and Glossopharyngeal Neuralgia.

Trigeminal neuralgia and glossopharyngeal neuralgia are craniofacial pain syndromes characterized by recurrent brief shock-like pains in the distributions of their respective cranial nerves. In this article, the authors aim to summarize each condition's characteristics, pathophysiology, and current pharmacotherapeutic and surgical interventions available for managing and treating these conditions.

Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition.

Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability. However, the local cellular-level effects of mTOR inhibition on glioma-induced neuronal alterations are not well understood. Here we employed neuron-specific profiling of ribosome-bound mRNA via 'RiboTag,' morphometric analysis of dendritic spines, and in vivo calcium imaging, along with pharmacological mTOR inhibition to investigate the impact of glioma burden and mTOR inhibition on these neuronal alterations. The RiboTag analysis of tumor-associated excitatory neurons showed a downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development, and an upregulation of transcripts encoding cytoskeletal proteins involved in dendritic spine turnover. Light and electron microscopy of tumor-associated excitatory neurons demonstrated marked decreases in dendritic spine density. In vivo two-photon calcium imaging in tumor-associated excitatory neurons revealed progressive alterations in neuronal activity, both at the population and single-neuron level, throughout tumor growth. This in vivo calcium imaging also revealed altered stimulus-evoked somatic calcium events, with changes in event rate, size, and temporal alignment to stimulus, which was most pronounced in neurons with high-tumor burden. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed the glioma-induced alterations on the excitatory neurons, including the alterations in ribosome-bound transcripts, dendritic spine density, and stimulus evoked responses seen by calcium imaging. These results point to mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma - manifested by alterations in ribosome-bound mRNA, dendritic spine density, and stimulus-evoked neuronal activity. Collectively, our work identifies the pathological changes that tumor-associated excitatory neurons experience as both hyperlocal and reversible under the influence of mTOR inhibition, providing a foundation for developing therapies targeting neuronal signaling in glioma.

Pulsation artifact removal from intra-operatively recorded local field potentials using sparse signal processing and data-specific dictionary.

Neural recordings frequently get contaminated by ECG or pulsation artifacts. These large amplitude components can mask the neural patterns of interest and make the visual inspection process difficult. The current study describes a sparse signal representation strategy that targets to denoise pulsation artifacts in local field potentials (LFPs) recorded intraoperatively. To estimate the morphology of the artifact, we first detect the QRS-peaks from the simultaneously recorded ECG trace as an anchor point. After the LFP data has been epoched with respect to each beat, a pool of raw data segments of a specific length is generated. Using the K-singular value decomposition (K-SVD) algorithm, we constructed a data-specific dictionary to represent each contaminated LFP epoch in a sparse fashion. Since LFP is aligned to each QRS complex and the background neural activity is uncorrelated to the anchor points, we assumed that constructed dictionary will be formed to mainly represent the pulsation artifact. In this scheme, we performed an orthogonal matching pursuit to represent each LFP epoch as a linear combination of the dictionary atoms. The denoised LFP data is thus obtained by calculating the residual between the raw LFP and its approximation. We discuss and demonstrate the improvements in denoised data and compare the results with respect to principal component analysis (PCA). We noted that there is a comparable change in the signal for visual inspection to observe various oscillating patterns in the alpha and beta bands. We also see a noticeable compression of signal strength in the lower frequency band (<13 Hz), which was masked by the pulsation artifact, and a strong increase in the signal-to-noise ratio (SNR) in the denoised data.Clinical Relevance- Pulsation artifact can mask relevant neural activity patterns and make their visual inspection difficult. Using sparse signal representation, we established a new approach to reconstruct the quasiperiodic pulsation template and computed the residue signal to achieve noise-free neural activity.

Construction of semi-supervised spatial projections to identify the source of beta- and high frequency oscillations in Parkinson's disease.

Traditional deep brain stimulation (DBS) treatment for Parkinson's disease (PD) targets the placement of DBS leads into subthalamic nucleus (STN). Extraction of neurobiomarkers from STN local field potential activity can be used for the optimization of DBS. Beta (12-30 Hz) and high frequency oscillations (200-450 Hz, HFO) of STN and their phase-amplitude coupling have been previously correlated with symptom severity in PD. The typical approach is to take bipolar derivations of electrode contacts in order to enhance recordings of local brain activity and suppress noise levels. This approach can often cancel the signals in correlated neighboring contacts and create ambiguity in which monopolar contact to select for the identification of the main source of the oscillatory signal. To improve local specificity and help identify the source of beta and HFO in terms of electrode contact, we propose a semi supervised blind-source separation method. This approach presents a novel perspective to investigate electrophysiology by projecting the recorded channels into a subspace of virtual channels. We show the contribution of each channel to the identified source and correlate the spatial information with imaging and postoperative programming parameters. We anticipate such a source identification strategy can be used in the future to investigate the distribution of beta and HFO on individual contacts of the DBS lead and can improve the interpretation of these signals.

Validating saliva as a biological sample for cost-effective, rapid and routine screening for SARS-CoV-2.

PURPOSE: Compared to nasopharyngeal/oropharyngeal swabs (N/OPS-VTM), non-invasive saliva samples have enormous potential for scalability and routine population screening of SARS-CoV-2. In this study, we investigate the efficacy of saliva samples relative to N/OPS-VTM for use as a direct source for RT-PCR based SARS-CoV-2 detection. METHODS: We collected paired nasopharyngeal/oropharyngeal swabs and saliva samples from suspected positive SARS-CoV-2 patients and tested using RT-PCR. We used generalized linear models to investigate factors that explain result agreement. Further, we used simulations to evaluate the effectiveness of saliva-based screening in restricting the spread of infection in a large campus such as an educational institution. RESULTS: We observed a 75.4% agreement between saliva and N/OPS-VTM, that increased drastically to 83% in samples stored for less than three days. Such samples processed within two days of collection showed 74.5% test sensitivity. Our simulations suggest that a test with 75% sensitivity, but high daily capacity can be very effective in limiting the size of infection clusters in a workspace. Guided by these results, we successfully implemented a saliva-based screening in the Bangalore Life Sciences Cluster (BLiSC) campus. CONCLUSION: These results suggest that saliva may be a viable alternate source for SARS-CoV-2 surveillance if samples are processed immediately. Although saliva shows slightly lower sensitivity levels when compared to N/OPS-VTM, saliva collection is logistically advantageous. We strongly recommend the implementation of saliva-based screening strategies for large workplaces and in schools, as well as for population-level screening and routine surveillance as we learn to live with the SARS-CoV-2 virus.

Trigeminal Neuralgia: Diagnosis and Treatment.

Trigeminal neuralgia is characterized classically by recurrent, evocable, unilateral brief, electric, shocklike pains with an abrupt onset and cessation that affects one or more divisions of the trigeminal nerve. In recent years, the classification of trigeminal neuralgia has been updated based on further understanding. In this manuscript, the authors aim to explain the current understanding of the pathophysiology of trigeminal neuralgia, current diagnosis criteria, and the pharmacologic management and surgical treatments of options currently available.

Association of clinical outcomes and connectivity in awake versus asleep deep brain stimulation for Parkinson disease.

OBJECTIVE: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes. METHODS: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis. RESULTS: The clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups. CONCLUSIONS: Compared to awake STN DBS, asleep procedures can achieve similarly optimal targeting-based on clinical outcomes, electrode placement, and connectivity estimates-in more efficient procedures and shorter operating room times.

Case report: MR-guided laser induced thermal therapy for palliative cingulotomy.

In end-stage cancer, oncologic pain refractory to medical management significantly reduces patients' quality of life. In recent years, ablative surgery has seen a resurgence in treating diffuse and focal cancer pain in terminal patients. The anterior cingulate gyrus has been a key focus as it plays a role in the cognitive and emotional processing of pain. While radiofrequency ablation of the dorsal anterior cingulate is well described for treating cancer pain, MRI-guided laser-induced thermal therapy (LITT) is novel. Our paper describes a patient treated with an MRI-guided LITT therapy of the anterior cingulate gyrus for intractable debilitating pain secondary to terminal metastatic cancer.

Recurrent liponeurocytoma: A case report and systematic review of the literature.

Background: Liponeurocytomas are rare neurocytic neoplasms that most often arise in the posterior fossa and affect individuals in the third and fifth decades of life. Most reported cases of this unique tumor in the literature have described a favorable clinical prognosis without recurrence. However, increasing reports of recurrent cases prompted the World Health Organization, in 2016, to recategorize the tumor from Grade I to the less favorable Grade II classification. We conducted a systematic review to identify recurrent cases of this unique tumor and to summarize differences between the primary and recurrent cases of liponeurocytoma. Methods: A systematic review exploring recurrent liponeurocytoma cases was conducted by searching the PubMed, Google Scholar, and Scopus databases for articles in English. Abstracts from articles were read and selected for full-text review according to a priori criteria. Relevant full-text articles were analyzed for symptoms, imaging, location, histological, pathological, treatment, and recurrence-free time between the primary and recurrent cases. Results: Of 4392 articles, 15 articles accounting for 18 patients were included (level of evidence: IV) in the study. Recurrence-free time decreased from an average of 82 months between the primary tumor resection to first recurrence to 31.3 months between the first and second recurrence. Recurrent tumors demonstrated increased pleomorphic neural cells, necrosis, vascular proliferation, and MIB-1 index when compared to the primary tumor. Several cases also demonstrated decreased lipidizing components when compared to the primary tumor, further indicating increased dedifferentiation. The primary treatment for this tumor was surgical resection with occasional adjunctive radiotherapy. Conclusion: Recurrent cases of liponeurocytoma have features of increased malignant proliferation compared to the primary cases. The standard treatment for these primary and recurrent tumors is gross total resection. The role of adjunctive radiotherapy remains a matter of debate.

Neuroablative central lateral thalamotomy for chronic neuropathic pain.

Chronic neuropathic pain refractory to medical management can be debilitating and can seriously affect one's quality of life. The interest of ablative surgery for the treatment or palliation of chronic neuropathic pain, cancer-related or chemotherapy-induced, has grown. Numerous regions along the nociceptive pathways have been prominent targets including the various nuclei of the thalamus. Traditional targets include the medial pulvinar, central median, and posterior complex thalamic nuclei. However, there has been little research regarding the role of the central lateral nucleus. In this paper, we aim to summarize the anatomy, pathophysiology, and patient experiences of the central lateral thalamotomy.

Robot-Assisted Deep Brain Stimulation: High Accuracy and Streamlined Workflow.

BACKGROUND: A number of stereotactic platforms are available for performing deep brain stimulation (DBS) lead implantation. Robot-assisted stereotaxy has emerged more recently demonstrating comparable accuracy and shorter operating room times compared with conventional frame-based systems. OBJECTIVE: To compare the accuracy of our streamlined robotic DBS workflow with data in the literature from frame-based and frameless systems. METHODS: We retrospectively reviewed 126 consecutive DBS lead placement procedures using a robotic stereotactic platform. Indications included Parkinson disease (n = 94), essential tremor (n = 21), obsessive compulsive disorder (n = 7), and dystonia (n = 4). Procedures were performed using a stereotactic frame for fixation and the frame pins as skull fiducials for robot registration. We used intraoperative fluoroscopic computed tomography for registration and postplacement verification. RESULTS: The mean radial error for the target point was 1.06 mm (SD: 0.55 mm, range 0.04-2.80 mm) on intraoperative fluoroscopic computed tomography. The mean operative time for an asleep, bilateral implant without implantable pulse generator placement was 238 minutes (SD: 52 minutes), and skin-to-skin procedure time was 116 minutes (SD: 42 minutes). CONCLUSION: We describe a streamlined workflow for DBS lead placement using robot-assisted stereotaxy with a comparable accuracy profile. Obviating the need for checking and switching coordinates, as is standard for frame-based DBS, also reduces the chance for human error and facilitates training.

Translational Organic Neural Interface Devices at Single Neuron Resolution.

Recording from the human brain at the spatiotemporal resolution of action potentials provides critical insight into mechanisms of higher cognitive functions and neuropsychiatric disease that is challenging to derive from animal models. Here, organic materials and conformable electronics are employed to create an integrated neural interface device compatible with minimally invasive neurosurgical procedures and geared toward chronic implantation on the surface of the human brain. Data generated with these devices enable identification and characterization of individual, spatially distribute human cortical neurons in the absence of any tissue penetration (n = 229 single units). Putative single-units are effectively clustered, and found to possess features characteristic of pyramidal cells and interneurons, as well as identifiable microcircuit interactions. Human neurons exhibit consistent phase modulation by oscillatory activity and a variety of population coupling responses. The parameters are furthermore established to optimize the yield and quality of single-unit activity from the cortical surface, enhancing the ability to investigate human neural network mechanisms without breaching the tissue interface and increasing the information that can be safely derived from neurophysiological monitoring.

Ablation Procedures.

Although ablation has a limited role in the management of chronic noncancer pain, ablation continues to help patients with treatment of refractory cancer-related pain. Interdisciplinary treatment involving supportive care, pain medicine, oncology, and neurosurgery is critical to optimizing the timing and outcome of neurosurgical ablative options for pain management. In this review, 3 targets for ablative surgery-the spinothalamic tract, the dorsal column's visceral pain pathway, and the anterior cingulate cortex-are discussed with a focus on patient selection and key aspects of surgical technique.

Intraoperative valence testing to adjudicate between ventral capsule/ventral striatum and bed nucleus of the stria terminalis target selection in deep brain stimulation for obsessive-compulsive disorder.

OBJECTIVE: Deep brain stimulation (DBS) is an accepted therapy for severe, treatment-refractory obsessive-compulsive disorder (trOCD). The optimal DBS target location within the anterior limb of the internal capsule, particularly along the anterior-posterior axis, remains elusive. Empirical evidence from several studies in the past decade has suggested that the ideal target lies in the vicinity of the anterior commissure (AC), either just anterior to the AC, above the ventral striatum (VS), or just posterior to the AC, above the bed nucleus of the stria terminalis (BNST). Various methods have been utilized to optimize target selection for trOCD DBS. The authors describe their practice of planning trajectories to both the VS and BNST and adjudicating between them with awake intraoperative valence testing to individualize permanent target selection. METHODS: Eight patients with trOCD underwent awake DBS with trajectories planned for both VS and BNST targets bilaterally. The authors intraoperatively assessed the acute effects of stimulation on mood, energy, and anxiety and implanted the trajectory with the most reliable positive valence responses and least stimulation-induced side effects. The method of intraoperative target adjudication is described, and the OCD outcome at last follow-up is reported. RESULTS: The mean patient age at surgery was 41.25 ± 15.1 years, and the mean disease duration was 22.75 ± 10.2 years. The median preoperative Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 39 (range 34-40). Two patients had previously undergone capsulotomy, with insufficient response. Seven (44%) of 16 leads were moved to the second target based on intraoperative stimulation findings, 4 of them to avoid strong negative valence effects. Three patients had an asymmetric implant (1 lead in each target). All 8 patients (100%) met full response criteria, and the mean Y-BOCS score reduction across the full cohort was 51.2% ± 12.8%. CONCLUSIONS: Planning and intraoperatively testing trajectories flanking the AC-superjacent to the VS anteriorly and to the BNST posteriorly-allowed identification of positive valence responses and acute adverse effects. Awake testing helped to select between possible trajectories and identify individually optimized targets in DBS for trOCD.

Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in obsessive-compulsive disorder.

Detection of neural signatures related to pathological behavioral states could enable adaptive deep brain stimulation (DBS), a potential strategy for improving efficacy of DBS for neurological and psychiatric disorders. This approach requires identifying neural biomarkers of relevant behavioral states, a task best performed in ecologically valid environments. Here, in human participants with obsessive-compulsive disorder (OCD) implanted with recording-capable DBS devices, we synchronized chronic ventral striatum local field potentials with relevant, disease-specific behaviors. We captured over 1,000 h of local field potentials in the clinic and at home during unstructured activity, as well as during DBS and exposure therapy. The wide range of symptom severity over which the data were captured allowed us to identify candidate neural biomarkers of OCD symptom intensity. This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders.

Genomic evidence for inbreeding depression and purging of deleterious genetic variation in Indian tigers.

Increasing habitat fragmentation leads to wild populations becoming small, isolated, and threatened by inbreeding depression. However, small populations may be able to purge recessive deleterious alleles as they become expressed in homozygotes, thus reducing inbreeding depression and increasing population viability. We used whole-genome sequences from 57 tigers to estimate individual inbreeding and mutation load in a small-isolated and two large-connected populations in India. As expected, the small-isolated population had substantially higher average genomic inbreeding (FROH = 0.57) than the large-connected (FROH = 0.35 and FROH = 0.46) populations. The small-isolated population had the lowest loss-of-function mutation load, likely due to purging of highly deleterious recessive mutations. The large populations had lower missense mutation loads than the small-isolated population, but were not identical, possibly due to different demographic histories. While the number of the loss-of-function alleles in the small-isolated population was lower, these alleles were at higher frequencies and homozygosity than in the large populations. Together, our data and analyses provide evidence of 1) high mutation load, 2) purging, and 3) the highest predicted inbreeding depression, despite purging, in the small-isolated population. Frequency distributions of damaging and neutral alleles uncover genomic evidence that purifying selection has removed part of the mutation load across Indian tiger populations. These results provide genomic evidence for purifying selection in both small and large populations, but also suggest that the remaining deleterious alleles may have inbreeding-associated fitness costs. We suggest that genetic rescue from sources selected based on genome-wide differentiation could offset any possible impacts of inbreeding depression.

A Novel Framework for Network-Targeted Neuropsychiatric Deep Brain Stimulation.

Deep brain stimulation (DBS) has emerged as a promising therapy for neuropsychiatric illnesses, including depression and obsessive-compulsive disorder, but has shown inconsistent results in prior clinical trials. We propose a shift away from the empirical paradigm for developing new DBS applications, traditionally based on testing brain targets with conventional stimulation paradigms. Instead, we propose a multimodal approach centered on an individualized intracranial investigation adapted from the epilepsy monitoring experience, which integrates comprehensive behavioral assessment, such as the Research Domain Criteria proposed by the National Institutes of Mental Health. In this paradigm-shifting approach, we combine readouts obtained from neurophysiology, behavioral assessments, and self-report during broad exploration of stimulation parameters and behavioral tasks to inform the selection of ideal DBS parameters. Such an approach not only provides a foundational understanding of dysfunctional circuits underlying symptom domains in neuropsychiatric conditions but also aims to identify generalizable principles that can ultimately enable individualization and optimization of therapy without intracranial monitoring.