Amygdala circuitry mediating reversible and bidirectional control of anxiety.

Anxiety--a sustained state of heightened apprehension in the absence of immediate threat--becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)--achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA--exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA-CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.

Salary Trends Across American Subspecialties in Academic Neurosurgery.

Enthusiasm for research and teaching are often the main reasons neurosurgical residents choose academic careers, and subspecialty choice usually stems from an interest in that particular field. However, recent salary data bring to light a work relative value unit-related trend in American academic neurosurgeon salaries, one that is similar to private practice, where compensation is strongly correlated with clinical productivity. In addition, there are significant disparities in how various subspecialties are remunerated in academic settings. For example, functional and pediatric specialists earn significantly lower salaries on average compared with their spine and endovascular colleagues. These trends have important implications both for neurosurgical trainees and for institutions in the United States.

Comparison of Intraoperative Computed Tomography Scan with Postoperative Magnetic Resonance Imaging for Determining Deep Brain Stimulation Electrode Coordinates.

BACKGROUND: Deep brain stimulation (DBS) is an effective therapy for a variety of refractory movement disorders. Accurate lead placement in the target nucleus is critical to ensure therapeutic effects and to minimize side effects, and intraoperative computed tomography (iCT) scan has been used to target and confirm lead position. The objective of this study is to compare the accuracy of determining the x, y, and z coordinates of final lead placement using iCT scan relative to postoperative magnetic resonance imaging (MRI). METHODS: We conducted a retrospective study on 83 patients who underwent insertion of 145 DBS leads from 2015 to 2017 at a single institution. iCT scan was merged with the preoperative MRI to determine lead coordinates on both magnetic resonance and computed tomography images independently, and the absolute differences between the x, y, and z coordinates between the 2 scans along with the Euclidean vectors were calculated. RESULTS: The mean absolute differences ± standard error of the mean between iCT scan and postoperative MRI coordinates were as follows: x = 0.01 ± 0.09 mm (P = 0.89), y = 1.67 ± 0.14 mm (P < 0.001), and z = 2.75 ± 0.15 mm (P < 0.001). The average Euclidean vector difference was 3.21 ± 0.15 mm (P < 0.001). CONCLUSIONS: Significant differences exist between iCT scan and postoperative MRI DBS y and z lead coordinates, but not with x coordinates. Based on this series, iCT scan is more accurate when confirming x coordinates, and less accurate for confirming y and z coordinates during DBS operations.

Refining Surgical Corridors with Whole Brain Tractography: A Case Series.

Recent advancements in automated diffusion tensor imaging (DTI) and whole brain tractography (WBT) may be of great use to the neurosurgeon in selecting surgical corridors that can minimize disruption of surrounding white matter tracts. This is especially important in cases where the lesion displaces white matter tracts and traditional operative approaches may inadvertently violate these fibers. Here, we present automated DTI seeding and WBT as a practical and efficient means for preoperative surgical planning, in an effort to spare white matter tracts that may be displaced by a variety of lesions and may be vulnerable during surgery. We retrospectively reviewed the records of seven patients with various intracranial lesions, who underwent preoperative magnetic resonance imaging (MRI) with automated DTI analysis. These images were used to guide operative planning so that we could select white matter corridors that would allow for minimal damage to vulnerable fiber tracts. The patients had various pathologies, ranging from neoplasms to intracranial hemorrhage, in a number of different intracranial locations. All the patients underwent preoperative intracranial imaging with post-processing of these images to generate white matter tracts. These images were then used to design an appropriate surgical approach that would minimize injury to white matter tracts. For the patients with neoplasms, all were totally or near-totally resected with a stability of symptoms postoperatively. In the case of the patient with intracranial hemorrhage, the hematoma was evacuated, with significant improvement in the postoperative period. Automated DTI seeding and WBT, which have become increasingly prevalent in recent years, can be of significant use to the neurosurgeon for preoperative planning. Their application is especially important in cases where white matter tracts are displaced by the lesion in question and are put at risk of injury during surgery. Using WBT to design customized surgical approaches appropriate to the case at hand can be of immense value in preserving these white matter tracts, minimizing postoperative deficits, and improving surgical outcomes. Further studies are needed to validate these results and better define their applicability to other regions and pathologies.

The effect of NACHRI children's hospital designation on outcome in pediatric malignant brain tumors.

OBJECTIVE Although current pediatric neurosurgery guidelines encourage the treatment of pediatric malignant brain tumors at specialized centers such as pediatric hospitals, there are limited data in support of this recommendation. Previous studies suggest that children treated by higher-volume surgeons and higher-volume hospitals may have better outcomes, but the effect of treatment at dedicated children's hospitals has not been investigated. METHODS The authors analyzed the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) from 2000-2009 and included all patients undergoing a craniotomy for malignant pediatric brain tumors based on ICD-9-CM codes. They investigated the effects of patient demographics, tumor location, admission type, and hospital factors on rates of routine discharge and mortality. RESULTS From 2000 through 2009, 83.6% of patients had routine discharges, and the in-hospital mortality rate was 1.3%. In multivariate analysis, compared with children treated at an institution designated as a pediatric hospital by NACHRI (National Association of Children's Hospitals and Related Institutions), children receiving treatment at a pediatric unit within an adult hospital (OR 0.5, p < 0.01) or a general hospital without a designated pediatric unit (OR 0.4, p < 0.01) were less likely to have routine discharges. Treatment at a large hospital (> 400 beds; OR 1.8, p = 0.02) and treatment at a teaching hospital (OR 1.7, p = 0.02) were independently associated with greater likelihood of routine discharge. However, patients transferred between facilities had a significantly decreased likelihood of routine discharge (OR 0.5, p < 0.01) and an increased likelihood of mortality (OR 5.0, p < 0.01). Procedural volume was not associated with rate of routine discharge or mortality. CONCLUSIONS These findings may have implications for planning systems of care for pediatric patients with malignant brain tumors. The authors hope to motivate future research into the specific factors that may lead to improved outcomes at designated pediatric hospitals.

The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells.

While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations.