SmartScope2: Simultaneous Imaging and Reconstruction of Neuronal Morphology.

Quantitative analysis of neuronal morphology is critical in cell type classification and for deciphering how structure gives rise to function in the brain. Most current approaches to imaging and tracing neuronal 3D morphology are data intensive. We introduce SmartScope2, the first open source, automated neuron reconstruction machine integrating online image analysis with automated multiphoton imaging. SmartScope2 takes advantage of a neuron\u27s sparse morphology to improve imaging speed and reduce image data stored, transferred and analyzed. We show that SmartScope2 is able to produce the complex 3D morphology of human and mouse cortical neurons with six-fold reduction in image data requirements and three times the imaging speed compared to conventional methods

Multi-modal characterization and simulation of human epileptic circuitry

Temporal lobe epilepsy is the fourth most common neurological disorder with about 40% of patients not responding to pharmacological treatment. Increased cellular loss in the hippocampus is linked to disease severity and pathological phenotypes such as heightened seizure propensity. While the hippocampus is the target of therapeutic interventions such as temporal lobe resection, the impact of the disease at the cellular level remains unclear in humans. Here we show that properties of hippocampal granule cells change with disease progression as measured in living, resected hippocampal tissue excised from epilepsy patients. We show that granule cells increase excitability and shorten response latency while also enlarging in cellular volume, surface area and spine density. Single-cell RNA sequencing combined with simulations ascribe the observed electrophysiological changes to gradual modification in three key ion channel conductances: BK, Cav2.2 and Kir2.1. In a bio-realistic computational network model, we show that the changes related to disease progression bring the circuit into a more excitable state. In turn, we observe that by reversing these changes in the three key conductances produces a less excitable, early disease-like state. These results provide mechanistic understanding of epilepsy in humans and will inform future therapies such as viral gene delivery to reverse the course of the disorder

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Viral genetic tools to target specific brain cell types in humans and non-genetic model organisms will transform basic neuroscience and targeted gene therapy. Here we used comparative epigenetics to identify thousands of human neuronal subclass-specific putative enhancers to regulate viral tools, and 34% of these were conserved in mouse. We established an AAV platform to evaluate cellular specificity of functional enhancers by multiplexed fluorescent in situ hybridization (FISH) and single cell RNA sequencing. Initial testing in mouse neocortex yields a functional enhancer discovery success rate of over 30%. We identify enhancers with specificity for excitatory and inhibitory classes and subclasses including PVALB, LAMP5, and VIP/LAMP5 cells, some of which maintain specificity in vivo or ex vivo in monkey and human neocortex. Finally, functional enhancers can be proximal or distal to cellular marker genes, conserved or divergent across species, and could yield brain-wide specificity greater than the most selective marker genes

Community is the Best Medicine

Ryder Gwinn, M.D., executive medical director of the Swedish Neuroscience Institute, moderates a conversation, between Dr. James Bowen and Dr. Nancy Isenberg, regarding Swedish’s comprehensive clinic model and how it builds community, decreases isolation and helps patients live well while managing complex neurologic conditions. To learn more and to donate to the Swedish MS Center or the Swedish Center for Healthy Aging, please visit: http://swedishfoundation.org/frontlin..

Deep Brain Stimulation Surgery Using a Mobile Intraoperative CT Scanner.

Introduction Deep brain stimulation (DBS) is widely used for the treatment of movement disorders. Precise placement of electrodes is critical for treatment success. The aim of this study was to analyze the accuracy of the intraoperative computer tomography (CT) images compared to that of a traditional fixed CT for patients undergoing DBS procedures. Methods We retrospectively analyzed the charts from 30 patients who underwent DBS. In group 1, 10 patients underwent electrode implantation surgery using a fixed CT scanner for pre- and post-operative (OP) images. In group 2, 20 patients underwent surgery using an intraoperative CT scanner for pre- and post-operative images, as well as a fixed CT scanner for post-operative images. We compared the average pre-operative localizer box registration error acquired in these two groups. We also analyzed, in group 2, the final electrode position given on each post-operative CT images. We compared the average Euclidean distances between each set of cartesian coordinates to assess target accuracy between both scanning methodologies. Results Thirty patients had ages ranging from 40 to 88 years, with a median of 69 years old. In the 20 patients who utilized an intraoperative CT scanner pre-operatively in group 2, the mean error, given by the Medtronic software (Medtronic Minimally Invasive Therapies, Minneapolis, MN) with the Leksell frame on, was 0.37. For the 10 pre-operative scans with the stealth fixed CT scanner in group 1, the mean error was 0.44 (p = 0.13). In group 2, the average of the 20 Euclidean distances for each target, in those 20 patients who had post-operative images with both scanners, was 0.36. Conclusion We concluded that the accuracy of the intraoperative CT scanner is comparable to the gold standard fixed CT scanner for DBS electrode planning and placement, as well as for positioning confirmation after the electrodes are in place