Printable microscale interfaces for long-term peripheral nerve mapping and precision control

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying advanced peripheral interfacing technologies. Here, we present a microscale implantable device – the nanoclip – for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high-resolution recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation can achieve a high degree of functionally-relevant modulatory specificity within the small scale of the device. These results highlight the potential of new microscale design and fabrication techniques for the realization of viable implantable devices for long-term peripheral interfacing.https://www.biorxiv.org/node/801468.fullFirst author draf

Fast Micron-Scale 3D Printing with a Resonant-Scanning Two-Photon Microscope

3D printing allows rapid fabrication of complex objects from digital designs. One 3D-printing process, direct laser writing, polymerises a light-sensitive material by steering a focused laser beam through the shape of the object to be created. The highest-resolution direct laser writing systems use a femtosecond laser to effect two-photon polymerisation. The focal (polymerisation) point is steered over the shape of the desired object with mechanised stages or galvanometer-controlled mirrors. Here we report a new high-resolution direct laser writing system that employs a resonant mirror scanner to achieve a significant increase in printing speed over galvanometer- or piezo-based methods while maintaining resolution on the order of a micron. This printer is based on a software modification to a commerically available resonant-scanning two-photon microscope. We demonstrate the complete process chain from hardware configuration and control software to the printing of objects of approximately $400\times 400\times 350\;\mu$m, and validate performance with objective benchmarks. Released under an open-source license, this work makes micro-scale 3D printing available the large community of two-photon microscope users, and paves the way toward widespread availability of precision-printed devices.Comment: Corresponding author: BWP ([email protected]). TJG and TMO contributed equally to this work. TJG is an employee of Neuralink In

The Basal Ganglia Is Necessary for Learning Spectral, but Not Temporal, Features of Birdsong

SummaryExecuting a motor skill requires the brain to control which muscles to activate at what times. How these aspects of control—motor implementation and timing—are acquired, and whether the learning processes underlying them differ, is not well understood. To address this, we used a reinforcement learning paradigm to independently manipulate both spectral and temporal features of birdsong, a complex learned motor sequence, while recording and perturbing activity in underlying circuits. Our results uncovered a striking dissociation in how neural circuits underlie learning in the two domains. The basal ganglia was required for modifying spectral, but not temporal, structure. This functional dissociation extended to the descending motor pathway, where recordings from a premotor cortex analog nucleus reflected changes to temporal, but not spectral, structure. Our results reveal a strategy in which the nervous system employs different and largely independent circuits to learn distinct aspects of a motor skill

Templated self-assembly of gold nanoparticles in smectic liquid crystals confined at 3D printed curved surfaces

The fabrication of assembled structures of topological defects in liquid crystals (LCs) has attracted much attention during the last decade, stemming from the potential application of these defects in modern technologies. A range of techniques can be employed to create large areas of engineered defects in LCs, including mechanical shearing, chemical surface treatment, external fields, or geometric confinement. The technology of 3D printing has recently emerged as a powerful method to fabricate novel patterning topographies inaccessible by other microfabrication techniques, especially confining geometries with curved topographies. In this work, we show the advantages of using 3D-printed curved surfaces and controlled anchoring properties to confine LCs and engineer new structures of topological defects, whose structure we elucidate by comparison with a novel application of Landau-de Gennes free energy minimization to the smectic A-nematic phase transition. We also demonstrate the ability of these defects to act as a scaffold for assembling gold (Au) nanoparticles (NPs) into reconfigurable 3D structures. We discuss the characteristics of this templated self-assembly (TSA) approach and explain the relationship between NP concentrations and defect structures with insights gained from numerical modeling. This work paves the way for a versatile platform of LC defect-templated assembly of a range of functional nanomaterials useful in the field of energy technology.Comment: Main text: 30 pages, 6 figures. Supplementary Information: 5 pages, 4 figure

Formalin Application for the Treatment of Radiation-Induced Hemorrhagic Proctitis

Radiation-induced hemorrhagic proctitis (RIHP) is a serious complication of pelvic irradiation, and a 4% formalin solution has been used for 20 years in treating this sequelae. The first case involving formalin application for treatment of RIHP in Korea was reported in 1996, but there are no additional studies beyond this date. Our study reviews the use of formalin instillation and selective application. The purpose of this study was to retrospectively evaluate the outcome of such treatments, beginning with the first case at our hospital. From 1996 to 2005, five RIHP patients had received formalin treatment for RIHP symptoms intractable to other medical treatments. All treatments were performed by a single surgeon in the operating room, under spinal anesthesia or intravenous sedation. The mean duration of symptoms before treatment was 15.6 months (which was longer than in other studies), and the transfusion before treatment varied from once per month to twice per week. Using sigmoidoscopy, 100ml of a 4% formalin solution was instilled directly (or by using a formalin-soaked gauze) and irrigated for five minutes. Formalin-soaked cotton was then applied selectively to focal remnant lesions. Four patients improved after the first treatment, but one patient received the treatment twice because of recurrent symptoms. Complications after treatment included perianal pain (one case), and aggravated incontinence (one case), which improved three months after conservative management. In conclusion, the formalin combination application method in our study is comparable to other formalin treatments for intractable RIHP

Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons

Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions.info:eu-repo/semantics/publishedVersio

Corticostriatal connectivity fingerprints:Probability maps based on resting-state functional connectivity

Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting-state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice-similarity values 0.40-1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non-human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478-1491, 2017. © 2016 Wiley Periodicals, Inc.status: publishe

Fast track multi-discipline treatment (FTMDT trial) versus conventional treatment in colorectal cancer--the design of a prospective randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Laparoscopy-assisted surgery, fast-track perioperative treatment are both increasingly used in colorectal cancer treatment, for their short-time benefits of enhanced recovery and short hospital stays. However, the benefits of the integration of the Laparoscopy-assisted surgery, fast-track perioperative treatment, and even with the Xelox chemotherapy, are still unknown. In this study, the three treatments integration is defined as "Fast Track Multi-Discipline Treatment Model" for colorectal cancer and this model extends the benefits to the whole treatment process of colorectal cancer. The main purpose of the study is to explore the feasibility of "Fast Track Multi-Discipline Treatment" model in treatment of colorectal cancer.</p> <p>Methods</p> <p>The trial is a prospective randomized controlled study with 2 × 2 balanced factorial design. Patients eligible for the study will be randomized to 4 groups: (I) Laparoscopic surgery with fast track perioperative treatment and Xelox chemotherapy; (II) Open surgery with fast track perioperative treatment and Xelox chemotherapy; (III) Laparoscopic surgery with conventional perioperative treatment and mFolfox6 chemotherapy; (IV) Open surgery with conventional perioperative treatment and mFolfox6 chemotherapy. The primary endpoint of this study is the hospital stays. The secondary endpoints are the quality of life, chemotherapy related adverse events, surgical complications and hospitalization costs. Totally, 340 patients will be enrolled with 85 patients in each group.</p> <p>Conclusions</p> <p>The study initiates a new treatment model "Fast Track Multi-Discipline Treatment" for colorectal cancer, and will provide feasibility evidence on the new model "Fast Track Multi-Discipline Treatment" for patients with colorectal cancer.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01080547">NCT01080547</a></p