Publications by authors named "Weijian Yang"

41 Publications

GEOMScope: Large Field-of-view 3D Lensless Microscopy with Low Computational Complexity.

Laser Photon Rev 2021 Aug 27;15(8). Epub 2021 Jun 27.

Department of Electrical and Computer Engineering, University of California, Davis, CA 95616, USA.

Imaging systems with miniaturized device footprint, real-time processing speed and high resolution three-dimensional (3D) visualization are critical to broad biomedical applications such as endoscopy. Most of existing imaging systems rely on bulky lenses and mechanically refocusing to perform 3D imaging. Here, we demonstrate GEOMScope, a lensless single-shot 3D microscope that forms image through a single layer of thin microlens array and reconstructs objects through an innovative algorithm combining geometrical-optics-based pixel back projection and background suppressions. We verify the effectiveness of GEOMScope on resolution target, fluorescent particles and volumetric objects. Comparing to other widefield lensless imaging devices, we significantly reduce the required computational resource and increase the reconstruction speed by orders of magnitude. This enables us to image and recover large volume 3D object in high resolution with near real-time processing speed. Such a low computational complexity is attributed to the joint design of imaging optics and reconstruction algorithms, and a joint application of geometrical optics and machine learning in the 3D reconstruction. More broadly, the excellent performance of GEOMScope in imaging resolution, volume, and reconstruction speed implicates that geometrical optics could greatly benefit and play an important role in computational imaging.
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http://dx.doi.org/10.1002/lpor.202100072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445384PMC
August 2021

Deep Compressed Imaging via Optimized-Pattern Scanning.

Photonics Res 2021 Mar 15;9(3):B57-B70. Epub 2021 Jan 15.

Department of Electrical and Computer Engineering, University of California, Davis, CA 95616, USA.

The need for high-speed imaging in applications such as biomedicine, surveillance and consumer electronics has called for new developments of imaging systems. While the industrial effort continuously pushes the advance of silicon focal plane array image sensors, imaging through a single-pixel detector has gained significant interests thanks to the development of computational algorithms. Here, we present a new imaging modality, Deep Compressed Imaging via Optimized-Pattern Scanning (DeCIOPS), which can significantly increase the acquisition speed for a single-detector-based imaging system. We project and scan an illumination pattern across the object and collect the sampling signal with a single-pixel detector. We develop an innovative end-to-end optimized auto-encoder, using a deep neural network and compressed sensing algorithm, to optimize the illumination pattern, which allows us to reconstruct faithfully the image from a small number of samples, and with a high frame rate. Compared with the conventional switching-mask based single-pixel camera and point scanning imaging systems, our method achieves a much higher imaging speed, while retaining a similar imaging quality. We experimentally validated this imaging modality in the settings of both continuous-wave (CW) illumination and pulsed light illumination and showed high-quality image reconstructions with a high compressed sampling rate. This new compressed sensing modality could be widely applied in different imaging systems, enabling new applications which require high imaging speed.
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http://dx.doi.org/10.1364/prj.410556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443127PMC
March 2021

Highly efficient As(III) removal in water using millimeter-sized porous granular MgO-biochar with high adsorption capacity.

J Hazard Mater 2021 08 8;416:125822. Epub 2021 Apr 8.

State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, PR China. Electronic address:

Biochar adsorbents for removing As(III) suffer from the problems of low adsorption capacity and ineffective removal. Herein, a granular MgO-embedded biochar (g-MgO-Bc) adsorbent is fabricated in the form of millimeter-sized particles through a simple gelation-calcination method using chitosan as biochar sources. High-density MgO nanoparticles are evenly dispersed throughout the biochar matrix and can be fully exposed to As(III) through the rich pores in g-MgO-Bc. These features endow the adsorbent with a high adsorption capacity of 249.1 mg/g for As(III). The g-MgO-Bc can efficiently remove As(III) over a wide pH of 3-10. The coexisting carbonate, nitrate, sulfate, silicate, and humic acid exert a negligible influence on As(III) removal. 300 μg/L of As(III) can be purified to far below 10 μg/L using only 0.3 g/L g-MgO-Bc. The spent g-MgO-Bc could be well regenerated by simple calcination. In fixed-bed column experiments, the effective treatment volume of As(III)-spiked groundwater achieves 1500 BV (30 L) (3 g of adsorbent, solution flow rate of 2.0 mL/min, C = 50 μg/L). The Mg(OH) generated in situ in g-MgO-Bc is responsible for the adsorption of As(III) through the inner-sphere complex mechanism. The work would extend the potential applicability of biochar adsorbent for As(III) removal to a great extent.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125822DOI Listing
August 2021

Boosting Electrocatalytic Oxygen Evolution: Superhydrophilic/Superaerophobic Hierarchical Nanoneedle/Microflower Arrays of CeCoO with Oxygen Vacancies.

ACS Appl Mater Interfaces 2021 Sep 6;13(36):42843-42851. Epub 2021 Sep 6.

State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, P. R. China.

The oxygen evolution reaction has become the bottleneck of electrochemical water splitting for its sluggish kinetics. Developing high-efficiency and low-cost non-noble-metal oxide electrocatalysts is crucial but challenging for industrial application. Herein, superhydrophilic/superaerophobic hierarchical nanoneedle/microflower arrays of Ce-substituted CoO (CeCoO) in situ grown on the nickel foam are successfully constructed. The hierarchical architecture and superhydrophilic/superaerophobic interface can be facilely regulated by controlling the introduction of Ce into CoO. The unique feature of hierarchical architecture and superhydrophilic/superaerophobic interface is in favor of electrolyte penetration and bubbles release. In addition, the presence of oxygen vacancy and Ce endows the catalyst with enhanced intrinsic activity. Benefiting from these advantages, the optimized CeCoO catalyst shows a superior electrocatalytic performance for the oxygen evolution reaction (OER) with an overpotential of 282 mV at 20 mA cm, and a Tafel slope of 81.4 mV dec. The turnover frequency of 0.0279 s for CeCoO is 9.3 times larger than that for CoO at an overpotential of 350 mV. Moreover, the optimized CeCoO catalyst shows a robust long-term stability in alkaline media.
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http://dx.doi.org/10.1021/acsami.1c11662DOI Listing
September 2021

Contribution of factor VII polymorphisms to coagulopathy in patients with isolated traumatic brain injury.

Clin Neurol Neurosurg 2021 Sep 23;208:106836. Epub 2021 Jul 23.

Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, China; Department of Neurosurgery, Shigatse People's Hospital, 28 Shanghai Zhong Road, Shigatse, Tibet, China; Neurosurgical Institute of Fudan University, China; Shanghai Clinical Medical Center of Neurosurgery, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, China. Electronic address:

Background: Coagulopathy is a severe complication of traumatic brain injury (TBI) and can cause secondary injuries and death. Decrease of FVII activity contributes to the coagulopathy and progressive hemorrhagic injury (PHI) in patients with isolated TBI. Some polymorphic loci of coagulation factor VII (FVII) are shown to be essential for FVII activity. However, the relationship between FVII gene polymorphisms and coagulopathy in patients with isolated TBI is still unknown. Therefore, the present study aimed to investigate the relationship between FVII gene polymorphisms and plasma FVIIa levels, and assess whether FVII polymorphisms were associated with TBI-related coagulopathy, PHI, and 6 months GOS in patients with isolated TBI.

Methods: One-hundred-forty-nine patients with isolated TBI (from East of China) admitted to Huashan Hospital's Neurological Trauma Center from March 2012 to March 2016 were enrolled in this study. The Polymorphism-Polymerase Chain Reaction (PCR) method was used to analyze the five FVII polymorphism loci (-323P0/P10, R353Q, -401G/T, -402G/A, and -670A/C) of these patients. Patients' blood was collected to test the activated partial thromboplastin time, international normalized ratio, platelet, and FVIIa concentrations. Other clinical characteristics were also recorded.

Results: The minor alleles of three genotypes of -323 P0/P10, R353Q, and -401G/T each independently associated with 23.3%, 28.6%, and 27.6% lower FVIIa levels, respectively. These polymorphisms explained 21% of the total variance of FVIIa levels (adjusted R:0.206). The genotype of -323P0/P10 was an independent risk factor for coagulopathy (OR = 2.77, p = 0.043) and PHI (OR = 3.47, p = 0.03) after adjustment for confounding factors in the logistic regression model. Polymorphisms of FVII were not independently associated with 6 months Glasgow Outcome Scale (GOS) of isolated TBI patients.

Conclusion: -323P0/P10, R353Q, and -401 G/T genotypes were associated with FVIIa levels. -323P0/P10 genotype was independently associated with traumatic coagulopathy and PHI in isolated TBI patients.
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http://dx.doi.org/10.1016/j.clineuro.2021.106836DOI Listing
September 2021

Manipulating neuronal circuits, in concert.

Authors:
Weijian Yang

Science 2021 Aug;373(6555):635

Department of Electrical and Computer Engineering, University of California, Davis, Davis, CA 95616, USA.

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http://dx.doi.org/10.1126/science.abj5260DOI Listing
August 2021

Cortical ensembles selective for context.

Proc Natl Acad Sci U S A 2021 04;118(14)

Department of Biological Sciences, Columbia University, New York, NY 10027.

Neural processing of sensory information is strongly influenced by context. For instance, cortical responses are reduced to predictable stimuli, while responses are increased to novel stimuli that deviate from contextual regularities. Such bidirectional modulation based on preceding sensory context is likely a critical component or manifestation of attention, learning, and behavior, yet how it arises in cortical circuits remains unclear. Using volumetric two-photon calcium imaging and local field potentials in primary visual cortex (V1) from awake mice presented with visual "oddball" paradigms, we identify both reductions and augmentations of stimulus-evoked responses depending, on whether the stimulus was redundant or deviant, respectively. Interestingly, deviance-augmented responses were limited to a specific subset of neurons mostly in supragranular layers. These deviance-detecting cells were spatially intermixed with other visually responsive neurons and were functionally correlated, forming a neuronal ensemble. Optogenetic suppression of prefrontal inputs to V1 reduced the contextual selectivity of deviance-detecting ensembles, demonstrating a causal role for top-down inputs. The presence of specialized context-selective ensembles in primary sensory cortex, modulated by higher cortical areas, provides a circuit substrate for the brain's construction and selection of prediction errors, computations which are key for survival and deficient in many psychiatric disorders.
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http://dx.doi.org/10.1073/pnas.2026179118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040629PMC
April 2021

Correction to: Holographic Imaging and Stimulation of Neural Circuits.

Adv Exp Med Biol 2021 ;1293:C1-C2

Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY, USA.

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http://dx.doi.org/10.1007/978-981-15-8763-4_45DOI Listing
January 2021

Holographic Imaging and Stimulation of Neural Circuits.

Adv Exp Med Biol 2021 ;1293:613-639

Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY, USA.

A critical neuroscience challenge is the need to optically image and manipulate neural activity with high spatiotemporal resolution over large brain volumes. The last three decades have seen the development of calcium imaging to record activity from neuronal populations, as well as optochemistry and optogenetics to optically manipulate neural activity. These methods are typically implemented with wide-field or laser-scanning microscopes. While the former approach has a good temporal resolution, it generally lacks spatial resolution or specificity, particularly in scattering tissues such as the nervous system; meanwhile, the latter approach, particularly when combined with two-photon excitation, has high spatial resolution and specificity but poor temporal resolution. As a new technique, holographic microscopy combines the advantages of both approaches. By projecting a holographic pattern on the brain through a spatial light modulator, the activity of specific groups of neurons in 3D brain volumes can be imaged or stimulated with high spatiotemporal resolution. In a combination of other techniques such as fast scanning or temporal focusing, this high spatiotemporal resolution can be further improved. Holographic microscopy enables all-optical interrogating of neural activity in 3D, a critical tool to dissect the function of neural circuits.
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http://dx.doi.org/10.1007/978-981-15-8763-4_43DOI Listing
February 2021

Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer's disease.

Alzheimers Res Ther 2020 07 23;12(1):89. Epub 2020 Jul 23.

Department of Dermatology, Institute for Regenerative Cures, University of California at Davis, School of Medicine, Sacramento, CA, 95817, USA.

Background: Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer's disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer's disease (5xFAD).

Methods And Results: We used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls.

Conclusion: Our results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD.
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http://dx.doi.org/10.1186/s13195-020-00656-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376967PMC
July 2020

Trends of Intra-Cranial Bacterial Infection in Patients Requiring Emergency Neurosurgery.

Surg Infect (Larchmt) 2020 Oct 16;21(8):677-683. Epub 2020 Jan 16.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Intra-cranial bacterial infection is a serious complication in emergency neurosurgical patients, and few data are available on the trends of these infections and the rates of antibacterial drug resistance. We surveyed retrospectively the patients with intra-cranial bacterial infection in our emergency neurosurgical center between January 2009 and December 2018. Demographic characteristics, causative bacteria, and antimicrobial susceptibility test results were collected. A total of 100 patients with intra-cranial bacterial infection, 1.41% of our patients, were enrolled. There were 123 strains of bacteria cultured from the cerebrospinal fluid (CSF), consisting of 96 strains of gram-negative (GN) bacteria and 27 strains of gram-positive (GP) bacteria. Compared with the GP bacteria, the percentage of GN bacteria increased to 75.0% of the total near the end of the study. Compared with , also showed an uptrend. Most of the bacteria were multi-drug-resistant (MDR). We further analyzed the consistency of CSF and sputum cultures from the same patient. The ratio of and to the corresponding strains in the CSF were 77.0% and 62.0%. The bacteria recovered from the CSF were mainly GN. The tendency of GN bacteria showed an uptrend, especially for . Furthermore, most of the bacteria were MDR.
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http://dx.doi.org/10.1089/sur.2019.317DOI Listing
October 2020

Controlling Visually Guided Behavior by Holographic Recalling of Cortical Ensembles.

Cell 2019 07 27;178(2):447-457.e5. Epub 2019 Jun 27.

NeuroTechnology Center, Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.

Neurons in cortical circuits are often coactivated as ensembles, yet it is unclear whether ensembles play a functional role in behavior. Some ensemble neurons have pattern completion properties, triggering the entire ensemble when activated. Using two-photon holographic optogenetics in mouse primary visual cortex, we tested whether recalling ensembles by activating pattern completion neurons alters behavioral performance in a visual task. Disruption of behaviorally relevant ensembles by activation of non-selective neurons decreased performance, whereas activation of only two pattern completion neurons from behaviorally relevant ensembles improved performance, by reliably recalling the whole ensemble. Also, inappropriate behavioral choices were evoked by the mistaken activation of behaviorally relevant ensembles. Finally, in absence of visual stimuli, optogenetic activation of two pattern completion neurons could trigger behaviorally relevant ensembles and correct behavioral responses. Our results demonstrate a causal role of neuronal ensembles in a visually guided behavior and suggest that ensembles implement internal representations of perceptual states.
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http://dx.doi.org/10.1016/j.cell.2019.05.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747687PMC
July 2019

Two-Color Volumetric Imaging of Neuronal Activity of Cortical Columns.

Cell Rep 2019 05;27(7):2229-2240.e4

Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

To capture the emergent properties of neural circuits, high-speed volumetric imaging of neural activity at cellular resolution is needed. Here, we introduce wavelength multiplexing to perform fast volumetric two-photon imaging of cortical columns (>2,000 neurons in 10 planes at 10 vol/s), using two different calcium indicators, an electrically tunable lens and a spatial light modulator. We image the activity of neuronal populations from layers 2/3 to 5 of primary visual cortex from awake mice, finding a lack of columnar structures in orientation responses and revealing correlations between layers which differ from trial to trial. We also simultaneously image functional correlations between presynaptic layer 1 axons and postsynaptic layer 2/3 neurons. Wavelength multiplexing enhances high-speed volumetric microscopy and can be combined with other optical multiplexing methods to easily boost imaging throughput.
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http://dx.doi.org/10.1016/j.celrep.2019.04.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582979PMC
May 2019

Brain maps at the nanoscale.

Nat Biotechnol 2019 Apr;37(4):378-380

Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY, USA.

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http://dx.doi.org/10.1038/s41587-019-0078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053416PMC
April 2019

Holographic imaging and photostimulation of neural activity.

Curr Opin Neurobiol 2018 06 13;50:211-221. Epub 2018 Apr 13.

Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address:

Optical imaging methods are powerful tools in neuroscience as they can systematically monitor the activity of neuronal populations with high spatiotemporal resolution using calcium or voltage indicators. Moreover, caged compounds and optogenetic actuators enable to optically manipulate neural activity. Among optical methods, computer-generated holography offers an enormous flexibility to sculpt the excitation light in three-dimensions (3D), particularly when combined with two-photon light sources. By projecting holographic light patterns on the sample, the activity of multiple neurons across a 3D brain volume can be simultaneously imaged or optically manipulated with single-cell precision. This flexibility makes two-photon holographic microscopy an ideal all-optical platform to simultaneously read and write activity in neuronal populations in vivo in 3D, a critical ability to dissect the function of neural circuits.
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http://dx.doi.org/10.1016/j.conb.2018.03.006DOI Listing
June 2018

LXRα is expressed at higher levels in healthy people compared to atherosclerosis patients and its over-expression polarizes macrophages towards an anti-inflammatory MΦ2 phenotype.

Clin Exp Hypertens 2018 8;40(3):213-217. Epub 2018 Feb 8.

a Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases , Tianjin , 300060 China.

Objectives: (1) To investigate the expression patterns of MΦ1 and MΦ2 phenotype markers of peripheral blood monocyte (PBMC)-derived macrophages in atherosclerosis patients and healthy controls, as well as the expression correlation among these genes. (2) To elucidate whether a high level of liver X receptor α (LXRα) expression is associated with anti-inflammatory MΦ2-type polarization.

Design: Peripheral blood monocytes (PBMCs) were obtained from 28 patients with carotid artery plaques and 10 normal persons, who did not have carotid artery plaques. M1 and M2 phenotype markers were analyzed after cellular differentiation into macrophages. Human macrophages derived from healthy donors were transfected with plasmid DNA encoding LXRα and control null-plasmids. Gene expression levels were quantified after further differentiation.

Results: Three genes (LXRα, CD68, and CD36) were expressed at a significantly lower rate in the atherosclerotic group than normal patients. There were correlations between the expression of LXRα, CD68, and peroxisome proliferator-activated receptor (PPARγ), and between CD163, CD36 and scavenger receptor class A (SRA1). Macrophages over-expressing LXRα exhibited enhanced expression level of MΦ2-type genes and decreased expression level of MΦ1-type genes.

Conclusions: PBMCs from healthy persons were predisposed to the MΦ2 differentiation phenotype, which exhibits elevated cholesterol uptake and anti-inflammatory properties. LXRα over-expression polarizes macrophages towards the anti-inflammatory MΦ2 phenotype.
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http://dx.doi.org/10.1080/10641963.2017.1288740DOI Listing
August 2018

Simultaneous two-photon imaging and two-photon optogenetics of cortical circuits in three dimensions.

Elife 2018 02 7;7. Epub 2018 Feb 7.

NeuroTechnology Center, Department of Biological Sciences, Columbia University, New York, United States.

The simultaneous imaging and manipulating of neural activity could enable the functional dissection of neural circuits. Here we have combined two-photon optogenetics with simultaneous volumetric two-photon calcium imaging to measure and manipulate neural activity in mouse neocortex in vivo in three-dimensions (3D) with cellular resolution. Using a hybrid holographic approach, we simultaneously photostimulate more than 80 neurons over 150 μm in depth in layer 2/3 of the mouse visual cortex, while simultaneously imaging the activity of the surrounding neurons. We validate the usefulness of the method by photoactivating in 3D selected groups of interneurons, suppressing the response of nearby pyramidal neurons to visual stimuli in awake animals. Our all-optical approach could be used as a general platform to read and write neuronal activity.
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http://dx.doi.org/10.7554/eLife.32671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832414PMC
February 2018

Very high efficiency optical coupler for silicon nanophotonic waveguide and single mode optical fiber.

Opt Express 2017 Jul;25(15):18462-18473

Integrated optical circuits are poised to open up an array of novel applications. A vibrant field of research has emerged around the monolithic integration of optical components onto the silicon substrates. Typically, single mode optical fibers deliver the external light to the chip, and submicron single-mode waveguides then guide the light on-chip for further processing. For such technology to be viable, it is critically important to be able to efficiently couple light into and out of the chip platform, and between the different components, with low losses. Due to the large volume mismatch between a fiber and silicon waveguide (on the order of 600), it has been extremely challenging to obtain high coupling efficient with large tolerance. To date, demonstrated coupling has been relatively lossy and effective coupling requires impractical alignment of optical components. Here, we propose the use of a high contrast metastructure (HCM) that overcomes these issues, and effectively couples the off-chip, out-of-plane light waves into on-chip, in-plane waveguides. By harnessing the resonance properties of the metastructure, we show that it is possible to spatially confine the incoming free-space light into subwavelength dimensions with a near-unity (up to 98%) efficiency. The underlying coupling mechanism is analyzed and designs for practical on-chip coupler and reflector systems are presented. Furthermore, we explore the two-dimensional HCM as an ultra-compact wavelength multiplexer with superior efficiency (90%).
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http://dx.doi.org/10.1364/OE.25.018462DOI Listing
July 2017

Multi-scale approaches for high-speed imaging and analysis of large neural populations.

PLoS Comput Biol 2017 Aug 3;13(8):e1005685. Epub 2017 Aug 3.

Department of Statistics, Grossman Center for the Statistics of Mind, and Center for Theoretical Neuroscience, Columbia University, New York, New York, United States of America.

Progress in modern neuroscience critically depends on our ability to observe the activity of large neuronal populations with cellular spatial and high temporal resolution. However, two bottlenecks constrain efforts towards fast imaging of large populations. First, the resulting large video data is challenging to analyze. Second, there is an explicit tradeoff between imaging speed, signal-to-noise, and field of view: with current recording technology we cannot image very large neuronal populations with simultaneously high spatial and temporal resolution. Here we describe multi-scale approaches for alleviating both of these bottlenecks. First, we show that spatial and temporal decimation techniques based on simple local averaging provide order-of-magnitude speedups in spatiotemporally demixing calcium video data into estimates of single-cell neural activity. Second, once the shapes of individual neurons have been identified at fine scale (e.g., after an initial phase of conventional imaging with standard temporal and spatial resolution), we find that the spatial/temporal resolution tradeoff shifts dramatically: after demixing we can accurately recover denoised fluorescence traces and deconvolved neural activity of each individual neuron from coarse scale data that has been spatially decimated by an order of magnitude. This offers a cheap method for compressing this large video data, and also implies that it is possible to either speed up imaging significantly, or to "zoom out" by a corresponding factor to image order-of-magnitude larger neuronal populations with minimal loss in accuracy or temporal resolution.
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http://dx.doi.org/10.1371/journal.pcbi.1005685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557609PMC
August 2017

Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI.

Sci Rep 2017 06 19;7(1):3805. Epub 2017 Jun 19.

Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300350, China.

In recent years, hypopituitarism caused by traumatic brain injury (TBI) has been explored in many clinical studies; however, few studies have focused on intracranial hypertension and stress caused by TBI. In this study, an intracranial hypertension model, with epidural hematoma as the cause, was used to explore the physiopathological and neuroendocrine changes in the hypothalamic-pituitary axis and hippocampus. The results demonstrated that intracranial hypertension increased the apoptosis rate, caspase-3 levels and proliferating cell nuclear antigen (PCNA) in the hippocampus, hypothalamus, pituitary gland and showed a consistent rate of apoptosis within each group. The apoptosis rates of hippocampus, hypothalamus and pituitary gland were further increased when intracranial pressure (ICP) at 24 hour (h) were still increased. The change rates of apoptosis in hypothalamus and pituitary gland were significantly higher than hippocampus. Moreover, the stress caused by surgery may be a crucial factor in apoptosis. To confirm stress leads to apoptosis in the hypothalamus and pituitary gland, we used rabbits to establish a standard stress model. The results confirmed that stress leads to apoptosis of neuroendocrine cells in the hypothalamus and pituitary gland, moreover, the higher the stress intensity, the higher the apoptosis rate in the hypothalamus and pituitary gland.
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http://dx.doi.org/10.1038/s41598-017-04008-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476648PMC
June 2017

In vivo imaging of neural activity.

Nat Methods 2017 Apr 31;14(4):349-359. Epub 2017 Mar 31.

Department of Biological Sciences, Neurotechnology Center, Columbia University, New York, New York, USA.

Since the introduction of calcium imaging to monitor neuronal activity with single-cell resolution, optical imaging methods have revolutionized neuroscience by enabling systematic recordings of neuronal circuits in living animals. The plethora of methods for functional neural imaging can be daunting to the nonexpert to navigate. Here we review advanced microscopy techniques for in vivo functional imaging and offer guidelines for which technologies are best suited for particular applications.
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http://dx.doi.org/10.1038/nmeth.4230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903578PMC
April 2017

Imaging and Optically Manipulating Neuronal Ensembles.

Annu Rev Biophys 2017 05 15;46:271-293. Epub 2017 Mar 15.

NeuroTechnology Center, Columbia University, New York, NY 10027.

The neural code that relates the firing of neurons to the generation of behavior and mental states must be implemented by spatiotemporal patterns of activity across neuronal populations. These patterns engage selective groups of neurons, called neuronal ensembles, which are emergent building blocks of neural circuits. We review optical and computational methods, based on two-photon calcium imaging and two-photon optogenetics, to detect, characterize, and manipulate neuronal ensembles in three dimensions. We review data using these methods in the mammalian cortex that demonstrate the existence of neuronal ensembles in the spontaneous and evoked cortical activity in vitro and in vivo. Moreover, two-photon optogenetics enable the possibility of artificially imprinting neuronal ensembles into awake, behaving animals and of later recalling those ensembles selectively by stimulating individual cells. These methods could enable deciphering the neural code and also be used to understand the pathophysiology of and design novel therapies for neurological and mental diseases.
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http://dx.doi.org/10.1146/annurev-biophys-070816-033647DOI Listing
May 2017

Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens.

Sci Rep 2016 08 24;6:32030. Epub 2016 Aug 24.

Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300060, China.

Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4(+)T/CD8(+)T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections.
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http://dx.doi.org/10.1038/srep32030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995514PMC
August 2016

Imprinting and recalling cortical ensembles.

Science 2016 Aug 11;353(6300):691-4. Epub 2016 Aug 11.

NeuroTechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion.
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http://dx.doi.org/10.1126/science.aaf7560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482530PMC
August 2016

Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data.

Neuron 2016 Jan 7;89(2):285-99. Epub 2016 Jan 7.

Department of Statistics, Center for Theoretical Neuroscience, and Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA; Department of Neuroscience and Kavli Institute of Brain Science, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA; Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address:

We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multi-neuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data.
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http://dx.doi.org/10.1016/j.neuron.2015.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881387PMC
January 2016

Simultaneous Multi-plane Imaging of Neural Circuits.

Neuron 2016 Jan 7;89(2):269-84. Epub 2016 Jan 7.

Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Recording the activity of large populations of neurons is an important step toward understanding the emergent function of neural circuits. Here we present a simple holographic method to simultaneously perform two-photon calcium imaging of neuronal populations across multiple areas and layers of mouse cortex in vivo. We use prior knowledge of neuronal locations, activity sparsity, and a constrained nonnegative matrix factorization algorithm to extract signals from neurons imaged simultaneously and located in different focal planes or fields of view. Our laser multiplexing approach is simple and fast, and could be used as a general method to image the activity of neural circuits in three dimensions across multiple areas in the brain.
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http://dx.doi.org/10.1016/j.neuron.2015.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724224PMC
January 2016

Surface-normal coupled four-wave mixing in a high contrast gratings resonator.

Opt Express 2015 Nov;23(23):29565-72

We demonstrate enhanced four-wave mixing using a silicon high contrast grating (HCG) resonator on a SOI (silicon-on-insulator) wafer directly coupled with free space Gaussian beam in surface-normal direction. The measured quality factor for HCG resonator is ~7330. Peak conversion efficiency of -19.5dB is achieved at low pumping power ~900µW. Surface-normal coupling allows for easily and robust alignment system. The very small footprint and high efficiency of our device provide an effective method for wavelength conversion in chip-scale integrated optics.
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http://dx.doi.org/10.1364/OE.23.029565DOI Listing
November 2015

Laser optomechanics.

Sci Rep 2015 Sep 3;5:13700. Epub 2015 Sep 3.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720, USA.

Cavity optomechanics explores the interaction between optical field and mechanical motion. So far, this interaction has relied on the detuning between a passive optical resonator and an external pump laser. Here, we report a new scheme with mutual coupling between a mechanical oscillator supporting the mirror of a laser and the optical field generated by the laser itself. The optically active cavity greatly enhances the light-matter energy transfer. In this work, we use an electrically-pumped vertical-cavity surface-emitting laser (VCSEL) with an ultra-light-weight (130 pg) high-contrast-grating (HCG) mirror, whose reflectivity spectrum is designed to facilitate strong optomechanical coupling, to demonstrate optomechanically-induced regenerative oscillation of the laser optomechanical cavity. We observe >550 nm self-oscillation amplitude of the micromechanical oscillator, two to three orders of magnitude larger than typical, and correspondingly a 23 nm laser wavelength sweep. In addition to its immediate applications as a high-speed wavelength-swept source, this scheme also offers a new approach for integrated on-chip sensors.
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http://dx.doi.org/10.1038/srep13700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558576PMC
September 2015

Heterogeneously integrated long-wavelength VCSEL using silicon high contrast grating on an SOI substrate.

Opt Express 2015 Feb;23(3):2512-23

We report an electrically pumped hybrid cavity AlGaInAs-silicon long-wavelength VCSEL using a high contrast grating (HCG) reflector on a silicon-on-insulator (SOI) substrate. The VCSEL operates at silicon transparent wavelengths ~1.57 μm with >1 mW CW power outcoupled from the semiconductor DBR, and single-mode operation up to 65 °C. The thermal resistance of our device is measured to be 1.46 K/mW. We demonstrate >2.5 GHz 3-dB direct modulation bandwidth, and show error-free transmission over 2.5 km single mode fiber under 5 Gb/s direct modulation. We show a theoretical design of SOI-HCG serving both as a VCSEL reflector as well as waveguide coupler for an in-plane SOI waveguide, facilitating integration of VCSEL with in-plane silicon photonic circuits. The novel HCG-VCSEL design, which employs scalable flip-chip eutectic bonding, may enable low cost light sources for integrated optical links.
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http://dx.doi.org/10.1364/OE.23.002512DOI Listing
February 2015

High speed optical phased array using high contrast grating all-pass filters.

Opt Express 2014 Aug;22(17):20038-44

We report a high speed 8x8 optical phased array using tunable 1550 nm all-pass filters with ultrathin high contrast gratings (HCGs) as the microelectromechanical-actuated top reflectors. The all-pass filter design enables a highly efficient phase tuning (1.7 π) with a small actuation voltage (10 V) and actuation displacement of the HCG (50 nm). The microelectromechanical HCG structure facilitates a high phase tuning speed >0.5 MHz. Beam steering is experimentally demonstrated with the optical phased array.
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http://dx.doi.org/10.1364/OE.22.020038DOI Listing
August 2014
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