Cortical layer-specific differences in stimulus selectivity revealed with high-field fMRI and single-vessel resolution optical imaging of the primary visual cortex.

The mammalian neocortex exhibits a stereotypical laminar organization, with feedforward inputs arriving primarily into layer 4, local computations shaping response selectivity in layers 2/3, and outputs to other brain areas emanating via layers 2/3, 5 and 6. It cannot be assumed a priori that these signatures of laminar differences in neuronal circuitry are reflected in hemodynamic signals that form the basis of functional magnetic resonance imaging (fMRI). Indeed, optical imaging of single-vessel functional responses has highlighted the potential limits of using vascular signals as surrogates for mapping the selectivity of neural responses. Therefore, before fMRI can be employed as an effective tool for studying critical aspects of laminar processing, validation with single-vessel resolution is needed. The primary visual cortex (V1) in cats, with its precise neuronal functional micro-architecture, offers an ideal model system to examine laminar differences in stimulus selectivity across imaging modalities. Here we used cerebral blood volume weighted (wCBV) fMRI to examine if layer-specific orientation-selective responses could be detected in cat V1. We found orientation preference maps organized tangential to the cortical surface that typically extended across depth in a columnar fashion. We then examined arterial dilation and blood velocity responses to identical visual stimuli by using two- and three- photon optical imaging at single-vessel resolution-which provides a measure of the hemodynamic signals with the highest spatial resolution. Both fMRI and optical imaging revealed a consistent laminar response pattern in which orientation selectivity in cortical layer 4 was significantly lower compared to layer 2/3. This systematic change in selectivity across cortical layers has a clear underpinning in neural circuitry, particularly when comparing layer 4 to other cortical layers.

LayNii: A software suite for layer-fMRI.

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifacts, including image blurring, image distortions, low SNR, and restricted coverage. These challenges often result in insufficient spatial accuracy of conventional analysis pipelines. Here we introduce a new software suite that is specifically designed for layer-specific functional MRI: LayNii. This toolbox is a collection of command-line executable programs written in C/C++ and is distributed opensource and as pre-compiled binaries for Linux, Windows, and macOS. LayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints and thus cannot be straightforwardly analyzed in alternative software packages. Some of the most popular programs of LayNii contain 'layerification' and columnarization in the native voxel space of functional data as well as many other layer-fMRI specific analysis tasks: layer-specific smoothing, model-based vein mitigation of GE-BOLD data, quality assessment of artifact dominated sub-millimeter fMRI, as well as analyses of VASO data.

Effect of Substrate Temperature on the Properties of Eu-Doped SrSnO3 Phosphor Thin Films Grown by Sputtering.

Eu3+-doped SrSnO3 (SrSnO3:Eu3+) phosphor thin films are deposited on sapphire substrates by radio-frequency magnetron sputtering. The substrate temperature is varied from 25 to 400 °C. All SrSnO3:Eu3+ films show amorphous behavior, while the band gap energies decrease with an increase in the substrate temperature and are determined to be 4.16-4.26 eV. The optical transmittance spectra exhibit an average transmittance of approximately 91% in the wavelength range 500-1100 nm; a gradual increase in emission intensity arising from the 5D0→7F2 transition (618 nm) of Eu3+ is observed with increasing substrate temperature. These results suggest that the optimum substrate temperature for depositing SrSnO3:Eu3+ red-emitting phosphor thin films is 400 °C.

The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity.

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect.

Dopamine Release in the Nonhuman Primate Caudate and Putamen Depends upon Site of Stimulation in the Subthalamic Nucleus.

UNLABELLED: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson's disease. Although DBS has recognized clinical utility, its biologic mechanisms are not fully understood, and whether dopamine release is a potential factor in those mechanisms is in dispute. We tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and the site of recording in the caudate and putamen. We conducted DBS with miniature, scaled-to-animal size, multicontact electrodes and used functional magnetic resonance imaging to identify the best dopamine recording site in the brains of nonhuman primates (rhesus macaques), which are highly representative of human brain anatomy and circuitry. Real-time stimulation-evoked dopamine release was monitored using in vivo fast-scan cyclic voltammetry. This study demonstrates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site. SIGNIFICANCE STATEMENT: Electrical stimulation of deep structures of the brain, or deep brain stimulation (DBS), is used to modulate pathological brain activity. However, technological limitations and incomplete understanding of the therapeutic mechanisms of DBS prevent personalization of this therapy and may contribute to less-than-optimal outcomes. We have demonstrated that DBS coincides with changes in dopamine neurotransmitter release in the basal ganglia. Here we mapped relationships between DBS and changes in neurochemical activity. Importantly, this study shows that DBS-evoked dopamine release can be reduced or increased by refocusing the DBS on a slightly different stimulation site.

Correction of metal-induced susceptibility artifacts for functional MRI during deep brain stimulation.

Functional magnetic resonance imaging (fMRI) is an emerging tool for investigating brain activation associated with, or modulated by, deep brain stimulation (DBS). However, DBS-fMRI generally suffers from severe susceptibility to artifacts in regions near the metallic stimulation electrodes, as well as near tissue/air boundaries of the brain. These result in strong intensity and geometric distortions along the phase-encoding (PE) (i.e., blipped) direction in gradient-echo echo-planar imaging (GE-EPI). Distortion presents a major challenge to conducting reliable data analysis and in interpreting the findings. A recent study showed that the point spread function (PSF) mapping-based reverse gradient approach has a potential to correct for distortions not only in spin-echo EPI, but also in GE-EPI acquired in both the forward and reverse PE directions. In this study, we adapted that approach in order to minimize severe metal-induced susceptibility artifacts for DBS-fMRI, and to evaluate the performance of the approach in a phantom study and a large animal DBS-fMRI study. The method combines the distortion-corrected GE-EPI pair with geometrically different intensity distortions due to the opposing encoding directions. The results demonstrate that the approach can minimize susceptibility artifacts that appear around the metallic electrodes, as well as in the regions near the tissue/air boundaries in the brain. We also demonstrated that an accurate geometric correction is important in improving BOLD contrast in the group dataset, especially in regions where strong susceptibility artifacts appear.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor.

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson's disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation.media-1vid110.1093/brain/aww145_video_abstractaww145_video_abstract.

Effect of nitrogen flow rate on the properties of copper nitride thin films.

Copper nitride (Cu3N) thin films were deposited at 300 degrees C on glass substrates by reactive magnetron sputtering method with changing various nitrogen flow rates. The results showed that the nitrogen flow rate has a significant effect on the properties of the Cu3N thin films. XRD data exhibited that two phases of Cu3N and Cu coexisted for the thin films deposited at 300 degrees C, irrespective of nitrogen flow rate. The preferential orientation of the film grown at 400 degrees C was transformed from Cu3N to Cu phase. The optical band gap was gradually increased with increasing the nitrogen flow rate. The grain size showed the minimum of 22 nm for the Cu3N thin film deposited at 30%, where the highest value of the carrier concentration was obtained. The results suggest that the properties of the Cu3N thin films can be controlled by the nitrogen flow rate.

Luminescence properties of GdVO4 blue phosphors doped with Tb3+ ions.

Gd(1-x)VO4:Tb3+ phosphor powders were synthesized with different Tb3+ concentrations by using a solid-state reaction method. The effects of Tb3+ concentrations on the structural, morphological, photoluminescence, and photoluminescence excitation properties of the Tb(3+)-doped GdVO4 phosphors were investigated. XRD data exhibited that the main peak of the phosphors occurred at (200) plane. The increase of grain size and the hexagonal pattern in shape were observed with increasing the concentration of Tb3+ ion. As for the optical properties, two excitation spectra centered at 241 and about 315 nm were observed. The blue 5D4-7F6 emission at 486 nm reached the maximum when the concentration of Tb3+ ion was 15 mol% and the emission intensity rapidly decreased at 20 mol% due to the concentration quenching.

Synthesis and luminescence properties of LaVO4:RE3+ (RE = Sm, Eu, Tb, Tm) phosphors.

Rare earth (RE)-doped lanthanide vanadate phosphors for multicolor display applications were synthesized with different activator ions by using a solid-state reaction method. The effects of activator ions on the structural, morphological, and optical properties of lanthanide vanadate phosphors were investigated. X-ray diffaction data exhibited that the main peak of the phosphors occurs at a (120) plane. Maximum grain size and hexagonal morphology are observed by incorporating Eu3+ activator ions into a host lattice. The emission spectra of RE ions-doped LaVO4 phosphors under excitation at 324 nm consist of multicolor emissions: the main red emission for Eu3+, Orange for Tm3+, green for Tb3+, and blue for Tm3+ activator ions. These results suggest that the multicolor emissions can be realized by controlling activator ions incorporated into host crystals.

Effects of nitrogen flow rate on the properties of indium oxide thin films.

Indium oxide thin films are deposited on glass substrates at nitrogen flow rates of 0-50% by rf reactive magnetron sputtering and are characterized for their structural, morphological, electrical, and optical properties. The experimental results showed that the control of nitrogen flow rate has a significant effect on the properties of the In2O3 thin films. The change in the preferred growth orientation from (222) to (400) planes is observed above a nitrogen flow rate of 10%. The average optical transmittance in the wavelength range of 400-1100 nm is increased from 85.4% at 0% to 86.7% at 50%, where the smallest value of the optical band gap energy is obtained. In addition to the improvement in crystallinity of the films, the nitrogen flow rate plays a crucial role in the fabrication of high-quality indium oxide films and devices.

Multivariate pattern classification on BOLD activation pattern induced by deep brain stimulation in motor, associative, and limbic brain networks.

Deep brain stimulation (DBS) has been shown to be an effective treatment for movement disorders and it is now being extended to the treatment of psychiatric disorders. Functional magnetic resonance imaging (fMRI) studies indicate that DBS stimulation targets dependent brain network effects, in networks that respond to stimulation. Characterizing these patterns is crucial for linking DBS-induced therapeutic and adverse effects. Conventional DBS-fMRI, however, lacks the sensitivity needed for decoding multidimensional information such as spatially diffuse patterns. We report here on the use of a multivariate pattern analysis (MVPA) to demonstrate that stimulation of three DBS targets (STN, subthalamic nucleus; GPi, globus pallidus internus; NAc, nucleus accumbens) evoked a sufficiently distinctive blood-oxygen-level-dependent (BOLD) activation in swine brain. The findings indicate that STN and GPi evoke a similar motor network pattern, while NAc shows a districted associative and limbic pattern. The findings show that MVPA could be effectively applied to overlapping or sparse BOLD patterns which are often found in DBS. Future applications are expected employ MVPA fMRI to identify the proper stimulation target dependent brain circuitry for a DBS outcome.

Size-invariant but location-specific object-viewpoint adaptation in the absence of awareness.

Perceiving object viewpoint is important for appropriate action. Here we investigated whether viewpoint information could be represented in the absence of awareness, by measuring viewpoint adaptation aftereffect from visual objects rendered invisible through interocular suppression. Participants adapted to either a visible or an invisible line-drawing cube with unambiguous viewpoint, then viewed an ambiguous Necker cube and reported its perceived viewpoint. In both the visible and invisible adaptation conditions, participants more likely perceived the Necker cube in opposite viewpoint compared to the adapting cube. Interestingly, this viewpoint aftereffect was still observed when the adapting and testing cubes were different in size. However, when the testing Necker cube was in a different location, the viewpoint aftereffect was only observed following visible adapting cube, abolished when the adapting cube was invisible. Thus object viewpoint representation could be established without awareness, and such unconscious viewpoint representation is size-invariant but location-specific. Object viewpoint representation requires conscious awareness to be globally accessible.

Resting-state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain.

INTRODUCTION: While the clinical efficacy of deep brain stimulation (DBS) the treatment of motor-related symptoms is well established, the mechanism of action of the resulting cognitive and behavioral effects has been elusive. METHODS: By combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood-oxygenation-level-dependent (BOLD) signal changes induced by stimulating the nucleus accumbens in a large animal model. RESULTS: We found that diffused BOLD activation across multiple functional networks, including the prefrontal, limbic, and thalamic regions during the stimulation, resulted in a significant change in inter-regional functional connectivity. More importantly, the magnitude of the modulation was closely related to the strength of the inter-regional resting-state functional connectivity. CONCLUSIONS: Nucleus accumbens stimulation affects the functional activity in networks that underlie cognition and behavior. Our study provides an insight into the nature of the functional connectivity, which mediates activation effect via brain networks.

Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation.

Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI). Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V). Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected < 0.001). During neurochemical measurements, stimulation time-locked changes in dopamine release were recorded in the NAc, confirming that mesolimbic dopaminergic neurons were stimulated by DBS. In the parametric study, BOLD signal changes were positively correlated with stimulation amplitude. Conclusions: In this study, the modulation of the neural circuitry associated with VTA-DBS was characterized in a large animal. Our findings suggest that VTA-DBS could affect the activity of neural systems and brain regions implicated in reward, mood regulation, and in the pathophysiology of MDD. In addition, we showed that a combination of fMRI and electrochemically-based neurochemical detection platform is an effective investigative tool for elucidating the circuitry involved in VTA-DBS.

Electrical and optical properties of Eu-doped indium oxide thin films deposited by radio-frequency magnetron sputtering.

Eu-doped In2O3 (EIO) thin films were deposited by radio-frequency magnetron sputtering on glass substrates with varying growth temperatures. All the EIO thin films showed a significant dependence on the growth temperature. From the figure of merit index data, the optimum growth temperature for depositing high-quality EIO thin films was found to be 300 degrees C. The ELO thin film deposited at 300 degrees C showed a highly preferential growth orientation along the (222) plane with an average particle size of 160 nm, bandgap energy of 3.94 eV, average optical transmittance of 65.2% in the wavelength range 450-1100 nm, and electrical resistivity of 2.5 x 10(-3) Ω cm. These results indicate that the electrical and optical properties of EIO thin films can be modulated by controlling growth temperature.

Effect of sputtering power on structural and optical properties of radio frequency-sputtered In2S3 thin films.

In this study, we investigated the structural and optical properties of indium sulfide (In2S3) thin films as a substitute for the CdS buffer layer in Cu(In,Ga)Se2 (CIGS) solar cells. The In2S3 films were deposited on glass substrates using radio frequency (RF) magnetron sputtering. The sputtering power was changed from 60 to 120 W in 20 W increments. The effects of sputtering power on the crystallinity, surface morphology, and optical properties of the films were characterized with X-ray diffraction (XRD), atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDS), and UV-visible spectrophotometry. The XRD analyses indicated that the films were polycrystalline ß-In2S3 structures with two preferred orientations along the (103) and (206) directions. The AFM images revealed that the films had nanosized grains and that the size increased from 7 nm for the samples prepared at 60 W to 13 nm for those prepared at 120 W. The optical band gap of the samples was found to vary between 2.88 and 2.43 eV.

Photoluminescence properties of Na(Sr,Ca)VO4:Eu(3+) phosphors.

Eu(3+)-activated novel alkaline earth metal (Sr and Ca) vanadate phosphors, Na(Sr(0.97-x), Ca(x))VO4:Eu0.03(3+) (x = 0 to 0.97) has been successfully synthesized using solid state reaction method and characterized by XRD, XPS, FE-SEM, luminescence (PLE, PL and CIE coordinate) and decay rate measurements as a function of Ca ion concentration. Phosphors show a broad excitation band (monitored for (5)D0 --> (7)F2 transition of Eu(3+)) in the 230-430 nm wavelength regions which make them highly suitable for LED chips. Material gives strong emission of Eu(3+) ion (λex = 323 nm) and intensity of this emission increases with increase in the doping concentration of Ca ions until a maximum is reached for Na(Sr0.22, Ca0.75)VO4:Eu0.03(3+) (x = 0.75) phase phosphor. The intensity ratio of (5)D0 --> (7)F2 to (5)D0 --> (7)F1 transition (monochromaticity, R) suggest that local symmetry around the Eu(3+) ion increases with increase in Ca ion concentration, which is responsible for enhanced emission.