scholarly journals A population MRI brain template and analysis tools for the macaque

2017 ◽  
Author(s):  
Jakob Seidlitz ◽  
Caleb Sponheim ◽  
Daniel Glen ◽  
Frank Q. Ye ◽  
Kadharbatcha S. Saleem ◽  
...  
Keyword(s):  
Data Analysis ◽  
Brain Regions ◽  
Single Subject ◽  
Tissue Segmentation ◽  
Brain Extraction ◽  
Surface Reconstructions ◽  
Morphometric Feature ◽  
Feature Estimation ◽  
Brain Template

AbstractThe use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the “National Institute of Mental Health Macaque Template”, or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies.

Analysis of cerebral glucose metabolism following experimental subarachnoid hemorrhage: an [18F]FDG-PET study over 7 days using an MRI-template based analysis tool

2022 ◽  
Author(s):  
Fabian Schadt ◽  
Ina Israel ◽  
Alexandra Beez ◽  
Kastriot Alushi ◽  
Judith Weiland ◽  
...  
Keyword(s):  
Data Analysis ◽  
Glucose Metabolism ◽  
Fdg Pet ◽  
Brain Regions ◽  
Sham Operation ◽  
Analysis Tool ◽  
Imaging Data ◽  
Sprague Dawley ◽  
Data Analysis Tool

Abstract Little is known about changes in brain metabolism following SAH, possibly leading towards secondary brain damage. Despite sustained progress in the last decade, analysis of in vivo acquired data still remains challenging. The present interdisciplinary study uses a semi-automated data analysis tool analyzing imaging data independently from the administrated radiotracer. The uptake of 2-[18F]Fluoro-2-deoxy-glucose ([18F]FDG) was evaluated in different brain regions in 14 male Sprague-Dawley rats, randomized into two groups: (1) SAH induced by the endovascular filament model and (2) sham operated controls. Serial [18F]FDG-PET measurements were performed. Quantitative image analysis was performed by uptake ratio using a self-developed MRI-template based data analysis tool. SAH animals showed significantly higher [18F]FDG accumulation in gray matter, neocortex and olfactory system as compared to animals of the sham group, while white matter and basal forebrain region showed significant reduced tracer accumulation in SAH animals. All significant metabolic changes were visualized from 3 hours, over 24 hours, day 4 and day 7 following SAH/sham operation. This [18F]FDG-PET study provides important insights into glucose metabolism alterations following SAH - for the first time in different brain regions and up to day 7 during course of disease. The present tool improves PET image quantification and provides more flexible data analysis advocating its clinical application.

scholarly journals A Precision Functional Atlas of Network Probabilities and Individual-Specific Network Topography

2022 ◽  
Author(s):  
Robert JM Hermosillo ◽  
Lucille A Moore ◽  
Eric J Feczko ◽  
Adam R Pines ◽  
Ally Dworetsky ◽  
...  
Keyword(s):  
Open Source ◽  
Template Matching ◽  
Functional Organization ◽  
Detection Algorithm ◽  
Brain Regions ◽  
Single Subject ◽  
Probabilistic Network ◽  
Community Detection Algorithm ◽  
Online Web

The brain is organized into a broad set of functional neural networks. These networks and their various characteristics have been described and scrutinized through in vivo resting state functional magnetic resonance imaging (rs-fMRI). While the basic properties of networks are generally similar between healthy individuals, there is vast variability in the precise topography across the population. These individual differences are often lost in population studies due to population averaging which assumes topographical uniformity. We leveraged precision brain mapping methods to establish a new open-source, method-flexible set of probabilistic functional network atlases: the Masonic Institute for the Developing Brain (MIDB) Precision Atlas. Using participants from the Adolescent Brain Cognitive Development (ABCD) study, single subject precision maps were generated with two supervised network-matching procedures (template matching and non-negative matrix factorization), as well as an unsupervised community detection algorithm (Infomap). We demonstrate that probabilistic network maps generated for two demographically-matched groups of n~3000 each were nearly identical, both between groups (Pearson r >0.999) and between methods (r=0.96), revealing both regions of high invariance and high variability. Compared to using parcellations based on groups averages, the MIDB Precision Atlases allowed us to derive a set of brain regions that are largely invariant in network topography and provide more reproducible statistical maps of executive function brain-wide associations. We explore an example use case for probabilistic maps, highlighting their potential for use in targeted neuromodulation. The MIDB Precision Atlas is expandable to alternative datasets and methods and is provided open-source with an online web interface to encourage the scientific community to experiment with probabilistic atlases and individual-specific topographies to more precisely relate network phenomenon to functional organization of the human brain.

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cody L. Call ◽  
Dwight E. Bergles
Keyword(s):  
Cortical Neurons ◽  
Regional Differences ◽  
Brain Regions ◽  
Axon Diameter ◽  
Neuronal Identity ◽  
Cortical Areas ◽  
Myelin Sheaths ◽  
Parvalbumin Interneurons ◽  
Selection Of

ABSTRACTAxons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

scholarly journals Topological Data Analysis Approaches to Uncovering the Timing of Ring Structure Onset in Filamentous Networks

2021 ◽  
Vol 83 (3) ◽  
Author(s):  
Maria-Veronica Ciocanel ◽  
Riley Juenemann ◽  
Adriana T. Dawes ◽  
Scott A. McKinley
Keyword(s):  
Time Series ◽  
Data Analysis ◽  
Actin Filaments ◽  
Time Series Data ◽  
Polymer Networks ◽  
Topological Data Analysis ◽  
Series Data ◽  
Topological Features ◽  
Topological Data

AbstractIn developmental biology as well as in other biological systems, emerging structure and organization can be captured using time-series data of protein locations. In analyzing this time-dependent data, it is a common challenge not only to determine whether topological features emerge, but also to identify the timing of their formation. For instance, in most cells, actin filaments interact with myosin motor proteins and organize into polymer networks and higher-order structures. Ring channels are examples of such structures that maintain constant diameters over time and play key roles in processes such as cell division, development, and wound healing. Given the limitations in studying interactions of actin with myosin in vivo, we generate time-series data of protein polymer interactions in cells using complex agent-based models. Since the data has a filamentous structure, we propose sampling along the actin filaments and analyzing the topological structure of the resulting point cloud at each time. Building on existing tools from persistent homology, we develop a topological data analysis (TDA) method that assesses effective ring generation in this dynamic data. This method connects topological features through time in a path that corresponds to emergence of organization in the data. In this work, we also propose methods for assessing whether the topological features of interest are significant and thus whether they contribute to the formation of an emerging hole (ring channel) in the simulated protein interactions. In particular, we use the MEDYAN simulation platform to show that this technique can distinguish between the actin cytoskeleton organization resulting from distinct motor protein binding parameters.

scholarly journals In vivo synaptic density relates to glucose metabolism at rest in healthy subjects, but is strongly modulated by regional differences

2021 ◽  
pp. 0271678X2098150
Author(s):  
June van Aalst ◽  
Jenny Ceccarini ◽  
Stefan Sunaert ◽  
Patrick Dupont ◽  
Michel Koole ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Medial Temporal Lobe ◽  
Regional Differences ◽  
Specific Binding ◽  
Aerobic Glycolysis ◽  
Glucose Consumption ◽  
Brain Regions ◽  
Synaptic Density ◽  
Energy Demands

Preclinical and postmortem studies have suggested that regional synaptic density and glucose consumption (CMRGlc) are strongly related. However, the relation between synaptic density and cerebral glucose metabolism in the human brain has not directly been assessed in vivo. Using [11C]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A) as indicator for synaptic density and [18F]FDG for measuring cerebral glucose consumption, we studied twenty healthy female subjects (age 29.6 ± 9.9 yrs) who underwent a single-day dual-tracer protocol (GE Signa PET-MR). Global measures of absolute and relative CMRGlc and specific binding of [11C]UCB-J were indeed highly significantly correlated ( r > 0.47, p < 0.001). However, regional differences in relative [18F]FDG and [11C]UCB-J uptake were observed, with up to 19% higher [11C]UCB-J uptake in the medial temporal lobe (MTL) and up to 17% higher glucose metabolism in frontal and motor-related areas and thalamus. This pattern has a considerable overlap with the brain regions showing different levels of aerobic glycolysis. Regionally varying energy demands of inhibitory and excitatory synapses at rest may also contribute to this difference. Being unaffected by astroglial and/or microglial energy demands, changes in synaptic density in the MTL may therefore be more sensitive to early detection of pathological conditions compared to changes in glucose metabolism.

scholarly journals Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jason L. He ◽  
Georg Oeltzschner ◽  
Mark Mikkelsen ◽  
Alyssa Deronda ◽  
Ashley D. Harris ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Strong Support ◽  
Empirical Support ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Resonance Spectroscopy ◽  
Primary Sensorimotor Cortex ◽  
Spectrum Disorders ◽  
Inhibitory Signaling

AbstractIndividuals on the autism spectrum are often reported as being hyper- and/or hyporeactive to sensory input. These sensory symptoms were one of the key observations that led to the development of the altered excitation-inhibition (E-I) model of autism, which posits that an increase ratio of excitatory to inhibitory signaling may explain certain phenotypical expressions of autism spectrum disorders (ASD). While there has been strong support for the altered E-I model of autism, much of the evidence has come from animal models. With regard to in-vivo human studies, evidence for altered E-I balance in ASD come from studies adopting magnetic resonance spectroscopy (MRS). Spectral-edited MRS can be used to provide measures of the levels of GABA + (GABA + macromolecules) and Glx (glutamate + glutamine) in specific brain regions as proxy markers of inhibition and excitation respectively. In the current study, we found region-specific elevations of Glx in the primary sensorimotor cortex (SM1) in ASD. There were no group differences of GABA+ in either the SM1 or thalamus. Higher levels of Glx were associated with more parent reported difficulties of sensory hyper- and hyporeactivity, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Critically, the finding of elevated Glx provides strong empirical support for increased excitation in ASD. Our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.

scholarly journals Cellular sources of TSPO expression in healthy and diseased brain

2021 ◽  
Author(s):  
Erik Nutma ◽  
Kelly Ceyzériat ◽  
Sandra Amor ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
...  
Keyword(s):  
Cell Activity ◽  
Brain Regions ◽  
Cellular Level ◽  
Translocator Protein ◽  
Disease Stage ◽  
Animal Models Of Disease ◽  
Positron Emission ◽  
Neuropsychiatric Diseases ◽  
Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

Physiology, Pharmacology, and Topography of Cholinergic Neocortical Oscillations In Vitro

1997 ◽  
Vol 77 (5) ◽  
pp. 2427-2445 ◽  
Author(s):  
Heath S. Lukatch ◽  
M. Bruce Maciver
Keyword(s):  
Current Source ◽  
Brain Slices ◽  
Receptor Activation ◽  
Brain Regions ◽  
Oscillatory Activity ◽  
Cortical Layers ◽  
Eeg Activity ◽  
Layer 2

Lukatch, Heath S. and M. Bruce MacIver. Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro. J. Neurophysiol. 77: 2427–2445, 1997. Rat neocortical brain slices generated rhythmic extracellular field [microelectroencephalogram (micro-EEG)] oscillations at theta frequencies (3–12 Hz) when exposed to pharmacological conditions that mimicked endogenous ascending cholinergic and GABAergic inputs. Use of the specific receptor agonist and antagonist carbachol and bicuculline revealed that simultaneous muscarinic receptor activation and γ-aminobutyric acid-A (GABAA)-mediated disinhibition werenecessary to elicit neocortical oscillations. Rhythmic activity was independent of GABAB receptor activation, but required intact glutamatergic transmission, evidenced by blockade or disruption of oscillations by 6-cyano-7-nitroquinoxaline-2,3-dione and (±)-2-amino-5-phosphonovaleric acid, respectively. Multisite mapping studies showed that oscillations were localized to areas 29d and 18b (Oc2MM) and parts of areas 18a and 17. Peak oscillation amplitudes occurred in layer 2/3, and phase reversals were observed in layers 1 and 5. Current source density analysis revealed large-amplitude current sinks and sources in layers 2/3 and 5, respectively. An initial shift in peak inward current density from layer 1 to layer 2/3 indicated that two processes underlie an initial depolarization followed by oscillatory activity. Laminar transections localized oscillation-generating circuitry to superficial cortical layers and sharp-spike-generating circuitry to deep cortical layers. Whole cell recordings identified three distinct cell types based on response properties during rhythmic micro-EEG activity: oscillation-on (theta-on) and -off (theta-off) neurons, and transiently depolarizing glial cells. Theta-on neurons displayed membrane potential oscillations that increased in amplitude with hyperpolarization (from −30 to −90 mV). This, taken together with a glutamate antagonist-induced depression of rhythmic micro-EEG activity, indicated that cholinergically driven neocortical oscillations require excitatory synaptic transmission. We conclude that under the appropriate pharmacological conditions, neocortical brain slices were capable of producing localized theta frequency oscillations. Experiments examining oscillation physiology, pharmacology, and topography demonstrated that neocortical brain slice oscillations share many similarities with the in vivo and in vitro theta EEG activity recorded in other brain regions.

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