scholarly journals Characterization of the brain functional architecture of psychostimulant withdrawal using single-cell whole brain imaging

2019 ◽  
Author(s):  
Adam Kimbrough ◽  
Lauren C. Smith ◽  
Marsida Kallupi ◽  
Sierra Simpson ◽  
Andres Collazo ◽  
...  
Keyword(s):  
Single Cell ◽  
Brain Imaging ◽  
Drugs Of Abuse ◽  
Brain Regions ◽  
Functional Architecture ◽  
Whole Brain ◽  
Similarities And Differences ◽  
Drug Dependent ◽  
The Brain

AbstractNumerous brain regions have been identified as contributing to addiction-like behaviors, but unclear is the way in which these brain regions as a whole lead to addiction. The search for a final common brain pathway that is involved in addiction remains elusive. To address this question, we used male C57BL/6J mice and performed single-cell whole-brain imaging of neural activity during withdrawal from cocaine, methamphetamine, and nicotine. We used hierarchical clustering and graph theory to identify similarities and differences in brain functional architecture. Although methamphetamine and cocaine shared some network similarities, the main common neuroadaptation between these psychostimulant drugs was a dramatic decrease in modularity, with a shift from a cortical- to subcortical-driven network, including a decrease in total hub brain regions. These results demonstrate that psychostimulant withdrawal produces the drug-dependent remodeling of functional architecture of the brain and suggest that the decreased modularity of brain functional networks and not a specific set of brain regions may represent the final common pathway that leads to addiction.Significance StatementA key aspect of treating drug abuse is understanding similarities and differences of how drugs of abuse affect the brain. In the present study we examined how the brain is altered during withdrawal from psychostimulants. We found that each drug produced a unique pattern of activity in the brain, but that brains in withdrawal from cocaine and methamphetamine shared similar features. Interestingly, we found the major common link between withdrawal from all psychostimulants, when compared to controls, was a shift in the broad organization of the brain in the form of reduced modularity. Reduced modularity has been shown in several brain disorders, including traumatic brain injury, and dementia, and may be the common link between drugs of abuse.

scholarly journals Characterization of the brain functional architecture of psychostimulant withdrawal using single-cell whole brain imaging

eNeuro ◽  
2021 ◽  
pp. ENEURO.0208-19.2021
Author(s):  
Adam Kimbrough ◽  
Marsida Kallupi ◽  
Lauren C. Smith ◽  
Sierra Simpson ◽  
Andres Collazo ◽  
...  
Keyword(s):  
Single Cell ◽  
Brain Imaging ◽  
Functional Architecture ◽  
Whole Brain ◽  
The Brain

scholarly journals Single-cell whole-brain imaging and network analysis provide evidence of the three-stage hypothesis of addiction

2018 ◽  
Author(s):  
Adam Kimbrough ◽  
Daniel J. Lurie ◽  
Andres Collazo ◽  
Max Kreifeldt ◽  
Harpreet Sidhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Brain Imaging ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Stage Theory ◽  
Incentive Salience ◽  
Neural Activation ◽  
Whole Brain ◽  
Single Dataset ◽  
Alcohol Dependent

SummaryThree main theories of the neurobiology of addiction have been proposed: (1) incentive salience mediated by a brainstem-striatal network, (2) habit mediated by a cortico-striato-thalamic network, and (3) hedonic allostasis mediated by an extended amygdala network. Efforts have been made to reconcile these theories within a three-stage model, but the relevance of each theory remains controversial. We tested the validity of each theory with a single dataset using unbiased single-cell whole-brain imaging and data-driven analyses of neuronal activity in a mouse model of alcohol use disorder. Abstinence in alcohol dependent mice decreased brain modularity and resulted in clustering of brain regions that correspond to each stage of the three-stage theory of addiction. Furthermore, we identified several brain regions whose activity highly predicted addiction-like behaviors and “hub” regions that may drive neural activation during abstinence. These results validate the three-stage theory of addiction and identify potential target regions for future study.

MicrogliaST: a web server for microglia spatiotemportal pattern analysis in normal and disordered brains

2022 ◽  
Author(s):  
Zhong Xiaoling ◽  
Li Feng ◽  
Tan Guiyuan ◽  
Yi Li ◽  
Zhao Jiaxin ◽  
...  
Keyword(s):  
Single Cell ◽  
Neural Development ◽  
Brain Regions ◽  
Disease Treatment ◽  
Sequencing Technologies ◽  
The Central Nervous System ◽  
Living Organisms ◽  
Analytical Tools ◽  
The Brain

Brain is the most complex organ of living organisms, as the celebrated cells in the brain, microglia play an indispensable role in the brain's immune microenvironment. Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative diseases and malignant of the central nervous system. However, little is known about the dynamic characteristics of microglia during development or disease conditions. Recently, the single-cell RNA sequencing technologies have become possible to characterize the heterogeneity of immune system in brain. But it posed computational challenges on integrating and utilizing the massive published datasets to dissect the spatiotemporal characterization of microglia. Here, we present microgliaST (bio-bigdata.hrbmu.edu.cn/MST), a database consisting of single-cell microglia transcriptomes across multiple brain regions and developmental periods. Based on high-quality microglia markers collected from published papers, we annotated and constructed human and mouse transcriptomic profiles of 273,374 microglias, comprising 12 regions, 12 periods and 3 conditions (normal, disease, treatment). In addition, MicrogliaST provides multiple analytical tools to elucidate the landscape of microglia under disorder conditions, conduct personalized difference analysis and spatiotemporal dynamic analysis. More importantly, microgliaST paves an ingenious way to the study of brain environment, and also provides insights into clinical therapy assessments.

scholarly journals Cerebrovascular responses of the rat brain to noxious stimuli as examined by functional near-infrared whole brain imaging

2012 ◽  
Vol 107 (10) ◽  
pp. 2853-2865 ◽  
Author(s):  
Ji-Wei He ◽  
Fenghua Tian ◽  
Hanli Liu ◽  
Yuan Bo Peng
Keyword(s):  
Brain Imaging ◽  
Near Infrared ◽  
Small Animal ◽  
Nir Spectroscopy ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Hemodynamic Changes ◽  
Whole Brain ◽  
Brain Hemodynamics

While near-infrared (NIR) spectroscopy has been increasingly used to detect stimulated brain activities with an advantage of dissociating regional oxy- and deoxyhemoglobin concentrations simultaneously, it has not been utilized much in pain research. Here, we investigated and demonstrated the feasibility of using this technique to obtain whole brain hemodynamics in rats and speculated on the functional relevance of the NIR-based hemodynamic signals during pain processing. NIR signals were emitted and collected using a 26-optodes array on rat's dorsal skull surface after the removal of skin. Following the subcutaneous injection of formalin (50 μl, 3%) into a hindpaw, several isolable brain regions showed hemodynamic changes, including the anterior cingulate cortex, primary/secondary somatosensory cortexes, thalamus, and periaqueductal gray ( n = 6). Time courses of hemodynamic changes in respective regions matched with the well-documented biphasic excitatory response. Surprisingly, an atypical pattern (i.e., a decrease in oxyhemoglobin concentration with a concomitant increase in deoxyhemoglobin concentration) was seen in phase II. In a separate group of rats with innocuous brush and noxious pinch of the same area ( n = 11), results confirmed that the atypical pattern occurred more likely in the presence of nociception than nonpainful stimulation, suggesting it as a physiological substrate when the brain processes pain. In conclusion, the NIR whole brain imaging provides a useful alternative to study pain in vivo using small-animal models. Our results support the notion that neurovascular response patterns depend on stimuli, bringing attention to the interpretation of vascular-based neuroimaging data in studies of pain.

scholarly journals Increased sensitivity to strong perturbations in a whole-brain model of LSD

2021 ◽  
Author(s):  
Beatrice M. Jobst ◽  
Selen Atasoy ◽  
Adrián Ponce-Alvarez ◽  
Ana Sanjuán ◽  
Leor Roseman ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
External Perturbation ◽  
Brain Regions ◽  
Lysergic Acid ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Whole Brain ◽  
Response Diversity ◽  
Brain States ◽  
The Brain

AbstractLysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain’s global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.HighlightsNovel offline perturbational method applied on functional magnetic resonance imaging (fMRI) data under the effect of lysergic acid diethylamide (LSD)Shift of brain’s global working point to more complex dynamics after LSD intakeConsistently longer recovery time after model perturbation under LSD influenceStrongest effects in resting state networks relevant for psychedelic experienceHigher response diversity across brain regions under LSD influence after an external in silico perturbation

scholarly journals A Graphlet-Based Topological Characterization of the Resting-State Network in Healthy People

2021 ◽  
Vol 15 ◽  
Author(s):  
Paolo Finotelli ◽  
Carlo Piccardi ◽  
Edie Miglio ◽  
Paolo Dulio
Keyword(s):  
Resting State ◽  
Brain Regions ◽  
Brain Network ◽  
Induced Subgraphs ◽  
Topological Characterization ◽  
Network Information ◽  
The Subject ◽  
Euclidean Distances ◽  
The Brain

In this paper, we propose a graphlet-based topological algorithm for the investigation of the brain network at resting state (RS). To this aim, we model the brain as a graph, where (labeled) nodes correspond to specific cerebral areas and links are weighted connections determined by the intensity of the functional magnetic resonance imaging (fMRI). Then, we select a number of working graphlets, namely, connected and non-isomorphic induced subgraphs. We compute, for each labeled node, its Graphlet Degree Vector (GDV), which allows us to associate a GDV matrix to each one of the 133 subjects of the considered sample, reporting how many times each node of the atlas “touches” the independent orbits defined by the graphlet set. We focus on the 56 independent columns (i.e., non-redundant orbits) of the GDV matrices. By aggregating their count all over the 133 subjects and then by sorting each column independently, we obtain a sorted node table, whose top-level entries highlight the nodes (i.e., brain regions) most frequently touching each of the 56 independent graphlet orbits. Then, by pairwise comparing the columns of the sorted node table in the top-k entries for various values of k, we identify sets of nodes that are consistently involved with high frequency in the 56 independent graphlet orbits all over the 133 subjects. It turns out that these sets consist of labeled nodes directly belonging to the default mode network (DMN) or strongly interacting with it at the RS, indicating that graphlet analysis provides a viable tool for the topological characterization of such brain regions. We finally provide a validation of the graphlet approach by testing its power in catching network differences. To this aim, we encode in a Graphlet Correlation Matrix (GCM) the network information associated with each subject then construct a subject-to-subject Graphlet Correlation Distance (GCD) matrix based on the Euclidean distances between all possible pairs of GCM. The analysis of the clusters induced by the GCD matrix shows a clear separation of the subjects in two groups, whose relationship with the subject characteristics is investigated.

Mental and behavioural disorders

2020 ◽  
pp. 333-365
Author(s):  
Fabrizio Benedetti
Keyword(s):  
Clinical Trials ◽  
Mental Disorders ◽  
Placebo Effect ◽  
Crucial Role ◽  
Drugs Of Abuse ◽  
Placebo Treatment ◽  
Brain Regions ◽  
Psychotherapeutic Interventions ◽  
Psychotherapeutic Outcome ◽  
The Brain

In this chapter some mental disorders are described. For example, in depression, fluoxetine treatment and a placebo treatment affect similar brain regions. In anxiety, patients’ expectations play a crucial role, as covert (unexpected) administration of anti-anxiety drugs is less effective than overt (expected) administration. The disruption of prefrontal executive control in Alzheimer’s disease decreases the magnitude of placebo responses. In addition, expectations appear to be particularly important when associated with the effects of drugs of abuse. Placebo effects appear to be powerful in psychotherapy as well, and the brain areas involved in the psychotherapeutic outcome are different from those involved in the placebo effect. As clinical trials for psychotherapeutic interventions represent a major problem, new recommendations are presented.

scholarly journals STAB: a spatio-temporal cell atlas of the human brain

2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Brain Regions ◽  
Molecular Characteristics ◽  
Great Effort ◽  
Brain Functions ◽  
Spatio Temporal ◽  
The Brain

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

Plastic Maps: The New Brain Cartographies of the 21th-Century Neurosciences

Nuncius ◽  
2017 ◽  
Vol 32 (2) ◽  
pp. 472-500
Author(s):  
Carmela Morabito
Keyword(s):  
Brain Mapping ◽  
Brain Regions ◽  
Individual Experience ◽  
Clinical Use ◽  
Functional Architecture ◽  
Early 19Th Century ◽  
New Models ◽  
Local Properties ◽  
The Brain ◽  
Over Time

Ever since the phrenological heads of the early 19th century, maps have translated into images our ideas, theories and models of the brain, making this organ at one and the same time scientific object and representation. Brain maps have always served as gateways for navigating and visualizing neuroscientific knowledge, and over time many different maps have been produced – firstly as tools to “read” and analyse the cerebral territory, then as instruments to produce new models of the brain. Over the last 150 years brain cartography has evolved from a way of identifying brain regions and localizing them for clinical use to an anatomical framework onto which information about local properties and functions can be integrated to provide a view of the brain’s structural and functional architecture. In this paper a historical and epistemological consideration of the topic is offered as a contribution to the understanding of contemporary brain mapping, based on the assumption that the brain continuously rewires itself in relation to individual experience.

scholarly journals Investigating the Cocaine-induced Reduction of Potassium Current on the Generation of Action Potentials Using a Computational Model

2021 ◽  
Author(s):  
Hadi Borjkhani ◽  
◽  
Mehdi Borjkhani ◽  
Morteza A. Sharif ◽  
◽  
...  
Keyword(s):  
Computational Model ◽  
Action Potentials ◽  
Potassium Current ◽  
Drugs Of Abuse ◽  
Potassium Conductance ◽  
Brain Regions ◽  
Chaotic Regime ◽  
Chaotic Oscillations ◽  
Sodium Potassium ◽  
The Brain

Introduction: Drugs of abuse, including cocaine, affect different brain regions and lead to pathological memories. These abnormal memories may occur due to the changes in synaptic transmissions or variations in synaptic properties of neurons. It has been shown that cocaine inhibits delayed rectifying potassium currents in affected regions of the brain and can have a role in the formation of pathological memories. Purpose: This study investigates how the change in the conductance of delayed rectifying potassium channels can affect the produced action potentials using a computational model. Methods: We present a computational model with different channels and receptors, including sodium, potassium, calcium, NMDARs, and AMPARs, which can produce burst-type action potentials. In the simulations, by changing the delayed rectifying potassium conductance bifurcation diagram is calculated. Conclusion: Results show that for a specific range of potassium conductance, a chaotic regime emerges in produced action potentials. These chaotic oscillations may play a role in inducing abnormal memories.

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