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.

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 Origin of Slow Spontaneous Resting-State Neuronal Fluctuations in Brain Networks

2017 ◽  
Author(s):  
Giri P. Krishnan ◽  
Oscar C. González ◽  
Maxim Bazhenov
Keyword(s):  
Computational Model ◽  
Resting State ◽  
Large Scale ◽  
Brain Activity ◽  
Brain Regions ◽  
Brain Network ◽  
Ion Concentration ◽  
Brain State ◽  
The Brain

AbstractResting or baseline state low frequency (0.01-0.2 Hz) brain activity has been observed in fMRI, EEG and LFP recordings. These fluctuations were found to be correlated across brain regions, and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (< 0.05 Hz) fluctuations could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra and extracellular K+ and Na+ and intracellular Cl- ions, Na+/K+ exchange pump, and KCC2 co-transporter. In the network model representing resting awake-like brain state, we observed slow fluctuations in the extracellular K+ concentration, Na+/K+ pump activation, firing rate of neurons and local field potentials. Holding K+ concentration constant prevented generation of these fluctuations. The amplitude and peak frequency of this activity were modulated by Na+/K+ pump, AMPA/GABA synaptic currents and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state networks observed in vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are observed as the resting-state fluctuations in fMRI and EEG recordings.

scholarly journals Action Video Game Experience Related to Altered Large-Scale White Matter Networks

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Diankun Gong ◽  
Weiyi Ma ◽  
Jinnan Gong ◽  
Hui He ◽  
Li Dong ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Deficits ◽  
Video Game ◽  
Neural Plasticity ◽  
Action Potentials ◽  
Large Scale ◽  
Brain Regions ◽  
Research Attention ◽  
Cognitive Benefits ◽  
The Brain

With action video games (AVGs) becoming increasingly popular worldwide, the cognitive benefits of AVG experience have attracted continuous research attention over the past two decades. Research has repeatedly shown that AVG experience can causally enhance cognitive ability and is related to neural plasticity in gray matter and functional networks in the brain. However, the relation between AVG experience and the plasticity of white matter (WM) network still remains unclear. WM network modulates the distribution of action potentials, coordinating the communication between brain regions and acting as the framework of neural networks. And various types of cognitive deficits are usually accompanied by impairments of WM networks. Thus, understanding this relation is essential in assessing the influence of AVG experience on neural plasticity and using AVG experience as an interventional tool for impairments of WM networks. Using graph theory, this study analyzed WM networks in AVG experts and amateurs. Results showed that AVG experience is related to altered WM networks in prefrontal networks, limbic system, and sensorimotor networks, which are related to cognitive control and sensorimotor functions. These results shed new light on the influence of AVG experience on the plasticity of WM networks and suggested the clinical applicability of AVG experience.

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 Transcriptional mechanisms of drug addiction

2019 ◽  
Vol 21 (4) ◽  
pp. 379-387 ◽  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Noncoding Rnas ◽  
Brain Regions ◽  
Chromatin Modifications ◽  
Addictive Drugs ◽  
Functional Remodeling ◽  
Brain Reward ◽  
The Brain

Drugs of abuse can modify gene expression in brain reward and motivation centers, which contribute to the structural and functional remodeling of these circuits that impacts the emergence of a state of addiction. Our understanding of how addictive drugs induce transcriptomic plasticity in addiction-relevant brain regions, particularly in the striatum, has increased dramatically in recent years. 􀀬ntracellular signaling machineries, transcription factors, chromatin modifications, and regulatory noncoding RNAs have all been implicated in the mechanisms through which addictive drugs act in the brain. 􀀫ere, we briefly summarize some of the molecular mechanisms through which drugs of abuse can exert their transcriptional effects in the brain region, with an emphasis on the role for microRNAs in this process.

Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle Based Targeted Drug Delivery System

2020 ◽  
Vol 21 ◽  
Author(s):  
Sayed Md Mumtaz ◽  
Gautam Bhardwaj ◽  
Shikha Goswami ◽  
Rajiv Kumar Tonk ◽  
Ramesh K. Goyal ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Glioblastoma Multiforme ◽  
Drug Delivery System ◽  
Delivery System ◽  
Genetic Disorder ◽  
Drug Regimen ◽  
Brain Regions ◽  
Radio Therapy ◽  
Novel Drug ◽  
The Brain

: The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhort tumor of star-shaped glial cell in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorder like neurofibromatosis and schwanomatosis which develop the tumor in the nervous system. The management of GBM with chemo-radio therapy leads to resistance and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind failure of drugs are due to DNA alkylation in cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bio-active compounds from plants known as phytochemicals, serve as vital sources for anti-cancer drugs. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, podophyllotoxin analogs, camptothecin, curcumin, aloe emodin, quercetin, berberine e.t.c. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancers. However the challenges posed by the presence of BBB/BBTB to restrict passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review we integrated nanotech as novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.

Neuro-Clinical Signatures of Language Impairments: A Theoretical Framework for Function-to-structure Mapping in Clinics

2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller
Keyword(s):  
Brain Mapping ◽  
Theoretical Framework ◽  
Brain Regions ◽  
Language Impairments ◽  
Structure Mapping ◽  
Language Functions ◽  
The Past ◽  
Language Recovery ◽  
The Brain ◽  
Bow Tie

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.

scholarly journals Neuroinflammation and protein pathology in Parkinson’s disease dementia

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Antonina Kouli ◽  
Marta Camacho ◽  
Kieren Allinson ◽  
Caroline H. Williams-Gray
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Lymphocytes ◽  
Substantia Nigra ◽  
Amyloid Β ◽  
Brain Regions ◽  
Parkinson’S Disease Dementia ◽  
Activated Microglia ◽  
Cell Counts ◽  
The Brain

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

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