The impairment of the prefrontal cortex due to high levels of dopamine and norepinephrine in relation to ADHD

Abstract only availableAttention- Deficit/ Hyperactivity Disorder (ADHD) affects many people from various backgrounds; however, not much is known about the disorder aside from clinical symptoms. Researchers are just beginning to dissect ADHD and its effects on the brain, specifically in the prefrontal cortex (PFC) region. The PFC controls attention, motivation, planning, and most importantly working memory. Working memory is temporary storage for short-term memory; it is essential for sequencing tasks and assists with internalized language. The working hypothesis implicates increased levels of Dopamine (DA) and Norepinephrine (NE) in the impairment of PFC cells, leading to inhibition of working memory, and the development of disorder. The interaction of pyramidal neurons in the various layers of the PFC is studied in order to discover the impact of the network level plasticity on the disorder. This interdisciplinary research examines the relative impact of DA and NE, and the relevant pathway interactions on affected cells. Relevant neurophysiological experimentation data is used to examine mechanisms of ADHD in rat PFC, and to develop a computational model of the pyramidal neurons located in the six layers of the PFC. An analysis of the cognitive effects of ADHD via computational modeling may predict brain function, uncover emergent properties, and assist in the development of treatment. Reliable computational modeling will help save money and time as well as avoid the frequent use of human trial subjects.NSF-REU Program in Biosystems Modeling and Analysi

Mathematical modeling of obsessive compulsive disorder

Abstract only availableWe all at some point become fixated with certain actions or ideas. However, for the two to three percent of the world population with obsessive compulsive disorder (OCD), these fixations become so intense that the individual is debilitated. The exact obsessions the patients experience vary from case to case, but most obsessions fall within five categories: contamination, hoarding, ordering / symmetry, religious, and danger. Suffers of OCD usually recognize that their obsessions are unreasonable and illogical, yet are unable to prevent them. To alleviate these obsessions, the patients perform compulsions or ritualistic acts. Functional imaging studies have consistently implicated the caudate nucleus, the anterior cingulate gyrus, and the orbitofrontal cortex as the major causes of OCD. All three parts of the brain show hyperactivity in OCD patients and decreased activity of patients post treatment. The caudate nucleus is a part of the basal ganglia and is connected to the neocortex through a series of thalamocortical loops. These loops start in certain parts of the neocortex, such as the anterior cingulate gyrus and the orbitofrontal cortex, and run through the basal ganglia to the thalamus and then back to the neocortex. OCD patients appear to become stuck in one of these loops. In an attempt to better understand the loops, a mathematical model is being constructed to represent the OCD network pathway. GEneral NEural SImulation System (GENESIS) is a computer program being employed in the construction of the network. Currently, the framework for the OCD model has been constructed. This model will be enhanced in the coming months to create a more biologically realistic model. We hope to be able to show the reoccurring loop of OCD patients. Ultimately, a better understanding of the thalamocortical loop may lead to better treatment of OCD.NSF-REU Biosystems Modelin

How do we know that we have Obsessive-Compulsive Disorder?

Abstract only availableThe brain is a network of neurons that control our pleasure, emotion, motivation and is important for all types of learning. The objective of the overall research in the OCD's group is to examine the changes in brain circuit, or neuroplasticity that cause Obsessive-Compulsive Disorder (OCD). Such interdisciplinary study requires information of many types: neuroanatomy (relevant regions), neurophysiology (cellular firing) and neurochemistry (neurotransmitters). The specific objectives were to assist with hypothesis development for OCD, to systematically collect information listed above and to work with modelers to develop a computational model for OCD in primates. The basis of this research is the hypothesis that the normal interactions of prefrontal cortical neurons with basal ganglia, thalamus, and amygdala are altered due to OCD, although the primary alterations and interactions remain unknown. Examination of the neuroplastic processes in these pathways will help uncover mechanisms of OCD. This analysis is facilitated by a two-tiered mathematical model for the representation of the brain circuits. At the cellular level (first tier), models can serve to highlight the mechanisms of neuroplasticity affecting firing of the neurons in the circuit. At the network level (second tier) the interactive effects between the brain regions can be studied. Data from primate and rat literature will be used to develop the model. A reliable computation model will help analyze the underlying causes systematically to comprehend the cellular/molecular mechanisms of OCD. After validation, the model can be used for predictive purposes including drug design and to further our understanding of the brain.NSF-REU Program in Biosystems Modeling and Analysi

Modeling firing patterns of medium spiny neurons

Abstract only availableThe alternation in firing patterns of medium spiny neurons of the Nucleus Accumbens , a key structure in the brain's reward pathway, due to chronic and acute cocaine use was investigated through change of ion channel and receptor properties. Cocaine causes cellular changes both in the proteomic and genomic level in medium spiny neurons by increasing the concentration of the neurotransmitter Dopamine in the synaptic region; therefore generating a biologically realistic model of the nucleus accumbens is necessary. Medium spiny neurons exhibit bistability, meaning that they pass through up (polarized) and down (hyperpolarized) phases of membrane potential periodically. Only in the up state will a cell fire a train of action potentials. First step in the long term project of studying cocaine addiction is modeling this complex firing pattern and quantifying what can cause it to change. This task required figuring out all the key ion channels and receptors that mediate bistability, the equations that govern their behavior, and finally putting everything together in a computer program called GENESIS.NSF-REU Biosystems Modelin

A prospective study of management of tibial plateau fractures by locking compression plate in adults

Background: Tibial plateau fractures are one of the most complex and disabling fractures of the knee. The tibial plateau is important in transmitting load through the knee. These fractures need a meticulous management protocol in order to minimize patient's disability in range of movement, stability and reducing the risk of documented complications. The aim of the present study is to study the outcome of tibial plateau fractures managed with a locked compression plate.Methods: This study was conducted at a tertiary-care medical college and hospital, Aurangabad specializing in post-graduate training, where all patients who underwent surgical treatment between September 2018 and October 2020 were included. Patients were assessed using the knee society score (KSS). These evaluations were done at 1, 3, 6, 9 and 12 months.Results: In our study we included 55 patients out of which we found union in 98% of patients with 83% of patients showing good flexion at knee joint (>110 degrees). 85% patients achieved union within 6 months. An excellent KSS grade was seen in 38.2% patients with another 43.6% showing good outcome. 4 patients showed infection and 1 showed non-union. A single case of malunion was seen in our study.Conclusions: Locked compression plates in tibial plateau fractures has revolutionized the way these fractures are managed. Anatomic reduction is of utmost importance. Early physiotherapy which plays key role in preventing knee stiffness, use of bone grafts and good fixation are important for successful outcome

Extracellular Glutamate: Functional Compartments Operate in Different Concentration Ranges

Extracellular glutamate of glial origin modulates glial and neuronal glutamate release and synaptic plasticity. Estimates of the tonic basal concentration of extracellular glutamate range over three orders of magnitude (0.02–20 μM) depending on the technology employed to make the measurement. Based upon binding constants for glutamate receptors and transporters, this range of concentrations translates into distinct physiological and pathophysiological roles for extracellular glutamate. Here we speculate that the difference in glutamate measurements can be explained if there is patterned membrane surface expression of glutamate release and transporter sites creating extracellular subcompartments that vary in glutamate concentration and are preferentially sampled by different technologies

Morphological Changes and Antihyperglycemic Effect of M. champaca Leaves Extract on Beta-cell in Alloxan Induced Diabetic Rats

Rapidly increasing diabetes mellitus is becoming a serious threat to mankind health in all parts of the world. The control of treatment depends upon the availability medicines without any side effects. Traditional anti-diabetic plants, which can counter the high cost and poor availability of the current medicines. So an attempt was made to study the beneficial effects of M. champaca leaves extracts on pancreas morphology of diabetic rat model. M. champaca leaf extracts (Ethanolic, Chloroform and Petroleum Ether) were administered at dose levels of 200 mg/kg body weight orally. A positive control and normal group received distilled water orally. Blood samples were collected from retro-orbital plexus of each rat and analyzed by GOD-POD test. After 21 days treatment among different extracts, the maximum reduction of serum glucose level showed significantly (