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

A functional computer modeling framework for post-traumatic stress disorder

Abstract only availablePost-traumatic stress disorder (PTSD) is a unique psychiatric condition in which the patient experiences diverse and intrusive psychological symptoms as a direct result of experiencing a traumatic event. As yet, no cure is available for PTSD, though some symptoms are treatable. A detailed, biologically realistic model of the specific neurological areas involved in generating the symptoms of PTSD would be useful in medical efforts to cure the condition. This model will aid in understanding of the mechanisms involved in producing the symptoms of PTSD as well as helping to identify crucial gaps in our knowledge of the brain systems involved in PTSD, thus providing goals for future research. The goal of this project was to identify the specific brain regions and circuits that would need to be included in a computer model for PTSD, and to begin creating this model. Modeling was begun using the GENESIS software package, which allows modeling of intracellular reactions, cellular potentials, signal transmission, and intercellular synaptic transmission. Thus large brain systems can be modeled in extreme detail. A multi-level framework for future GENESIS modeling was developed by generating a skeleton model that includes basic neurons and brain structures. This model can incorporate more detailed information at all levels from genetic and proteomic to intercellular and circuitry-related as this information becomes available.NSF-REU Biosystems Modelin

A prospective study to evaluate functional results of PHILOS locking plate system in management of proximal humerus fractures in adults

Background: Various management options are available for management of proximal humerus fractures where PHILOS plating is one of them. But data available in literature on its use and efficacy in management of all types of proximal humerus fractures is still dicey. So, we through our study attempted to grow our knowledge regarding its functional results, complication rates, etc. for use in coming future.Methods: 30 patients with proximal humerus fractures classified on the basis of Neer’s classification were included in study who were operated from 2018 to 2020 at our institute. These patients were operated by PHILOS locking plate system with either delto-pectoral or trans-deltoid approach and they are followed up at regular intervals to assess them clinicoradiologicallly and functionally by Neer’s criteria.Results: In our study we found maximum incidence of these fracture between age group of 40-80 years (66.66%) with male to female ratio of 2:1 with 19 patients having left sided and 11 patients having right sided proximal humerus fracture. Complications were found in 11 patients (36.67%). Functional evaluation was carried out using Neer’s criteria at final follow up which came to excellent results in 3, satisfactory in 18, unsatisfactory in 7 and failure in 2 patients. Average time of fracture union was 12.62 weeks.Conclusions: PHILOS locking plate system serves good purpose in management of fractures of proximal humerus but requires trained faculty to do this operation who has detailed knowledge about shoulder anatomy and mechanism of injury to reduce complications associated with this type of modality

Computational model of extracellular glutamate in the nucleus accumbens predicts neuroadaptations by chronic cocaine

Notice: this is the author's version of a work that was accepted for publication in Neuroscience. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuroscience, Vol. 158, Issue #4 (2008) doi:10.1016/j.neuroscience.2008.11.014 . http://journals.elsevier.com/03064522/neuroscience/Chronic cocaine administration causes instability in extracellular glutamate in the nucleus accumbens that is thought to contribute to the vulnerability to relapse. A computational framework was developed to model glutamate in the extracellular space, including synaptic and nonsynaptic glutamate release, glutamate elimination by glutamate transporters and diffusion, and negative feedback on synaptic release via metabotropic glutamate receptors (mGluR2/3). This framework was used to optimize the geometry of the glial sheath surrounding excitatory synapses, and by inserting physiological values, accounted for known stable extracellular, extrasynaptic concentrations of glutamate measured by microdialysis and glutamatergic tone on mGluR2/3. By using experimental values for cocaine-induced reductions in cystine-glutamate exchange and mGluR2/3 signaling, the computational model successfully represented the experimentally observed increase in glutamate that is seen in rats during cocaine-seeking. This model provides a mathematical framework for describing how pharmacological or pathological conditions influence glutamate transmission measured by microdialysis

Coregulation of Ion Channel Conductances Preserves Output in a Computational Model of a Crustacean Cardiac Motor Neuron

This item also falls under Society for Neuroscience copyright. For more information, please visit http://www.jneurosci.org/cgi/content/full/30/25/8637?maxtoshow=&hits=10&RESULTFORMAT=1&author1=nair&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT&eaf . Link active as of 1/29/2011. Link maintenance is the responsibility of the Society for Neuroscience.Digital Object Identifier 10.1523/JNEUROSCI.6435-09.2010Similar activity patterns at both neuron and network levels can arise from different combinations of membrane and synaptic conductance values. A strategy by which neurons may preserve their electrical output is via cell type-dependent balances of inward and outward currents. Measurements of mRNA transcripts that encode ion channel proteins within motor neurons in the crustacean cardiac ganglion recently revealed correlations between certain channel types. To determine whether balances of intrinsic currents potentially resulting from such correlations preserve certain electrical cell outputs, we developed a nominal biophysical model of the crustacean cardiac ganglion using biological data. Predictions from the nominal model showed that coregulation of ionic currents may preserve the key characteristics of motor neuron activity. We then developed a methodology of sampling a multidimensional parameter space to select an appropriate model set for meaningful comparison with variations in correlations seen in biological datasets