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basal ganglia model

Elżbieta Lorenc-Koci, Anna Czarnecka, Kinga Kamińska, Joanna Knutelska, Małgorzata Zygmunt, Magdalena Dudek
BACKGROUND: Interaction between dopaminergic and nitrergic neurotransmission in the brain plays a crucial role in the control of motor function and in the regulation of blood pressure (BP). In Parkinson's disease (PD), dopaminergic denervation of the striatum leads to disturbances in the nitrergic system in the basal ganglia. Recently, it has been demonstrated that addition of a low dose of the nitric oxide donor molsidomine to l-DOPA therapy improves dopaminergic neurotransmission in the denervated nigrostriatal system and weakens dyskinesias in rodent models of the disease...
September 28, 2016: Pharmacological Reports: PR
Sohair M Khojah, Anthony P Payne, Dagmara McGuinness, Paul G Shiels
There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16(Ink4a), Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16(INK4a) expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions...
October 17, 2016: Cells
A Kibleur, G Gras-Combe, D Benis, J Bastin, T Bougerol, S Chabardès, M Polosan, O David
High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical-cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task...
October 18, 2016: Translational Psychiatry
Naser Amini, Nasim Vousooghi, Mansoureh Soleimani, Ali Samadikuchaksaraei, Mehdi Akbari, Hosein Safakheil, Pezhman Atafimanesh, Ali Shahbazi, Peiman Brouki Milan, Sara Ramezani, Masoud Mozafari, Mohammad Taghi Joghataei
INTRODUCTION: Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin. METHODS: For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1 g) were used...
October 13, 2016: Journal of Pharmacological and Toxicological Methods
Maximilian H Beck, Jens K Haumesser, Johanna Kühn, Jennifer Altschüler, Andrea A Kühn, Christoph van Riesen
Abnormally enhanced beta oscillations have been found in deep brain recordings from human Parkinson's disease (PD) patients and in animal models of PD. Recent correlative evidence suggests that beta oscillations are related to disease-specific symptoms such as akinesia and rigidity. However, this hypothesis has also been repeatedly questioned by studies showing no changes in beta power in animal models using an acute pharmacologic dopamine blockade. To further investigate the temporal dynamics of exaggerated beta synchrony in PD, we investigated the reserpine model, which is characterized by an acute and stable disruption of dopamine transmission, and compared it to the chronic progressive 6-hydroxydopamine (6-OHDA) model...
October 12, 2016: Experimental Neurology
Timothy J Hohman, Logan Dumitrescu, Nancy J Cox, Angela L Jefferson
Preclinical Alzheimer's disease (AD) is characterized by amyloid deposition in the absence of overt clinical impairment. There is substantial heterogeneity in the long-term clinical outcomes among amyloid positive individuals, yet limited work has focused on identifying molecular factors driving resilience from amyloid-related cognitive impairment. We apply a recently developed predicted gene expression analysis (PrediXcan) to identify genes that modify the association between baseline amyloid deposition and longitudinal cognitive changes...
October 14, 2016: Brain Imaging and Behavior
Henrik B W Larsson, Mark B Vestergaard, Ulrich Lindberg, Helle K Iversen, Stig P Cramer
PURPOSE: Capillary transit time heterogeneity, measured as CTH, may set the upper limit for extraction of substances in brain tissue, e.g., oxygen. The purpose of this study was to investigate the feasibility of dynamic contrast-enhanced T1 weighted MRI (DCE-MRI) at 3 Tesla (T), in estimating CTH based on a gamma-variate model of the capillary transit time distribution. In addition, we wanted to investigate if a subtle increase of the blood-brain barrier permeability can be incorporated into the model, still allowing estimation of CTH...
October 12, 2016: Journal of Magnetic Resonance Imaging: JMRI
Omid Talakoub, Bogdan Neagu, Kaviraja Udupa, Eric Tsang, Robert Chen, Milos R Popovic, Willy Wong
We are interested in characterizing how brain networks interact and communicate with each other during voluntary movements. We recorded electrical activities from the globus pallidus pars interna (GPi), subthalamic nucleus (STN) and the motor cortex during voluntary wrist movements. Seven patients with dystonia and six patients with Parkinson's disease underwent bilateral deep brain stimulation (DBS) electrode placement. Local field potentials from the DBS electrodes and scalp EEG from the electrodes placed over the motor cortices were recorded while the patients performed externally triggered and self-initiated movements...
October 11, 2016: Scientific Reports
Johan Lundberg, Emma Jussing, Zhenjiang Liu, Qingda Meng, Martin Rao, Erik Samén, Rikard Grankvist, Peter Damberg, Ernest Dodoo, Markus Maeurer, Staffan Holmin
Glioblastoma (GBM) is the most common and most severe form of malignant gliomas. The prognosis is poor with current combinations of pharmaceutical-, radio- and surgical therapy. A continuous search for new treatments has therefore been ongoing for many years. Therapy with tumor-infiltrating lymphocytes (TIL) is a clinically promising strategy to treat various cancers, including GBM. An endovascular intra-arterial injection of TIL as a method of delivery may, instead of intravenous infusion, result in better retention of effector cells within the tumor...
October 7, 2016: Cell Transplantation
Omar S Mabrouk
Parkinson's disease (PD) is a progressive neurodegenerative disorder that compromises multiple neurochemical substrates including dopamine, norepinephrine, serotonin, acetylcholine, and glutamate systems. Loss of these transmitter systems initiates a cascade of neurological deficits beginning with motor function and ending with dementia. Current therapies primarily address the motor symptoms of the disease via dopamine replacement therapy. Exogenous dopamine replacement brings about additional challenges since after years of treatment it almost invariably gives rise to dyskinesia as a side effect...
October 8, 2016: Handbook of Experimental Pharmacology
Anna Castrioto, Odeya Marmor, Marc Deffains, Dafna Willner, Eduard Linetsky, Hagai Bergman, Zvi Israel, Renana Eitan, David Arkadir
Classical rate models of basal ganglia circuitry associate discharge rate of the globus pallidus external and internal segments (GPe, GPi respectively) solely with dopaminergic state and predict an inverse ratio between the discharge rates of the two pallidal segments. In contrast, the effects of other rate modulators such as general anesthesia (GA) on this ratio have been ignored. To respond to this need, we recorded the neuronal activity in the GPe and GPi in awake and anesthetized human patients with dystonia (57 and 53 trajectories respectively) and in awake patients with Parkinson's disease (PD, 16 trajectories) undergoing deep brain stimulation procedures...
September 26, 2016: European Journal of Neuroscience
Erwin B Montgomery
Theories impact the movement disorders clinic, not only affecting the development of new therapies but determining how current therapies are used. Models are theories that are procedural rather than declarative. Theories and models are important because, as argued by Kant, one cannot know the thing-in-itself (das Ding an sich) and only a model is knowable. Further, biological variability forces higher level abstraction relevant for all variants. It is that abstraction that is raison d'être of theories and models...
2016: Frontiers in Human Neuroscience
Alekhya Mandali, V Srinivasa Chakravarthy
Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN...
2016: Frontiers in Human Neuroscience
Eitan Schechtman, Maria Imelda Noblejas, Aviv D Mizrahi, Omer Dauber, Hagai Bergman
The basal ganglia (BG) network has been divided into interacting actor and critic components, modulating the probabilities of different state-action combinations through learning. Most models of learning and decision making in the BG focus on the roles of the striatum and its dopaminergic inputs, commonly overlooking the complexities and interactions of BG downstream nuclei. In this study, we aimed to reveal the learning-related activity of the external segment of the globus pallidus (GPe), a downstream structure whose computational role has remained relatively unexplored...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Nicholas T Van Dam, David O'Connor, Enitan T Marcelle, Erica J Ho, R Cameron Craddock, Russell H Tobe, Vilma Gabbay, James J Hudziak, F Xavier Castellanos, Bennett L Leventhal, Michael P Milham
BACKGROUND: Data-driven approaches can capture behavioral and biological variation currently unaccounted for by contemporary diagnostic categories, thereby enhancing the ability of neurobiological studies to characterize brain-behavior relationships. METHODS: A community-ascertained sample of individuals (N = 347, 18-59 years of age) completed a battery of behavioral measures, psychiatric assessment, and resting-state functional magnetic resonance imaging in a cross-sectional design...
July 19, 2016: Biological Psychiatry
Ariana Q Farrand, Rebecca A Gregory, Cristina M Bäckman, Kristi L Helke, Heather A Boger
Mitochondrial dysfunction has been implicated in the degeneration of dopamine (DA) neurons in Parkinson's disease (PD). In addition, animal models of PD utilizing neurotoxins, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have shown that these toxins disrupt mitochondrial respiration by targeting complex I of the electron transport chain, thereby impairing DA neurons in these models. A MitoPark mouse model was created to mimic the mitochondrial dysfunction observed in the DA system of PD patients...
September 19, 2016: Brain Research
Adam M Chekroud, Geetha Anand, Jean Yong, Michael Pike, Holly Bridge
AIM: Opsoclonus-myoclonus syndrome (OMS) is a rare, poorly understood condition that can result in long-term cognitive, behavioural, and motor sequelae. Several studies have investigated structural brain changes associated with this condition, but little is known about changes in function. This study aimed to investigate changes in brain functional connectivity in patients with OMS. METHOD: Seven patients with OMS and 10 age-matched comparison participants underwent 3T magnetic resonance imaging (MRI) to acquire resting-state functional MRI data (whole-brain echo-planar images; 2mm isotropic voxels; multiband factor ×2) for a cross-sectional study...
September 23, 2016: Developmental Medicine and Child Neurology
P B Tran, R E Miller, S Ishihara, R J Miller, A M Malfait
OBJECTIVE: Microgliosis, the activation of microglial cells, is thought to contribute to synaptic transmission in the dorsal horn and thereby promote chronic pain. The primary aim of this study was to document the temporal profile of dorsal horn microgliosis after destabilization of the medial meniscus (DMM) in wild type (WT) and Adamts5 null mice. Since neuronal fractalkine (CX3CL1) contributes to microgliosis, we assessed its release from dorsal root ganglia (DRG) cultures after DMM...
September 16, 2016: Osteoarthritis and Cartilage
Takafumi Arakaki, Séverine Mahon, Stéphane Charpier, Arthur Leblois, David Hansel
UNLABELLED: Absence seizures are characterized by brief interruptions of conscious experience accompanied by oscillations of activity synchronized across many brain areas. Although the dynamics of the thalamocortical circuits are traditionally thought to underlie absence seizures, converging experimental evidence supports the key involvement of the basal ganglia (BG). In this theoretical work, we argue that the BG are essential for the maintenance of absence seizures. To this end, we combine analytical calculations with numerical simulations to investigate a computational model of the BG-thalamo-cortical network...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
M Jaber
SCIENTIFIC BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning...
September 8, 2016: L'Encéphale
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