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basal ganglia model

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https://www.readbyqxmd.com/read/28073788/dopamine-controls-parkinson-s-tremor-by-inhibiting-the-cerebellar-thalamus
#1
Michiel F Dirkx, Hanneke E M den Ouden, Esther Aarts, Monique H M Timmer, Bastiaan R Bloem, Ivan Toni, Rick C Helmich
Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor...
January 9, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28062203/semi-mechanistic-computer-simulation-of-psychotic-symptoms-in-schizophrenia-with-a-model-of-a-humanized-cortico-striatal-thalamocortical-loop
#2
Athan Spiros, Patrick Roberts, Hugo Geerts
Despite new insights into the pathophysiology of schizophrenia and clinical trials with highly selective drugs, no new therapeutic breakthroughs have been identified. We present a semi-mechanistic Quantitative Systems Pharmacology (QSP) computer model of a biophysically realistic cortical-striatal-thalamo-cortical loop. The model incorporates the direct, indirect and hyperdirect pathway of the basal ganglia and CNS drug targets that modulate neuronal firing, based on preclinical data about their localization and coupling to voltage-gated ion channels...
January 3, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28053151/optimized-temporal-pattern-of-brain-stimulation-designed-by-computational-evolution
#3
David T Brocker, Brandon D Swan, Rosa Q So, Dennis A Turner, Robert E Gross, Warren M Grill
Brain stimulation is a promising therapy for several neurological disorders, including Parkinson's disease. Stimulation parameters are selected empirically and are limited to the frequency and intensity of stimulation. We varied the temporal pattern of deep brain stimulation to ameliorate symptoms in a parkinsonian animal model and in humans with Parkinson's disease. We used model-based computational evolution to optimize the stimulation pattern. The optimized pattern produced symptom relief comparable to that from standard high-frequency stimulation (a constant rate of 130 or 185 Hz) and outperformed frequency-matched standard stimulation in a parkinsonian rat model and in patients...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28039987/a-neural-mass-model-of-basal-ganglia-nuclei-simulates-pathological-beta-rhythm-in-parkinson-s-disease
#4
Fei Liu, Jiang Wang, Chen Liu, Huiyan Li, Bin Deng, Chris Fietkiewicz, Kenneth A Loparo
An increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with movement disorder, such as Parkinson's disease. The motor cortex and an excitatory-inhibitory neuronal network composed of the subthalamic nucleus (STN) and the external globus pallidus (GPe) are thought to play an important role in the generation of these oscillations. In this paper, we propose a neuron mass model of the basal ganglia on the population level that reproduces the Parkinsonian oscillations in a reciprocal excitatory-inhibitory network...
December 2016: Chaos
https://www.readbyqxmd.com/read/28039797/impulsivity-and-aggression-mediate-regional-brain-responses-in-borderline-personality-disorder-an-fmri-study
#5
Paul H Soloff, Kristy Abraham, Ashley Burgess, Karthik Ramaseshan, Asadur Chowdury, Vaibhav A Diwadkar
Fronto-limbic brain networks involved in regulation of impulsivity and aggression are abnormal in Borderline Personality Disorder (BPD). However, it is unclear whether, or to what extent, these personality traits actually modulate brain responses during cognitive processing. Using fMRI, we examined the effects of trait impulsivity, aggression, and depressed mood on regional brain responses in 31 female BPD and 25 control subjects during a Go No-Go task using Ekman faces as targets. First-level contrasts modeled effects of negative emotional context...
December 16, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/28024798/zonisamide-attenuates-lactacystin-induced-parkinsonism-in-mice-without-affecting-system-xc
#6
Eduard Bentea, Joeri Van Liefferinge, Lise Verbruggen, Katleen Martens, Sho Kobayashi, Lauren Deneyer, Thomas Demuyser, Giulia Albertini, Katrien Maes, Hideyo Sato, Ilse Smolders, Jan Lewerenz, Ann Massie
Zonisamide (ZNS), an anticonvulsant drug exhibiting symptomatic effects in Parkinson's disease (PD), was recently reported to exert neuroprotection in rodent models. One of the proposed neuroprotective mechanisms involves increased protein expression of xCT, the specific subunit of the cystine/glutamate antiporter system xc(-), inducing glutathione (GSH) synthesis. Here, we investigated the outcome of ZNS treatment in a mouse model of PD based on intranigral proteasome inhibition, and whether the observed effects would be mediated by system xc(-)...
December 24, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28019687/improving-with-practice-a-neural-model-of-mathematical-development
#7
Sean Aubin, Aaron R Voelker, Chris Eliasmith
The ability to improve in speed and accuracy as a result of repeating some task is an important hallmark of intelligent biological systems. Although gradual behavioral improvements from practice have been modeled in spiking neural networks, few such models have attempted to explain cognitive development of a task as complex as addition. In this work, we model the progression from a counting-based strategy for addition to a recall-based strategy. The model consists of two networks working in parallel: a slower basal ganglia loop and a faster cortical network...
December 26, 2016: Topics in Cognitive Science
https://www.readbyqxmd.com/read/28018198/time-processing-and-motor-control-in-movement-disorders
#8
REVIEW
Laura Avanzino, Elisa Pelosin, Carmelo M Vicario, Giovanna Lagravinese, Giovanni Abbruzzese, Davide Martino
The subjective representation of "time" is critical for cognitive tasks but also for several motor activities. The neural network supporting motor timing comprises: lateral cerebellum, basal ganglia, sensorimotor and prefrontal cortical areas. Basal ganglia and associated cortical areas act as a hypothetical "internal clock" that beats the rhythm when the movement is internally generated. When timing information is processed to make predictions on the outcome of a subjective or externally perceived motor act, cerebellar processing and outflow pathways appear to be primarily involved...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28011948/molecular-hydrogen-affords-neuroprotection-in-a-translational-piglet-model-of-hypoxic-ischemic-encephalopathy
#9
J Nemeth, V Toth-Szuki, V Varga, V Kovacs, G Remzso, F Domoki
Hypoxic-ischemic encephalopathy (HIE) is the major consequence of perinatal asphyxia (PA) in term neonates. Although the newborn piglet is an accepted large animal PA/HIE model, there is no consensus on PA-induction methodology to produce clinically relevant HIE. We aimed to create and to characterize a novel PA model faithfully reproducing all features of asphyxiation including severe hypercapnia resulting in HIE, and to test whether H2 is neuroprotective in this model. Piglets were anaesthetised, artificially ventilated, and intensively monitored (electroencephalography, core temperature, O2 saturation, arterial blood pressure and blood gases)...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28011263/prenatal-alcohol-exposure-potentiates-chronic-neuropathic-pain-spinal-glial-and-immune-cell-activation-and-alters-sciatic-nerve-and-drg-cytokine-levels
#10
Shahani Noor, Joshua J Sanchez, Arden G Vanderwall, Melody S Sun, Jessie R Maxwell, Suzy Davies, Lauren L Jantzie, Timothy R Petersen, Daniel D Savage, Erin D Milligan
A growing body of evidence indicates that prenatal alcohol exposure (PAE) may predispose individuals to secondary medical disabilities later in life. Animal models of PAE reveal neuroimmune sequelae such as elevated brain astrocyte and microglial activation with corresponding region-specific changes in immune signaling molecules such as cytokines and chemokines. The aim of this study was to evaluate the effects of moderate PAE on the development and maintenance of allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in adult male rat offspring...
December 20, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28002987/decision-making-under-uncertainty-in-a-spiking-neural-network-model-of-the-basal-ganglia
#11
Charlotte Héricé, Radwa Khalil, Marie Moftah, Thomas Boraud, Martin Guthrie, André Garenne
The mechanisms of decision-making and action selection are generally thought to be under the control of parallel cortico-subcortical loops connecting back to distinct areas of cortex through the basal ganglia and processing motor, cognitive and limbic modalities of decision-making. We have used these properties to develop and extend a connectionist model at a spiking neuron level based on a previous rate model approach. This model is demonstrated on decision-making tasks that have been studied in primates and the electrophysiology interpreted to show that the decision is made in two steps...
December 21, 2016: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/27995895/early-dysfunction-and-progressive-degeneration-of-the-subthalamic-nucleus-in-mouse-models-of-huntington-s-disease
#12
Jeremy F Atherton, Eileen L McIver, Matthew Rm Mullen, David L Wokosin, D James Surmeier, Mark D Bevan
The subthalamic nucleus (STN) is an element of cortico-basal ganglia-thalamo-cortical circuitry critical for action suppression. In Huntington's disease (HD) action suppression is impaired, resembling the effects of STN lesioning or inactivation. To explore this potential linkage, the STN was studied in BAC transgenic and Q175 knock-in mouse models of HD. At <2 and 6 months of age autonomous STN activity was impaired due to activation of KATP channels. STN neurons exhibited prolonged NMDA receptor-mediated synaptic currents, caused by a deficit in glutamate uptake, and elevated mitochondrial oxidant stress, which was ameliorated by NMDA receptor antagonism...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27995326/using-a-novel-pv-cre-rat-model-to-characterize-pallidonigral-cells-and-their-terminations
#13
Yoon-Mi Oh, Fuyuki Karube, Susumu Takahashi, Kenta Kobayashi, Masahiko Takada, Motokazu Uchigashima, Masahiko Watanabe, Kayo Nishizawa, Kazuto Kobayashi, Fumino Fujiyama
In the present study, we generated a novel parvalbumin (PV)-Cre rat model and conducted detailed morphological and electrophysiological investigations of axons from PV neurons in globus pallidus (GP). The GP is considered as a relay nucleus in the indirect pathway of the basal ganglia (BG). Previous studies have used molecular profiling and projection patterns to demonstrate cellular heterogeneity in the GP; for example, PV-expressing neurons are known to comprise approximately 50% of GP neurons and represent majority of prototypic neurons that project to the subthalamic nucleus and/or output nuclei of BG, entopeduncular nucleus and substantia nigra (SN)...
December 19, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27989846/cortical-areas-involved-in-behavioral-expression-of-external-pallidum-dysfunctions-a-pet-imaging-study-in-non-human-primates
#14
Laurent Galineau, Aurélie Kas, Yulia Worbe, Marion Chaigneau, Anne-Sophie Herard, Martine Guillermier, Thierry Delzescaux, Jean Féger, Philippe Hantraye, Léon Tremblay
The external pallidum (GPe) is a component of the indirect pathway centrally placed in the basal ganglia. Studies already demonstrated that the pharmacological disinhibition of the sensorimotor, associative, and limbic GPe produced dyskinesia, hyperactivity, and compulsive behaviors, respectively. The aim of this study was to investigate the cortical regions altered by the disinhibition of each GPe functional territory. Thus, 5 macaques were injected with bicuculline in sensorimotor, associative, and limbic sites of the GPe producing dyskinesia, hyperactivity, and compulsive behaviors, and underwent in vivo positron tomography with (18)F-2-fluoro-2-deoxy-D-glucose to identify cortical dysfunctions related to GPe disinhibition...
October 28, 2016: NeuroImage
https://www.readbyqxmd.com/read/27989609/limbic-circuitry-activation-in-ethanol-withdrawal-is-regulated-by-a-chromosome-1-locus
#15
Kari J Buck, Gang Chen, Laura B Kozell
Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force sustaining alcohol use/abuse and contributing to relapse in alcoholics. Although no animal model exactly duplicates alcoholism, models for specific factors, including the withdrawal syndrome, are useful for identifying potential genetic and neural determinants of liability in humans. We previously identified highly significant quantitative trait loci (QTLs) with large effects on predisposition to withdrawal after chronic and acute alcohol exposure in mice and mapped these loci to the same region of chromosome 1 (Alcdp1 and Alcw1, respectively)...
December 8, 2016: Alcohol
https://www.readbyqxmd.com/read/27983564/dysregulation-of-corticostriatal-connectivity-in-huntington-s-disease-a%C3%A2-role-for-dopamine-modulation
#16
Claudia Rangel-Barajas, George V Rebec
Aberrant communication between striatum, the main information processing unit of the basal ganglia, and cerebral cortex plays a critical role in the emergence of Huntington's disease (HD), a fatal monogenetic condition that typically strikes in the prime of life. Although both striatum and cortex undergo substantial cell loss over the course of HD, corticostriatal circuits become dysfunctional long before neurons die. Understanding the dysfunction is key to developing effective strategies for treating a progressively worsening triad of motor, cognitive, and psychiatric symptoms...
December 15, 2016: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/27965590/electrode-position-and-current-amplitude-modulate-impulsivity-after-subthalamic-stimulation-in-parkinsons-disease-a-computational-study
#17
Alekhya Mandali, V Srinivasa Chakravarthy, Roopa Rajan, Sankara Sarma, Asha Kishore
Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27917146/a-unified-theoretical-framework-for-cognitive-sequencing
#18
Tejas Savalia, Anuj Shukla, Raju S Bapi
The capacity to sequence information is central to human performance. Sequencing ability forms the foundation stone for higher order cognition related to language and goal-directed planning. Information related to the order of items, their timing, chunking and hierarchical organization are important aspects in sequencing. Past research on sequencing has emphasized two distinct and independent dichotomies: implicit vs. explicit and goal-directed vs. habits. We propose a theoretical framework unifying these two streams...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27916455/phosphodiesterase-10a-inhibition-improves-cortico-basal-ganglia-function-in-huntington-s-disease-models
#19
Vahri Beaumont, Sheng Zhong, Hai Lin, WenJin Xu, Amyaouch Bradaia, Esther Steidl, Melanie Gleyzes, Kristian Wadel, Bruno Buisson, Fernando E Padovan-Neto, Shreaya Chakroborty, Karen M Ward, John F Harms, Jose Beltran, Mei Kwan, Afshin Ghavami, Jenny Häggkvist, Miklós Tóth, Christer Halldin, Andrea Varrone, Christoph Schaab, J Nikolaj Dybowski, Sarah Elschenbroich, Kimmo Lehtimäki, Taneli Heikkinen, Larry Park, James Rosinski, Ladislav Mrzljak, Daniel Lavery, Anthony R West, Christopher J Schmidt, Margaret M Zaleska, Ignacio Munoz-Sanjuan
Huntington's disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models, and PDE10 loss may represent a homeostatic adaptation to maintain signaling...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27911752/frontosubthalamic-circuits-for-control-of-action-and-cognition
#20
Adam R Aron, Damian M Herz, Peter Brown, Birte U Forstmann, Kareem Zaghloul
The subthalamic nucleus (STN) of the basal ganglia appears to have a potent role in action and cognition. Anatomical and imaging studies show that different frontal cortical areas directly project to the STN via so-called hyperdirect pathways. This review reports some of the latest findings about such circuits, including simultaneous recordings from cortex and the STN in humans, single-unit recordings in humans, high-resolution fMRI, and neurocomputational modeling. We argue that a major function of the STN is to broadly pause behavior and cognition when stop signals, conflict signals, or surprise signals occur, and that the fronto-STN circuits for doing this, at least for stopping and conflict, are dissociable anatomically and in terms of their spectral reactivity...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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