Sample records for abnormal basal ganglia

  1. Basal Ganglia and Learning

    NSDL National Science Digital Library

    2009-04-14

    The basal ganglia, a group of interconnected brain areas located deep in the cerebral cortex, have proved to be at work in learning, the formation of good and bad habits, and some psychiatric and addictive disorders.

  2. The Robot Basal Ganglia

    Microsoft Academic Search

    Tony J. Prescott; Kevin Gurney; Fernando Montes-Gonzalez; Mark Humphries; Peter Redgrave

    \\u000a Action selection is the task of resolving conflicts between multiple sensorimotor systems seeking access to the final common\\u000a motor path. Recently,1,2 we proposed that the basal ganglia may act to provide a biological solution to the problem of selection. To test this notion\\u000a we have implemented a high level computational model of intrinsic basal ganglia circuitry and its interactions with

  3. Abnormal basal ganglia outflow in Parkinson's disease identified with PET. Implications for higher cortical functions.

    PubMed

    Owen, A M; Doyon, J; Dagher, A; Sadikot, A; Evans, A C

    1998-05-01

    In this study we examined the effects of striatal dopamine depletion on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Regional cerebral blood flow was measured in six patients with moderate Parkinson's disease and in six age-matched control subjects while they performed easy and difficult versions of a modified Tower of London planning task and a mnemonic variant of this task that required short-term retention and reproduction of problem solutions, as well as a control condition that involved identical visual stimuli and motor responses. Relative to control conditions, the planning task was associated with an increase in cerebral blood flow centred on the internal segment of the right globus pallidus in the age-matched control subjects, and a decrease in the same region in the patients with Parkinson's disease. A similar inverse relationship between the task-specific blood flow change observed in the control group and that observed in the Parkinson's disease patients was not found in any other subcortical or cortical area examined, including regions of the dorsolateral frontal cortex known to be involved in this task. When blood flow in the spatial working memory task was examined, a similarly specific dissociation between the two groups of subjects was observed at similar coordinates in the right pallidum. We conclude that striatal dopamine depletion disrupts the normal pattern of basal ganglia outflow in Parkinson's disease and consequently, affects the expression of frontal-lobe functions by interrupting normal transmission of information through frontostriatal circuitry. PMID:9619196

  4. [Anti-basal ganglia antibody].

    PubMed

    Hayashi, Masaharu

    2013-04-01

    Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS. PMID:23568985

  5. The basal ganglia Ann M. Graybiel

    E-print Network

    Graybiel, Ann M.

    of the basal ganglia lead to devastating motor disorders, including Parkinson's disease and Huntington of the cortical input to the basal ganglia. Degeneration of neurons in the striatum leads to Huntington's disease The leading model for motor disorders such as Parkinson's and Huntington's diseases is that the basal ganglia

  6. Basal Ganglia Shapes Predict Social, Communication, and Motor Dysfunctions in Boys with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Qiu, Anqi; Adler, Marcy; Crocetti, Deana; Miller, Michael I.; Mostofsky, Stewart H.

    2010-01-01

    Objective: Basal ganglia abnormalities have been suggested as contributing to motor, social, and communicative impairments in autism spectrum disorder (ASD). Volumetric analyses offer limited ability to detect localized differences in basal ganglia structure. Our objective was to investigate basal ganglia shape abnormalities and their association…

  7. Mössbauer spectroscopy of Basal Ganglia

    SciTech Connect

    Miglierini, Marcel, E-mail: marcel.miglierini@stuba.sk [Institute of Nuclear and Physical Engineering, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovi?ova 3, 812 19 Bratislava, Slovakia and Regional Centre of Advanced Technologies and Materials (Czech Republic); Lan?ok, Adriana [Institute of Inorganic Chemistry AS CR, v. v. i., 250 68 Husinec-?ež 1001 (Czech Republic); Kopáni, Martin [Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Sasinkova 2, 811 08 Bratislava (Slovakia); Bo?a, Roman [Department of Chemistry, Faculty of Natural Sciences, University of SS. Cyril and Methodius, 917 01 Trnava (Slovakia)

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 ?m in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  8. The expanding universe of disorders of the basal ganglia.

    PubMed

    Obeso, Jose A; Rodriguez-Oroz, Maria C; Stamelou, Maria; Bhatia, Kailash P; Burn, David J

    2014-08-01

    The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made. PMID:24954674

  9. Striatal plasticity and basal ganglia circuit function

    PubMed Central

    Kreitzer, Anatol C.; Malenka, Robert C.

    2009-01-01

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways—distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function. PMID:19038213

  10. The Basal Ganglia-Circa 1982

    NASA Technical Reports Server (NTRS)

    Mehler, William R.

    1981-01-01

    Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

  11. Synaptic organisation of the basal ganglia

    PubMed Central

    BOLAM, J. P.; HANLEY, J. J.; BOOTH, P. A. C.; BEVAN, M. D.

    2000-01-01

    The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context-dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is ‘processed’ within the striatum and passed via the so-called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical ‘premotor’ regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed-forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic integration of functionally diverse information derived from the cortex. It is concluded that the essential concept of the direct and indirect pathways of information flow through the basal ganglia remains intact but that the role of the indirect pathway is more complex than previously suggested and that neurons of the globus pallidus are in a position to control the activity of virtually the whole of the basal ganglia. PMID:10923985

  12. Extrastriatal Dopaminergic Circuits of the Basal Ganglia

    PubMed Central

    Rommelfanger, Karen S.; Wichmann, Thomas

    2010-01-01

    The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction. PMID:21103009

  13. The connectome of the basal ganglia.

    PubMed

    Schmitt, Oliver; Eipert, Peter; Kettlitz, Richard; Leßmann, Felix; Wree, Andreas

    2014-11-29

    The basal ganglia of the laboratory rat consist of a few core regions that are specifically interconnected by efferents and afferents of the central nervous system. In nearly 800 reports of tract-tracing investigations the connectivity of the basal ganglia is documented. The readout of connectivity data and the collation of all the connections of these reports in a database allows to generate a connectome. The collation, curation and analysis of such a huge amount of connectivity data is a great challenge and has not been performed before (Bohland et al. PloS One 4:e7200, 2009) in large connectomics projects based on meta-analysis of tract-tracing studies. Here, the basal ganglia connectome of the rat has been generated and analyzed using the consistent cross-platform and generic framework neuroVIISAS. Several advances of this connectome meta-study have been made: the collation of laterality data, the network-analysis of connectivity strengths and the assignment of regions to a hierarchically organized terminology. The basal ganglia connectome offers differences in contralateral connectivity of motoric regions in contrast to other regions. A modularity analysis of the weighted and directed connectome produced a specific grouping of regions. This result indicates a correlation of structural and functional subsystems. As a new finding, significant reciprocal connections of specific network motifs in this connectome were detected. All three principal basal ganglia pathways (direct, indirect, hyperdirect) could be determined in the connectome. By identifying these pathways it was found that there exist many further equivalent pathways possessing the same length and mean connectivity weight as the principal pathways. Based on the connectome data it is unknown why an excitation pattern may prefer principal rather than other equivalent pathways. In addition to these new findings the local graph-theoretical features of regions of the connectome have been determined. By performing graph theoretical analyses it turns out that beside the caudate putamen further regions like the mesencephalic reticular formation, amygdaloid complex and ventral tegmental area are important nodes in the basal ganglia connectome. The connectome data of this meta-study of tract-tracing reports of the basal ganglia are available for further network studies, the integration into neocortical connectomes and further extensive investigations of the basal ganglia dynamics in population simulations. PMID:25432770

  14. Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease.

    PubMed

    Scherfler, Christoph; Esterhammer, Regina; Nocker, Michael; Mahlknecht, Philipp; Stockner, Heike; Warwitz, Boris; Spielberger, Sabine; Pinter, Bernadette; Donnemiller, Eveline; Decristoforo, Clemens; Virgolini, Irene; Schocke, Michael; Poewe, Werner; Seppi, Klaus

    2013-10-01

    Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0.48, P < 0.01) and between mean putaminal 6-[(18)F] fluorolevodopa uptake and the total odour score (r = 0.58; P < 0.05) as well as the Unified Parkinson's Disease Rating Scale motor score (r = -0.53, P < 0.05). This study reports a significant association between increased mean diffusivity signal and decreased 6-[(18)F] fluorolevodopa uptake, indicating that microstructural degradation of the substantia nigra and the olfactory tract parallels progression of putaminal dopaminergic dysfunction in Parkinson's disease. Since increases in nigral mean diffusivity signal also correlated with motor dysfunction, diffusion tensor imaging may serve as a surrogate marker for disease progression in future studies of putative disease modifying therapies. PMID:24014521

  15. Basal ganglia physiology and pathophysiology: A reappraisal

    Microsoft Academic Search

    Erwin B. Montgomery Jr

    Current theories of basal ganglia (BG) function based on suppression of activity in the ventrolateral thalamic-cortical circuits by the globus pallidus internal segment are inconsistent with accumulating evidence, demonstrating the need for reconsideration. Changes in busting, oscillatory and synchronous neuronal activities have been indicted as pathophyisological mechanisms but they are unaccompanied by any mechanistic explanatory theory and rely on the

  16. Genetics Home Reference: Biotin-thiamine-responsive basal ganglia disease

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Biotin-thiamine-responsive basal ganglia disease On this page: ... names Glossary definitions Reviewed January 2014 What is biotin-thiamine-responsive basal ganglia disease? Biotin-thiamine-responsive ...

  17. Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop

    Microsoft Academic Search

    André Parent; Lili-Naz Hazrati

    1995-01-01

    This paper reviews some of the recent findings on different aspects of the anatomical organization of the basal ganglia. Attempts have been made to delineate the anatomical substrate of information processing along the cortico-basal ganglia-thalamo-cortical loop. Emphasis has been placed on data obtained with highly sensitive anterograde tract-tracing methods applied to the study of the main axis of the loop,

  18. 368 Dispatch Basal ganglia: New therapeutic approaches to Parkinson's disease

    E-print Network

    Graybiel, Ann M.

    368 Dispatch Basal ganglia: New therapeutic approaches to Parkinson's disease Ann M. Graybiel As the search for molecular therapies for basal ganglia disorders, such as Parkinson's disease, accelerates, new-9822 The motor symptoms of basal ganglia disorders fall at two extremes. In Parkinson's disease and related

  19. Traumatic bilateral basal ganglia hematoma: A report of two cases

    PubMed Central

    Bhargava, Pranshu; Grewal, Sarvpreet Singh; Gupta, Bharat; Jain, Vikas; Sobti, Harman

    2012-01-01

    Traumatic Basal ganglia hemorrhage is relatively uncommon. Bilateral basal ganglia hematoma after trauma is extremely rare and is limited to case reports. We report two cases of traumatic bilateral basal ganglia hemorrhage, and review the literature in brief. Both cases were managed conservatively. PMID:23293672

  20. Active Decorrelation in the Basal Ganglia

    PubMed Central

    Wilson, Charles J.

    2013-01-01

    The cytoarchitecturally-homogeneous appearance of the globus pallidus, subthalamic nucleus and substantia nigra has long been said to imply a high degree of afferent convergence and sharing of inputs by nearby neurons. Moreover, axon collaterals of neurons in the external segment of the globus pallidus and the substantia nigra pars reticulata arborize locally and make inhibitory synapses on other cells of the same type. These features suggest that the connectivity of the basal ganglia may impose spike-time correlations among the cells, and it has been puzzling that experimental studies have failed to demonstrate such correlations. One possible solution arises from studies of firing patterns in basal ganglia cells, which reveal that they are nearly all pacemaker cells. Their high rate of firing does not depend on synaptic excitation, but they fire irregularly because a dense barrage of synaptic inputs normally perturbs the timing of their autonomous activity. Theoretical and computational studies show that the responses of repetitively firing neurons to shared input or mutual synaptic coupling often defy classical intuitions about temporal synaptic integration. The patterns of spike timing among such neurons depend on the ionic mechanism of pacemaking, the level of background uncorrelated cellular and synaptic noise, and the firing rates of the neurons, as well as the properties of their synaptic connections. Application of these concepts to the basal ganglia circuitry suggests that the connectivity and physiology of these nuclei may be configured to prevent the establishment of permanent spike-timing relationships between neurons. The development of highly synchronous oscillatory patterns of activity in Parkinson’s disease may result from the loss of pacemaking by some basal ganglia neurons, and accompanying breakdown of the mechanisms responsible for active decorrelation. PMID:23892007

  1. Oscillators and Oscillations in the Basal Ganglia.

    PubMed

    Wilson, Charles J

    2014-12-01

    What is the meaning of an action potential? There must be different answers for neurons that fire spontaneously, even in the absence of synaptic input, and those driven to fire from a resting membrane potential. In spontaneously firing neurons, the occurrence of the next action potential is guaranteed; only variations in its timing can carry the message. In the basal ganglia, the globus pallidus, the substantia nigra, and the subthalamic nucleus consist of neurons firing spontaneously. They each receive thousands of synaptic inputs, but these are not required to maintain their background firing. Instead, synaptic interactions among basal ganglia nuclei comprise a system of coupled oscillators that produces a complex resting pattern of activity. Normally, this pattern is highly irregular and uncorrelated, so that the firing of each cell is statistically independent of the others. This maximizes the potential information that may be transmitted by the basal ganglia to its target structures. In Parkinson's disease, the resting pattern of activity is dominated by a slow oscillation shared by nearly all of the neurons. Treatment with deep brain stimulation may gain its therapeutic value by disrupting this shared pathological oscillation, and restoring independent action by each neuron in the network. PMID:25449134

  2. The Basal Ganglia and Adaptive Motor Control

    NASA Astrophysics Data System (ADS)

    Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

    1994-09-01

    The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

  3. Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder

    E-print Network

    Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder Fay Y. Womer a,n , Lei of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using Free

  4. Basal ganglia anatomy and schizophrenia: the role of antipsychotic treatment.

    PubMed

    Zampieri, E; Bellani, M; Crespo-Facorro, B; Brambilla, P

    2014-12-01

    Progressive enlargement of basal ganglia volume has been observed in schizophrenia individuals, potentially being sustained by chronic administration of antipsychotic drugs. Here we briefly summarise the state of the art of the role of antipsychotic in leading to increased basal ganglia in schizophrenia, particularly focusing on the caudate nucleus. PMID:25335548

  5. Basal ganglia damage and impaired visual function in the newborn infant

    PubMed Central

    Mercuri, E.; Atkinson, J.; Braddick, O.; Anker, S.; Cowan, F.; Rutherford, M.; Pennock, J.; Dubowitz, L.

    1997-01-01

    AIM—To examine the effects of early lesions in the visual pathway on visual function; and to identify early prognostic indicators of visual abnormalities.?METHODS—The visual function of 37 infants with perinatal brain lesions on magnetic resonance imaging was assessed using behavioural and electrophysiological variables.?RESULTS—Normal visual behaviour was observed in most infants with large bilateral occipital lesions, but all the infants with associated basal ganglia involvement had abnormal visual function. Visual abnormalities were also present in six infants with isolated basal ganglia lesions.?CONCLUSIONS—These observations suggest that basal ganglia may have an integral role in human visual development and that their presence on neonatal MRI could be an early marker of abnormal visual function.?? PMID:9377131

  6. Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder.

    PubMed

    Womer, Fay Y; Wang, Lei; Alpert, Kathryn I; Smith, Matthew J; Csernansky, John G; Barch, Deanna M; Mamah, Daniel

    2014-08-30

    In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies. PMID:24957866

  7. Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

    PubMed Central

    Criswell, Susan R; Perlmutter, Joel S; Huang, John L; Golchin, Nima; Flores, Hubert P; Hobson, Angela; Aschner, Michael; Erikson, Keith M; Checkoway, Harvey; Racette, Brad A

    2013-01-01

    Objectives Manganese exposure leads to diffuse cerebral metal deposition with the highest concentration in the globus pallidus associated with increased T1-weighted MRI signal. T1 signal intensity in extra-pallidal basal ganglia (caudate and putamen) has not been studied in occupationally exposed workers. Diffusion weighted imaging is a non-invasive measure of neuronal damage and may provide a quantification of neurotoxicity associated with welding and manganese exposure. This study investigated extra-pallidal T1 basal ganglia signal intensity as a marker of manganese exposure and basal ganglia diffusion weighted imaging abnormalities as a potential marker of neurotoxicity. Methods A 3T MR case:control imaging study was performed on 18 welders and 18 age- and gender-matched controls. Basal ganglia regions of interest were identified for each subject. T1-weighted intensity indices and apparent diffusion coefficients were generated for each region. Results All regional indices were higher in welders than controls (p?0.05). Combined basal ganglia (?=0.610), caudate (?=0.645), anterior (?=0.595) and posterior putamen (?=0.511) indices were more correlated with exposure than pallidal (?=0.484) index. Welder apparent diffusion coefficient values were lower than controls for globus pallidus (p=0.03) and anterior putamen (p=0.004). Conclusions Welders demonstrated elevated T1 indices throughout the basal ganglia. Combined basal ganglia, caudate and putamen indices were more correlated with exposure than pallidal index suggesting more inclusive basal ganglia sampling results in better exposure markers. Elevated indices were associated with diffusion weighted abnormalities in the pallidum and anterior putamen suggesting neurotoxicity in these regions. PMID:22447645

  8. Functional anatomy: dynamic States in Basal Ganglia circuits.

    PubMed

    Garcia-Munoz, Marianela; Carrillo-Reid, Luis; Arbuthnott, Gordon W

    2010-01-01

    The most appealing models of how the basal ganglia function propose distributed patterns of cortical activity selectively interacting with striatal networks to yield the execution of context-dependent movements. If movement is encoded by patterns of activity then these may be disrupted by influences at once more subtle and more devastating than the increase or decrease of neuronal firing that dominate the usual models of the circuit. In the absence of dopamine the compositional capabilities of cell assemblies in the network could be disrupted by the generation of dominant synchronous activity that engages most of the system. Experimental evidence about Parkinson's disease suggests that dopamine loss produces abnormal patterns of activity in different nuclei. For example, increased oscillatory activity arises in the GPe, GPi, and STN and is reflected as increased cortical beta frequency coherence disrupting the ability to produce motor sequences. When the idea of deep brain stimulation was proposed - it was supported by the information that lesions of the subthalamus reversed the effects of damage to the dopamine input to the system. However, it seems increasingly unlikely that the stimulation acts by silencing the nucleus as was at first proposed. Perhaps the increased cortical beta activity caused by the lack of dopamine could have disabled the patterning of network activity. Stimulation of the subthalamic nucleus disrupts the on-going cortical rhythms. Subsequently asynchronous firing is reinstated and striatal cell assemblies and the whole basal ganglia circuit engage in a more normal pattern of activity. We will review the different variables involved in the generation of sequential activity patterns, integrate our data on deep brain stimulation and network population dynamics, and thus provide a novel interpretation of functional aspects of basal ganglia circuitry. PMID:21151374

  9. Time representation in reinforcement learning models of the basal ganglia

    E-print Network

    Gershman, Samuel J.

    Reinforcement learning (RL) models have been influential in understanding many aspects of basal ganglia function, from reward prediction to action selection. Time plays an important role in these models, but there is still ...

  10. Pseudohypoparathyroidism, parkinsonism syndrome, with no basal ganglia calcification.

    PubMed Central

    Evans, B K; Donley, D K

    1988-01-01

    A 20 year old woman with pseudohypoparathyroidism, Parkinsonism and no basal ganglia calcifications shown by computed tomography is reported. She has typical features of pseudohypoparathyroidism and biochemical evidence of end-organ resistance to parathyroid hormone. She is mentally retarded and has tremor, rigidity, bradykinesia, and stooped posture. The cause of Parkinsonism in pseudohypoparathyroidism is thought to be basal ganglia calcification. This patient must have another pathophysiology, perhaps directly related to a G protein defect, causing impaired neurotransmission. Images PMID:3404168

  11. Numerical deficits in a single case of basal ganglia dysfunction.

    PubMed

    Zamarian, L; Bodner, T; Revkin, S K; Benke, T; Boesch, S; Donnemiller, E; Delazer, M

    2009-10-01

    The present investigation assesses specific numerical difficulties in a patient (SJ) with basal ganglia (BG) dysfunction. While previous studies on number processing in BG disorders typically tested arithmetic facts by production tasks, the present study uses production, recognition (verification, multiple-choice) and indirect (number-matching) arithmetic tasks. Patient SJ was severely impaired in production and to a lesser extent in verification and multiple-choice tasks. In number-matching, an abnormal latency pattern was found. This study extends previous research by indicating that BG dysfunction may not only affect production processes and sequencing, as was found in previous investigations, but may lead to a breakdown of semantic relationships of arithmetic facts. PMID:19370479

  12. CODING OF BEHAVIORAL SEQUENCES IN THE BASAL GANGLIA

    E-print Network

    Berridge, Kent

    and thoughts of obsessive-compulsive disorder,8 both of which are associated with pathology of the basal disorders of the basal ganglia strongly supports a motor function. However, close scrutiny suggests is disturbed by this disorder. Huntington's patients also have deficits in related high-level "ideomotor

  13. CODING OF BEHAVIORAL SEQUENCES IN THE BASAL GANGLIA

    E-print Network

    Berridge, Kent

    and thoughts of obsessive-compulsive disorder8 , both of which are associated with pathology of the basal disorders of the basal ganglia strongly supports a motor function. However, close scrutiny suggests is disturbed by this disorder. Huntington's patients also have deficits in related high-level "ideomotor

  14. Loss of Specificity in Basal Ganglia Related Movement Disorders

    PubMed Central

    Bronfeld, Maya; Bar-Gad, Izhar

    2011-01-01

    The basal ganglia (BG) are a group of interconnected nuclei which play a pivotal part in limbic, associative, and motor functions. This role is mirrored by the wide range of motor and behavioral abnormalities directly resulting from dysfunction of the BG. Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events. In the normal BG, this modulation is highly specific, with each neuron related only to a small subset of behavioral events depending on specific combinations of movement parameters and context. In many pathological conditions involving BG dysfunction and motor abnormalities, this neuronal specificity is lost. Loss of specificity (LOS) manifests in neuronal activity related to a larger spectrum of events and consequently a large overlap of movement-related activation patterns between different neurons. We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG. The prevalence of LOS in a many BG-related disorders suggests that neuronal specificity may represent a key feature of normal information processing in the BG system. Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control. PMID:21687797

  15. Basal ganglia and Dopamine Contributions to Probabilistic Category Learning

    PubMed Central

    Shohamy, D.; Myers, C.E.; Kalanithi, J.; Gluck, M.A.

    2009-01-01

    Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge. PMID:18061261

  16. Basal ganglia and dopamine contributions to probabilistic category learning.

    PubMed

    Shohamy, D; Myers, C E; Kalanithi, J; Gluck, M A

    2008-01-01

    Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge. PMID:18061261

  17. Time representation in reinforcement learning models of the basal ganglia

    PubMed Central

    Gershman, Samuel J.; Moustafa, Ahmed A.; Ludvig, Elliot A.

    2014-01-01

    Reinforcement learning (RL) models have been influential in understanding many aspects of basal ganglia function, from reward prediction to action selection. Time plays an important role in these models, but there is still no theoretical consensus about what kind of time representation is used by the basal ganglia. We review several theoretical accounts and their supporting evidence. We then discuss the relationship between RL models and the timing mechanisms that have been attributed to the basal ganglia. We hypothesize that a single computational system may underlie both RL and interval timing—the perception of duration in the range of seconds to hours. This hypothesis, which extends earlier models by incorporating a time-sensitive action selection mechanism, may have important implications for understanding disorders like Parkinson's disease in which both decision making and timing are impaired. PMID:24409138

  18. BASAL GANGLIA PATHOLOGY IN SCHIZOPHRENIA: DOPAMINE CONNECTIONS and ANOMALIES

    PubMed Central

    Perez-Costas, Emma; Melendez-Ferro, Miguel; Roberts, Rosalinda C.

    2010-01-01

    Schizophrenia is a severe mental illness that affects 1% of the world population. The disease usually manifests itself in early adulthood with hallucinations, delusions, cognitive and emotional disturbances and disorganized thought and behavior. Dopamine was the first neurotransmitter to be implicated in the disease, and though no longer the only suspect in schizophrenia pathophysiology, it obviously plays an important role. The basal ganglia are the site of most of the dopamine neurons in the brain and the target of antipsychotic drugs. In this review we will start with an overview of basal ganglia anatomy emphasizing dopamine circuitry. Then, we will review the major deficits in dopamine function in schizophrenia, emphasizing the role of excessive dopamine in the basal ganglia and the link to psychosis. PMID:20089137

  19. Altered functional connectivity of basal ganglia circuitry in dental phobia.

    PubMed

    Scharmüller, Wilfried; Leutgeb, Verena; Schöngaßner, Florian; Hermann, Andrea; Stark, Rudolf; Schienle, Anne

    2014-10-01

    Recent symptom provocation studies that compared patients suffering from dental phobia with healthy controls identified hyperactivation of basal ganglia structures, but none have assessed striatal functional connectivity. We reanalyzed data from a previous functional magnetic resonance imaging study on dental phobia. Patients (20 men, 25 women) and healthy controls (18 men, 23 women) had been exposed to pictures showing dental treatment, and neutral contents. We conducted connectivity analyses via psychophysiological interactions (PPIs). Relative to non-phobic controls, the patients showed decreased connectivity between prefrontal and basal ganglia regions. Moreover, the clinical group was characterized by increased internal basal ganglia connectivity, which was more pronounced in female compared with male patients. This study provides first evidence for an altered information flow within a fronto-striatal network in dentophobic individuals during visual symptom provocation, which can be considered a neuromarker of this disorder. PMID:24084590

  20. Adenosine A2A receptors and basal ganglia physiology

    PubMed Central

    Schiffmann, S.N.; Fisone, G.; Moresco, R.; Cunha, R.A.; Ferré, S.

    2007-01-01

    Adenosine A2A receptors are highly enriched in the basal ganglia system. They are predominantly expressed in enkephalin-expressing GABAergic striatopallidal neurons and therefore are highly relevant to the function of the indirect efferent pathway of the basal ganglia system. In these GABAergic enkephalinergic neurons, the A2A receptor tightly interacts structurally and functionally with the dopamine D2 receptor. Both by forming receptor heteromers and by targeting common intracellular signaling cascades, A2A and D2 receptors exhibit reciprocal antagonistic interactions that are central to the function of the indirect pathway and hence to basal ganglia control of movement, motor learning, motivation and reward. Consequently, this A2A / D2 receptors antagonistic interaction is also central to basal ganglia dysfunction in Parkinson's disease. However, recent evidence demonstrates that, in addition to this postsynaptic site of action, striatal A2A receptors are also expressed and have physiological relevance on presynaptic glutamatergic terminals of the cortico-limbic-striatal and thalamo-striatal pathways, where they form heteromeric receptor complexes with adenosine A1 receptors. Therefore, A2A receptors play an important fine-tuning role, boosting the efficiency of glutamatergic information flow in the indirect pathway by exerting control, either pre- and/or post-synaptically, over other key modulators of glutamatergic synapses, including D2 receptors, group I metabotropic mGlu5 glutamate receptors and cannabinoid CB1 receptors, and by triggering the cAMP-protein kinase A signaling cascade. PMID:17646043

  1. Multidimensional Sequence Learning in Patients with Focal Basal Ganglia Lesions

    ERIC Educational Resources Information Center

    Shin, J.C.; Aparicio, P.; Ivry, R.B.

    2005-01-01

    Parkinson's patients have been found to be impaired in learning movement sequences. In the current study, patients with unilateral basal ganglia lesions due to stroke were tested on a serial reaction time task in which responses were based on the spatial location of each stimulus. The spatial locations either followed a fixed sequence or were…

  2. ANATOMY REVIEW: Basal Ganglia A group of subcortical nuclei

    E-print Network

    Sergio, Lauren E.

    experienced by patients with cerebellar damage Cerebellum of a (former) alcoholicCerebellar atrophy Cerebellar by involuntary purposeless movements CIRCUITRY As with cerebellum, basal ganglia act indirectly · Highly brainstem and rest of cerebellum Cerebellum overview1. 2. 3. Regulatory system within a regulatory system

  3. The role of basal ganglia-forebrain circuitry in the vocal learning of songbirds

    E-print Network

    Andalman, Aaron Samuel

    2009-01-01

    The basal ganglia form the largest sub-cortical structure in the human brain and are implicated in numerous human diseases. In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and ...

  4. A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds

    E-print Network

    Goldberg, Jesse H.

    The pallido-recipient thalamus transmits information from the basal ganglia to the cortex and is critical for motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the basal ganglia, ...

  5. Functional Coupling Between Substantia Nigra and Basal Ganglia Homologues in Amphibians

    E-print Network

    Ryan, Michael J.

    Functional Coupling Between Substantia Nigra and Basal Ganglia Homologues in Amphibians Kim L. Hoke the existence of a homologue of the mam- malian substantia nigra­basal ganglia circuit in the amphibian brain proposed that homologous basal ganglia circuits may exist in both amphibians and mammals (reviewed

  6. Metabolite Alterations in Basal Ganglia Associated with Methamphetamine-related Psychiatric Symptoms: A Proton MRS Study

    Microsoft Academic Search

    Yoshimoto Sekine; Yoshio Minabe; Masayoshi Kawai; Katsuaki Suzuki; Masaomi Iyo; Haruo Isoda; Harumi Sakahara; Charles R Ashby; Nori Takei; Norio Mori

    2002-01-01

    Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in

  7. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

    PubMed

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  8. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds

    PubMed Central

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D.

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  9. Proactive Selective Response Suppression Is Implemented via the Basal Ganglia

    PubMed Central

    Majid, D. S. Adnan; Cai, Weidong; Corey-Bloom, Jody

    2013-01-01

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway. PMID:23946385

  10. A selective role for right insula—basal ganglia circuits in appetitive stimulus processing

    PubMed Central

    Vijayaraghavan, Lavanya; Adolphs, Ralph; Kennedy, Daniel P.; Cassell, Martin; Tranel, Daniel; Paradiso, Sergio

    2013-01-01

    Hemispheric lateralization of hedonic evaluation (‘liking’) and incentive motivation (‘wanting’) in neural networks connecting the basal ganglia and insula (BG-I) in humans was examined. Participants with brain damage restricted to the BG-I of the right (n = 5) or left (n = 5) hemisphere, and 26 healthy participants matched on age, sex and intelligence quotient were tested on positively and negatively valenced pictures drawn from varied stimulus categories (Vijayaraghavan et al., 2008). Liking was assessed with explicit ratings of pleasantness using a nine-point Likert scale. Wanting was quantified as the amount of work (via repeated keypresses) that participants expended to increase (approach) or decrease (withdraw) viewing time. Right-lesion patients showed abnormally low viewing times and liking ratings for positive images. For a subset of positive images depicting sexual content, right-lesion patients exhibited active withdrawal, while the other two groups approached such stimuli. These results suggest that the right basal ganglia–insula complex plays a greater role than the left in supporting hedonic evaluation and motivational approach to positively valenced stimuli. The finding that active avoidance of stimuli that were not ‘liked’ was spared in both right- and left-sided lesion subjects suggests that unilateral damage to insula/basal ganglia circuits may not be sufficient to affect general incentive motivation independent of preference. PMID:22798397

  11. Familial idiopathic basal ganglia calcification (Fahr`s disease).

    PubMed

    Mufaddel, Amir A; Al-Hassani, Ghanem A

    2014-07-01

    Familial idiopathic basal ganglia calcification (Fahr`s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr`s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr`s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr`s disease. PMID:24983277

  12. Saccade learning with concurrent cortical and subcortical basal ganglia loops

    PubMed Central

    N'Guyen, Steve; Thurat, Charles; Girard, Benoît

    2014-01-01

    The Basal Ganglia (BG) is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks. We propose a model of saccade generation with reinforcement learning capabilities based on our previous BG and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of the saccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks. The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not). Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate. PMID:24795615

  13. Zonisamide regulates basal ganglia transmission via astroglial kynurenine pathway.

    PubMed

    Fukuyama, Kouji; Tanahashi, Shunske; Hoshikawa, Masamitsu; Shinagawa, Rika; Okada, Motohiro

    2014-01-01

    To clarify the anti-parkinsonian mechanisms of action of zonisamide (ZNS), we determined the effects of ZNS on tripartite synaptic transmission associated with kynurenine (KYN) pathway (KP) in cultured astrocytes, and transmission in both direct and indirect pathways of basal ganglia using microdialysis. Interactions between cytokines [interferon-? (IFN?) and tumor-necrosis factor-? (TNF?)] and ZNS on astroglial releases of KP metabolites, KYN, kynurenic-acid (KYNA), xanthurenic-acid (XTRA), cinnabarinic-acid (CNBA) and quinolinic-acid (QUNA), were determined by extreme liquid-chromatography with mass-spectrometry. Interaction among metabotropic glutamate-receptor (mGluR), KP metabolites and ZNS on striato-nigral, striato-pallidal GABAergic and subthalamo-nigral glutamatergic transmission was examined by microdialysis with extreme liquid-chromatography fluorescence resonance-energy transfer detection. Acute and chronic ZNS administration increased astroglial release of KYN, KYNA, XTRA and CNBA, but not QUNA. Chronic IFN? administration increased the release of KYN, KYNA, CNBA and QUNA, but had minimal inhibitory effect on XTRA release. Chronic TNF? administration increased CNBA and QUNA, but not KYN, KYNA or XTRA. ZNS inhibited IFN?-induced elevation of KYN, KYNA and QUNA, but enhanced IFN?-induced that of CNBA. TNF?-induced rises in CNBA and QUNA were inhibited by ZNS. ZNS inhibited striato-nigral GABAergic, striato-pallidal GABAergic and subthalamo-nigral glutamatergic transmission via activation of groups II and III mGluRs. ZNS enhanced astroglial release of endogenous agonists of group II mGluR, XTRA and group III mGluR, CNBA. Activated endogenous mGluR agonists inhibited transmission in direct and indirect pathways of basal ganglia. These mechanisms contribute to effectiveness and well tolerability of ZNS as an adjunct treatment for Parkinson's disease during l-DOPA monotherapy. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. PMID:23973311

  14. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry

    Microsoft Academic Search

    Alexxai V. Kravitz; Benjamin S. Freeze; Philip R. L. Parker; Kenneth Kay; Myo T. Thwin; Karl Deisseroth; Anatol C. Kreitzer

    2010-01-01

    Neural circuits of the basal ganglia are critical for motor planning and action selection. Two parallel basal ganglia pathways have been described, and have been proposed to exert opposing influences on motor function. According to this classical model, activation of the `direct' pathway facilitates movement and activation of the `indirect' pathway inhibits movement. However, more recent anatomical and functional evidence

  15. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry

    E-print Network

    Schnitzer, Mark

    LETTERS Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia of basal ganglia circuitry in vivo, using optogenetic control11­14 of direct- and indirect-pathway medium motor deficits. To obtain selective optogenetic control of the direct and indirect pathways in vivo, we

  16. Actor critic models of the basal ganglia: new anatomical and computational perspectives

    Microsoft Academic Search

    Daphna Joel; Yael Niv; Eytan Ruppin

    A large number of computational models of information processing in the basal ganglia have been developed in recent years. Prominent in these are actor- critic models of basal ganglia functioning, which build on the strong resemblance between dopamine neuron activity and the temporal difference prediction error signal in the critic, and between dopamine-dependent long-term synaptic plasticity in the striatum and

  17. Dopaminergic Control of the Exploration-Exploitation Trade-Off via the Basal Ganglia

    PubMed Central

    Humphries, Mark D.; Khamassi, Mehdi; Gurney, Kevin

    2012-01-01

    We continuously face the dilemma of choosing between actions that gather new information or actions that exploit existing knowledge. This “exploration-exploitation” trade-off depends on the environment: stability favors exploiting knowledge to maximize gains; volatility favors exploring new options and discovering new outcomes. Here we set out to reconcile recent evidence for dopamine’s involvement in the exploration-exploitation trade-off with the existing evidence for basal ganglia control of action selection, by testing the hypothesis that tonic dopamine in the striatum, the basal ganglia’s input nucleus, sets the current exploration-exploitation trade-off. We first advance the idea of interpreting the basal ganglia output as a probability distribution function for action selection. Using computational models of the full basal ganglia circuit, we showed that, under this interpretation, the actions of dopamine within the striatum change the basal ganglia’s output to favor the level of exploration or exploitation encoded in the probability distribution. We also found that our models predict striatal dopamine controls the exploration-exploitation trade-off if we instead read-out the probability distribution from the target nuclei of the basal ganglia, where their inhibitory input shapes the cortical input to these nuclei. Finally, by integrating the basal ganglia within a reinforcement learning model, we showed how dopamine’s effect on the exploration-exploitation trade-off could be measurable in a forced two-choice task. These simulations also showed how tonic dopamine can appear to affect learning while only directly altering the trade-off. Thus, our models support the hypothesis that changes in tonic dopamine within the striatum can alter the exploration-exploitation trade-off by modulating the output of the basal ganglia. PMID:22347155

  18. Basal ganglia outputs map instantaneous position coordinates during behavior.

    PubMed

    Barter, Joseph W; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A; Bartholomew, Ryan A; Yin, Henry H

    2015-02-11

    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions. PMID:25673860

  19. Origins of basal ganglia output signals in singing juvenile birds.

    PubMed

    Pidoux, Morgane; Bollu, Tejapratap; Riccelli, Tori; Goldberg, Jesse H

    2015-02-01

    Across species, complex circuits inside the basal ganglia (BG) converge on pallidal output neurons that exhibit movement-locked firing patterns. Yet the origins of these firing patterns remain poorly understood. In songbirds during vocal babbling, BG output neurons homologous to those found in the primate internal pallidal segment are uniformly activated in the tens of milliseconds prior to syllable onsets. To test the origins of this remarkably homogenous BG output signal, we recorded from diverse upstream BG cell types during babbling. Prior to syllable onsets, at the same time that internal pallidal segment-like neurons were activated, putative medium spiny neurons, fast spiking and tonically active interneurons also exhibited transient rate increases. In contrast, pallidal neurons homologous to those found in primate external pallidal segment exhibited transient rate decreases. To test origins of these signals, we performed recordings following lesion of corticostriatal inputs from premotor nucleus HVC. HVC lesions largely abolished these syllable-locked signals. Altogether, these findings indicate a striking homogeneity of syllable timing signals in the songbird BG during babbling and are consistent with a role for the indirect and hyperdirect pathways in transforming cortical inputs into BG outputs during an exploratory behavior. PMID:25392171

  20. Role of the indirect pathway of the Basal Ganglia in perceptual decision making.

    PubMed

    Wei, Wei; Rubin, Jonathan E; Wang, Xiao-Jing

    2015-03-01

    The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed-accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease. PMID:25740532

  1. Anatomy of a songbird basal ganglia circuit essential for vocal learning and plasticity

    PubMed Central

    Gale, Samuel D.; Perkel, David J.

    2009-01-01

    Vocal learning in songbirds requires an anatomically discrete and functionally dedicated circuit called the anterior forebrain pathway (AFP). The AFP is homologous to cortico-basal ganglia-thalamo-cortical loops in mammals. The basal ganglia portion of this pathway, Area X, shares many features characteristic of the mammalian striatum and pallidum, including cell-types and connectivity. The AFP also deviates from mammalian basal ganglia circuits in fundamental ways. In addition, the microcircuitry, role of neuromodulators, and function of Area X are still unclear. Elucidating the mechanisms by which both mammalian-like and unique features of the AFP contribute to vocal learning may help lead to a broad understanding of the sensorimotor functions of basal ganglia circuits. PMID:19596062

  2. A basal ganglia-forebrain circuit in the songbird biases motor output to avoid vocal errors

    E-print Network

    Andalman, Aaron S.

    In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and production of complex motor behaviors; however, the precise role of these circuits remains unknown. It has recently been shown ...

  3. The involvement of the primate frontal cortex-basal ganglia system in arbitrary visuomotor association learning

    E-print Network

    Machon, Michelle S

    2009-01-01

    It is the goal of this thesis to examine the frontal cortex-basal ganglia system during arbitrary visuomotor association learning, the forming of arbitrary links between visual stimuli and motor responses (e.g. red means ...

  4. Structural Findings in the Basal Ganglia in Genetically Determined and Idiopathic Parkinson's Disease

    E-print Network

    Gaser, Christian

    likely have an increased risk to develop Parkinson's disease (PD). We hypothesized BG morphological Key words: basal ganglia; magnetic resonance imaging; Parkinson's disease; Parkin mutation carriers; voxel-based morphometry Parkinson's disease (PD) is a common, slowly pro- gressive neurodegenerative

  5. Modeling the role of the basal ganglia in motor control and motor programming

    E-print Network

    Mao, Zhi-Hong, 1972-

    2005-01-01

    The basal ganglia (BG) are a group of highly interconnected nuclei buried deep in the brain. They are involved in an important range of brain functions, including both lower-level movement control and higher-level cognitive ...

  6. Basal Ganglia Subcircuits Distinctively Encode the Parsing and Concatenation of Action Sequences

    PubMed Central

    Jin, Xin; Tecuapetla, Fatuel; Costa, Rui M

    2014-01-01

    Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral sequence at the neural level. Using a task where mice learn rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. Besides start/stop activity signaling sequence parsing, we found neurons displaying inhibited or sustained activity throughout the execution of an entire sequence. This sustained activity covaried with the rate of execution of individual sequence elements, consistent with motor concatenation. Direct and indirect pathways of basal ganglia were concomitantly active during sequence initiation, but behaved differently during sequence performance, revealing a more complex functional organization of these circuits than previously postulated. These results have important implications for understanding the functional organization of basal ganglia during the learning and execution of action sequences. PMID:24464039

  7. Extensive basal ganglia edema caused by a traumatic carotid-cavernous fistula: a rare presentation related to a basal vein of Rosenthal anatomical variation.

    PubMed

    Ract, Isabelle; Drier, Aurélie; Leclercq, Delphine; Sourour, Nader; Gabrieli, Joseph; Yger, Marion; Nouet, Aurélien; Dormont, Didier; Chiras, Jacques; Clarençon, Frédéric

    2014-07-01

    The authors report a very rare presentation of traumatic carotid-cavernous fistula (CCF) with extensive edema of the basal ganglia and brainstem because of an anatomical variation of the basal vein of Rosenthal (BVR). A 45-year-old woman was admitted to the authors' institution for left hemiparesis, dysarthria, and a comatose state caused by right orbital trauma from a thin metal rod. Brain MRI showed a right CCF and vasogenic edema of the right side of the brainstem, right temporal lobe, and basal ganglia. Digital subtraction angiography confirmed a high-flow direct CCF and revealed a hypoplastic second segment of the BVR responsible for the hypertension in inferior striate veins and venous congestion. Endovascular treatment was performed on an emergency basis. One month after treatment, the patient's symptoms and MRI signal abnormalities almost totally disappeared. Basal ganglia and brainstem venous congestion may occur in traumatic CCF in cases of a hypoplastic or agenetic second segment of the BVR and may provoke emergency treatment. PMID:24527815

  8. Quantitation of the human basal ganglia with Positron Emission Tomography

    SciTech Connect

    Bendriem, B.; Dewey, S.L.; Schlyer, D.J.; Wolf, A.P.; Volkow, N.D.

    1990-01-01

    The accurate measurement of the concentration of a radioisotope in small structures with PET requires a correction for quantitation loss due to the partial volume effect and the effect of scattered radiation. To evaluate errors associated with measures in the human basal ganglia (BG) we have built a unilateral model of the BG that we have inserted in a 20 cm cylinder. The recovery coefficient (RC = measured activity/true activity) for our BG phantom has been measured on a CTI tomograph (model 931-08/12) with different background concentrations (contrast) and at different axial locations in the gantry. The BG was visualized on 4 or 5 slices depending on its position in the gantry and on the contrast used. The RC was 0.75 with no background (contrast equal to 1.0). Increasing the relative radioactivity concentration in the background increased the RC from 0.75 to 2.00 when the contrast was {minus}0.7 (BG < Background). The RC was also affected by the size and the shape of the region of interest (ROI) used (RC from 0.75 to 0.67 with ROI size from 0.12 to 1.41 cm{sup 2}). These results show that accurate RC correction depends not only on the volume of the structure but also on its contrast with its surroundings as well as on the selection of the ROI. They also demonstrate that the higher the contrast the more sensitive to axial positioning PET measurements in the BG are. These data provide us with some information about the variability of PET measurements in small structure like the BG and we have proposed some strategies to improve the reproducibility. 18 refs., 3 figs., 5 tabs.

  9. Dissociating hippocampal and basal ganglia contributions to category learning using stimulus novelty and subjective judgments

    PubMed Central

    Seger, Carol A.; Dennison, Christina S.; Lopez-Paniagua, Dan; Peterson, Erik J.; Roark, Aubrey A.

    2011-01-01

    We identified factors leading to hippocampal and basal ganglia recruitment during categorization learning. Subjects alternated between blocks of a standard trial and error category learning task and a subjective judgment task. In the subjective judgments task subjects categorized the stimulus and then instead of receiving feedback they indicated the basis of their response using 4 options: Remember: Conscious episodic memory of previous trials. Know-Automatic: Automatic, rapid response accompanied by conscious awareness of category membership. Know-Intuition: A “gut feeling” without fully conscious knowledge of category membership. Guess: Guessing. In addition, new stimuli were introduced throughout the experiment to examine effects of novelty. Categorization overall recruited both the basal ganglia and posterior hippocampus. However, basal ganglia activity was found during Know judgments (both Automatic and Intuition), whereas posterior hippocampus activity was found during Remember judgments. Granger causality mapping indicated interactions between the basal ganglia and hippocampus, with the putamen exerting directed influence on the posterior hippocampus, which in turn exerted directed influence on the posterior caudate nucleus. We also found a region of anterior hippocampus that showed decreased activity relative to baseline during categorization overall, and showed a strong novelty effect. Our results indicate that subjective measures may be effective in dissociating basal ganglia from hippocampal dependent learning, and that the basal ganglia are involved in both conscious and unconscious learning. They also indicate a dissociation within the hippocampus, in which the anterior regions are sensitive to novelty, and the posterior regions are involved in memory based categorization learning. PMID:21255655

  10. Automated segmentation of multifocal basal ganglia T2*-weighted MRI hypointensities.

    PubMed

    Glatz, Andreas; Bastin, Mark E; Kiker, Alexander J; Deary, Ian J; Wardlaw, Joanna M; Valdés Hernández, Maria C

    2015-01-15

    Multifocal basal ganglia T2*-weighted (T2*w) hypointensities, which are believed to arise mainly from vascular mineralization, were recently proposed as a novel MRI biomarker for small vessel disease and ageing. These T2*w hypointensities are typically segmented semi-automatically, which is time consuming, associated with a high intra-rater variability and low inter-rater agreement. To address these limitations, we developed a fully automated, unsupervised segmentation method for basal ganglia T2*w hypointensities. This method requires conventional, co-registered T2*w and T1-weighted (T1w) volumes, as well as region-of-interest (ROI) masks for the basal ganglia and adjacent internal capsule generated automatically from T1w MRI. The basal ganglia T2*w hypointensities were then segmented with thresholds derived with an adaptive outlier detection method from respective bivariate T2*w/T1w intensity distributions in each ROI. Artefacts were reduced by filtering connected components in the initial masks based on their standardised T2*w intensity variance. The segmentation method was validated using a custom-built phantom containing mineral deposit models, i.e. gel beads doped with 3 different contrast agents in 7 different concentrations, as well as with MRI data from 98 community-dwelling older subjects in their seventies with a wide range of basal ganglia T2*w hypointensities. The method produced basal ganglia T2*w hypointensity masks that were in substantial volumetric and spatial agreement with those generated by an experienced rater (Jaccard index = 0.62 ± 0.40). These promising results suggest that this method may have use in automatic segmentation of basal ganglia T2*w hypointensities in studies of small vessel disease and ageing. PMID:25451469

  11. Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons using cholera toxin subunit B (CTB).

    PubMed

    Luquin, Natasha; Sierra, Salvador; Rico, Alberto J; Gómez-Bautista, Virginia; Roda, Elvira; Conte-Perales, Lorena; Franco, Rafael; McCormick, Peter; Labandeira-García, José L; Lanciego, José L

    2012-09-01

    The A(2A)R has become a therapeutic target in Parkinson disease due to its functional role in the striatum, capable of modulating dopaminergic neurotransmission in the basal ganglia. No conclusive evidence, however, has been provided to demonstrate the existence of A(2A)Rs in the output nuclei of the basal ganglia: the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr). Using immunohistochemistry and in situ hybridization techniques we have confirmed the presence of A(2A)Rs in both the striatum (medium spiny and cholinergic neurons) and the external segment of the globus pallidus (GPe), in the monkey. The antibody routinely used to label A(2A)Rs failed to detect A(2A)R-positive neurons in the GPi and SNr, however, in situ hybridization showed that A(2A)R mRNA transcripts were indeed present in both these nuclei. Surprisingly, by labeling pallidothalamic and nigrothalamic projection neurons originating in the GPi and SNr with the neuronal retrograde tracer cholera toxin subunit B (CTB), the receptor protein was unmasked and detectable using the antibody. This unmasking of the protein was specific to CTB and not an artifact of the tracer. We have shown unequivocally that the A(2A)R is present in the output nuclei of the primate basal ganglia, however, to be able to detect the receptor immunohistochemically, unmasking the protein with CTB was necessary. The presence of A(2A)Rs in the GPi and SNr suggests that these output nuclei could be targeted therapeutically in Parkinson disease to restore abnormal activity in the basal ganglia. PMID:22659306

  12. Do Basal Ganglia Amplify Willed Action by Stochastic Resonance? A Model

    PubMed Central

    Chakravarthy, V. Srinivasa

    2013-01-01

    Basal ganglia are usually attributed a role in facilitating willed action, which is found to be impaired in Parkinson's disease, a pathology of basal ganglia. We hypothesize that basal ganglia possess the machinery to amplify will signals, presumably weak, by stochastic resonance. Recently we proposed a computational model of Parkinsonian reaching, in which the contributions from basal ganglia aid the motor cortex in learning to reach. The model was cast in reinforcement learning framework. We now show that the above basal ganglia computational model has all the ingredients of stochastic resonance process. In the proposed computational model, we consider the problem of moving an arm from a rest position to a target position: the two positions correspond to two extrema of the value function. A single kick (a half-wave of sinusoid, of sufficiently low amplitude) given to the system in resting position, succeeds in taking the system to the target position, with high probability, only at a critical noise level. But for suboptimal noise levels, the model arm's movements resemble Parkinsonian movement symptoms like akinetic rigidity (low noise) and dyskinesias (high noise). PMID:24302984

  13. Conditional Routing of Information to the Cortex: A Model of the Basal Ganglia’s Role in Cognitive Coordination

    PubMed Central

    Stocco, Andrea; Lebiere, Christian; Anderson, John R.

    2010-01-01

    The basal ganglia play a central role in cognition and are involved in such general functions as action selection and reinforcement learning. Here, we present a model exploring the hypothesis that the basal ganglia implement a conditional information-routing system. The system directs the transmission of cortical signals between pairs of regions by manipulating separately the selection of sources and destinations of information transfers. We suggest that such a mechanism provides an account for several cognitive functions of the basal ganglia. The model also incorporates a possible mechanism by which subsequent transfers of information control the release of dopamine. This signal is used to produce novel stimulus–response associations by internalizing transferred cortical representations in the striatum. We discuss how the model is related to production systems and cognitive architectures. A series of simulations is presented to illustrate how the model can perform simple stimulus–response tasks, develop automatic behaviors, and provide an account of impairments in Parkinson’s and Huntington’s diseases. PMID:20438237

  14. A review of pathologies associated with high T1W signal intensity in the basal ganglia on Magnetic Resonance Imaging

    PubMed Central

    Zaitout, Zahia; Romanowski, Charles; Karunasaagarar, Kavitasagary; Connolly, Daniel; Batty, Ruth

    2014-01-01

    Summary With several functions and a fundamental influence over cognition and motor functions, the basal ganglia are the cohesive centre of the brain. There are several conditions which affect the basal ganglia and these have various clinical and radiological manifestations. Nevertheless, on magnetic resonance imaging there is a limited differential diagnosis for those conditions presenting with T1 weighted spin echo hyperintensity within the central nervous system in general and the basal ganglia in particular. The aim of our review is to explore some of these basal ganglia pathologies and provide image illustrations. PMID:24900164

  15. Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease

    PubMed Central

    Redgrave, Peter; Rodriguez, Manuel; Smith, Yoland; Rodriguez-Oroz, Maria C.; Lehericy, Stephane; Bergman, Hagai; Agid, Yves; DeLong, Mahlon R.; Obeso, Jose A.

    2011-01-01

    Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson’s disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson’s disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. PMID:20944662

  16. Dopamine transporter SPECT/CT and perfusion brain SPECT imaging in idiopathic basal ganglia calcinosis.

    PubMed

    Paschali, Anna; Lakiotis, Velissarios; Messinis, Lambros; Markaki, Elli; Constantoyannis, Constantine; Ellul, John; Vassilakos, Pavlos

    2009-07-01

    A case of idiopathic basal ganglia calcification in a 56-year-old woman with parkinsonism and cognitive impairment is described. The nigrostriatal dopaminergic pathway and regional cerebral blood flow were evaluated using dopamine transporter (DAT) brain single photon emission tomography combined with a low-dose x-ray computerized tomography transmission (hybrid SPECT/CT) and Tc-99m HMPAO brain perfusion SPECT study, respectively. DAT SPECT/CT imaging revealed a reduction in DAT binding in both striatum regions coinciding with bilateral calcifications in the basal ganglia. Brain perfusion scan showed hypoperfusion in basal ganglia regions, posterior parietal cortex bilaterally, left frontopolar and dorsolateral prefrontal cortex, and left temporal lobe. These findings correlated well with the clinical condition of the patient. Mineralization may play a critical role in the pathogenesis of neuronal degeneration. Cortical perfusion changes in patients may better explain the patient's altered cognitive and motor functions. PMID:19542944

  17. Motor functions of cerebellum and basal ganglia: the cerebellocortical saccadic (ballistic) clock, the cerebellonuclear hold regulator, and the basal ganglia ramp (voluntary speed smooth movement) generator

    Microsoft Academic Search

    H. H. Kornhuber

    1971-01-01

    A theory of the motor functions of the cerebellum and the basal ganglia is presented. It is based on the following observations:1.Dysmetria of saccadic eye and rapid arm movements as well as adiadochokinesis as a consequence of cerebellar cortical lesions.2.Holding tremor of the arm and eyes (pendular nystagmus) due to lesions of the cerebellar nuclei.3.The precentral motor cortex is unnecessary

  18. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy

    Microsoft Academic Search

    M-L Welter; P Burbaud; S Fernandez-Vidal; E Bardinet; J Coste; B Piallat; M Borg; S Besnard; P Sauleau; B Devaux; B Pidoux; P Chaynes; S Tézenas du Montcel; A Bastian; N Langbour; A Teillant; W Haynes; J Yelnik; C Karachi; L Mallet

    2011-01-01

    Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive–compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed

  19. Conditional Routing of Information to the Cortex: A Model of the Basal Ganglia's Role in Cognitive Coordination

    ERIC Educational Resources Information Center

    Stocco, Andrea; Lebiere, Christian; Anderson, John R.

    2010-01-01

    The basal ganglia play a central role in cognition and are involved in such general functions as action selection and reinforcement learning. Here, we present a model exploring the hypothesis that the basal ganglia implement a conditional information-routing system. The system directs the transmission of cortical signals between pairs of regions…

  20. Distribution of GABA B binding sites in the thalamus and basal ganglia of the rhesus monkey ( Macaca mulatta)

    Microsoft Academic Search

    N. G. Bowery; K. Parry; G. Goodrich; I. Ilinsky; K. Kultas-Ilinsky

    1999-01-01

    The regional distribution of GABAB receptor binding sites in the thalamus and basal ganglia of rhesus monkey has been determined by receptor autoradiography using the agonist ligand, [3H]-GABA. Whilst binding sites were evident throughout the thalamus, the internuclear differences in the Bmax were up to 10-fold. In the basal ganglia the binding density was on average lower than in the

  1. Synchronized Neuronal Discharge in the Basal Ganglia of Parkinsonian Patients Is Limited to Oscillatory Activity

    Microsoft Academic Search

    Ron Levy; William D. Hutchison; Andres M. Lozano; Jonathan O. Dostrovsky

    2002-01-01

    It has been proposed that an increase in synchronization be- tween neurons in the basal ganglia contributes to the clinical features of Parkinson's disease (PD). To examine this hypothe- sis, we looked for correlations in the discharge activity of pairs of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and the substantia nigra pars reticulata (SNr). Recordings

  2. Stuttering and the Basal Ganglia Circuits: A Critical Review of Possible Relations

    ERIC Educational Resources Information Center

    Alm, Per A.

    2004-01-01

    The possible relation between stuttering and the basal ganglia is discussed. Important clues to the pathophysiology of stuttering are given by conditions known to alleviate dysfluency, like the rhythm effect, chorus speech, and singing. Information regarding pharmacologic trials, lesion studies, brain imaging, genetics, and developmental changes…

  3. How may the basal ganglia contribute to auditory categorization and speech perception?

    PubMed Central

    Lim, Sung-Joo; Fiez, Julie A.; Holt, Lori L.

    2014-01-01

    Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language-specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood. PMID:25136291

  4. Visuo-Motor and Cognitive Procedural Learning in Children with Basal Ganglia Pathology

    ERIC Educational Resources Information Center

    Mayor-Dubois, C.; Maeder, P.; Zesiger, P.; Roulet-Perez, E.

    2010-01-01

    We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (less than 1 year old, n=9), later…

  5. The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

    PubMed Central

    Brown, Jennifer; Pan, Wei-Xing; Dudman, Joshua Tate

    2014-01-01

    Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function. DOI: http://dx.doi.org/10.7554/eLife.02397.001 PMID:24849626

  6. New Syndrome Characterized by Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum

    Microsoft Academic Search

    Marjo S. van der Knaap; SakkuBai Naidu; Petra J. W. Pouwels; Simona Bonavita; Rudy van Coster; Lieven Lagae; Jurgen Sperner; Robert Surtees; Raphael Schiffmann; Jakob Valk

    2002-01-01

    BACKGROUND AND PURPOSE: Leukoencephalopathies of unknown origin constitute a considerable problem in child neurology. The purpose of our ongoing study of the subject was to define new disease entities among them by using primarily MR imaging pattern recognition. METHODS: We identified seven unrelated patients with a distinct MR imaging pattern consisting of hypomyelination and atrophy of the basal ganglia (neostriatum)

  7. Differential contributions of basal ganglia and thalamus to song initiation, tempo, and structure

    PubMed Central

    Chen, J. R.; Doupe, A. J.

    2013-01-01

    Basal ganglia-thalamocortical circuits are multistage loops critical to motor behavior, but the contributions of individual components to overall circuit function remain unclear. We addressed these issues in a songbird basal ganglia-thalamocortical circuit (the anterior forebrain pathway, AFP) specialized for singing and critical for vocal plasticity. The major known afferent to the AFP is the premotor cortical nucleus, HVC. Surprisingly, previous studies found that lesions of HVC alter song but do not eliminate the ability of the AFP to drive song production. We therefore used this AFP-driven song to investigate the role of basal ganglia and thalamus in vocal structure, tempo, and initiation. We found that lesions of the striatopallidal component (Area X) slowed song and simplified its acoustic structure. Elimination of the thalamic component (DLM) further simplified the acoustic structure of song and regularized its rhythm but also dramatically reduced song production. The acoustic structure changes imply that sequential stages of the AFP each add complexity to song, but the effects of DLM lesions on song initiation suggest that thalamus is a locus of additional inputs important to initiation. Together, our results highlight the cumulative contribution of stages of a basal ganglia-thalamocortical circuit to motor output along with distinct involvement of thalamus in song initiation or “gating.” PMID:24174647

  8. Basal ganglia and supplementary motor area subtend duration perception: an fMRI study

    Microsoft Academic Search

    A. M. Ferrandez; L. Hugueville; S. Lehericy; J. B. Poline; C. Marsault; V. Pouthasa

    2003-01-01

    Brain imaging studies on duration perception usually report the activation of a network that includes the frontal and mesiofrontal cortex (supplementary motor area, SMA), parietal cortex, and subcortical areas (basal ganglia, thalamus, and cerebellum). To address the question of the specific involvement of these structures in temporal processing, we contrasted two visual discrimination tasks in which the relevant stimulus dimension

  9. Effects of Focal Basal Ganglia Lesions on Timing and Force Control

    ERIC Educational Resources Information Center

    Aparicio, P.; Diedrichsen, J.; Ivry, R.B.

    2005-01-01

    Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of…

  10. Bidirectional Plasticity in Striatonigral Synapses: A Switch to Balance Direct and Indirect Basal Ganglia Pathways

    ERIC Educational Resources Information Center

    Aceves, Jose J.; Rueda-Orozco, Pavel E.; Hernandez-Martinez, Ricardo; Galarraga, Elvira; Bargas, Jose

    2011-01-01

    There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral…

  11. Changes in basal ganglia processing of cortical input following magnetic stimulation in Parkinsonism

    E-print Network

    Bar-Gad, Izhar

    -basal ganglia (CBG) loop. Initially, the study of these changes focused on the baseline firing rate., 1997; Nini et al., 1995). Studies of functional changes in the CBG loop neurophysiology have revealed all assess the modulation of neuronal activity in the CBG loop in a static manner that reflects

  12. Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease?

    PubMed Central

    Bunzeck, Nico; Singh-Curry, Victoria; Eckart, Cindy; Weiskopf, Nikolaus; Perry, Richard J.; Bain, Peter G.; Düzel, Emrah; Husain, Masud

    2013-01-01

    Background In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Methods Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. Results We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Conclusions Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease. PMID:24025315

  13. Activity Patterns in a Model for the Subthalamopallidal Network of the Basal Ganglia

    E-print Network

    - struction of dopaminergic neurons in Parkinson's disease and in animal models of parkinsonism. Key words; Parkinson's disease Most current models of the basal ganglia are static models, in that they represent, com- monly used to explain the symptoms of Parkinsonism, views the interactions of the direct

  14. Providing Explicit Information Disrupts Implicit Motor Learning after Basal Ganglia Stroke

    ERIC Educational Resources Information Center

    Boyd, Lara A.; Winstein, Carolee J.

    2004-01-01

    Despite their purported neuroanatomic and functional isolation, empirical evidence suggests that sometimes conscious explicit processes can influence implicit motor skill learning. Our goal was to determine if the provision of explicit information affected implicit motor-sequence learning after damage to the basal ganglia. Individuals with stroke…

  15. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  16. The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia

    Microsoft Academic Search

    Paolo Calabresi; Antonio Pisani; Nicola B. Mercuri; Giorgio Bernardi

    1996-01-01

    Corticostriatal transmission has an important function in the regulation of the neuronal activity of the basal ganglia. The firing activity of corticostriatal neurones excites striatal cells via the release of glutamate. Presynaptic receptors that are located on corticostriatal terminals and that regulate the release of glutamate in the striatum have been postulated for dopamine and glutamate. Activation of these receptors

  17. Dissociation between medial temporal lobe and basal ganglia memory systems in schizophrenia

    E-print Network

    Gluck, Mark

    Dissociation between medial temporal lobe and basal ganglia memory systems in schizophrenia with schizophrenia. Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent generalization. Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated

  18. Contributions of the Prefrontal Cortex and Basal Ganglia to Set Shifting

    Microsoft Academic Search

    Susan M. Ravizza; Michael A. Ciranni

    2002-01-01

    Impairments of set shifting have been associated with damage to both the prefrontal cortex (PFC) and to the basal ganglia. The purpose of these experiments was to determine whether damage to the PFC was associated with shifting impairments per se or whether any switching deficits could be attributed to a reduction of working memory capacity. In contrast, shifting impairments were

  19. The Differential Effects of Thalamus and Basal Ganglia on Facial Emotion Recognition

    ERIC Educational Resources Information Center

    Cheung, Crystal C. Y.; Lee, Tatia M. C.; Yip, James T. H.; King, Kristin E.; Li, Leonard S. W.

    2006-01-01

    This study examined if subcortical stroke was associated with impaired facial emotion recognition. Furthermore, the lateralization of the impairment and the differential profiles of facial emotion recognition deficits with localized thalamic or basal ganglia damage were also studied. Thirty-eight patients with subcortical strokes and 19 matched…

  20. Basal Ganglia Atrophy in Prodromal Huntington's Disease Is Detectable Over One Year Using Automated Segmentation

    E-print Network

    Aron, Adam

    Basal Ganglia Atrophy in Prodromal Huntington's Disease Is Detectable Over One Year Using Automated disorders. VC 2011 Movement Disorder Society Key Words: Huntington's disease; prodromal HD; lon- gitudinal that modify the course of Huntington's disease (HD).1 For example, methods such as RNA interfer- ence have

  1. Dynamical states of the cortico basal ganglia circuits Thesis submitted for the degree of

    E-print Network

    anatomical pathways of the cortico-basal ganglia-thalamic (CBT) circuit. The model explains the appearance. Nevertheless, I hypothesize that the overall negative feedback structure of the CBT circuit can give rise, in addition to single-unit discharge, in search of global oscillations throughout the CBT circuit

  2. The pallial basal ganglia pathway modulates the behaviorally driven gene expression of the

    E-print Network

    Jarvis, Erich D.

    The pallial basal ganglia pathway modulates the behaviorally driven gene expression of the motor and Genetics, Moyzesova 61, 90028 Ivanka pri Dunaji, Slovakia Keywords: immediate-early gene, motor-driven gene activity-induced gene ZENK (or egr-1), which shows singing-regulated expression in a social context

  3. A biologically constrained model of the whole basal ganglia addressing the paradoxes of connections and selection.

    PubMed

    Liénard, Jean; Girard, Benoît

    2014-06-01

    The basal ganglia nuclei form a complex network of nuclei often assumed to perform selection, yet their individual roles and how they influence each other is still largely unclear. In particular, the ties between the external and internal parts of the globus pallidus are paradoxical, as anatomical data suggest a potent inhibitory projection between them while electrophysiological recordings indicate that they have similar activities. Here we introduce a theoretical study that reconciles both views on the intra-pallidal projection, by providing a plausible characterization of the relationship between the external and internal globus pallidus. Specifically, we developed a mean-field model of the whole basal ganglia, whose parameterization is optimized to respect best a collection of numerous anatomical and electrophysiological data. We first obtained models respecting all our constraints, hence anatomical and electrophysiological data on the intrapallidal projection are globally consistent. This model furthermore predicts that both aforementioned views about the intra-pallidal projection may be reconciled when this projection is weakly inhibitory, thus making it possible to support similar neural activity in both nuclei and for the entire basal ganglia to select between actions. Second, we predicts that afferent projections are substantially unbalanced towards the external segment, as it receives the strongest excitation from STN and the weakest inhibition from the striatum. Finally, our study strongly suggests that the intrapallidal connection pattern is not focused but diffuse, as this latter pattern is more efficient for the overall selection performed in the basal ganglia. PMID:24077957

  4. Mineral composition of and the relationships between them of human basal ganglia in very old age.

    PubMed

    Tohno, Yoshiyuki; Tohno, Setsuko; Azuma, Cho; Minami, Takeshi; Ke, Lining; Ongkana, Nutcharin; Sinthubua, Apichat; Mahakkanukrauh, Pasuk

    2013-01-01

    Trace elements and the relationships among them were investigated by direct chemical analysis in three basal ganglia regions in very old age individuals and age- and gender-related differences were assessed. After ordinary dissections at Nara Medical University were finished, the caudate nucleus, putamen, and globus pallidus belonging to the basal ganglia were removed from the identical cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years (average age?=?83.3?±?7.5 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca, P, and Mg contents increased significantly in the putamen with aging and the Mg content increased significantly in the globus pallidus with aging, but no elements increased significantly in the caudate nucleus with aging. Regarding the relationships among elements in the basal ganglia, extremely significant direct correlations were found among the Ca, P, and Mg contents in the putamen. These results suggested that slight calcification occurred in the putamen in very old age. With regard to seven elements of Ca, P, S, Mg, Zn, Fe, and Na, it was examined whether there were significant correlations among the caudate nucleus, putamen, and globus pallidus. It was found that there were extremely significant direct correlations among all of the three basal ganglia in the P content. Likewise, with regard to the Fe content, there were extremely or very significant direct correlations among all of the three basal ganglia. Regarding the gender difference in elements, it was found that the Ca content of the caudate nucleus was significantly higher in women than in men. PMID:23111949

  5. Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue

    PubMed Central

    Miller, Andrew H.; Jones, James F.; Drake, Daniel F.; Tian, Hao; Unger, Elizabeth R.; Pagnoni, Giuseppe

    2014-01-01

    Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation. In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling) task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses. Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p?=?0.01) and right globus pallidus (p?=?0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2?=?0.49, p?=?0.001), general fatigue (r2?=?0.34, p?=?0.01) and reduced activity (r2?=?0.29, p?=?0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects. These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks. PMID:24858857

  6. Singing-Related Neural Activity Distinguishes Two Putative Pallidal Cell Types in the Songbird Basal Ganglia: Comparison to the Primate Internal and External Pallidal Segments

    E-print Network

    Goldberg, Jesse H.

    The songbird area X is a basal ganglia homolog that contains two pallidal cell types—local neurons that project within the basal ganglia and output neurons that project to the thalamus. Based on these projections, it has ...

  7. Endoscopic Evacuation of Basal Ganglia Hemorrhage via Keyhole Approach Using an Adjustable Cannula in Comparison with Craniotomy

    PubMed Central

    Zhang, Heng-Zhu; Li, Yu-Ping; Yan, Zheng-cun; Wang, Xing-dong; She, Lei; Wang, Xiao-dong; Dong, Lun

    2014-01-01

    Neuroendoscopic (NE) surgery as a minimal invasive treatment for basal ganglia hemorrhage is a promising approach. The present study aims to evaluate the efficacy and safety of NE approach using an adjustable cannula to treat basal ganglia hemorrhage. In this study, we analysed the clinical and radiographic outcomes between NE group (21 cases) and craniotomy group (30 cases). The results indicated that NE surgery might be an effective and safe approach for basal ganglia haemorrhage, and it is also suggested that NE approach may improve good functional recovery. However, NE approach only suits the selected patient, and the usefulness of NE approach needs further randomized controlled trials (RCTs) to evaluate. PMID:24949476

  8. Acute Psychosis Associated with Subcortical Stroke: Comparison between Basal Ganglia and Mid-Brain Lesions

    PubMed Central

    McMurtray, Aaron; Tseng, Ben; Diaz, Natalie; Chung, Julia; Mehta, Bijal; Saito, Erin

    2014-01-01

    Acute onset of psychosis in an older or elderly individual without history of previous psychiatric disorders should prompt a thorough workup for neurologic causes of psychiatric symptoms. This report compares and contrasts clinical features of new onset of psychotic symptoms between two patients, one with an acute basal ganglia hemorrhagic stroke and another with an acute mid-brain ischemic stroke. Delusions and hallucinations due to basal ganglia lesions are theorized to develop as a result of frontal lobe dysfunction causing impairment of reality checking pathways in the brain, while visual hallucinations due to mid-brain lesions are theorized to develop due to dysregulation of inhibitory control of the ponto-geniculate-occipital system. Psychotic symptoms occurring due to stroke demonstrate varied clinical characteristics that depend on the location of the stroke within the brain. Treatment with antipsychotic medications may provide symptomatic relief. PMID:25309765

  9. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease

    SciTech Connect

    Akiyama, H.; Harrop, R.; McGeer, P.L.; Peppard, R.; McGeer, E.G.

    1989-04-01

    We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using /sup 18/F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices, while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis.

  10. Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy

    PubMed Central

    Schroll, Henning; Hamker, Fred H.

    2013-01-01

    Over the past 15 years, computational models have had a considerable impact on basal-ganglia research. Most of these models implement multiple distinct basal-ganglia pathways and assume them to fulfill different functions. As there is now a multitude of different models, it has become complex to keep track of their various, sometimes just marginally different assumptions on pathway functions. Moreover, it has become a challenge to oversee to what extent individual assumptions are corroborated or challenged by empirical data. Focusing on computational, but also considering non-computational models, we review influential concepts of pathway functions and show to what extent they are compatible with or contradict each other. Moreover, we outline how empirical evidence favors or challenges specific model assumptions and propose experiments that allow testing assumptions against each other. PMID:24416002

  11. [Decision-making and learning by cortico-basal ganglia network].

    PubMed

    Hikosaka, Okihide

    2008-07-01

    Animals and humans have a wide variety of motor repertoires, and for this reason they have to choose one motor action among many others. The mechanisms in the basal ganglia seem ideal for this purpose. The basal ganglia normally keep inhibiting their target structures, including the thalamocortical networks and the subcortical motor netwoks. This tonic inhibition can be removed by direct inhibitory inputs from the striatum carrying specific sensorimotor signals, leading to the execution of a particular movement, or can be enhanced by indirect inputs from the striatum carrying more diverse signals, leading to the suppression of unwanted movements. An important question is when this selection mechanism is deployed. Suppose you choose an action A, but not B. It may be because first, you can obtain more rewards by doing A than B, and second, you would be punished by doing B. Many recent studies have been aimed at understanding the first type of selection, reward-obtaining actions. Experiments on monkeys and humans performing goal-directed behaviors have shown that sensorimotor signals carried by striatal neurons are strongly modulated by the expected value of rewards. Such reward-dependent modulation may be caused by inputs from dopamine neurons located in the substantia nigra and surrounding areas. Importantly, the dopamine signal represents reward prediction errors which would guide the cortico-basal ganglia network to choose the optimal output for obtaining rewards. In contrast, the mechanisms for punishment-avoiding behaviors are less well known. If a punishment is predicted after an action, the indirect mechanism in the basal ganglia may become active to suppress the action. This enhancement of the indirect mechanism may be caused by a punishment-predictive signal which originates from the lateral habenula and is mediated by dopamine neurons. PMID:18646620

  12. Processing of temporal information and the basal ganglia: new evidence from fMRI

    Microsoft Academic Search

    Igor Nenadic; Christian Gaser; Hans-Peter Volz; Thomas Rammsayer; Frank Häger; Heinrich Sauer

    2003-01-01

    .   Temporal information processing is a fundamental brain function, which might include central timekeeping mechanisms independent\\u000a of sensory modality. Psychopharmacological and patient studies suggest a crucial role of the basal ganglia in time estimation.\\u000a In this study, functional magnetic resonance imaging (fMRI) was applied in 15 healthy right-handed male subjects performing\\u000a an auditory time estimation task (duration discrimination of tone

  13. Contrast optimization of Macaca mulatta basal ganglia in magnetic resonance images at 4.7 Tesla

    Microsoft Academic Search

    J.-M Bonny; F Durif; J. E Bazin; E Touraille; J Yelnik; J.-P Renou

    2001-01-01

    To determine whether high field MRI could distinguish among the different regions of the basal ganglia, the brains of two Macaca mulatta monkeys were explored in vivo using a 4.7 T MR imager. Gradient-echo (GE) and spin-echo images were acquired with proton-density, T1 and T2(*) weightings. Five GE images with increased susceptibility effects were generated using a GESFID sequence, from

  14. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward.

    PubMed

    Humphries, Mark D; Prescott, Tony J

    2010-04-01

    The basal ganglia are often conceptualised as three parallel domains that include all the constituent nuclei. The 'ventral domain' appears to be critical for learning flexible behaviours for exploration and foraging, as it is the recipient of converging inputs from amygdala, hippocampal formation and prefrontal cortex, putatively centres for stimulus evaluation, spatial navigation, and planning/contingency, respectively. However, compared to work on the dorsal domains, the rich potential for quantitative theories and models of the ventral domain remains largely untapped, and the purpose of this review is to provide the stimulus for this work. We systematically review the ventral domain's structures and internal organisation, and propose a functional architecture as the basis for computational models. Using a full schematic of the structure of inputs to the ventral striatum (nucleus accumbens core and shell), we argue for the existence of many identifiable processing channels on the basis of unique combinations of afferent inputs. We then identify the potential information represented in these channels by reconciling a broad range of studies from the hippocampal, amygdala and prefrontal cortex literatures with known properties of the ventral striatum from lesion, pharmacological, and electrophysiological studies. Dopamine's key role in learning is reviewed within the three current major computational frameworks; we also show that the shell-based basal ganglia sub-circuits are well placed to generate the phasic burst and dip responses of dopaminergic neurons. We detail dopamine's modulation of ventral basal ganglia's inputs by its actions on pre-synaptic terminals and post-synaptic membranes in the striatum, arguing that the complexity of these effects hint at computational roles for dopamine beyond current ideas. The ventral basal ganglia are revealed as a constellation of multiple functional systems for the learning and selection of flexible behaviours and of behavioural strategies, sharing the common operations of selection-by-disinhibition and of dopaminergic modulation. PMID:19941931

  15. Processing emotional tone from speech in Parkinson’s disease: A role for the basal ganglia

    Microsoft Academic Search

    Marc D. Pell; Carol L. Leonard

    2003-01-01

    In this study, individuals with Parkinson’s disease were tested as a model for basal ganglia dysfunction to infer how these\\u000a structures contribute to the processing of emotional speech tone (emotional prosody). Nondemented individuals with and without Parkinson’s disease (n = 21\\/group) completed neuropsychological tests and tasks that required them to process the meaning of emotional prosody in\\u000a various ways (discrimination,

  16. Interruption of a basal ganglia-forebrain circuit prevents plasticity of learned vocalizations

    NASA Astrophysics Data System (ADS)

    Brainard, Michael S.; Doupe, Allison J.

    2000-04-01

    Birdsong, like speech, is a learned vocal behaviour that relies greatly on hearing; in both songbirds and humans the removal of auditory feedback by deafening leads to a gradual deterioration of adult vocal production. Here we investigate the neural mechanisms that contribute to the processing of auditory feedback during the maintenance of song in adult zebra finches. We show that the deleterious effects on song production that normally follow deafening can be prevented by a second insult to the nervous system-the lesion of a basal ganglia-forebrain circuit. The results suggest that the removal of auditory feedback leads to the generation of an instructive signal that actively drives non-adaptive changes in song; they also suggest that this instructive signal is generated within (or conveyed through) the basal ganglia-forebrain pathway. Our findings provide evidence that cortical-basal ganglia circuits may participate in the evaluation of sensory feedback during calibration of motor performance, and demonstrate that damage to such circuits can have little effect on previously learned behaviour while conspicuously disrupting the capacity to adaptively modify that behaviour.

  17. The role of the basal ganglia in learning and memory: Insight from Parkinson's disease

    PubMed Central

    2013-01-01

    It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. PMID:21945835

  18. Tortuosity of terminal arterioles in the basal ganglia is increased in status lacunaris.

    PubMed

    Poni, Esteban S; Liwnicz, Boleslaw H; Ying-Ying, Yue; North, Mary

    2003-06-01

    The goal of this study was to evaluate the participation of small (diameter between 26 microns and 90 microns) and terminal (diameter between 10 microns and 25 microns) arterioles in the status lacunaris of the basal ganglia and to classify tortuous vascular profiles based on morphometry. Paraffin sections, 40 microns thick, of the basal ganglia from autopsied patients over the age of 45, were stained with PAS. A three-dimensional microscope, R400 (edge) was used to evaluate the structure of the blood vessels. Six patterns of the tortuous profiles were identified: simple kink, loop, knot, tangle, coil, and wave, and well as their combinations. Tortuous arterioles in the basal ganglia were present both in control group and status lacunaris cases. However, statistical Student's t-test analysis revealed a significant increment in the number of microfields containing tortuous terminal arterioles in the status lacunaris group (mean 7.50 +/- 4.62) versus the control group (mean 2.92 +/- 1.38) (p = 0.001). A risk for status lacunaris was associated with the increased frequency of tortuous terminal arterioles (Odd ratio = 1.94, 95%-Confidence Interval = 1.17-3.22) (p = 0.008) but not small arterioles (Odd ratio = 1.64, 95%-Confidence Interval = 0.62-4.38) (p = 0.39). Our findings suggest than an increased number of tortuous terminal arterioles is associated with status lacunaris. Six characteristic patterns of the tortuous profiles as well as their combinations were identified. PMID:12815844

  19. Brain tissue properties differentiate between motor and limbic basal ganglia circuits

    PubMed Central

    Accolla, Ettore A; Dukart, Juergen; Helms, Gunther; Weiskopf, Nikolaus; Kherif, Ferath; Lutti, Antoine; Chowdhury, Rumana; Hetzer, Stefan; Haynes, John-Dylan; Kühn, Andrea A; Draganski, Bogdan

    2014-01-01

    Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome. PMID:24777915

  20. Independent circuits in the basal ganglia for the evaluation and selection of actions

    PubMed Central

    Stephenson-Jones, Marcus; Kardamakis, Andreas A.; Robertson, Brita; Grillner, Sten

    2013-01-01

    The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (GPh) neurons, exists within the basal ganglia. The GPh neurons are glutamatergic and can drive the activity of the lateral habenula, which, in turn, provides an indirect inhibitory influence on midbrain dopamine neurons. We show that GPh neurons receive inhibitory input from the striosomal compartment of the striatum. The striosomal input can reduce the excitatory drive to the lateral habenula and, consequently, decrease the inhibition onto the dopaminergic system. Dopaminergic neurons, in turn, provide feedback that inhibits the GPh. In addition, GPh neurons receive direct projections from the pallium (cortex in mammals), which can increase the GPh activity to drive the lateral habenula to increase the inhibition of the neuromodulatory systems. This circuitry, thus, differs markedly from the “direct” and “indirect” pathways that regulate the pallidal (e.g., globus pallidus) output nuclei involved in the control of motion. Our results show that a distinct reward–evaluation circuit exists within the basal ganglia, in parallel to the direct and indirect pathways, which select actions. Our results suggest that these circuits are part of the fundamental blueprint that all vertebrates use to select actions and evaluate their outcome. PMID:24003130

  1. A basal ganglia-forebrain circuit in the songbird biases motor output to avoid vocal errors

    PubMed Central

    Andalman, Aaron S.; Fee, Michale S.

    2009-01-01

    In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and production of complex motor behaviors; however, the precise role of these circuits remains unknown. It has recently been shown that a basal ganglia-forebrain circuit in the songbird, which projects directly to vocal–motor circuitry, has a premotor function driving exploration necessary for vocal learning. It has also been hypothesized that this circuit, known as the anterior forebrain pathway (AFP), may generate an instructive signal that improves performance in the motor pathway. Here, we show that the output of the AFP directly implements a motor correction that reduces vocal errors. We use disruptive auditory feedback, contingent on song pitch, to induce learned changes in song structure over the course of hours and find that reversible inactivation of the output of the AFP produces an immediate regression of these learned changes. Thus, the AFP is involved in generating an error-reducing bias, which could increase the efficiency of vocal exploration and instruct synaptic changes in the motor pathway. We also find that learned changes in the song generated by the AFP are incorporated into the motor pathway within 1 day. Our observations support a view that basal ganglia-related circuits directly implement behavioral adaptations that minimize errors and subsequently stabilize these adaptations by training premotor cortical areas. PMID:19597157

  2. Using point process models to determine the impact of visual cues on basal ganglia activity and behavior of Parkinson's patients

    E-print Network

    Brown, Emery N.

    Deep brain stimulation is an effective therapy for Parkinson's disease (PD) that has enabled microelectrode recordings from single-unit cells in the sub-thalamic nucleus (STN) of the basal ganglia. This rare data is important ...

  3. Connections of the basal ganglia with the limbic system: implications for neuromodulation therapies of anxiety and affective disorders

    Microsoft Academic Search

    P. Stathis; I. G. Panourias; M. S. Themistocleous; Damianos E. Sakas

    The basal ganglia are best known for their role in motor planning and execution. However, it is currently widely accepted\\u000a that they are also involved in cognitive and emotional behaviors. Parts of the basal ganglia play a key role in reward and\\u000a reinforcement, addictive behaviors and habit formation. Pathophysiological processes underlying psychiatric disorders such\\u000a as depression, obsessive compulsive disorder and

  4. Post-stroke affective or apathetic depression and lesion location: left frontal lobe and bilateral basal ganglia

    Microsoft Academic Search

    Seiji Hama; Hidehisa Yamashita; Masaya Shigenobu; Atsuko Watanabe; Kaoru Kurisu; Shigeto Yamawaki; Tamotsu Kitaoka

    2007-01-01

    This study was designed to examine the correlation between damage to the basal ganglia or frontal lobe and depression status\\u000a (both affective and apathetic dimensions) in 243 stroke patients. We assessed the affective dimension in post-stroke depression\\u000a (PSD) using the Zung Self-rating Depression Scale (SDS) and the apathetic dimension in PSD using the apathy scale (AS). We\\u000a classified basal ganglia

  5. Blood Oxygenation Level Dependent Activation in Basal Ganglia Nuclei Relates to Specific Symptoms in De Novo Parkinson's Disease

    PubMed Central

    Prodoehl, Janey; Spraker, Mathew; Corcos, Daniel; Comella, Cynthia; Vaillancourt, David

    2010-01-01

    To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify non-invasive measures of basal ganglia function that are sensitive to disease severity. This study examines the relation between blood oxygenation level dependent (BOLD) activation in every nucleus of the basal ganglia and symptom-specific disease severity in early stage, de novo PD. BOLD activation measured at 3 Tesla was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the basal ganglia nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified Parkinson's Disease Rating Scale (UPDRS) and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the basal ganglia and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the basal ganglia relates most consistently to bradykinesia. The findings demonstrate that functional magnetic resonance imaging has strong potential to serve as a non-invasive marker for the state of basal ganglia function in de novo PD. PMID:20725915

  6. Increased volume and impaired function: the role of the basal ganglia in writer’s cramp

    PubMed Central

    Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Hefter, Harald; Hallett, Mark; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten

    2015-01-01

    Introduction The pathophysiology of writer's cramp, a task-specific dystonia, remains unclear. The objective of this study was to investigate the basal ganglia circuit and the cerebellum during a complex motor sequence learning task carried out with the nonaffected hand in writer's cramp patients. Methods We applied structural and functional imaging in 22 writer's cramp patients and 28 matched controls using 3T MRI. With the asymptomatic left hand all participants learned a complex, sequential, five-element sequence-tapping task as accurately and quickly as possible. Functional imaging was measured during a repeated (15 times), fixed block design with tapping (30 sec) and rest (30 sec). Additionally, gray matter volume of the basal ganglia was analyzed using voxel-based morphometry (VBM). Results While behavior was comparable between groups, after small volume correction the anterior part of the right putamen and the left globus pallidus exhibited reduced blood oxygen level-dependent (BOLD) activity in patients during the sequential finger-tapping task. VBM analysis showed larger gray matter volume bilateral in the posterior part of the putamen and globus pallidus. There were no group differences in the cerebellum. Conclusion The results indicate an impairment of anterior basal ganglia loops involved in producing complex sequential movements of the unaffected hand. These findings are in line with previous reports of reduced neuronal activity in the globus pallidus internus. Higher gray matter volume of the putamen and globus pallidus may stem from elevated activity of the direct pathway, which could reflect a compensatory phenomenon or a primary predisposition, that is, endophenotypic trait. PMID:25642386

  7. Dopaminergic Mechanisms of Reduced Basal Ganglia Responses to Hedonic Reward During Interferon Alfa Administration

    PubMed Central

    Capuron, Lucile; Pagnoni, Giuseppe; Drake, Daniel F.; Woolwine, Bobbi J.; Spivey, James R.; Crowe, Ronald J.; Votaw, John R.; Goodman, Mark M.; Miller, Andrew H.

    2013-01-01

    Context Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. Objectives To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. Design Cross-sectional and longitudinal studies. Setting Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. Patients Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. Main Outcome Measures Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using positron emission tomography, and interferon alfa–induced depression, anhedonia, fatigue, and neurotoxicity. Results Patients with HCV receiving interferon alfa for 4 to 6 weeks (n=14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n=14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n=12) exhibited significantly increased 18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in 18F-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. Conclusions These data replicate and extend findings that inflammatory stimuli, including inflammatory cytokines, such as interferon alfa, alter basal ganglia activity and behavior in association with significant changes in presynaptic striatal dopamine function consistent with decreased dopamine synthesis or release. PMID:23026954

  8. Role of the basal ganglia in the control of sleep and wakefulness

    PubMed Central

    Lazarus, Michael; Chen, Jiang-Fan; Urade, Yoshihiro; Huang, Zhi-Li

    2013-01-01

    The basal ganglia (BG) act as a cohesive functional unit that regulates motor function, habit formation, and reward/addictive behaviors; but the debate has only recently started on how the BG maintain wakefulness and suppress sleep to achieve all these fundamental functions of the BG. Neurotoxic lesioning, pharmacological approaches, and the behavioral analyses of genetically modified animals revealed that the striatum and globus pallidus are important for the control of sleep and wakefulness. Here, we discuss anatomical and molecular mechanisms for sleep-wake regulation in the BG and propose a plausible model in which the nucleus accumbens integrates behavioral processes with wakefulness through adenosine and dopamine receptors. PMID:23465424

  9. Creation of Computerized 3D MRI-Integrated Atlases of the Human Basal Ganglia and Thalamus.

    PubMed

    Sadikot, Abbas F; Chakravarty, M Mallar; Bertrand, Gilles; Rymar, Vladimir V; Al-Subaie, Fahd; Collins, D Louis

    2011-01-01

    Functional brain imaging and neurosurgery in subcortical areas often requires visualization of brain nuclei beyond the resolution of current magnetic resonance imaging (MRI) methods. We present techniques used to create: (1) a lower resolution 3D atlas, based on the Schaltenbrand and Wahren print atlas, which was integrated into a stereotactic neurosurgery planning and visualization platform (VIPER); and (2) a higher resolution 3D atlas derived from a single set of manually segmented histological slices containing nuclei of the basal ganglia, thalamus, basal forebrain, and medial temporal lobe. Both atlases were integrated to a canonical MRI (Colin27) from a young male participant by manually identifying homologous landmarks. The lower resolution atlas was then warped to fit the MRI based on the identified landmarks. A pseudo-MRI representation of the high-resolution atlas was created, and a non-linear transformation was calculated in order to match the atlas to the template MRI. The atlas can then be warped to match the anatomy of Parkinson's disease surgical candidates by using 3D automated non-linear deformation methods. By way of functional validation of the atlas, the location of the sensory thalamus was correlated with stereotactic intraoperative physiological data. The position of subthalamic electrode positions in patients with Parkinson's disease was also evaluated in the atlas-integrated MRI space. Finally, probabilistic maps of subthalamic stimulation electrodes were developed, in order to allow group analysis of the location of contacts associated with the best motor outcomes. We have therefore developed, and are continuing to validate, a high-resolution computerized MRI-integrated 3D histological atlas, which is useful in functional neurosurgery, and for functional and anatomical studies of the human basal ganglia, thalamus, and basal forebrain. PMID:21922002

  10. Molecular microcircuitry underlies functional specification in a basal ganglia circuit dedicated to vocal learning

    PubMed Central

    Hilliard, Austin T.; Miller, Julie E.; Fraley, Elizabeth; Horvath, Steve; White, Stephanie A.

    2012-01-01

    Summary Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication; a complex phenotype likely supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene co-expression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ~2,000 singing-regulated genes comprising 3 co-expression groups unique to area X, the basal ganglia subregion dedicated to learned vocalizations. These contained known targets of human FOXP2 and potential avian targets. We validated novel biological pathways for vocalization. Higher order gene co-expression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that likely bear on human motor disorders, especially those affecting speech. PMID:22325205

  11. Modeling effects of cerebellar and basal ganglia lesions on adaptation and anticipation during sensorimotor synchronization.

    PubMed

    van der Steen, M C Marieke; Schwartze, Michael; Kotz, Sonja A; Keller, Peter E

    2015-03-01

    This study addressed the role of subcortical brain structures in temporal adaptation and anticipation during sensorimotor synchronization. The performance of patients with cerebellar or basal ganglia lesions was compared with that of healthy control participants on tasks requiring the synchronization of drum strokes with adaptive and tempo-changing auditory pacing sequences. The precision of sensorimotor synchronization was generally lower in patients relative to controls (i.e., variability of asynchronies was higher in patients), although synchronization accuracy (mean asynchrony) was commensurate. A computational model of adaptation and anticipation (ADAM) was used to examine potential sources of individual differences in precision by estimating participants' use of error correction, temporal prediction, and the amount of variability associated with central timekeeping and peripheral motor processes. Parameter estimates based on ADAM indicate that impaired precision was attributable to increased variability of timekeeper and motor processes as well as to reduced temporal prediction in both patient groups. Adaptive processes related to continuously applied error correction were, by contrast, intact in patients. These findings highlight the importance of investigating how subcortical structures, including the cerebellum and basal ganglia, interact with a broader network of cortical regions to support temporal adaptation and anticipation during sensorimotor synchronization. PMID:25773623

  12. Basal Ganglia Neuronal Activity during Scanning Eye Movements in Parkinson’s Disease

    PubMed Central

    Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Ji?í; Novák, Daniel; R?ži?ka, Filip; Urgošík, Dušan; R?ži?ka, Evžen; Gaymard, Bertrand; Jech, Robert

    2013-01-01

    The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinso?s disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control. PMID:24223158

  13. A volumetric study of basal ganglia structures in individuals with early-treated phenylketonuria.

    PubMed

    Bodner, Kimberly E; Aldridge, Kristina; Moffitt, Amanda J; Peck, Dawn; White, Desirée A; Christ, Shawn E

    2012-11-01

    Whereas the impact of early-treated phenylketonuria (ETPKU) on cortical white matter is well documented, relatively little is known regarding the potential impact of this metabolic disorder on deep gray matter structures such as the basal ganglia. The current study used high-resolution (1mm(3)) magnetic resonance imaging to investigate bilateral basal ganglia structures (i.e., putamen, caudate nucleus, and nucleus accumbens) in a sample of 13 individuals with ETPKU and a demographically-matched sample of 13 neurologically intact individuals without PKU. Consistent with previous research, we found smaller whole brain volumes in the ETPKU group compared with the non-PKU group. Individuals with ETPKU also had significantly larger putamen volumes than non-PKU individuals. In addition, the degree of putamen enlargement was correlated with blood phenylalanine levels and full scale IQ in the ETPKU group. These findings are consistent with the hypothesis that ETPKU-related increases in phenylalanine lead to decreased central dopamine levels thus impacting dopamine-dependent brain regions such as the putamen that play an important role in cognition. PMID:23006929

  14. Deep intracerebral (basal ganglia) haematomas in fatal non-missile head injury in man.

    PubMed Central

    Adams, J H; Doyle, D; Graham, D I; Lawrence, A E; McLellan, D R

    1986-01-01

    Deep intracerebral (basal ganglia) haematomas were found post mortem in 63 of 635 fatal non-missile head injuries. In patients with a basal ganglia haematoma, contusions were more severe, there was a reduced incidence of a lucid interval, and there was an increased incidence of road traffic accidents, gliding contusions and diffuse axonal injury than in patients without this type of haematoma. Intracranial haematoma is usually thought to be a secondary event, that is a complication of the original injury, but these results suggest that a deep intracerebral haematoma is a primary event. If a deep intracerebral haematoma is identified on an early CT scan it is likely that the patient has sustained severe diffuse brain damage at the time of injury. In the majority of head injuries damage to blood vessels or axons predominates. In patients with a traumatic deep intracerebral haematoma, it would appear that the deceleration/acceleration forces are such that both axons and blood vessels within the brain are damaged at the time of injury. Images PMID:3760892

  15. Orexinergic innervation of the extended amygdala and basal ganglia in the rat.

    PubMed

    Schmitt, Oliver; Usunoff, Kamen G; Lazarov, Nikolai E; Itzev, Dimitar E; Eipert, Peter; Rolfs, Arndt; Wree, Andreas

    2012-04-01

    The orexinergic system interacts with several functional states of emotions, stress, hunger, wakefulness and behavioral arousal through four pathways originating in the lateral hypothalamus (LH). Hundreds of orexinergic efferents have been described by tracing studies and direct immunohistochemistry of orexin in the forebrain, olfactory regions, hippocampus, amygdala, septum, basal ganglia, thalamus, hypothalamus, brain stem and spinal cord. Most of these tracing studies investigated the whole orexinergic projection to all regions of the intracranial part of the CNS. To identify the orexinergic efferents at the subnuclear level of resolution, we focussed on the orexinergic target in the amygdala, which is substantially involved in the LH output and contributes mostly to the functional outcome of the orexinergic system and the basal ganglia. Immunohistochemical identification of axonal orexin A and orexin B in male adult rats has been performed on serial sections. In the extended amygdala many new orexinergic targets were found in the anterior amygdaloid area (dense), anterior cortical nucleus (moderate), amygdalostriatal transition region (moderate), basolateral regions (moderate), basomedial nucleus (moderate), several bed nucleus of the stria terminals regions (few to dense), central amygdaloid subdivisions (dense), posteromedial cortical nucleus (moderate) and medial amygdaloid subnuclei (dense). Furthermore, the entopeduncular nucleus has been newly identified as another target for orexinergic fibers with a high density. These results suggest that subdivisions and subnuclei of the extended amygdala are specific targets of the orexinergic system. PMID:21935673

  16. Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

    SciTech Connect

    Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A. (Sandoz Pharma Ltd., Basel (Switzerland))

    1991-02-01

    Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ({sup 125}I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease.

  17. Atypical location of germinoma in basal ganglia in adolescents: radiological features and treatment outcomes

    PubMed Central

    Rasalkar, D D; Chu, W C W; Cheng, F W T; Paunipagar, B K; Shing, M K; Li, C K

    2010-01-01

    The objective of this work is to describe the imaging findings, clinical profile and treatment response in four Chinese adolescent patients presenting with ectopic germinoma arising from basal ganglia. The clinical presentation, treatment regimens and the imaging findings at presentation and after treatment were described upon retrospective review of four Chinese adolescent patients. CT of the brain showed mixed solid cystic mass lesions in three patients. In one patient, only ill-defined hyperdensity was noted in the affected basal ganglia. Correlative MRI brain studies showed similar findings of large solid cystic masses in three patients, whereas the fourth patient showed small hyperintensities on T2 weighted and fluid-attenuated inversion-recovery sequences. All lesions were confirmed to be germinomas on biopsy. Chemotherapy followed by radiotherapy was given to three patients. There was a dramatic response, with complete resolution of tumour bulk in two patients and >80% reduction in tumour bulk in one patient. Debulking surgery was performed in one subject who had received cranial radiotherapy; the last follow-up MRI showed no evidence of residual disease. PMID:19752170

  18. Learning processing in the basal ganglia: a mosaic of broken mirrors.

    PubMed

    Da Cunha, Claudio; Wietzikoski, Evellyn Claudia; Dombrowski, Patrícia; Bortolanza, Mariza; Santos, Lucélia Mendes; Boschen, Suelen Lucio; Miyoshi, Edmar

    2009-04-12

    In the present review we propose a model to explain the role of the basal ganglia in sensorimotor and cognitive functions based on a growing body of behavioural, anatomical, physiological, and neurochemical evidence accumulated over the last decades. This model proposes that the body and its surrounding environment are represented in the striatum in a fragmented and repeated way, like a mosaic consisting of the fragmented images of broken mirrors. Each fragment forms a functional unit representing articulated parts of the body with motion properties, objects of the environment which the subject can approach or manipulate, and locations the subject can move to. These units integrate the sensory properties and movements related to them. The repeated and widespread distribution of such units amplifies the combinatorial power of the associations among them. These associations depend on the phasic release of dopamine in the striatum triggered by the saliency of stimuli and will be reinforced by the rewarding consequences of the actions related to them. Dopamine permits synaptic plasticity in the corticostriatal synapses. The striatal units encoding the same stimulus/action send convergent projections to the internal segment of the globus pallidus (GPi) and to the substantia nigra pars reticulata (SNr) that stimulate or hold the action through a thalamus-frontal cortex pathway. According to this model, this is how the basal ganglia select actions based on environmental stimuli and store adaptive associations as nondeclarative memories such as motor skills, habits, and memories formed by Pavlovian and instrumental conditioning. PMID:18977393

  19. Distribution of divalent metal transporter-1 in the monkey basal ganglia.

    PubMed

    Huang, E; Ong, W Y; Connor, J R

    2004-01-01

    An accumulation of iron occurs in the brain with age, and it is thought that this may contribute to the pathology of certain neurodegenerative diseases, including Parkinson's disease. In this study, we elucidated the distribution of divalent metal transporter-1 (DMT1) in the monkey basal ganglia by immunocytochemistry, and compared it with the distribution of ferrous iron in these nuclei by Turnbull's Blue histochemical staining. We observed a general correlation between levels of DMT1, and iron staining. Thus, regions such as the caudate nucleus, putamen, and substantia nigra pars reticulata contained dense staining of DMT1 in astrocytic processes, and were also observed to contain large numbers of ferrous iron granules. The exceptions were the globus pallidus externa and interna, which contained light DMT1 staining, but large numbers of ferrous iron granules. The thalamus, subthalamic nucleus, and substantia nigra pars compacta contained neurons that were lightly stained for DMT1, but few or no iron granules. The high levels of DMT1 expression in some of the nuclei of the basal ganglia, particularly the caudate nucleus, putamen, and substantia nigra pars reticulata, may account for the high levels of iron in these regions. PMID:15381278

  20. [Traumatic hematoma in the basal ganglia (caudate) with favorable prognosis: report of two cases].

    PubMed

    Kimura, M; Sobata, E; Suzuki, S; Nonogaki, Y; Iwabuchi, T

    1994-02-01

    Two cases of traumatic basal ganglial hematoma with fairly good prognosis were reported. Several cases with similarly favorable prognosis could be also found in the recent literature. In these cases, post-traumatic disturbance in consciousness was mostly slight or moderate and the patients were rarely comatose. The inquiries in these cases were commonly associated with superficial injuries such as skull fracture, epi-or sub-dural hematoma, brain contusion, or another traumatic ICH. The hematomas in the basal ganglia usually showed a mass effect causing focal neurological signs such as hemiparesis. Neurological improvement was achieved in the operated cases, and final outcome was mostly fair with some fully recovered cases. These clinical features are quite different from those of most cases of traumatic basal ganglial hematoma reported so far, which closely resemble diffuse axonal injury and whose prognoses are extremely poor. There may be two different categories in the traumatic basal ganglial hematomas, those with fair outcomes, and those with poor outcomes. PMID:8115011

  1. Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

    PubMed Central

    Galvan, Adriana; Kuwajima, Masaaki; Smith, Yoland

    2006-01-01

    GABA and glutamate, the main transmitters in the basal ganglia, exert their effects through ionotropic and metabotropic receptors. The dynamic activation of these receptors in response to released neurotransmitter depends, among other factors, on their precise localization in relation to corresponding synapses. The use of high resolution quantitative electron microscope immunocytochemical techniques has provided in-depth description of the subcellular and subsynaptic localization of these receptors in the CNS. In this article, we review recent findings on the ultrastructural localization of GABA and glutamate receptors and transporters in the basal ganglia, at synaptic, extrasynaptic and presynaptic sites. The anatomical evidence supports numerous potential locations for receptor-neurotransmitter interactions, and raises important questions regarding mechanisms of activation and function of synaptic versus extrasynaptic receptors in the basal ganglia. PMID:17059868

  2. Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

    PubMed

    Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

    2015-04-01

    The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. PMID:25595501

  3. Pure hemidystonia with basal ganglion abnormalities on positron emission tomography

    SciTech Connect

    Perlmutter, J.S.; Raichle, M.E.

    1984-03-01

    We present a patient with hemidystonia and an abnormality of the contralateral basal ganglion seen only with positron emission tomography. A 50-year-old sinistral man suffered minor trauma to the right side of his head and neck. Within 20 minutes he developed paroxysmal intermittent dystonic posturing of his right face, forearm, hand, and foot, with weaker contractions of the left foot, lasting several seconds and recurring every few minutes. Neurological findings between spells were normal. The following were also normal: electrolyte, calcium, magnesium, and arterial blood gas levels, and findings of drug screen, cerebrospinal fluid examination, electroencephalography with nasopharyngeal leads, computed tomographic scanning (initially and four weeks later), and cerebral angiography. Positron emission tomographic scanning revealed abnormalities in the left basal ganglion region, including decreased oxygen metabolism, decreased oxygen extraction, increased blood volume, and increased blood flow.

  4. The highs and lows of beta activity in cortico-basal ganglia loops.

    PubMed

    Brittain, John-Stuart; Sharott, Andrew; Brown, Peter

    2014-06-01

    Oscillatory activity in the beta (13-30 Hz) frequency band is widespread in cortico-basal ganglia circuits, and becomes prominent in Parkinson's disease (PD). Here we develop the hypothesis that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information-coding space and hence computational capacity. Task and context drive this dynamic gating, so that for each state there will be an optimal level of network synchrony, and levels lower or higher than this will impair behavioural performance. Thus, both the pathological exaggeration of synchrony, as observed in PD, and the ability of interventions like deep brain stimulation (DBS) to excessively suppress synchrony can potentially lead to impairments in behavioural performance. Indeed, under physiological conditions, the manipulation of computational capacity by beta activity may itself present a mechanism of action selection and maintenance. PMID:24890470

  5. FROM REINFORCEMENT LEARNING MODELS OF THE BASAL GANGLIA TO THE PATHOPHYSIOLOGY OF PSYCHIATRIC AND NEUROLOGICAL DISORDERS

    PubMed Central

    Maia, Tiago V.; Frank, Michael J.

    2013-01-01

    Over the last decade and a half, reinforcement learning models have fostered an increasingly sophisticated understanding of the functions of dopamine and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits. More recently, these models, and the insights that they afford, have started to be used to understand key aspects of several psychiatric and neurological disorders that involve disturbances of the dopaminergic system and CBGTC circuits. We review this approach and its existing and potential applications to Parkinson’s disease, Tourette’s syndrome, attention-deficit/hyperactivity disorder, addiction, schizophrenia, and preclinical animal models used to screen novel antipsychotic drugs. The approach’s proven explanatory and predictive power bodes well for the continued growth of computational psychiatry and computational neurology. PMID:21270784

  6. Robust representation of stable object values in the oculomotor Basal Ganglia.

    PubMed

    Yasuda, Masaharu; Yamamoto, Shinya; Hikosaka, Okihide

    2012-11-21

    Our gaze tends to be directed to objects previously associated with rewards. Such object values change flexibly or remain stable. Here we present evidence that the monkey substantia nigra pars reticulata (SNr) in the basal ganglia represents stable, rather than flexible, object values. After across-day learning of object-reward association, SNr neurons gradually showed a response bias to surprisingly many visual objects: inhibition to high-valued objects and excitation to low-valued objects. Many of these neurons were shown to project to the ipsilateral superior colliculus. This neuronal bias remained intact even after >100 d without further learning. In parallel with the neuronal bias, the monkeys tended to look at high-valued objects. The neuronal and behavioral biases were present even if no value was associated during testing. These results suggest that SNr neurons bias the gaze toward objects that were consistently associated with high values in one's history. PMID:23175843

  7. Learning to Select Actions with Spiking Neurons in the Basal Ganglia

    PubMed Central

    Stewart, Terrence C.; Bekolay, Trevor; Eliasmith, Chris

    2012-01-01

    We expand our existing spiking neuron model of decision making in the cortex and basal ganglia to include local learning on the synaptic connections between the cortex and striatum, modulated by a dopaminergic reward signal. We then compare this model to animal data in the bandit task, which is used to test rodent learning in conditions involving forced choice under rewards. Our results indicate a good match in terms of both behavioral learning results and spike patterns in the ventral striatum. The model successfully generalizes to learning the utilities of multiple actions, and can learn to choose different actions in different states. The purpose of our model is to provide both high-level behavioral predictions and low-level spike timing predictions while respecting known neurophysiology and neuroanatomy. PMID:22319465

  8. New roles for the external globus pallidus in basal ganglia circuits and behavior.

    PubMed

    Gittis, Aryn H; Berke, Joshua D; Bevan, Mark D; Chan, C Savio; Mallet, Nicolas; Morrow, Michelle M; Schmidt, Robert

    2014-11-12

    The development of methodology to identify specific cell populations and circuits within the basal ganglia is rapidly transforming our ability to understand the function of this complex circuit. This mini-symposium highlights recent advances in delineating the organization and function of neural circuits in the external segment of the globus pallidus (GPe). Although long considered a homogeneous structure in the motor-suppressing "indirect-pathway," the GPe consists of a number of distinct cell types and anatomical subdomains that contribute differentially to both motor and nonmotor features of behavior. Here, we integrate recent studies using techniques, such as viral tracing, transgenic mice, electrophysiology, and behavioral approaches, to create a revised framework for understanding how the GPe relates to behavior in both health and disease. PMID:25392486

  9. A basal ganglia pathway drives selective auditory responses in songbird dopaminergic neurons via disinhibition

    PubMed Central

    Gale, Samuel D.; Perkel, David J.

    2010-01-01

    Dopaminergic neurons in mammals respond to rewards and reward-predicting cues, and are thought to play an important role in learning actions or sensory cues that lead to reward. The anatomical sources of input that drive or modulate such responses are not well understood; these ultimately define the range of behavior to which dopaminergic neurons contribute. Primary rewards are not the immediate objective of all goal-directed behavior. For example, a goal of vocal learning is to imitate vocal-communication signals. Here, we demonstrate activation of dopaminergic neurons in songbirds driven by a basal ganglia region required for vocal learning, Area X. Dopaminergic neurons in anesthetized zebra finches respond more strongly to bird's own song (BOS) than to other sounds, and Area X is critical for these responses. Direct pharmacological modulation of Area X output, in the absence of auditory stimulation, is sufficient to bidirectionally modulate the firing rate of dopaminergic neurons. The only known pathway from song-control regions to dopaminergic neurons involves a projection from Area X to the ventral pallidum (VP), which in turn projects to dopaminergic regions. We show that VP neurons are spontaneously active and inhibited preferentially by BOS, suggesting that Area X disinihbits dopaminergic neurons by inhibiting VP. Supporting this model, auditory-response latencies are shorter in Area X than VP, and shorter in VP than dopaminergic neurons. Thus, dopaminergic neurons can be disinhibited selectively by complex sensory stimuli via input from the basal ganglia. The functional pathway we identify may allow dopaminergic neurons to contribute to vocal learning. PMID:20089911

  10. Endoscopic considerations treating hydrocephalus caused by basal ganglia and large thalamic tumors

    PubMed Central

    Roth, Jonathan; Ram, Zvi; Constantini, Shlomi

    2015-01-01

    Background: Deep basal-ganglia and large thalamic (BGT) tumors may cause secondary hydrocephalus by compressing the lateral and third ventricles. The ventricular distortion, as well as the infiltrative nature and friability of these tumors, raise specific considerations and risks when treating these patients. Treatment goals may therefore focus on cerebrospinal fluid (CSF) diversion and tissue sampling, followed by nonsurgical treatment options. We present our experience in applying endoscopic techniques for the initial management of such patients. Methods: Over a period of 15 months (January 2013 to April 2014), six patients with BGT tumors presented with signs and symptoms of increased intracranial pressure secondary to hydrocephalus. Data was collected retrospectively, including clinical, surgical, and outcome variables. Results: Six patients aged 9–41 years (25.6 ± 12.5) were included. Endoscopic procedures included endoscopic third ventriculostomy (4), septum pellucidotomy (5), foramen of Monro stenting (2), and endoscopic biopsy (3). One patient underwent a ventriculoperitoneal shunt placement and another stereotactic biopsy. Indications for endoscopic treatment included the infiltrative nature of the tumor preventing a resective procedure, combined with clinical deterioration related to increased intracranial pressure secondary to hydrocephalus. Pathology results included anaplastic astrocytoma (3) and anaplastic oligodendroglioma (1). Pathological sampling was not possible in two patients. Five patients enjoyed a good clinical recovery with no associated morbidity. There was one perioperative death, secondary to preoperative herniation. Conclusions: Endoscopic surgery may potentially play a significant role in the initial management of patients with large basal ganglia and large thalamic tumors causing obstructive hydrocephalus. Technical nuances and individualized goals are crucial for optimal outcomes.

  11. Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and Parkinsonian monkeys.

    PubMed

    Hadipour-Niktarash, Arash; Rommelfanger, Karen S; Masilamoni, Gunasingh J; Smith, Yoland; Wichmann, Thomas

    2012-03-01

    According to traditional models of the basal ganglia-thalamocortical network of connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through actions on striatal neurons that give rise to the "indirect" pathway, secondarily affecting the activity in the internal and external pallidal segments (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr). However, accumulating evidence from the rodent literature suggests that D2LR activation also directly influences synaptic transmission in these nuclei. To further examine this issue in primates, we combined in vivo electrophysiological recordings and local intracerebral microinjections of drugs with electron microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian) monkeys. D2LR activation with quinpirole increased firing in most GPe neurons, likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local application of quinpirole reduced firing in GPi and SNr, possibly through D2LR-mediated effects on glutamatergic inputs. Injections of the D2LR antagonist sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2 receptor immunoreactivity was most prevalent in putative striatal-like GABAergic terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant proportion of immunoreactive boutons also displayed ultrastructural features of glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity were maintained in the parkinsonian state. Thus, in addition to their preferential effects on indirect pathway striatal neurons, extrastriatal D2LR activation in GPi and SNr also influences direct pathway elements in the primate basal ganglia under normal and parkinsonian conditions. PMID:22131382

  12. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

    PubMed Central

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

  13. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

    PubMed

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

  14. Deep Arteriovenous Malformations in the Basal Ganglia, Thalamus, and Insula: Microsurgical Management, Techniques, and Results

    PubMed Central

    Potts, Matthew B.; Young, William L.; Lawton, Michael T.

    2014-01-01

    Background Arteriovenous malformations (AVMs) in the basal ganglia, thalamus, and insula are considered inoperable given their depth, eloquence, and limited surgical exposure. While many neurosurgeons opt for radiosurgery or observation, others have challenged the belief that deep AVMs are inoperable. Further discussion of patient selection, technique, and multimodality management is needed. Objective To describe and discuss the technical considerations of microsurgical resection for deep-seated AVMs. Methods Patients with deep AVMs who underwent surgery during a 14-year period were reviewed using a prospective AVM registry. Results Microsurgery was performed in 48 patients with AVMs in the basal ganglia (n=10), thalamus (n=13), or insula (n=25). The most common Spetzler-Martin grade was III- (68%). Surgical approaches included transsylvian (67%), transcallosal (19%), and transcortical (15%). Complete resection was achieved in 34 patients (71%), and patients with incomplete resection were treated with radiosurgery. Forty-five patients (94%) were improved or unchanged (mean follow-up 1.6 years). Conclusion This experience advances the notion that select deep AVMs may be operable lesions. Patients were highly selected for small size, hemorrhagic presentation, young age, and compactness – factors embodied in the Spetzler-Martin and Supplementary grading systems. Overall, 10 different approaches were used, exploiting direct, transcortical corridors created by hemorrhage or maximizing anatomical corridors through subarachnoid spaces and ventricles that minimize brain transgression. The same cautious attitude exercised in selecting patients for surgery was also exercised in deciding extent of resection, opting for incomplete resection and radiosurgery more than with other AVMs to prioritize neurological outcomes. PMID:23728451

  15. Beta Frequency Synchronization in Basal Ganglia Output during Rest and Walk in a Hemiparkinsonian Rat

    PubMed Central

    Avila, Irene; Parr-Brownlie, Louise C.; Brazhnik, Elena; Castañeda, Edward; Bergstrom, Debra A.; Walters, J. R.

    2012-01-01

    Synchronized oscillatory neuronal activity in the beta frequency range has been observed in the basal ganglia of Parkinson’s disease patients and hypothesized to be antikinetic. The unilaterally lesioned rat model of Parkinson’s disease allows examination of this hypothesis by direct comparison of beta activity in basal ganglia output in non-lesioned and dopamine cell lesioned hemispheres during motor activity. Bilateral substantia nigra pars reticulata (SNpr) recordings of units and local field potentials (LFP) were obtained with EMG activity from the scapularis muscle in control and unilaterally nigrostriatal lesioned rats trained to walk on a rotary treadmill. After left hemispheric lesion, rats had difficulty walking contraversive on the treadmill but could walk in the ipsiversive direction. During inattentive rest, SNpr LFP power in the 12–25 Hz range (low beta) was significantly greater in the dopamine-depleted hemisphere than in non-lesioned and control hemispheres. During walking, low beta power was reduced in all hemispheres, while 25–40 Hz (high beta) activity was selectively increased in the lesioned hemisphere. High beta power increases were reduced by L-DOPA administration. SNpr spiking was significantly more synchronized with SNpr low beta LFP oscillations during rest and high beta LFP oscillations during walking in the dopamine-depleted hemispheres compared with non-lesioned hemispheres. Data show that dopamine loss is associated with opposing changes in low and high beta range SNpr activity during rest and walk and suggest that increased synchronization of high beta activity in SNpr output from the lesioned hemisphere during walking may contribute to gait impairment in the hemiparkinsonian rat. PMID:19948166

  16. Modeling the Contributions of Basal Ganglia and Hippocampus to Spatial Navigation Using Reinforcement Learning

    PubMed Central

    Sukumar, Deepika; Rengaswamy, Maithreye; Chakravarthy, V. Srinivasa

    2012-01-01

    A computational neural model that describes the competing roles of Basal Ganglia and Hippocampus in spatial navigation is presented. Model performance is evaluated on a simulated Morris water maze explored by a model rat. Cue-based and place-based navigational strategies, thought to be subserved by the Basal ganglia and Hippocampus respectively, are described. In cue-based navigation, the model rat learns to directly head towards a visible target, while in place-based navigation the target position is represented in terms of spatial context provided by an array of poles placed around the pool. Learning is formulated within the framework of Reinforcement Learning, with the nigrostriatal dopamine signal playing the role of Temporal Difference Error. Navigation inherently involves two apparently contradictory movements: goal oriented movements vs. random, wandering movements. The model hypothesizes that while the goal-directedness is determined by the gradient in Value function, randomness is driven by the complex activity of the SubThalamic Nucleus (STN)-Globus Pallidus externa (GPe) system. Each navigational system is associated with a Critic, prescribing actions that maximize value gradients for the corresponding system. In the integrated system, that incorporates both cue-based and place-based forms of navigation, navigation at a given position is determined by the system whose value function is greater at that position. The proposed model describes the experimental results of [1], a lesion-study that investigates the competition between cue-based and place-based navigational systems. The present study also examines impaired navigational performance under Parkinsonian-like conditions. The integrated navigational system, operated under dopamine-deficient conditions, exhibits increased escape latency as was observed in experimental literature describing MPTP model rats navigating a water maze. PMID:23110073

  17. Functional contributions of the basal ganglia to emotional prosody: evidence from ERPs.

    PubMed

    Paulmann, Silke; Pell, Marc D; Kotz, Sonja A

    2008-06-27

    The basal ganglia (BG) have been functionally linked to emotional processing [Pell, M.D., Leonard, C.L., 2003. Processing emotional tone form speech in Parkinson's Disease: a role for the basal ganglia. Cogn. Affec. Behav. Neurosci. 3, 275-288; Pell, M.D., 2006. Cerebral mechanisms for understanding emotional prosody in speech. Brain Lang. 97 (2), 221-234]. However, few studies have tried to specify the precise role of the BG during emotional prosodic processing. Therefore, the current study examined deviance detection in healthy listeners and patients with left focal BG lesions during implicit emotional prosodic processing in an event-related brain potential (ERP)-experiment. In order to compare these ERP responses with explicit judgments of emotional prosody, the same participants were tested in a follow-up recognition task. As previously reported [Kotz, S.A., Paulmann, S., 2007. When emotional prosody and semantics dance cheek to cheek: ERP evidence. Brain Res. 1151, 107-118; Paulmann, S. & Kotz, S.A., 2008. An ERP investigation on the temporal dynamics of emotional prosody and emotional semantics in pseudo- and lexical sentence context. Brain Lang. 105, 59-69], deviance of prosodic expectancy elicits a right lateralized positive ERP component in healthy listeners. Here we report a similar positive ERP correlate in BG-patients and healthy controls. In contrast, BG-patients are significantly impaired in explicit recognition of emotional prosody when compared to healthy controls. The current data serve as first evidence that focal lesions in left BG do not necessarily affect implicit emotional prosodic processing but evaluative emotional prosodic processes as demonstrated in the recognition task. The results suggest that the BG may not play a mandatory role in implicit emotional prosodic processing. Rather, executive processes underlying the recognition task may be dysfunctional during emotional prosodic processing. PMID:18501336

  18. Left and right basal ganglia and frontal activity during language generation: Contributions to lexical, semantic, and phonological processes

    Microsoft Academic Search

    BRUCE CROSSON; HOPE BENEFIELD; M. ALLISON CATO; JOSEPH R. SADEK; ANNA BACON MOORE; CHRISTINA E. WIERENGA; KAUNDINYA GOPINATH; DAVID SOLTYSIK; RUSSELL M. BAUER; EDWARD J. AUERBACH; DIDEM GÖKÇAY; CHRISTIANA M. LEONARD; RICHARD W. BRIGGS

    2003-01-01

    f MRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During f MRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation

  19. Lrrk2 localization in the primate basal ganglia and thalamus: a light and electron microscopic analysis in monkeys.

    PubMed

    Lee, H; Melrose, H L; Yue, M; Pare, Jean-Francois; Farrer, M J; Smith, Y

    2010-08-01

    The Leucine Rich Repeat Kinase-2 (LRRK2) gene is a common mutation target in Parkinson's disease (PD), but the cellular mechanisms by which such mutations underlie the pathophysiology of PD remain poorly understood. Thus, to better characterize the neuronal target sites of LRRK2 mutations in the primate brain, we studied the cellular and ultrastructural localization of Lrrk2 immunoreactivity in the monkey basal ganglia. As previously described, the monkey striatum was the most enriched basal ganglia structure in Lrrk2 labeling. Both projection neurons and parvalbumin-containing GABAergic interneurons displayed Lrrk2 immunoreactivity. At the electron microscopic level, striatal Lrrk2 labeling was associated predominantly with dendritic shafts and subsets of putative glutamatergic axon terminals. At the pallidal level, moderate cellular Lrrk2 immunostaining was found in the external globus pallidus (GPe), while neurons in the internal globus pallidus (GPi) were devoid of Lrrk2 immunoreactivity. Strong labeling was associated with cholinergic neurons in the nucleus basalis of Meynert. Midbrain dopaminergic neurons in the primate substantia nigra pars compacta (SNc) and ventral tegmental area harbored a significant level of Lrrk2 labeling, while neurons in the subthalamic nucleus were lightly immunostained. Most thalamic nuclei were enriched in Lrrk2 immunoreactivity, except for the centromedian nucleus that was completely devoid of labeling. Thus, Lrrk2 protein is widely distributed in the monkey basal ganglia, suggesting that gene mutations in PD may result in multifarious pathophysiological effects that could impact various target sites in the functional circuitry of the primate basal ganglia. PMID:20483355

  20. Where neuroscience and dynamic system theory meet autonomous robotics: A contracting basal ganglia model for action selection

    Microsoft Academic Search

    Benoît Girard; Nicolas Tabareau; Quang-cuong Pham; Alain Berthoz; Jean-jacques E. Slotine

    2008-01-01

    Action selection, the problem of choosing what to do next, is central to any autonomous agent architecture. We use here a multi-disciplinary approach at the convergence of neuroscience, dynamical system theory and autonomous robotics, in order to propose an efficient action selection mechanism based on a new model of the basal ganglia. We first describe new developments of contraction theory

  1. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance

    Microsoft Academic Search

    Dara S. Manoach; Randy L. Gollub; Etienne S. Benson; Meghan M. Searl; Donald C. Goff; Elkan Halpern; Clifford B. Saper; Scott L. Rauch

    2000-01-01

    Background: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to

  2. Comparative processing of emotional prosody and semantics following basal ganglia infarcts: ERP evidence of selective impairments for disgust and fear.

    PubMed

    Paulmann, Silke; Pell, Marc D; Kotz, Sonja A

    2009-10-27

    There is evidence from neuroimaging and clinical studies that functionally link the basal ganglia to emotional speech processes. However, in most previous studies, explicit tasks were administered. Thus, the underlying mechanisms substantiating emotional speech are not separated from possibly process-related task effects. Therefore, the current study tested emotional speech processing in an event-related potential (ERP) experiment using an implicit emotional processing task (probe verification). The interactive time course of emotional prosody in the context of emotional semantics was investigated using a cross-splicing method. As previously demonstrated, combined prosodic and semantic expectancy violations elicit N400-like negativities irrespective of emotional categories in healthy listeners. In contrast, basal ganglia patients show this negativity only for the emotions of happiness and anger, but not for fear or disgust. The current data serve as first evidence that lesions within the left basal ganglia affect the comparative online processing of fear and disgust prosody and semantics. Furthermore, the data imply that previously reported emotional speech recognition deficits in basal ganglia patients may be due to misaligned processing of emotional prosody and semantics. PMID:19664605

  3. Radiation Absorbed Dose to the Basal Ganglia from Dopamine Transporter Radioligand 18F-FPCIT

    PubMed Central

    Robeson, William; Dhawan, Vijay; Ma, Yilong; Bjelke, David; Margouleff, Claude; Chaly, Thomas; Eidelberg, David

    2014-01-01

    Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers, 18F-FDOPA and 18F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using 18F-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations. S-factors were computed using the MIRDOSE3 nodule model for each caudate and putamen. For 18F-FPCIT, BG dose ranged from 0.029 to 0.069 mGy/MBq. In half of all subjects, BG dose exceeded 85% of the published critical organ (bladder) dose, and in three of those, the BG dose exceeded that for the bladder. The BG can become the dose-limiting organ in studies using dopamine transporter ligands. For some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure. PMID:25093172

  4. Technical Integration of Hippocampus, Basal Ganglia and Physical Models for Spatial Navigation

    PubMed Central

    Fox, Charles; Humphries, Mark; Mitchinson, Ben; Kiss, Tamas; Somogyvari, Zoltan; Prescott, Tony

    2008-01-01

    Computational neuroscience is increasingly moving beyond modeling individual neurons or neural systems to consider the integration of multiple models, often constructed by different research groups. We report on our preliminary technical integration of recent hippocampal formation, basal ganglia and physical environment models, together with visualisation tools, as a case study in the use of Python across the modelling tool-chain. We do not present new modeling results here. The architecture incorporates leaky-integrator and rate-coded neurons, a 3D environment with collision detection and tactile sensors, 3D graphics and 2D plots. We found Python to be a flexible platform, offering a significant reduction in development time, without a corresponding significant increase in execution time. We illustrate this by implementing a part of the model in various alternative languages and coding styles, and comparing their execution times. For very large-scale system integration, communication with other languages and parallel execution may be required, which we demonstrate using the BRAHMS framework's Python bindings. PMID:19333376

  5. Emotional Speech Perception Unfolding in Time: The Role of the Basal Ganglia

    PubMed Central

    Paulmann, Silke; Ott, Derek V. M.; Kotz, Sonja A.

    2011-01-01

    The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages. PMID:21437277

  6. Impaired Frontal-Basal Ganglia Connectivity in Adolescents with Internet Addiction

    PubMed Central

    Li, Baojuan; Friston, Karl J.; Liu, Jian; Liu, Yang; Zhang, Guopeng; Cao, Fenglin; Su, Linyan; Yao, Shuqiao; Lu, Hongbing; Hu, Dewen

    2014-01-01

    Understanding the neural basis of poor impulse control in Internet addiction (IA) is important for understanding the neurobiological mechanisms of this syndrome. The current study investigated how neuronal pathways implicated in response inhibition were affected in IA using a Go-Stop paradigm and functional magnetic resonance imaging (fMRI). Twenty-three control subjects aged 15.2 ± 0.5 years (mean ± S.D.) and eighteen IA subjects aged 15.1 ± 1.4 years were studied. Effective connectivity within the response inhibition network was quantified using (stochastic) dynamic causal modeling (DCM). The results showed that the indirect frontal-basal ganglia pathway was engaged by response inhibition in healthy subjects. However, we did not detect any equivalent effective connectivity in the IA group. This suggests the IA subjects fail to recruit this pathway and inhibit unwanted actions. This study provides a clear link between Internet addiction as a behavioral disorder and aberrant connectivity in the response inhibition network. PMID:24848380

  7. Eyes on MEGDEL: Distinctive Basal Ganglia Involvement in Dystonia Deafness Syndrome.

    PubMed

    Wortmann, Saskia B; van Hasselt, Peter M; Bari?, Ivo; Burlina, Alberto; Darin, Niklas; Hörster, Friederike; Coker, Mahmut; Kalkan Ucar, Sema; Krumina, Zita; Naess, Karin; Ngu, Lock H; Pronicka, Ewa; Riordan, Gilian; Santer, Rene; Wassmer, Evangeline; Zschocke, Johannes; Schiff, Manuel; de Meirleir, Linda; Alowain, Mohammed A; Smeitink, Jan A M; Morava, Eva; Kozicz, Tamas; Wevers, Ron A; Wolf, Nicole I; Willemsen, Michel A

    2015-04-01

    Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings. PMID:25642805

  8. Neurocomputational models of basal ganglia function in learning, memory and choice

    PubMed Central

    Cohen, Michael X; Frank, Michael J.

    2009-01-01

    The basal ganglia (BG) are critical for the coordination of several motor, cognitive, and emotional functions and become dysfunctional in several pathological states ranging from Parkinson's disease to Schizophrenia. Here we review principles developed within a neurocomputational framework of BG and related circuitry which provide insights into their functional roles in behavior. We focus on two classes of models: those that incorporate aspects of biological realism and constrained by functional principles, and more abstract mathematical models focusing on the higher level computational goals of the BG. While the former are arguably more “realistic”, the latter have a complementary advantage in being able to describe functional principles of how the system works in a relatively simple set of equations, but are less suited to making specific hypotheses about the roles of specific nuclei and neurophysiological processes. We review the basic architecture and assumptions of these models, their relevance to our understanding of the neurobiological and cognitive functions of the BG, and provide an update on the potential roles of biological details not explicitly incorporated in existing models. Empirical studies ranging from those in transgenic mice to dopaminergic manipulation, deep brain stimulation, and genetics in humans largely support model predictions and provide the basis for further refinement. Finally, we discuss possible future directions and possible ways to integrate different types of models. PMID:18950662

  9. Reduced basal ganglia function when elderly switch between coordinated movement patterns.

    PubMed

    Coxon, James P; Goble, Daniel J; Van Impe, Annouchka; De Vos, Jeroen; Wenderoth, Nicole; Swinnen, Stephan P

    2010-10-01

    Structural and neurochemical changes in frontostriatal circuits are thought to underlie age-related behavioral deficits on cognitive tasks. Here, we test the hypothesis that age-related motor switching deficits are associated with reduced basal ganglia (BG) function. Right-handed volunteers (15 Old, and 15 Young) made spatially and temporally coupled bimanual circular motions during event-related FMRI. A visual cue signaled the right hand to Switch or Continue its circling direction. Switching from mirror symmetric to asymmetric (SW»ASYMM) took longer and resulted in more contralateral (left-) hand disruptions than vice versa. These effects were more pronounced in the elderly, showing that the ability to suppress and flexibly adapt motor behavior (agility) declines with age. For both groups, switching activated the BG and a typical network for task-set implementation, including dorsal anterior cingulate cortex/supplementary motor area (pre-SMA, SMA-proper) and anterior insula/inferior frontal gyrus. A region of interest analysis revealed significantly reduced SW»ASYMM activation in bilateral subthalamic nucleus and right globus pallidus, only in the elderly. Age-related behavioral deficits may be related to inefficient recruitment of cortico-BG loops to suppress undesired movements. The elderly may use an alternative strategy to select the required movement pattern as indicated by increased activation of prefrontal cortex. PMID:20080932

  10. The functional connectivity of intralaminar thalamic nuclei in the human basal ganglia.

    PubMed

    Rodriguez-Sabate, Clara; Llanos, Catalina; Morales, Ingrid; Garcia-Alvarez, Roberto; Sabate, Magdalena; Rodriguez, Manuel

    2015-04-01

    Projections of the centromedian-parafasicularis neurons of the intralaminar thalamus are major inputs of the striatum. Their functional role in the activity of human basal ganglia (BG) is not well known. The aim of this work was to study the functional connectivity of intralaminar thalamic nuclei with other BG by using the correlations of the BOLD signal recorded during "resting" and a motor task. Intralaminar nuclei showed a marked functional connectivity with all the tested BG, which was observed during "resting" and did not change with the motor task. As regards the intralaminar nuclei, BG connectivity was much lower for the medial dorsal nucleus (a thalamic nucleus bordering the intralaminar nuclei) and for the default mode network (although intralaminar nuclei showed a negative correlation with the default mode network). After the "regression" of intralaminar nuclei activity (partial correlation), the functional connectivity of the caudate and putamen nuclei with other BG decreased (but not with the primary sensorimotor cortex). Present data provide evidence that intralaminar nuclei are not only critical for striatal activity but also for the global performance of human BG, an action involving subcortical BG loops more than cortico-subcortical loops. The high correlation found between BG suggest that, similarly to that reported in other brain centers, the very-slow frequency fluctuations are relevant for the functional activity of these centers. Hum Brain Mapp 36:1335-1347, 2015. © 2014 Wiley Periodicals, Inc. PMID:25429921

  11. Role of Beta-Arrestin 2 Downstream of Dopamine Receptors in the Basal Ganglia

    PubMed Central

    Del’Guidice, Thomas; Lemasson, Morgane; Beaulieu, Jean-Martin

    2011-01-01

    Multifunctional scaffolding protein beta-arrestins (?Arr) and the G protein-receptor kinases are involved in the desensitization of several G protein-coupled receptors (GPCR). However, arrestins can also contribute to GPCR signaling independently from G proteins. In this review, we focus on the role of ?Arr in the regulation of dopamine receptor functions in the striatum. First, we present in vivo evidence supporting a role for these proteins in the regulation of dopamine receptor desensitization. Second, we provide an overview of the roles of ?Arr2 in the regulation of extracellular-signal-regulated kinases/MAP kinases and Akt/GSK3 signaling pathways downstream of the D1 and D2 dopamine receptors. Thereafter, we examine the possible involvement of ?Arr-mediated signaling in the action of dopaminergic drugs used for the treatment of mental disorders. Finally, we focus on different potential cellular proteins regulated by ?Arr-mediated signaling which could contribute to the regulation of behavioral responses to dopamine. Overall, the identification of a cell signaling function for ?Arr downstream of dopamine receptors underscores the intricate complexity of the intertwined mechanisms regulating and mediating cell signaling in the basal ganglia. Understanding these mechanisms may lead to a better comprehension of the several roles played by these structures in the regulation of mood and to the development of new psychoactive drugs having better therapeutic efficacy. PMID:21922001

  12. Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

    PubMed Central

    Ellens, Damien J.; Leventhal, Daniel K.

    2014-01-01

    Incomplete understanding of the systems-level pathophysiology of Parkinson Disease (PD) remains a significant barrier to improving its treatment. Substantial progress has been made, however, due to the availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons. This review discusses the in vivo electrophysiology of basal ganglia (BG), thalamic, and cortical regions after dopamine-depleting lesions. These include firing rate changes, neuronal burst-firing, neuronal oscillations, and neuronal synchrony that result from a combination of local microanatomic changes and network-level interactions. While much is known of the clinical and electrophysiological phenomenology of dopamine loss, a critical gap in our conception of PD pathophysiology is the link between them. We discuss potential mechanisms by which these systems-level electrophysiological changes may emerge, as well as how they may relate to clinical parkinsonism. Proposals for an updated understanding of BG function are reviewed, with an emphasis on how emerging frameworks will guide future research into the pathophysiology and treatment of PD. PMID:23948994

  13. Emotional speech perception unfolding in time: the role of the basal ganglia.

    PubMed

    Paulmann, Silke; Ott, Derek V M; Kotz, Sonja A

    2011-01-01

    The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages. PMID:21437277

  14. Lrrk2 Localization in the Primate Basal ganglia and Thalamus: A Light and Electron Microscopic Analysis in Monkeys

    PubMed Central

    Lee, H.; Melrose, H.L.; Yu, M.; Pare, Jean-Francois; Farrer, M.J.; Smith, Y.

    2010-01-01

    The Leucine Rich Repeat Kinase-2 (LRRK2) gene is a common mutation target in Parkinson’s disease (PD), but the cellular mechanisms by which such mutations underlie the pathophysiology of PD remain poorly understood. Thus, to better characterize the neuronal target sites of LRRK2 mutations in the primate brain, we studied the cellular and ultrastructural localization of Lrrk2 immunoreactivity in the monkey basal ganglia. As previously described, the monkey striatum was the most enriched basal ganglia structure in Lrrk2 labeling. Both projection neurons and parvalbumin-containing GABAergic interneurons displayed Lrrk2 immunoreactivity. At the electron microscopic level, striatal Lrrk2 labeling was associated predominantly with dendritic shafts and subsets of putative glutamatergic axon terminals. At the pallidal level, moderate cellular Lrrk2 immunostaining was found in the external globus pallidus (GPe), while neurons in the internal globus pallidus (GPi) were devoid of Lrrk2 immunoreactivity. Strong labeling was associated with cholinergic neurons in the nucleus basalis of Meynert. Midbrain dopaminergic neurons in the primate substantia nigra pars compacta (SNc) and ventral tegmental area harbored a significant level of Lrrk2 labeling, while neurons in the subthalamic nucleus were lightly immunostained. Most thalamic nuclei were enriched in Lrrk2 immunoreactivity, except for the centromedian nucleus that was completely devoid of labeling. Thus, Lrrk2 protein is widely distributed in the monkey basal ganglia, suggesting that gene mutations in PD may result in multifarious pathophysiological effects that could impact various target sites in the functional circuitry of the primate basal ganglia. PMID:20483355

  15. Vasogenic Edema of the Basal Ganglia after Intra-Arterial Administration of Nimodipine for Treatment of Vasospasm

    PubMed Central

    Ryu, Chang-Woo; Yu, Seung-Young; Kim, Eui-Jong

    2011-01-01

    The intra-arterial administration of nimodipine (IAN) is commonly used for cerebral vasospasm refractory to medical treatments. We report two cases of vasogenic edema after IAN. Our patients with aneurismal subarachnoid hemorrhage presented with vasospasm, which was treated by IAN. Consequently, vasogenic edema developed in the basal ganglia. Reperfusion following IAN for vasospasm may have the potential for inciting vasogenic edema in the ischemic brain. PMID:21519500

  16. GENSAT BAC Cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits

    PubMed Central

    Gerfen, Charles R.; Paletzki, Ronald; Heintz, Nathaniel

    2013-01-01

    Summary Recent development of molecular genetic techniques are rapidly advancing understanding of the functional role of brain circuits in behavior. Critical to this approach is the ability to target specific neuron populations and circuits. The collection of over 250 BAC Cre-recombinase driver lines produced by the GENSAT project provides a resource for such studies. Here we provide characterization of GENSAT BAC-Cre driver lines with expression in specific neuroanatomical pathways within the cerebral cortex and basal ganglia. PMID:24360541

  17. A pilot study of basal ganglia and thalamus structure by high dimensional mapping in children with Tourette syndrome

    PubMed Central

    Black, Kevin J.

    2013-01-01

    Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).  A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. Objective: Pilot the HDBM-LD method in children and estimate effect sizes. Methods: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age.  The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. Results: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry.  Effect sizes were greater for shape analysis than for volume. Conclusion: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences. PMID:24715957

  18. Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system?

    PubMed Central

    Caparros-Lefebvre, D; Destee, A; Petit, H

    1997-01-01

    BACKGROUND—Striatal necrosis has been related to various clinical syndromes, with acute or chronic progression, and juvenile or late occurrence, but the most common type is Leigh's encephalopathy.?METHODS—Between 1967 and 1995, six out of seven related patients with chronic familial dystonia were examined. MRIs were performed in four, between 1992-1994. The seven members, affected over three generations, were the father, three daughters (one surviving), and three surviving grandsons.?RESULTS—The leading symptoms were gait disorders and dystonia in all, dysarthria in six, verbal and motor stereotypies in two, and parkinsonian and cerebellar signs in three. Optic neuropathy was found in three. A frontal lobe syndrome without amnesia occurred in two. Symptoms occurred between the second and the fifth decade, with progressive deterioration. Magnetic resonance imaging, performed in four, showed in the two patients with severe neurological signs diffuse striatopallidal abnormal hyposignal (comparable with CSF signal) in T1 weighted images, suggesting extensive necrosis of the striatum and pallidum, associated with thalamo-subthalamo-rubro-dentato-nigral and substantia innominata hypersignals in T2 weighted images suggesting gliosis in these respective areas. The same images were described to a lesser extent in a third patient. Concentrations of lactate in CSF and serum were normal in three. Muscle biopsy, performed in four, was shown to be normal. Enzyme histochemistry showed complex I, III, and IV deficiency in surviving patients.?CONCLUSION—This familial dystonia of chronic progression may be related to basal ganglia necrosis or gliosis, associated with alterations in the respiratory chain. These metabolic alterations probably play a part in the pathophysiology of these unusual brain lesions.?? PMID:9285458

  19. TESTING BASAL GANGLIA MOTOR FUNCTIONS THROUGH REVERSIBLE INACTIVATIONS IN THE POSTERIOR INTERNAL GLOBUS PALLIDUS

    PubMed Central

    Desmurget, M.; Turner, R.S.

    2010-01-01

    To test current hypotheses on the contribution of the basal ganglia (BG) to motor control, we examined the effects of muscimol-induced inactivations in the skeletomotor region of the internal globus pallidus (sGPi) on visually-directed reaching. Injections were made in 2 monkeys trained to perform four out-and-back reaching movements in quick succession toward four randomly-selected target locations. Following sGPi inactivations: (1) Peak velocity and acceleration were decreased in nearly all sessions whereas movement duration lengthened inconsistently. (2) Reaction times were unaffected on average, although minor changes were observed in several individual sessions. (3) Outward reaches showed a substantial hypometria that correlated closely with bradykinesia, but directional accuracy was unaffected. (4) End-point accuracy was preserved for the slow visually-guided return movements. (5) No impairments were found in the rapid chaining of out-and-back movements, in the selection or initiation of four independent reaches in quick succession, or in the quick on-line correction of initially mis-directed reaches. (6) Inactivation-induced reductions in the magnitude of movement-related muscle activity (EMG) correlated with the severity of slowing and hypometria. There was no evidence for inactivation-induced alterations in the relative timing of EMG bursts, excessive co-contraction, or impaired suppression of antagonist EMG. Therefore, disconnecting the BG motor pathway consistently produced bradykinesia and hypometria, but seldom affected movement initiation time, feedback-mediated guidance, the capacity to produce iterative reaches, or the ability to abruptly reverse movement direction. These results are discussed with reference to the idea that the BG motor loop may regulate energetic expenditures during movement (i.e., movement “vigor”). PMID:18077663

  20. Neurobrucellosis with transient ischemic attack, vasculopathic changes, intracerebral granulomas and basal ganglia infarction: a case report

    PubMed Central

    2010-01-01

    Introduction Central nervous system involvement is a rare but serious manifestation of brucellosis. We present an unusual case of neurobrucellosis with transient ischemic attack, intracerebral vasculopathy granulomas, seizures, and paralysis of sixth and seventh cranial nerves. Case presentation A 17-year-old Caucasian man presented with nausea and vomiting, headache, double vision and he gave a history of weakness in the left arm, speech disturbance and imbalance. Physical examination revealed fever, doubtful neck stiffness and left abducens nerve paralysis. An analysis of his cerebrospinal fluid showed a pleocytosis (lymphocytes, 90%), high protein and low glucose levels. He developed generalized tonic-clonic seizures, facial paralysis and left hemiparesis. Cranial magnetic resonance imaging demonstrated intracerebral vasculitis, basal ganglia infarction and granulomas, mimicking the central nervous system involvement of tuberculosis. On the 31st day of his admission, neurobrucellosis was diagnosed with immunoglobulin M and immunoglobulin G positivity by standard tube agglutination test and enzyme-linked immunosorbent assay in both serum and cerebrospinal fluid samples (the tests had been negative until that day). He was treated successfully with trimethoprim and sulfamethoxazole, doxycyline and rifampicin for six months. Conclusions Our patient illustrates the importance of suspecting brucellosis as a cause of meningoencephalitis, even if cultures and serological tests are negative at the beginning of the disease. As a result, in patients who have a history of residence or travel to endemic areas, neurobrucellosis should be considered in the differential diagnosis of any neurologic symptoms. If initial tests fail, repetition of these tests at appropriate intervals along with complementary investigations are indicated. PMID:20973948

  1. Side of basal ganglia degeneration influences freezing of gait in Parkinson's disease.

    PubMed

    Pieruccini-Faria, Frederico; Ehgoetz Martens, Kaylena A; Silveira, Carolina R A; Jones, Jeffery A; Almeida, Quincy J

    2015-04-01

    Although the role of hemispheric laterality in freezing of gait (FOG) remains a topic of debate, important new evidence has suggested that individuals with Parkinson's disease (PD) who experience freezing of gait (PD-FOG) may have decreased activity in the circuitry of the right fronto-parietal cortices, irrespective of the side of basal ganglia (BG) degeneration. Because the right hemisphere plays an important role in monitoring sensorimotor information during movements, and cortical regions interact with BG loops, one could expect that right cortical dysfunction in PD-FOG might be exacerbated by right sided BG damage (compared to left). The current study aimed to evaluate the influence of asymmetrical BG degeneration on self-paced gait in PD-FOG and PD-nonFOG. This study compared gait performance in predominantly left- or right-side affected PD patients with or without freezing of gait (LFOG = 11, RFOG = 10, LPD = 15, RPD = 11). Participants were instructed to walk 10m on a GaitRite® carpet. As expected, gait parameters in PD-FOG were worse compared to PD-nonFOG. The spatiotemporal aspects of gait did not differ between LPD and RPD (nonFOG patients). Contrary to our hypothesis, RFOG (predominantly right side symptoms) had a shorter step length, increased step time variability and tended to walk slower compared with LFOG. Thus, rather than severely impaired right hemisphere circuitries exacerbating gait impairments, worse gait may be a consequence of both hemispheres being affected in PD-FOG. (PsycINFO Database Record PMID:25730121

  2. Lack of depotentiation at basal ganglia output neurons in PD patients with levodopa-induced dyskinesia.

    PubMed

    Prescott, I A; Liu, L D; Dostrovsky, J O; Hodaie, M; Lozano, A M; Hutchison, W D

    2014-11-01

    Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease which produces bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (L-Dopa) is the most effective treatment for the amelioration of PD signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L-Dopa-induced dyskinesias. In animal models of PD, a form of plasticity called depotentiation, or the reversal of previous potentiation, is selectively lost after the development of dyskinetic movements following L-Dopa treatment. We investigated whether low frequency stimulation (LFS) in the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr) could induce depotentiation at synapses that had already undergone high frequency stimulation (HFS)-induced potentiation. To do so, we measured the field potentials (fEPs) evoked by stimulation from a nearby microelectrode in 28 patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN) or GPi. We found that GPi and SNr synapses in patients with less severe dyskinesia underwent greater depotentiation following LFS than in patients with more severe dyskinesia. This demonstration of impaired depotentiation in basal ganglia output nuclei in PD patients with dyskinesia is an important validation of animal models of levodopa-induced dyskinesia. The ability of a synapse to reverse previous potentiation may be crucial to the normal function of the BG, perhaps by preventing saturation of the storage capacity required in motor learning and optimal motor function. Loss of this ability at the output nuclei may underlie, or contribute to the cellular basis of dyskinetic movements. PMID:25116960

  3. Developmental changes in the organization of functional connections between the basal ganglia and cerebral cortex.

    PubMed

    Greene, Deanna J; Laumann, Timothy O; Dubis, Joseph W; Ihnen, S Katie; Neta, Maital; Power, Jonathan D; Pruett, John R; Black, Kevin J; Schlaggar, Bradley L

    2014-04-23

    The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rs-fcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor "face" system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BG-cortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BG-cortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome). PMID:24760844

  4. Neuronal activity (c-Fos) delineating interactions of the cerebral cortex and basal ganglia

    PubMed Central

    Qiu, Mei-Hong; Chen, Michael C.; Huang, Zhi-Li; Lu, Jun

    2014-01-01

    The cerebral cortex and basal ganglia (BG) form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos) in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave electroencephalography but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine [N-methyl-d-aspartate (NMDA) receptor antagonist] and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist). Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN) input to internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr), while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu) dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe), and STN but increased activity of the GPi, SNr, and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders. PMID:24723855

  5. Ultra-high field magnetic resonance imaging of the basal ganglia and related structures

    PubMed Central

    Plantinga, Birgit R.; Temel, Yasin; Roebroeck, Alard; Uluda?, Kâmil; Ivanov, Dimo; Kuijf, Mark L.; ter Haar Romenij, Bart M.

    2014-01-01

    Deep brain stimulation is a treatment for Parkinson's disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct targeting of structures can be challenging. Non-clinical MR scanners with ultra-high magnetic field (7T or higher) have the potential to improve the quality of these images. This technology report provides an overview of the current possibilities of visualizing deep brain stimulation targets and their related structures with the aid of ultra-high field MRI. Reviewed studies showed improved resolution, contrast- and signal-to-noise ratios at ultra-high field. Sequences sensitive to magnetic susceptibility such as T2* and susceptibility weighted imaging and their maps in general showed the best visualization of target structures, including a separation between the subthalamic nucleus and the substantia nigra, the lamina pallidi medialis and lamina pallidi incompleta within the globus pallidus and substructures of the thalamus, including the ventral intermediate nucleus (Vim). This shows that the visibility, identification, and even subdivision of the small deep brain stimulation targets benefit from increased field strength. Although ultra-high field MR imaging is associated with increased risk of geometrical distortions, it has been shown that these distortions can be avoided or corrected to the extent where the effects are limited. The availability of ultra-high field MR scanners for humans seems to provide opportunities for a more accurate targeting for deep brain stimulation in patients with Parkinson's disease and related disorders. PMID:25414656

  6. Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

    PubMed Central

    Crittenden, Jill R.; Graybiel, Ann M.

    2011-01-01

    The striatum is composed principally of GABAergic, medium spiny striatal projection neurons (MSNs) that can be categorized based on their gene expression, electrophysiological profiles, and input–output circuits. Major subdivisions of MSN populations include (1) those in ventromedial and dorsolateral striatal regions, (2) those giving rise to the direct and indirect pathways, and (3) those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input–output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia, and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in these disorders. PMID:21941467

  7. Volumetric Changes in the Basal Ganglia After Antipsychotic Monotherapy: A Systematic Review

    PubMed Central

    Ebdrup, B.H; Nørbak, H; Borgwardt, S; Glenthøj, B

    2013-01-01

    Introduction: Exposure to antipsychotic medication has been extensively associated with structural brain changes in the basal ganglia (BG). Traditionally antipsychotics have been divided into first and second generation antipsychotics (FGAs and SGAs) however, the validity of this classification has become increasingly controversial. To address if specific antipsychotics induce differential effects on BG volumes or whether volumetric effects are explained by FGA or SGA classification, we reviewed longitudinal structural magnetic resonance imaging (MRI) studies investigating effects of antipsychotic monotherapy. Material and Methods: We systematically searched PubMed for longitudinal MRI studies of patients with schizophrenia or non-affective psychosis who had undergone a period of antipsychotic monotherapy. We used specific, predefined search terms and extracted studies were hand searched for additional studies. Results: We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs) have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged from 3-24 months. Unexpectedly, no studies found that specific FGAs induce significant BG volume increases. Conversely, both volumetric increases and decreases in the BG have been associated with SGA monotherapy. Discussion: Induction of striatal volume increases is not a specific feature of FGAs. Except for clozapine treatment in chronic patients, volume reductions are not restricted to specific SGAs. The current review adds brain structural support to the notion that antipsychotics should no longer be classified as either FGAs or SGAs. Future clinical MRI studies should strive to elucidate effects of specific antipsychotic drugs. PMID:23157636

  8. Function of basal ganglia in bridging cognitive and motor modules to perform an action

    PubMed Central

    Nagano-Saito, Atsuko; Martinu, Kristina; Monchi, Oury

    2014-01-01

    The basal ganglia (BG) are thought to be involved in the integration of multiple sources of information, and their dysfunction can lead to disorders such as Parkinson's disease (PD). PD patients show motor and cognitive dysfunction with specific impairments in the internal generation of motor actions and executive deficits, respectively. The role of the BG, then, would be to integrate information from several sources in order to make a decision on a resulting action adequate for the required task. Reanalyzing the data set from our previous study (Martinu et al., 2012), we investigated this hypothesis by applying a graph theory method to a series of fMRI data during the performance of self-initiated (SI) finger movement tasks obtained in healthy volunteers (HV) and early stage PD patients. Dorsally, connectivity strength between the medial prefrontal areas (mPFC) and cortical regions including the primary motor area (M1), the extrastriate visual cortex, and the associative cortex, was reduced in the PD patients. The connectivity strengths were positively correlated to activity in the striatum in both groups. Ventrally, all connectivity between the striatum, the thalamus, and the extrastriate visual cortex decreased in strength in the PD, as did the connectivity between the striatum and the ventrolateral PFC (VLPFC). Individual response time (RT) was negatively correlated to connectivity strength between the dorsolateral PFC (DLPFC) and the striatum and positively correlated to connectivity between the VLPFC and the striatum in the HV. These results indicate that the BG, with the mPFC and thalamus, are involved in integrating multiple sources of information from areas such as DLPFC, and VLPFC, connecting to M1, thereby determining a network that leads to the adequate decision and performance of the resulting action. PMID:25071432

  9. [Gait disturbances related to dysfunction of the cerebral cortex and basal ganglia].

    PubMed

    Takezawa, Nobuo; Mizuno, Toshiki; Seo, Kazuya; Kondo, Masaki; Nakagawa, Masanori

    2010-11-01

    This review aimed to characterize the gait disturbances in Parkinson disease (PD) and highlight how a rehabilitation program would affect the care of patients with PD. The typical PD gait is a type of hypokinetic gait characterized by reduced stride length and velocity; shortening of the swing phase; and increase in the stance phase, double-limb support duration, and cadence rate. In the advanced phase of PD, start hesitation, shuffling and festinating gait, propulsion, and freezing of gait (FOG) become remarkable. Notably, in PD, attention may influence gait control, and sensory cueing may improve the stride length. Our study on gait impairment in PD by using a three-dimensional motion analysis system revealed that the stride length and walking speed decreased, but there was no change in cadence. The decreased stride length was due to reduction in the range of movement at the leg and pelvic joints. A 4-week physical rehabilitation program for PD improved the stride length and walking speed;this was achieved by increasing the range of movement of at the leg and pelvic joints. We also assessed the effects of a rehabilitation program for patients with PD who experienced FOG. Although the lower limb function was more impaired in patients with PD and FOG than in those with PD without FOG, the rehabilitation program was effective even for patients with PD and FOG. FOG might be associated with functional impairment of the lower limb as well as dysfunction of the fronto-basal ganglia circuit. We also reported 3 cases of camptocormia (bent spine syndrome) with autonomic dysfunction and rapid eye movement (REM) sleep behavior disorders (RBD) and compared their symptoms with those reported elsewhere. We think that the pedunculopontine nuclear area may control the postural muscle tone and locomotion in PD. On the basis of the results of our rehabilitation programs, we speculate that physical modalities may modify synaptic plasticity by utilizing the cerebellar and/or afferent sensory system. These alternative systems are believed to be functionally intact in patients with PD. PMID:21068456

  10. Xenon-CT study of regional cerebral blood flow around hematoma in patients with basal ganglia hemorrhage

    Microsoft Academic Search

    H. Y. Ding; X. Han; C. Z. Lv; Q. Dong

    \\u000a \\u000a Background  Xenon-CT is a quantitive technique for estimating cerebral blood flow. To investigate whether penumbra exists around hematoma,\\u000a regional cerebral blood flow (rCBF) was measured by Xenon-CT in patients with intracerebral hemorrhage (ICH).\\u000a \\u000a \\u000a \\u000a Methods  Xenon-CT was performed on 15 patients with basal ganglia hemorrhage and hematoma volume <50mL. rCBF was measured within 36h\\u000a of onset and an average of 13 days later

  11. A toxic fraction from scolopendra venom increases the basal release of neurotransmitters in the ventral ganglia of crustaceans.

    PubMed

    Gutiérrez, María del Carmen; Abarca, Carolina; Possani, Lourival D

    2003-06-01

    A toxic fraction from centipede (Scolopendra sp.) venom was tested in neurotransmitter release experiments. The venom was fractionated by DEAE-cellulose with a linear gradient from 20 mM to 1.0 M of ammonium acetate pH 4.7. Lethality tests were performed by injections into the third abdominal dorsolateral segment of sweet water crayfishes of the species Cambarellus cambarellus. Only fraction V (TF) was toxic. Analysis by SDS-PAGE showed that this fraction contains at least seven proteins. It induces an increase of basal gamma-amino butyric acid (GABA) and glutamate release from ventral abdominal ganglia of C. cambarellus. Assays conducted with this fraction in the presence of several drugs that affect ion channel function suggested that TF modifies membrane permeability by increasing basal release of neurotransmitters was very likely through sodium channels. PMID:12860060

  12. Phenotyping dividing cells in mouse models of neurodegenerative basal ganglia diseases

    PubMed Central

    2013-01-01

    Background Mice generated by a Cre/LoxP transgenic paradigm were used to model neurodegenerative basal ganglia disease of which Huntington disease (HD) is the prototypical example. In HD, death occurs in striatal projection neurons as well as cortical neurons. Cortical and striatal neurons that express the D1 dopamine receptor (Drd1a) degenerate in HD. The contribution that death of specific neuronal cell populations makes to the HD disease phenotype and the response of the brain to loss of defined cell subtypes is largely unknown. Methods Drd1a-expressing cells were targeted for cell death and three independent lines generated; a striatal-restricted line, a cortical-restricted line and a global line in which Drd1a cells were deleted from both the striatum and cortex. Two independent experimental approaches were used. In the first, the proliferative marker Ki-67 was used to identify proliferating cells in eighty-week-old mice belonging to a generic global line, a global in which Drd1a cells express green fluorescent protein (GFP-global) and in eighty-week-old mice of a cortical line. In the second experiment, the proliferative response of four-week-old mice belonging to GFP-global and striatal lines was assessed using the thymidine analogue BrdU. The phenotype of proliferating cells was ascertained by double staining for BrdU and Olig2 (an oligodendrocyte marker), Iba1 (a microglial cell marker), S100? (an astroglial cell marker), or NeuN (a neuronal cell marker). Results In the first study, we found that Ki-67-expressing cells were restricted to the striatal side of the lateral ventricles. Control mice had a greater number of Ki-67+ cells than mutant mice. There was no overlap between Ki-67 and GFP staining in control or mutant mice, suggesting that cells did not undergo cell division once they acquired a Drd1a phenotype. In contrast, in the second study we found that BrdU+ cells were identified throughout the cortex, striatum and periventricular region of control and mutant mice. Mutant mice from the GFP-global line showed increased BrdU+ cells in the cortex, striatum and periventricular region relative to control. Striatal line mutant mice had an increased number of BrdU+ cells in the striatum and periventricular region, but not the cortex. The number of microglia, astrocytes, oligodendrocytes and neurons generated from dividing progenitors was increased relative to control mice in most brain regions in mutant mice from the GFP-global line. In contrast, striatal line mutant mice displayed an increase only in the number of dividing microglia in striatal and periventricular regions. Conclusions Genetically programmed post-natal ablation of Drd1a-expressing neurons is associated with an extensive proliferative response involving multiple cell lineages. The nature of the tissue response has the potential not only to remove cellular debris but also to forge physiologically meaningful brain repair. Age related deficits in proliferation are seen in mutant lines. A blunted endogenous reparative response may underlie the cumulative deficits characteristic of age related neurodegeneration. PMID:24090101

  13. Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage

    PubMed Central

    Zou, Wei; Chen, Qiu-xin; Sun, Xiao-wei; Chi, Qing-bin; Kuang, Hong-yu; Yu, Xue-ping; Dai, Xiao-hong

    2015-01-01

    Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduction pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups: in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-heparinized blood into the brain. In the acupuncture group, modeled rats had Baihui (DU20) and Qubin (GB7) acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 ?g/mL DAPT solution (10 mL) infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch1 and Hes1 protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by inhibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage. PMID:25878596

  14. Alterations in the basal ganglia in patients with brain tumours may be due to excessive iron deposition

    PubMed Central

    HERYNEK, VÍT; WAGNEROVÁ, DITA; MALUCELLI, ALBERTO; VYMAZAL, JOSEF; SAMEŠ, MARTIN; HÁJEK, MILAN

    2015-01-01

    The accumulation of iron in the brain is a common physiological process. However, alterations in the deposition of iron or other paramagnetic substances are associated with various diseases. In the present study, the deposition of paramagnetic substances in patients with brain tumours was evaluated using T2 relaxometry. A total of 23 patients with untreated tumours or with recurrent tumours following treatment, together with a group of 19 age-matched healthy controls, were examined using T2 relaxometry at 3T. The relaxation times in the basal ganglia, thalamus and white matter were evaluated. Significantly lower T2 relaxation times were identified in the basal ganglia and thalamus of the patients with tumours, as compared with those of the controls (P<0.05). No statistically significant difference was identified between patients with untreated or recurrent brain tumours. The reduction in T2 relaxation times in the brain tumour patients was possibly caused by the accumulation of iron, since iron homeostasis is known to be altered in patients with tumours. We propose that increased iron deposition is a consequence of a higher risk of oxidative stress caused by an increased iron concentration in the plasma or cerebrospinal fluid. PMID:25435931

  15. Beyond the basal ganglia: cFOS expression in the cerebellum in response to acute and chronic dopaminergic alterations.

    PubMed

    Herrera-Meza, G; Aguirre-Manzo, L; Coria-Avila, G A; Lopez-Meraz, M L; Toledo-Cárdenas, R; Manzo, J; Garcia, L I; Miquel, M

    2014-05-16

    The suggestion of an anatomical and functional relationship between the basal ganglia and cerebellum is recent. Traditionally, these structures were considered as neuronal circuits working separately to organize and control goal-directed movements and cognitive functions. However, several studies in rodents and primates have described an anatomical interaction between cortico-basal and cortico-cerebellar networks. Most importantly, functional changes have been observed in one of these circuits when altering the other one. In this context, we aimed to accomplish an extensive description of cerebellar activation patterns using cFOS expression (cFOS-IR) after acute and chronic manipulation of dopaminergic activity. In the acute study, substantia nigra pars compacta (SNc) activity was stimulated or suppressed by intra cerebral administration of picrotoxin or lidocaine, respectively. In addition, we analyzed cerebellar activity after the induction of a parkinsonism model, the tremulous jaw movements. In this model, tremulous jaw movements were induced in male rats by IP chronic administration of the dopamine antagonist haloperidol (1.5mg/kg). Acute stimulation of SNc by picrotoxin increased cFOS-IR in the vermis and cerebellar hemispheres. However, lidocaine did not produce an effect. After 14days of haloperidol treatment, the vermis and cerebellar hemispheres showed an opposite regulation of cFOS expression. Chronic dopaminergic antagonism lessened cFOS expression in the vermis but up-regulated such expression in the cerebellar hemisphere. Overall, the present data indicate a very close functional relationship between the basal ganglia and the cerebellum and they may allow a better understanding of disorders in which there are dopamine alterations. PMID:24631673

  16. Basal ganglia structures differentially contribute to verbal fluency: Evidence from Human Immunodeficiency Virus (HIV)-infected adults

    PubMed Central

    Thames, April D.; Foley, Jessica M.; Wright, Matthew J.; Panos, Stella E.; Ettenhofer, Mark; Ramezani, Amir; Streiff, Vanessa; El-Saden, Suzie; Goodwin, Scott; Bookheimer, Susan Y.; Hinkin, Charles H.

    2013-01-01

    Background The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to lexicosemantic verbal fluency performance among older HIV infected adults. Method 20 older (50+ years) HIV+ adults underwent MRI and were administered measures of semantic and phonemic fluency. BG (caudate, putamen) regions of interest were extracted. Results Performance on phonemic word generation significantly predicted caudate volume, whereas performance on phonemic switching predicted putamen volume. Conclusions These findings suggest a double dissociation of BG involvement in verbal fluency tasks with the caudate subserving word generation and the putamen associated with switching. As such, verbal fluency tasks appear to be selective to BG function. PMID:22223078

  17. Age-related differences and relationships between elements in human amygdala and other limbic system or basal ganglia.

    PubMed

    Tohno, Yoshiyuki; Tohno, Setsuko; Azuma, Cho; Ongkana, Nutcharin; Mahakkanukrauh, Pasuk; Minami, Takeshi; Suwannahoy, Patipath; Viwatpinyo, Kittikun; Ke, Lining

    2013-05-01

    To elucidate the compositional changes of the amygdala with aging, the authors investigated age-related differences of elements in human amygdalae. In addition, the relationships between the amygdala and other brain regions were investigated from a viewpoint of elements. After ordinary dissections at Nara Medical University were finished, the amygdalae were removed from the cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years. In addition, the hippocampus, dentate gyrus, mammillary body of the limbic system and the caudate nucleus, putamen, and globus pallidus of the basal ganglia were also removed from the identical cerebra. After the brain samples were incinerated with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that both the Ca and Mg contents increased significantly in the amygdalae with aging, but the other five element contents (P, S, Zn, Fe, and Na) did not change significantly in the amygdalae with aging. Regarding the relationships among elements, very significant or significant direct correlations were found among the Ca, P, and Mg contents in the amygdalae. To explore the relationships between the amygdala and either other limbic system or basal ganglia, the correlations between seven elements of the amygdala and hippocampus, dentate gyrus, or mammillary body, and between those of the amygdala and caudate nucleus, putamen, or globus pallidus which derived from the identical cerebra, were analyzed with Pearson's correlation. It was found that regarding the four elements of Ca, P, Mg, and Fe, a close relationship existed between the amygdala and hippocampus, globus pallidus, or mammillary body. PMID:23354542

  18. The Role of the Basal Ganglia and Its Cortical Connections in Sequence Learning: Evidence from Implicit and Explicit Sequence Learning in Parkinson's Disease

    ERIC Educational Resources Information Center

    Wilkinson, Leonora; Khan, Zunera; Jahanshahi, Marjan

    2009-01-01

    Implicit (unconscious/incidental) and explicit (conscious/intentional) learning are considered to have distinct neural substrates. It is proposed that implicit learning is mediated by the basal ganglia (BG), while explicit learning has been linked to the medial temporal lobes (MTL). To test such a dissociation we investigated implicit and explicit…

  19. BASAL GANGLIA NEURAL CODING OF NATURAL ACTION SEQUENCES 65 * J.W. Aldridge, Department of Neurology, Department of Psychology, University of Michigan. K.C.

    E-print Network

    Berridge, Kent

    and the tormenting habits and thoughts of obsessive compulsive disorder32 , both of which are associated disorders of the basal ganglia strongly supports a motor function. However, close scrutiny suggests, organisational aspect of motor control is disturbed by this disorder. Huntington's patients have been shown

  20. Clinical Significance of Basal Ganglia Alterations at Brain MRI and 1 H MRS in Cirrhosis and Role in the Pathogenesis of Hepatic Encephalopathy

    Microsoft Academic Search

    Laurent Spahr; Pierre R. Burkhard; Hannelore Grötzsch; Antoine Hadengue

    2002-01-01

    In hepatic encephalopathy, a progressive and diffuse impairment in brain function is associated with gradual alterations that can be detected by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS). In some patients, a variety of movement disorders suggestive of extrapyramidal impairment points toward basal ganglia (BG) alterations. Accordingly, (i) hyperintensities at MRI predominant in the pallidum, an

  1. Expression of 10 GABA A receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry

    Microsoft Academic Search

    K Kultas-Ilinsky; V Leontiev; P. J Whiting

    1998-01-01

    In situ hybridization histochemistry technique with [35S]UTP-labelled riboprobes was used to study the expression pattern of 10 GABAA receptor subunit messenger RNAs in the basal ganglia and motor thalamic nuclei of rhesus monkey. Human transcripts were used for the synthesis of ?2, ?4, ?2, ?3, ?1 and ? subunit messenger RNA probes. Rat complementary DNAs were used for generating ?1,

  2. [Mineralization of the basal ganglia as the supposed cause of poor tolerance of zuclopenthixol in a patient with long-term untreated paranoid schizophrenia].

    PubMed

    Wichowicz, Hubert M; Wilkowska, Alina; Banecka-Majkutewicz, Zyta; Kummer, ?ukasz; Konarzewska, Joanna; Raczak, Alicja

    2013-01-01

    Formations described as intracranial calcifications can appear in the course of diseases of the central nervous system, other systems and organs (e.g. endocrine), but also as a disorder of idiopathic character. They are frequently located in subcortical nuclei and usually constitute an incidental finding. This report presents the case of a patient suffering from paranoid schizophrenia for approximately 40 years, who did not agree to any treatment and was hospitalized against her will because she was the threat to the lives of others. She was treated with zuklopentixol resulting in positive symptoms reduction and considerable improvement in social functioning. Unfortunately neurological symptoms appeared: bradykinesis, rigidity--of the type of the lead pipe, balance, posture and gait abnormalities, disturbances in precise hands movements, double-sided Rossolimo's sign, plantar reflex without the participation of the big toe on the left. Neuroimaging studies have demonstrated changes in the form of lenticular nuclei calcification and reduction of signal intensity in posterior parts of both putamens. Neurological symptoms decreased significantly after switching to atypical neuroleptic (olanzapine), and the patient did not require any additional treatment. Mineralization of the basal ganglia can often be associated with psychiatric disorders and it shouldn't be neglected because it can require modification of pharmacotherapy or additional neurological treatment. PMID:24946467

  3. IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice

    PubMed Central

    Hisatsune, Chihiro; Miyamoto, Hiroyuki; Hirono, Moritoshi; Yamaguchi, Naohide; Sugawara, Takeyuki; Ogawa, Naoko; Ebisui, Etsuko; Ohshima, Toshio; Yamada, Masahisa; Hensch, Takao K.; Hattori, Mitsuharu; Mikoshiba, Katsuhiko

    2013-01-01

    The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca2+ channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking IP3R1 specifically in the cerebellum and brainstem experience dystonia and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific dystonic movements. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate IP3R1-dependent PC firing patterns in cerebellum in motor coordination and the expression of dystonia through the olivo-cerebellar pathway. PMID:24109434

  4. Ensemble neural activity of the frontal cortical basal ganglia system predicts reaction time task performance in rats

    PubMed Central

    Li, Xianghong; Luo, Fei; Shi, Lihong; Woodward, Donald J.; Chang, Jingyu

    2015-01-01

    The question pursued in this study was when neural activity appears in the cortico-basal ganglia system that could predict alternate behavioral responses in a reaction time (RT) task. In this protocol, rats first performed a nose poke to initiate a trial, depressed a lever when presented, and then released the lever after a tone cue. Multiple-channel, single-unit recordings (up to 62 units) were obtained simultaneously from the prefrontal cortex, the dorsal medial striatum, the globus pallidus, and the substantia nigra pars reticulata in a single rat during a session. Results indicated that (1) global alterations of neural activity appeared in clusters, which was associated with different behavioral components and observed in each of the targeted areas; (2) small independent subsets of neurons responded differently between error (lever was released before tone presentation) and correct trials (lever was released within 0.5 s after tone onset) during these behavioral episodes; (3) significant correlations between RTs and single units activities were found in the early preparation phases of the task. The results reveal that complex early preparatory activity exists several seconds before the final movements in a RT task, which may determine executive functions leading to rapid decoding of alternate behavioral performances. PMID:21781993

  5. Oculomotor learning revisited: a model of reinforcement learning in the basal ganglia incorporating an efference copy of motor actions

    PubMed Central

    Fee, Michale S.

    2012-01-01

    In its simplest formulation, reinforcement learning is based on the idea that if an action taken in a particular context is followed by a favorable outcome, then, in the same context, the tendency to produce that action should be strengthened, or reinforced. While reinforcement learning forms the basis of many current theories of basal ganglia (BG) function, these models do not incorporate distinct computational roles for signals that convey context, and those that convey what action an animal takes. Recent experiments in the songbird suggest that vocal-related BG circuitry receives two functionally distinct excitatory inputs. One input is from a cortical region that carries context information about the current “time” in the motor sequence. The other is an efference copy of motor commands from a separate cortical brain region that generates vocal variability during learning. Based on these findings, I propose here a general model of vertebrate BG function that combines context information with a distinct motor efference copy signal. The signals are integrated by a learning rule in which efference copy inputs gate the potentiation of context inputs (but not efference copy inputs) onto medium spiny neurons in response to a rewarded action. The hypothesis is described in terms of a circuit that implements the learning of visually guided saccades. The model makes testable predictions about the anatomical and functional properties of hypothesized context and efference copy inputs to the striatum from both thalamic and cortical sources. PMID:22754501

  6. Double dissociation of error inhibition and correction deficits after basal ganglia or dorsomedial frontal damage in humans.

    PubMed

    Hochman, Eldad Yitzhak; Wang, Seqian; Milner, Theodor E; Fellows, Lesley K

    2015-03-01

    Effective self-control relies on the rapid adjustment of inappropriate responses. Understanding the brain basis of these processes has the potential to inform neurobiological models of the many neuropsychiatric disorders that are marked by maladaptive responding. Research on error processing in particular has implicated the dorsomedial frontal lobe (DMF) and basal ganglia (BG) in error detection, inhibition and correction. However there is controversy regarding the specific contributions of these regions to each of these component processes. Here we examined the effects of lesions affecting DMF or BG on these error-related processes. A flanker task was used to induce errors that in turn led to spontaneous, online corrections, while response kinematics were measured with high spatiotemporal resolution. The acceleration of errors was initially greater than that of correct responses. Errors then showed slower acceleration compared to correct responses, consistent with engagement of inhibition shortly after error response onset. BG damage disproportionately disrupted this early inhibitory phenomenon, above and beyond effects on baseline motor performance, but did not affect the kinematics of the corrective response. DMF damage showed the opposite pattern, with relatively delayed onset and weaker initial acceleration of the corrective response, but error suppression kinematics similar to that of the control group. This work clarifies the component processes and neural substrates of online post-error control, providing evidence for dissociable contributions of BG to error inhibition, but not correction, and DMF to rapid error correction, but not error suppression. PMID:25600344

  7. Reduced Topological Efficiency in Cortical-Basal Ganglia Motor Network of Parkinson's Disease: A Resting State fMRI Study

    PubMed Central

    Long, Zhiliang; Wu, Guo-Rong; Hu, Xiaofei; Zhang, Yanling; Wang, Jian

    2014-01-01

    Parkinson's disease (PD) is mainly characterized by dopamine depletion of the cortico-basal ganglia (CBG) motor circuit. Given that dopamine dysfunction could affect functional brain network efficiency, the present study utilized resting-state fMRI (rs-fMRI) and graph theoretical approach to investigate the topological efficiency changes of the CBG motor network in patients with PD during a relatively hypodopaminergic state (12 hours after a last dose of dopamimetic treatment). We found that PD compared with controls had remarkable decreased efficiency in the CBG motor network, with the most pronounced changes observed in rostral supplementary motor area (pre-SMA), caudal SMA (SMA-proper), primary motor cortex (M1), primary somatosensory cortex (S1), thalamus (THA), globus pallidus (GP), and putamen (PUT). Furthermore, reduced efficiency in pre-SMA, M1, THA and GP was significantly correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in PD patients. Together, our results demonstrate that individuals with PD appear to be less effective at information transfer within the CBG motor pathway, which provides a novel perspective on neurobiological explanation for the motor symptoms in patients. These findings are in line with the pathophysiology of PD, suggesting that network efficiency metrics may be used to identify and track the pathology of PD. PMID:25279557

  8. The Substantia Nigra Conveys Target-Dependent Excitatory and Inhibitory Outputs from the Basal Ganglia to the Thalamus

    PubMed Central

    Antal, Miklos; Beneduce, Brandon M.

    2014-01-01

    The basal ganglia (BG), which influence cortical activity via the thalamus, play a major role in motor activity, learning and memory, sensory processing, and many aspects of behavior. The substantia nigra (SN) consists of GABAergic neurons of the pars reticulata that inhibit thalamic neurons and provide the primary output of the BG, and dopaminergic neurons of the pars compacta that modulate thalamic excitability. Little is known about the functional properties of the SN?thalamus synapses, and anatomical characterization has been controversial. Here we use a combination of anatomical, electrophysiological, genetic, and optogenetic approaches to re-examine these synaptic connections in mice. We find that neurons in the SN inhibit neurons in the ventroposterolateral nucleus of the thalamus via GABAergic synapses, excite neurons in the thalamic nucleus reticularis, and both excite and inhibit neurons within the posterior nucleus group. Glutamatergic SN neurons express the vesicular glutamate receptor transporter vGluT2 and receive inhibitory synapses from striatal neurons, and many also express tyrosine hydroxylase, a marker of dopaminergic neurons. Thus, in addition to providing inhibitory outputs, which is consistent with the canonical circuit, the SN provides glutamatergic outputs that differentially target thalamic nuclei. This suggests that an increase in the activity of glutamatergic neurons in the SN allows the BG to directly excite neurons in specific thalamic nuclei. Elucidating an excitatory connection between the BG and the thalamus provides new insights into how the BG regulate thalamic activity, and has important implications for understanding BG function in health and disease. PMID:24899724

  9. Investigating complex basal ganglia circuitry in the regulation of motor behaviour, with particular focus on orofacial movement.

    PubMed

    Ikeda, Hiroko; Adachi, Kazunori; Fujita, Satoshi; Tomiyama, Katsunori; Saigusa, Tadashi; Kobayashi, Masayuki; Koshikawa, Noriaki; Waddington, John L

    2015-02-01

    Current concepts of basal ganglia function have evolved from the essentially motoric, to include a range of extramotoric functions that involve not only dopaminergic but also cholinergic, ?-aminobutyric acid (GABA)ergic and glutamatergic mechanisms. We consider these mechanisms and their efferent systems, including spiralling, feed-forward striato-nigro-striatal circuitry, involving the dorsal and ventral striatum and the nucleus accumbens (NAc) core and shell. These processes are illustrated using three behavioural models: turning-pivoting, orofacial movements in rats and orofacial movements in genetically modified mice. Turning-pivoting indicates that dopamine-dependent behaviour elicited from the NAc shell is funnelled through the NAc-nigro-striato-nigro-pedunculopontine pathway, whereas acetylcholine-dependent behaviour elicited from the NAc shell is funnelled through the NAc-ventral pallidum-mediodorsal thalamus pathway. Cooperative/synergistic interactions between striatal D1-like and D2-like dopamine receptors regulate individual topographies of orofacial movements that are funnelled through striatal projection pathways and involve interactions with GABAergic and glutamatergic receptor subtypes. This application of concerted behavioural, neurochemical and neurophysiological techniques implicates a network that is yet broader and interacts with other neurotransmitters and neuropeptides within subcortical, cortical and brainstem regions to 'sculpt' aspects of behaviour into its topographical collective. PMID:25485640

  10. The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects

    PubMed Central

    Sperlágh, Beáta; Vizi, E. Sylvester

    2011-01-01

    Now there is general agreement that the purine nucleoside adenosine is an important neuromodulator in the central nervous system, playing a crucial role in neuronal excitability and synaptic/non-synaptic transmission in the hippocampus and basal ganglia. Adenosine is derived from the breakdown of extra- or intracellular ATP and is released upon a variety of physiological and pathological stimuli from neuronal and non-neuronal sources, i.e. from glial cells and exerts effects diffusing far away from release sites. The resultant elevation of adenosine levels in the extracellular space reaches micromolar level, and leads to the activation A1, A2A, A2B and A3 receptors, localized to pre- and postsynaptic as well as extrasynaptic sites. Activation of presynaptic A1 receptors inhibits the release of the majority of transmitters including glutamate, acetylcholine, noradrenaline, 5-HT and dopamine, whilst the stimulation of A2A receptors facilitates the release of glutamate and acetylcholine and inhibits the release of GABA. These actions underlie modulation of neuronal excitability, synaptic plasticity and coordination of neural networks and provide intriguing target sites for pharmacological intervention in ischemia and Parkinson’s disease. However, despite that adenosine is also released during ischemia, A1 adenosine receptors do not participate in the modulation of excitotoxic glutamate release, which is nonsynaptic and is due to the reverse operation of transporters. Instead, extrasynaptic A1 receptors might be responsible for the neuroprotection afforded by A1 receptor activation. PMID:21401497

  11. Transsylvian-Transinsular Approaches to the Insula and Basal Ganglia: Operative Techniques and Results with Vascular Lesions

    PubMed Central

    Potts, Matthew B.; Chang, Edward F.; Young, William L.; Lawton, Michael T.

    2011-01-01

    BACKGROUND Lesions in the insula and basal ganglia can be risky to resect due to their depth and proximity to critical structures, particularly in the dominant hemisphere. Transsylvian approaches shorten the surgical distance to these lesions, preserve perisylvian temporal and frontal cortex, and minimize brain transgression. OBJECTIVE We report our experience with transsylvian-transinsular approaches to vascular lesions. METHODS The anterior approach opened the sphenoidal and insular portions of the Sylvian fissure and exposed the limen insulae and short gyri, whereas the posterior approach opened the insular and opercular portions of the Sylvian fissure and exposed the circular sulcus and long gyri. RESULTS 41 patients with vascular lesions (24 arteriovenous malformations (AVM) and 17 cavernous amlformations (CM)) were treated surgically with a transsylvian-transinsular approach. Complete resection was obtained in 87.5% of AVMs and 95% of CMs. Permanent neurologic morbidity related to surgery was observed in 2 AVM patients (5%), with the remaining 39 patients (95%) improved or unchanged postoperatively (modified Rankin Scale scores 0–2 in 83%). There were no new language deficits in patients with dominant hemisphere lesions. CONCLUSION Transsylvian-transinsular approaches safely expose vascular pathology in or deep to the insula while preserving overlying eloquent cortex in the frontal and temporal lobes. The anterior transsylvian-transinsular approach can be differentiated from the posterior approach based on technical differences in splitting the Sylvian fissure and anatomical differences in final exposure. Discriminating patient selection and careful microsurgical technique are essential. PMID:21937930

  12. The Allocation of Attention to Learning of Goal-Directed Actions: A Cognitive Neuroscience Framework Focusing on the Basal Ganglia

    PubMed Central

    Franz, E. A.

    2012-01-01

    The present paper builds on the idea that attention is largely in service of our actions. A framework and model which captures the allocation of attention for learning of goal-directed actions is proposed and developed. This framework highlights an evolutionary model based on the notion that rudimentary functions of the basal ganglia have become embedded into increasingly higher levels of networks which all contribute to adaptive learning. Supporting the proposed model, background literature is presented alongside key evidence based on experimental studies in the so-called “split-brain” (surgically divided cerebral hemispheres), and selected evidence from related areas of research. Although overlap with other existing findings and models is acknowledged, the proposed framework is an original synthesis of cognitive experimental findings with supporting evidence of a neural system and a carefully formulated model of attention. It is the hope that this new synthesis will be informative in fields of cognition and other fields of brain sciences and will lead to new avenues for experimentation across domains. PMID:23267335

  13. Emotional blunting following left basal ganglia stroke: The role of depression and fronto-limbic functional alterations

    PubMed Central

    Paradiso, Sergio; Ostedgaard, Katharine; Vaidya, Jatin; Ponto, Laura Boles; Robinson, Robert

    2014-01-01

    Disorders of the basal ganglia (BG) alter perception and experience of emotions. Left hemisphere BG (LBG) stroke is also associated with depression. The interplay between depression and alterations in emotional processing following LBG stroke was examined. Evoked affective responses to emotion-laden pictorial stimuli were compared among LBG stroke and healthy participants and participants with stroke damage in brain regions not including the LBG selected to equate depression severity (measured using the Hamilton Depression Scale) with LBG damage participants. Brain activity {[O15]water PET} was measured in LBG stroke relative to healthy participants to identify changes in regions associated with emotion processing and depression. LBG stroke subjects reported less intense emotions compared with healthy, but not stroke comparison participants. Depression negatively correlated with emotional experience for positive and negative emotions. In response to positive stimuli, LBG subjects exhibited higher activity in amygdala, anterior cingulate, dorsal prefrontal cortex, and insula compared to healthy volunteers. In response to negative stimuli, LBG subjects demonstrated lower activity in right frontal-polar region and fusiform gyrus. Higher baseline activity in amygdala and ventral and mesial prefrontal cortex and lower activity in left dorsal lateral prefrontal cortex were associated with higher depression scores. LBG stroke led to blunted emotions, and brain activity alterations accounting for reduced affective experience, awareness and depression. Depression and fronto-limbic activity changes may contribute to emotional blunting following LBG stroke. PMID:23176970

  14. Defect in succinate oxidation by isolated muscle mitochondria in a patient with symmetrical lesions in the basal ganglia.

    PubMed

    Martin, J J; Van de Vyver, F L; Scholte, H R; Roodhooft, A M; Ceuterick, C; Martin, L; Luyt-Houwen, I E

    1988-04-01

    A 3-year-old boy was referred for evaluation of psychomotor retardation. He had a waddling gait with proximal hypotonia and paresis. Computed tomography (CT scan) and magnetic resonance imaging (MRI) of the brain demonstrated symmetrical lesions in the basal ganglia suggesting bilateral necrosis. Lactate and pyruvate levels in blood and cerebrospinal fluid were persistently elevated. A biopsy of the quadriceps muscle showed normal light microscopic findings except for a slightly raised number of lipid droplets. Electron microscopy confirmed this and also showed a rather large number of subsarcolemmal mitochondria without crystalline inclusions. Biochemical studies showed a normal carnitine level and normal mitochondrial enzyme activities in muscle homogenate, including succinate-cytochrome c reductase. However, intact isolated mitochondria failed to oxidize succinate. An explanation for this paradoxical finding is a deficiency in that part of the coenzyme Q (CoQ) that is reduced by the succinate dehydrogenase complex. The differential diagnosis between Leigh's syndrome and infantile bilateral striatal necrosis (IBSN) is discussed. The role of neuroradiology in prompting complementary investigations is stressed. PMID:3379446

  15. Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI.

    PubMed

    Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

    2015-01-01

    Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

  16. Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

    PubMed Central

    Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

    2015-01-01

    Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

  17. Basal ganglia serotonin 1B receptors in parkinsonian monkeys with L-DOPA-induced dyskinesia.

    PubMed

    Riahi, Golnasim; Morissette, Marc; Samadi, Pershia; Parent, Martin; Di Paolo, Thérèse

    2013-10-01

    L-DOPA-induced dyskinesias (LID)s are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease (PD). Serotonin receptors are thought to contribute to LID but serotonin 1B (5-HT1B) receptors have never been investigated in any primate models of PD and LID. Therefore, we measured 5-HT1B receptors with [(3)H]GR 125743 autoradiography in controls, MPTP-lesioned monkeys, and L-DOPA-treated MPTP monkeys, with or without Ro 61-8048 treatment, a kynurenine hydroxylase inhibitor alleviating LID. In normal condition, 5-HT1B receptor specific binding was highest in the substantia nigra pars reticulata (SNr), high in the globus pallidus (GP), nucleus accumbens and substantia innominata and lower in the caudate nucleus and putamen. 5-HT1B receptors were increased in caudate nucleus, putamen and SNr of MPTP monkeys compared to controls. L-DOPA-treated MPTP monkeys had elevated 5-HT1B receptor specific binding in caudate nucleus, putamen, SNr and internal GP. In all these brain regions, increases were prevented by co-administration of Ro 61-8048. No effect of MPTP lesion or treatment was observed for 5-HT1B specific binding in the external GP, nucleus accumbens and substantia innominata. This study is the first description in primates of altered brain 5-HT1B receptors associated with prevention of LID. PMID:23954709

  18. Dopamine Transporter Density in the Basal Ganglia in Obsessive-Compulsive Disorder, Measured with [123I]IPT SPECT before and after Treatment with Serotonin Reuptake Inhibitors

    Microsoft Academic Search

    C. H. Kim; K. A. Cheon; M.-S. Koo; Y. H. Ryu; J. D. Lee; J. W. Chang; H. S. Lee

    2007-01-01

    It has been suggested that dopamine as well as serotonin are associated with the pathophysiology of obsessive-compulsive disorder (OCD). 5-Hydroxytryptophan inhibits dopamine release in healthy persons as well as in patients with OCD, and serotonin tonic inhibition affects dopamine function in basal ganglia, indicating a close relationship between serotonin and the dopamine system. Using iodine-123-labeled N-(3-iodopropen-2-yl)-2?-carbomethoxy-3?-(4-chlorophenyl) tropane ([123I]IPT) single photon

  19. Dopaminergic dysbalance in distinct basal ganglia neurocircuits: Implications for the pathophysiology of parkinson’s disease, schizophrenia and attention deficit hyperactivity disorder

    Microsoft Academic Search

    C. Mehler-Wex; P. Riederer; M. Gerlach

    2006-01-01

    The basal ganglia form a forebrain system that collects signals from a large part of the neocortex, redistributes these cortical\\u000a inputs both with respect to one another and with respect to inputs from the limbic system, and then focuses the inputs of\\u000a this redistributed, integrated signals into particular regions of the frontal lobes and brainstem involved in aspects of motor

  20. An Age and Gender Dependency of Metabolite Concentrations in Basal Ganglia in Children with Spastic Diplegia: Proton Magnetic Resonance Spectroscopy Study

    Microsoft Academic Search

    Wojciech Kulak; Wojciech Sobaniec; Joanna ?migielska-Kuzia; Bo?ena Kubas; Bozena Zawada; Dorota Otapowicz

    2009-01-01

    We determined metabolite profile in spastic diplegic children compared to controls in left basal ganglia of brain in using proton magnetic resonance spectroscopy in correlation with age and gender. Twenty-four patients with spastic diplegia and twenty-six healthy children were examined. The relative concentrations of N-acetylaspartate, choline, and myoinositol were measured in relation to creatine and different combinations of metabolites within

  1. Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control

    PubMed Central

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms. PMID:25389391

  2. Effects of rTMS of Pre-Supplementary Motor Area on Fronto Basal Ganglia Network Activity during Stop-Signal Task.

    PubMed

    Watanabe, Takamitsu; Hanajima, Ritsuko; Shirota, Yuichiro; Tsutsumi, Ryosuke; Shimizu, Takahiro; Hayashi, Toshihiro; Terao, Yasuo; Ugawa, Yoshikazu; Katsura, Masaki; Kunimatsu, Akira; Ohtomo, Kuni; Hirose, Satoshi; Miyashita, Yasushi; Konishi, Seiki

    2015-03-25

    Stop-signal task (SST) has been a key paradigm for probing human brain mechanisms underlying response inhibition, and the inhibition observed in SST is now considered to largely depend on a fronto basal ganglia network consisting mainly of right inferior frontal cortex, pre-supplementary motor area (pre-SMA), and basal ganglia, including subthalamic nucleus, striatum (STR), and globus pallidus pars interna (GPi). However, causal relationships between these frontal regions and basal ganglia are not fully understood in humans. Here, we partly examined these causal links by measuring human fMRI activity during SST before and after excitatory/inhibitory repetitive transcranial magnetic stimulation (rTMS) of pre-SMA. We first confirmed that the behavioral performance of SST was improved by excitatory rTMS and impaired by inhibitory rTMS. Afterward, we found that these behavioral changes were well predicted by rTMS-induced modulation of brain activity in pre-SMA, STR, and GPi during SST. Moreover, by examining the effects of the rTMS on resting-state functional connectivity between these three regions, we showed that the magnetic stimulation of pre-SMA significantly affected intrinsic connectivity between pre-SMA and STR, and between STR and GPi. Furthermore, the magnitudes of changes in resting-state connectivity were also correlated with the behavioral changes seen in SST. These results suggest a causal relationship between pre-SMA and GPi via STR during response inhibition, and add direct evidence that the fronto basal ganglia network for response inhibition consists of multiple top-down regulation pathways in humans. PMID:25810512

  3. Golf and G, in Rat Basal Ganglia: Possible Involvement of Golf in the Coupling of Dopamine D, Receptor with Adenylyl Cyclase

    Microsoft Academic Search

    Denis Herv; Isabel Marey-Semper; Catherine Verney; Jacques Glowinski; Jean-Antoine Girault

    1993-01-01

    Using specific antibodies and cDNA probes, we have inves- tigated, in rat basal ganglia, the distribution and the regu- lation of the expression of the a subunits of G, and G,,,, two GTP-binding proteins (G-proteins) that stimulate adenylyl cyclase. We confirmed that G,,,cu is highly expressed in cau- date-putamen, nucleus accumbens, and olfactory tubercle, whereas G,a is less abundant in

  4. A theory about a role of the hyper direct pathway in pattern expression by the basal ganglia.

    PubMed

    Jourdan, Ivan; Barttfeld, Pablo; Zanutto, B Silvano

    2010-01-01

    The Basal Ganglia (BG) are a group of nuclei, in the brain of mammalians and other vertebrates, strongly connected with the cerebral cortex, thalamus and other brain areas. The BG are associated with several brain functions including learning and motor control. When there is cortical activation, there is a strong synchronization between BG and cortex, i.e. when a given task is being executed or in the case of Parkinson disease[1], [2]. If we consider the internal segment of the Globus Pallidus (GPi) there is synchronism between GPi-cortex at frequencies as low as 3Hz to as high as 85Hz [1], [3]. In the other hand, in a delta sleep or in an anesthetized case, a very low frequency correlation is observed (1-10 Hz), but no high frequency correlation between GPi-cortex [1], [2], [3]. It is unknown why this decorrelation happens. But It is agreement that when there is no pattern to select, like in delta sleep or with an anesthetized model, the BG network would maintain the GPi and cortex decorrelated at high frequencies. Many thalamus-BG and thalamus-BG-cortex loops are modulators of the BG activity. Particularly there exists an anatomic thalamus-BG loop, formed by GPi, intralaminar thalamic nuclei (IL) and Subthalamic Nucleus (STN) [4]. Using a computational model, based on an "Integrate and Fire" neural network, we analyzed the IL nucleus as a modulator of the so-called hyper direct pathway. Our results show that, in an anesthetic case, this thalamic path could be relevant to allow a high frequency decorrelated state between the GPi and cortex. PMID:21096287

  5. Emergent structured transition from variation to repetition in a biologically-plausible model of learning in basal ganglia

    PubMed Central

    Shah, Ashvin; Gurney, Kevin N.

    2014-01-01

    Often, when animals encounter an unexpected sensory event, they transition from executing a variety of movements to repeating the movement(s) that may have caused the event. According to a recent theory of action discovery (Redgrave and Gurney, 2006), repetition allows the animal to represent those movements, and the outcome, as an action for later recruitment. The transition from variation to repetition often follows a non-random, structured, pattern. While the structure of the pattern can be explained by sophisticated cognitive mechanisms, simpler mechanisms based on dopaminergic modulation of basal ganglia (BG) activity are thought to underlie action discovery (Redgrave and Gurney, 2006). In this paper we ask the question: can simple BG-mediated mechanisms account for a structured transition from variation to repetition, or are more sophisticated cognitive mechanisms always necessary? To address this question, we present a computational model of BG-mediated biasing of behavior. In our model, unlike most other models of BG function, the BG biases behavior through modulation of cortical response to excitation; many possible movements are represented by the cortical area; and excitation to the cortical area is topographically-organized. We subject the model to simple reaching tasks, inspired by behavioral studies, in which a location to which to reach must be selected. Locations within a target area elicit a reinforcement signal. A structured transition from variation to repetition emerges from simple BG-mediated biasing of cortical response to excitation. We show how the structured pattern influences behavior in simple and complicated tasks. We also present analyses that describe the structured transition from variation to repetition due to BG-mediated biasing and from biasing that would be expected from a type of cognitive biasing, allowing us to compare behavior resulting from these types of biasing and make connections with future behavioral experiments. PMID:24575067

  6. Elucidating information processing in primate basal ganglia circuitry: a novel technique for pathway-selective ablation mediated by immunotoxin.

    PubMed

    Takada, Masahiko; Inoue, Ken-Ichi; Koketsu, Daisuke; Kato, Shigeki; Kobayashi, Kazuto; Nambu, Atsushi

    2013-01-01

    Employing a neuron-specific retrograde gene-transfer vector (NeuRet vector), we have recently developed a novel technique that achieves pathway-selective ablation in the primate brain. This technique is mediated by immunotoxin (IT) and eliminates a neuronal population that constitutes a particular pathway, leaving other pathways intact. By means of this technique, we have made an attempt to remove the hyperdirect pathway selectively from basal ganglia circuitry. The hyperdirect pathway links the motor cortex to the subthalamic nucleus (STN) directly and plays a crucial role in motor control. After electrical stimulation in the motor cortex, triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually elicited in the internal pallidal segment (GPi). Several pieces of pharmacophysiological evidence imply that the early excitation may be derived from the hyperdirect pathway. In our experiments, the NeuRet vector expressing human interleukin-2 receptor ?-subunit was injected into the STN of macaque monkeys. Then, IT injections were performed into the supplementary motor area (SMA). When single neuron activity in the GPi was recorded in response to the SMA stimulation, it was found that the early excitation was significantly reduced with neither the inhibition nor the late excitation affected. The spontaneous firing rate and pattern of GPi neurons remained to be altered. This clearly indicates that IT-mediated tract targeting successfully eliminated the hyperdirect pathway with spontaneous activity of STN neurons unaffected. The electrophysiological findings were histologically confirmed by retrograde and anterograde neuronal labeling. The overall data define that the motor cortically driven early excitation in GPi neurons is conveyed through the hyperdirect pathway. The IT-mediated pathway-selective ablation technique will provide a powerful tool for elucidating information processing in various neural networks. PMID:24027499

  7. Origins of multisynaptic projections from the basal ganglia to rostrocaudally distinct sectors of the dorsal premotor area in macaques.

    PubMed

    Saga, Yosuke; Hirata, Yoshihiro; Takahara, Daisuke; Inoue, Ken-Ichi; Miyachi, Shigehiro; Nambu, Atsushi; Tanji, Jun; Takada, Masahiko; Hoshi, Eiji

    2011-01-01

    We examined the organization of multisynaptic projections from the basal ganglia (BG) to the dorsal premotor area in macaques. After injection of the rabies virus into the rostral sector of the caudal aspect of the dorsal premotor area (F2r) and the caudal sector of the caudal aspect of the dorsal premotor area (F2c), second-order neuron labeling occurred in the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr). Labeled GPi neurons were found in the caudoventral portion after F2c injection, and in the dorsal portion at the rostrocaudal middle level after F2r injection. In the SNr, F2c and F2r injections led to labeling in the caudal or rostral part, respectively. Subsequently, third-order neuron labeling was observed in the external segment of the globus pallidus (GPe), the subthalamic nucleus (STN), and the striatum. After F2c injection, labeled neurons were observed over a broad territory in the GPe, whereas after F2r injection, labeled neurons tended to be restricted to the rostral and dorsal portions. In the STN, F2c injection resulted in extensive labeling over the nucleus, whereas F2r injection resulted in labeling in the ventral portion only. After both F2r and F2c injections, labeled neurons in the striatum were widely observed in the striatal cell bridge region and neighboring areas, as well as in the ventral striatum. The present results revealed that the origins of multisynaptic projections to F2c and F2r in the BG are segregated in the output stations of the BG, whereas intermingling rather than segregation is evident with respect to their input station. PMID:21070393

  8. Dynamic Stereotypic Responses of Basal Ganglia Neurons to Subthalamic Nucleus High-Frequency Stimulation in the Parkinsonian Primate

    PubMed Central

    Moran, Anan; Stein, Edward; Tischler, Hadass; Belelovsky, Katya; Bar-Gad, Izhar

    2011-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD); however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia (BG) during high-frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro-stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, BG output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial effect of DBS in PD. PMID:21559345

  9. Striatal dopamine ramping may indicate flexible reinforcement learning with forgetting in the cortico-basal ganglia circuits

    PubMed Central

    Morita, Kenji; Kato, Ayaka

    2014-01-01

    It has been suggested that the midbrain dopamine (DA) neurons, receiving inputs from the cortico-basal ganglia (CBG) circuits and the brainstem, compute reward prediction error (RPE), the difference between reward obtained or expected to be obtained and reward that had been expected to be obtained. These reward expectations are suggested to be stored in the CBG synapses and updated according to RPE through synaptic plasticity, which is induced by released DA. These together constitute the “DA=RPE” hypothesis, which describes the mutual interaction between DA and the CBG circuits and serves as the primary working hypothesis in studying reward learning and value-based decision-making. However, recent work has revealed a new type of DA signal that appears not to represent RPE. Specifically, it has been found in a reward-associated maze task that striatal DA concentration primarily shows a gradual increase toward the goal. We explored whether such ramping DA could be explained by extending the “DA=RPE” hypothesis by taking into account biological properties of the CBG circuits. In particular, we examined effects of possible time-dependent decay of DA-dependent plastic changes of synaptic strengths by incorporating decay of learned values into the RPE-based reinforcement learning model and simulating reward learning tasks. We then found that incorporation of such a decay dramatically changes the model's behavior, causing gradual ramping of RPE. Moreover, we further incorporated magnitude-dependence of the rate of decay, which could potentially be in accord with some past observations, and found that near-sigmoidal ramping of RPE, resembling the observed DA ramping, could then occur. Given that synaptic decay can be useful for flexibly reversing and updating the learned reward associations, especially in case the baseline DA is low and encoding of negative RPE by DA is limited, the observed DA ramping would be indicative of the operation of such flexible reward learning. PMID:24782717

  10. Identification of a novel genetic locus on chromosome 8p21.1-q11.23 for idiopathic basal ganglia calcification.

    PubMed

    Dai, Xiaohua; Gao, Yong; Xu, Zhenping; Cui, Xiaoniu; Liu, Juan; Li, Yulei; Xu, Haibo; Liu, Mugen; Wang, Qing K; Liu, Jing Yu

    2010-10-01

    Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative disorder that is characterized by basal ganglia and extrabasal ganglia calcification, and usually inherited in an autosomal dominant pattern. To date, two genetic loci for IBGC were identified on chromosomes 14q and 2q, but further genetic heterogeneity clearly exists. In this study, a large Chinese family with autosomal dominant IBGC was characterized. Linkage analysis excluded the 14q13 and 2q37 loci. The large family was then characterized by genome-wide linkage analysis to identify a novel genetic locus for IBGC. Significant linkage was identified with markers on chromosome 8p21.1-q11.23 with a maximum LOD score of 4.10. Fine mapping defined the new genetic locus within a 25?Mb region between markers D8S1809 and D8S1833. Future studies of the candidate genes at the 8p21.1-q11.23 locus may lead to identification of a disease-causing gene with IBGC. PMID:20552677

  11. Dynamical model of salience gated working memory, action selection and reinforcement based on basal ganglia and dopamine feedback.

    PubMed

    Ponzi, Adam

    2008-01-01

    A simple working memory model based on recurrent network activation is proposed and its application to selection and reinforcement of an action is demonstrated as a solution to the temporal credit assignment problem. Reactivation of recent salient cue states is generated and maintained as a type of salience gated recurrently active working memory, while lower salience distractors are ignored. Cue reactivation during the action selection period allows the cue to select an action while its reactivation at the reward period allows the reinforcement of the action selected by the reactivated state, which is necessarily the action which led to the reward being found. A down-gating of the external input during the reactivation and maintenance prevents interference. A double winner-take-all system which selects only one cue and only one action allows the targeting of the cue-action allocation to be modified. This targeting works both to reinforce a correct cue-action allocation and to punish the allocation when cue-action allocations change. Here we suggest a firing rate neural network implementation of this system based on the basal ganglia anatomy with input from a cortical association layer where reactivations are generated by signals from the thalamus. Striatum medium spiny neurons represent actions. Auto-catalytic feedback from a dopamine reward signal modulates three-way Hebbian long term potentiation and depression at the cortical-striatal synapses which represent the cue-action associations. The model is illustrated by the numerical simulations of a simple example--that of associating a cue signal to a correct action to obtain reward after a delay period, typical of primate cue reward tasks. Through learning, the model shows a transition from an exploratory phase where actions are generated randomly, to a stable directed phase where the animal always chooses the correct action for each experienced state. When cue-action allocations change, we show that this is noticed by the model, the incorrect cue-action allocations are punished and the correct ones discovered. PMID:18280108

  12. Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

    PubMed

    Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

    2015-02-01

    The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. PMID:25443764

  13. Signal enhancement in the output stage of the basal ganglia by synaptic short-term plasticity in the direct, indirect, and hyperdirect pathways

    PubMed Central

    Lindahl, Mikael; Kamali Sarvestani, Iman; Ekeberg, Örjan; Kotaleski, Jeanette Hellgren

    2013-01-01

    Many of the synapses in the basal ganglia display short-term plasticity. Still, computational models have not yet been used to investigate how this affects signaling. Here we use a model of the basal ganglia network, constrained by available data, to quantitatively investigate how synaptic short-term plasticity affects the substantia nigra reticulata (SNr), the basal ganglia output nucleus. We find that SNr becomes particularly responsive to the characteristic burst-like activity seen in both direct and indirect pathway striatal medium spiny neurons (MSN). As expected by the standard model, direct pathway MSNs are responsible for decreasing the activity in SNr. In particular, our simulations indicate that bursting in only a few percent of the direct pathway MSNs is sufficient for completely inhibiting SNr neuron activity. The standard model also suggests that SNr activity in the indirect pathway is controlled by MSNs disinhibiting the subthalamic nucleus (STN) via the globus pallidus externa (GPe). Our model rather indicates that SNr activity is controlled by the direct GPe-SNr projections. This is partly because GPe strongly inhibits SNr but also due to depressing STN-SNr synapses. Furthermore, depressing GPe-SNr synapses allow the system to become sensitive to irregularly firing GPe subpopulations, as seen in dopamine depleted conditions, even when the GPe mean firing rate does not change. Similar to the direct pathway, simulations indicate that only a few percent of bursting indirect pathway MSNs can significantly increase the activity in SNr. Finally, the model predicts depressing STN-SNr synapses, since such an assumption explains experiments showing that a brief transient activation of the hyperdirect pathway generates a tri-phasic response in SNr, while a sustained STN activation has minor effects. This can be explained if STN-SNr synapses are depressing such that their effects are counteracted by the (known) depressing GPe-SNr inputs. PMID:23801960

  14. Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum.

    PubMed

    Bogenpohl, James W; Ritter, Stefanie L; Hall, Randy A; Smith, Yoland

    2012-02-15

    The adenosine A(2A) receptor (A(2A) R) is a potential drug target for the treatment of Parkinson's disease and other neurological disorders. In rodents, the therapeutic efficacy of A(2A) R modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A(2A) R localization in the primate basal ganglia and to assess the degree of A(2A) R/mGluR5 colocalization in the striatum. A(2A) R immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A(2A) R immunoreactivity. At the electron microscopic level, striatal A(2A) R labeling was most commonly localized in postsynaptic elements (58% ± 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% ± 5%) or glial (27% ± 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A(2A) R immunoreactivity. Striatal A(2A) R/mGluR5 colocalization was commonly found; 60-70% of A(2A) R-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A(2A) R in the primate basal ganglia and demonstrate that A(2A) R and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A(2A) R could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism. PMID:21858817

  15. A preliminary study of the frequency of anti-basal ganglia antibodies and streptococcal infection in attention deficit\\/hyperactivity disorder

    Microsoft Academic Search

    Rocio Sanchez-Carpintero; Sergio Aguilera Albesa; Nerea Crespo; Pablo Villoslada; Juan Narbona

    2009-01-01

    Attention deficit\\/hyperactivity disorder (ADHD) is often present in patients with post-streptococcal neuropsychiatric disorders\\u000a such as Sydenham’s chorea and PANDAS, in which anti-basal ganglia antibodies (ABGA) have been frequently found. Our study\\u000a investigates the hypothesis that pharyngeal group A ?-hemolytic streptococcus (GABHS) infections and serum ABGA are more frequent\\u000a in children with ADHD non-comorbid (nc-ADHD) with obsessive-compulsive disorder or tics than

  16. Proceedings of the workshop on Cerebellum, Basal Ganglia and Cortical Connections Unmasked in Health and Disorder Held in Brno, Czech Republic, October 17th, 2013.

    PubMed

    Bareš, Martin; Apps, Richard; Kikinis, Zora; Timmann, Dagmar; Oz, Gulin; Ashe, James J; Loft, Michaela; Koutsikou, Stella; Cerminara, Nadia; Bushara, Khalaf O; Kašpárek, Tomáš

    2015-04-01

    The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). The contributions from individual distinguished speakers cover the neuroanatomical research of complex networks, neuroimaging data showing that the cerebellum and BG are connected to a wide range of other central nervous system structures involved in movement control. Especially, the cerebellum plays a more complex role in how the brain functions than previously thought. PMID:25205331

  17. Combining Self-organizing Maps with Mixtures of Experts: Applicationto an Actor-Critic Model of Reinforcement Learning in the BasalGanglia

    Microsoft Academic Search

    Mehdi Khamassi; Louis-Emmanuel Martinet; AgnÃs Guillot

    2006-01-01

    In a reward-seeking task performed in a continuous environment, our\\u000a\\u0009previous work compared several {Actor-Critic} {(AC)} architectures\\u000a\\u0009implementing dopamine-like reinforcement learning mechanisms in the\\u000a\\u0009rat’s basal ganglia. The task complexity imposes the coordination\\u000a\\u0009of several {AC} submodules, each module being an expert trained in\\u000a\\u0009a particular subset of the task. We showed that the classical method\\u000a\\u0009where the choice of

  18. Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease

    NASA Technical Reports Server (NTRS)

    Hausdorff, J. M.; Cudkowicz, M. E.; Firtion, R.; Wei, J. Y.; Goldberger, A. L.

    1998-01-01

    The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

  19. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug.

    PubMed

    Glenthoj, Andreas; Glenthoj, Birte Y; Mackeprang, Torben; Pagsberg, Anne K; Hemmingsen, Ralf P; Jernigan, Terry L; Baaré, William F C

    2007-04-15

    The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin. PMID:17360162

  20. Unilateral Basal Ganglia Infarcts: a Red Flag for Ipsilateral Cranio-Cervical Arterial Occlusive Disease. A Report on Two Children with Moya-moya Disease.

    PubMed

    El Beltagi, A H; El-Nil, H; Norbash, A; El-Sheikh, A; Asbeutah, A

    2012-03-01

    Steno-occlusive disease of the internal carotid arteries and/or the circle of Willis with development of collateral perforator vessels attempting to supply under-perfused parenchyma are the basis for moya-moya phenomenon with the classic "puff of smoke" appearance on cerebral angiogram. We describe two cases of moya-moya with unilateral macroangiopathy of the internal carotid artery and ipsilateral middle cerebral artery in two 11-year-old girls: a Down's syndrome patient, and a second idiopathic patient. The arteriopathy in our cases differs from typical or classically described moya-moya disease in that it was exclusively unilateral rather than symmetric and bilateral. The association of predominant deep grey matter (basal ganglia) strokes in children with coexisting ipsilateral parainsular infarcts, as in our cases, is potentially a red flag for ipsilateral macroangiopathy. PMID:24028882

  1. Comparing the neural correlates of affective and cognitive theory of mind using fMRI: Involvement of the basal ganglia in affective theory of mind

    PubMed Central

    Bodden, Maren E.; Kübler, Dorothee; Knake, Susanne; Menzler, Katja; Heverhagen, Johannes T.; Sommer, Jens; Kalbe, Elke; Krach, Sören; Dodel, Richard

    2013-01-01

    Theory of Mind (ToM) is the ability to infer other people’s mental states like intentions or desires. ToM can be differentiated into affective (i.e., recognizing the feelings of another person) and cognitive (i.e., inferring the mental state of the counterpart) subcomponents. Recently, subcortical structures such as the basal ganglia (BG) have also been ascribed to the multifaceted concept ToM and most BG disorders have been reported to elicit ToM deficits. In order to assess both the correlates of affective and cognitive ToM as well as involvement of the basal ganglia, 30 healthy participants underwent event-related fMRI scanning, neuropsychological testing, and filled in questionnaires concerning different aspects of ToM and empathy. Directly contrasting affective (aff) as well as cognitive (cog) ToM to the control (phy) condition, activation was found in classical ToM regions, namely parts of the temporal lobe including the superior temporal sulcus, the supplementary motor area, and parietal structures in the right hemisphere. The contrast aff > phy yielded additional activation in the orbitofrontal cortex on the right and the cingulate cortex, the precentral and inferior frontal gyrus and the cerebellum on the left. The right BG were recruited in this contrast as well. The direct contrast aff > cog showed activation in the temporoparietal junction and the cingulate cortex on the right as well as in the left supplementary motor area. The reverse contrast cog > aff however did not yield any significant clusters. In summary, affective and cognitive ToM partly share neural correlates but can also be differentiated anatomically. Furthermore, the BG are involved in affective ToM and thus their contribution is discussed as possibly providing a motor component of simulation processes, particularly in affective ToM. PMID:23853676

  2. Real-time simulation of a spiking neural network model of the basal ganglia circuitry using general purpose computing on graphics processing units.

    PubMed

    Igarashi, Jun; Shouno, Osamu; Fukai, Tomoki; Tsujino, Hiroshi

    2011-11-01

    Real-time simulation of a biologically realistic spiking neural network is necessary for evaluation of its capacity to interact with real environments. However, the real-time simulation of such a neural network is difficult due to its high computational costs that arise from two factors: (1) vast network size and (2) the complicated dynamics of biologically realistic neurons. In order to address these problems, mainly the latter, we chose to use general purpose computing on graphics processing units (GPGPUs) for simulation of such a neural network, taking advantage of the powerful computational capability of a graphics processing unit (GPU). As a target for real-time simulation, we used a model of the basal ganglia that has been developed according to electrophysiological and anatomical knowledge. The model consists of heterogeneous populations of 370 spiking model neurons, including computationally heavy conductance-based models, connected by 11,002 synapses. Simulation of the model has not yet been performed in real-time using a general computing server. By parallelization of the model on the NVIDIA Geforce GTX 280 GPU in data-parallel and task-parallel fashion, faster-than-real-time simulation was robustly realized with only one-third of the GPU's total computational resources. Furthermore, we used the GPU's full computational resources to perform faster-than-real-time simulation of three instances of the basal ganglia model; these instances consisted of 1100 neurons and 33,006 synapses and were synchronized at each calculation step. Finally, we developed software for simultaneous visualization of faster-than-real-time simulation output. These results suggest the potential power of GPGPU techniques in real-time simulation of realistic neural networks. PMID:21764258

  3. Population and computational analysis of the MGEA6 P521A variation as a risk factor for familial idiopathic basal ganglia calcification (Fahr's disease).

    PubMed

    Lemos, Roberta R; Oliveira, Danyllo F; Zatz, Mayana; Oliveira, João R M

    2011-03-01

    Familial idiopathic basal ganglia calcification, also known as "Fahr's disease" (FD), is a neuropsychiatric disorder with autosomal dominant pattern of inheritance and characterized by symmetric basal ganglia calcifications and, occasionally, other brain regions. Currently, there are three loci linked to this devastating disease. The first one (IBGC1) is located in 14q11.2-21.3 and the other two have been identified in 2q37 (IBGC2) and 8p21.1-q11.13 (IBGC3). Further studies identified a heterozygous variation (rs36060072) which consists in the change of the cytosine to guanine located at MGEA6/CTAGE5 gene, present in all of the affected large American family linked to IBGC1. This missense substitution, which induces changes of a proline to alanine at the 521 position (P521A), in a proline-rich and highly conserved protein domain was considered a rare variation, with a minor allele frequency (MAF) of 0.0058 at the US population. Considering that the population frequency of a given variation is an indirect indicative of potential pathogenicity, we screened 200 chromosomes in a random control set of Brazilian samples and in two nuclear families, comparing with our previous analysis in a US population. In addition, we accomplished analyses through bioinformatics programs to predict the pathogenicity of such variation. Our genetic screen found no P521A carriers. Polling these data together with the previous study in the USA, we have now a MAF of 0.0036, showing that this mutation is very rare. On the other hand, the bioinformatics analysis provided conflicting findings. There are currently various candidate genes and loci that could be involved with the underlying molecular basis of FD etiology, and other groups suggested the possible role played by genes in 2q37, related to calcium metabolism, and at chromosome 8 (NRG1 and SNTG1). Additional mutagenesis and in vivo studies are necessary to confirm the pathogenicity for variation in the P521A MGEA6. PMID:20838928

  4. Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys: ultrastructural localization and electrophysiological effects of activation in the striatopallidal complex.

    PubMed

    Bogenpohl, James; Galvan, Adriana; Hu, Xing; Wichmann, Thomas; Smith, Yoland

    2013-03-01

    Group III metabotropic glutamate receptors (mGluR4,7,8) are widely distributed in the basal ganglia. Injection of group III mGluR agonists into the striatopallidal complex alleviates parkinsonian symptoms in 6-hydroxydopamine-treated rats. In vitro rodent studies have suggested that this may be partly due to modulation of synaptic transmission at striatopallidal and corticostriatal synapses through mGluR4 activation. However, the in vivo electrophysiological effects of group III mGluRs activation upon basal ganglia neurons activity in nonhuman primates remain unknown. Thus, in order to examine the anatomical substrates and physiological effects of group III mGluRs activation upon striatal and pallidal neurons in monkeys, we used electron microscopy immunohistochemistry to localize mGluR4, combined with local administration of the group III mGluR agonist L-AP4, or the mGluR4 positive allosteric modulator VU0155041, to assess the effects of group III mGluR activation on the firing rate and pattern of striatal and pallidal neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys. At the ultrastructural level, striatal mGluR4 immunoreactivity was localized in pre- (60%) and post-synaptic (30%) elements, while in the GPe, mGluR4 was mainly expressed pre-synaptically (90%). In the putamen, terminals expressing mGluR4 were evenly split between putative excitatory and inhibitory terminals, while in the GPe, most labeled terminals displayed the ultrastructural features of striatal-like inhibitory terminals, though putative excitatory boutons were also labeled. No significant difference was found between normal and parkinsonian monkeys. Extracellular recordings in awake MPTP-treated monkeys revealed that local microinjections of small volumes of L-AP4 resulted in increased firing rates in one half of striatal cells and one third of pallidal cells, while a significant number of neurons in both structures showed either opposite effects, or did not display any significant rate changes following L-AP4 application. VU0155041 administration had little effect on firing rates. Both compounds also had subtle effects on bursting and oscillatory properties, acting to increase the irregularity of firing. The occurrence of pauses in firing was reduced in the majority (80%) of GPe neurons after L-AP4 injection. Our findings indicate that glutamate can mediate multifarious physiological effects upon striatal and pallidal neurons through activation of pre-synaptic group III mGluRs at inhibitory and excitatory synapses in parkinsonian monkeys. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. PMID:22634360

  5. Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys: Ultrastructural localization and electrophysiological effects of activation in the striatopallidal complex

    PubMed Central

    Bogenpohl, James; Galvan, Adriana; Hu, Xing; Wichmann, Thomas; Smith, Yoland

    2012-01-01

    Group III metabotropic glutamate receptors (mGluR4,7,8) are widely distributed in the basal ganglia. Injection of group III mGluR agonists into the striatopallidal complex alleviates parkinsonian symptoms in 6-hydroxydopamine-treated rats. In vitro rodent studies have suggested that this may be partly due to modulation of synaptic transmission at striatopallidal and corticostriatal synapses through mGluR4 activation. However, the in vivo electrophysiological effects of group III mGluRs activation upon basal ganglia neurons activity in nonhuman primates remain unknown. Thus, in order to examine the anatomical substrates and physiological effects of group III mGluRs activation upon striatal and pallidal neurons in monkeys, we used electron microscopy immunohistochemistry to localize mGluR4, combined with local administration of the group III mGluR agonist L-AP4, or the mGluR4 positive allosteric modulator VU0155041, to assess the effects of group III mGluR activation on the firing rate and pattern of striatal and pallidal neurons in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys. At the ultrastructural level, striatal mGluR4 immunoreactivity was localized in pre- (60%) and post-synaptic (30%) elements, while in the GPe, mGluR4 was mainly expressed presynaptically (90%). In the putamen, terminals expressing mGluR4 were evenly split between putative excitatory and inhibitory terminals, while in the GPe, most labeled terminals displayed the ultrastructural features of striatal-like inhibitory terminals, though putative excitatory boutons were also labeled. No significant difference was found between normal and parkinsonian monkeys. Extracellular recordings in awake MPTP-treated monkeys revealed that local microinjections of small volumes of L-AP4 resulted in increased firing rates in one half of striatal cells and one third of pallidal cells, while a significant number of neurons in both structures showed either opposite effects, or did not display any significant rate changes following L-AP4 application. VU0155041 administration had little effect on firing rates. Both compounds also had subtle effects on bursting and oscillatory properties, acting to increase the irregularity of firing. The occurrence of pauses in firing was reduced in the majority (80%) of GPe neurons after L-AP4 injection. Our findings indicate that glutamate can mediate multifarious physiological effects upon striatal and pallidal neurons through activation of pre-synaptic group III mGluRs at inhibitory and excitatory synapses in parkinsonian monkeys. PMID:22634360

  6. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-01-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6? immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

  7. Manganese-Induced Atypical Parkinsonism Is Associated with Altered Basal Ganglia Activity and Changes in Tissue Levels of Monoamines in the Rat

    PubMed Central

    Bouabid, Safa; Delaville, Claire; De Deurwaerdère, Philippe; Lakhdar-Ghazal, Nouria; Benazzouz, Abdelhamid

    2014-01-01

    Manganese neurotoxicity is associated with motor and cognitive disturbances known as Manganism. However, the mechanisms underlying these deficits remain unknown. Here we investigated the effects of manganese intoxication on motor and non-motor parkinsonian-like deficits such as locomotor activity, motor coordination, anxiety and “depressive-like” behaviors. Then, we studied the impact of this intoxication on the neuronal activity, the globus pallidus (GP) and subthalamic nucleus (STN). At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, norepinephrine and serotonin) has been determined. The experiments were carried out in adult Sprague-Dawley rats, daily treated with MnCl2 (10 mg/kg/, i.p.) for 5 weeks. We show that manganese progressively reduced locomotor activity as well as motor coordination in parallel with the manifestation of anxiety and “depressive-like” behaviors. Electrophysiological results show that, while majority of GP and STN neurons discharged regularly in controls, manganese increased the number of GP and STN neurons discharging irregularly and/or with bursts. Biochemical results show that manganese significantly decreased tissue levels of norepinephrine and serotonin with increased metabolism of dopamine in the striatum. Our data provide evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism. PMID:24896650

  8. Recurrent interactions between the input and output of a songbird cortico-basal ganglia pathway are implicated in vocal sequence variability

    PubMed Central

    Hamaguchi, Kosuke; Mooney, Richard

    2012-01-01

    Complex brain functions, such as the capacity to learn and modulate vocal sequences, depend on activity propagation in highly distributed neural networks. To explore the synaptic basis of activity propagation in such networks, we made dual in vivo intracellular recordings in anesthetized zebra finches from the input (nucleus HVC) and output (lateral magnocellular nucleus of the anterior nidopallium (LMAN)) neurons of a songbird cortico-basal ganglia (BG) pathway necessary to the learning and modulation of vocal motor sequences. These recordings reveal evidence of bidirectional interactions, rather than only feedforward propagation of activity from HVC to LMAN, as had been previously supposed. A combination of dual and triple recording configurations and pharmacological manipulations was used to map out circuitry by which activity propagates from LMAN to HVC. These experiments indicate that activity travels to HVC through at least two independent ipsilateral pathways, one of which involves fast signaling through a midbrain dopaminergic cell group, reminiscent of recurrent mesocortical loops described in mammals. We then used in vivo pharmacological manipulations to establish that augmented LMAN activity is sufficient to restore high levels of sequence variability in adult birds, suggesting that recurrent interactions through highly distributed forebrain – midbrain pathways can modulate learned vocal sequences. PMID:22915110

  9. Ether-à-go-go 1 (Eag1) potassium channel expression in dopaminergic neurons of basal ganglia is modulated by 6-hydroxydopamine lesion.

    PubMed

    Ferreira, N R; Mitkovski, M; Stühmer, W; Pardo, L A; Del Bel, E A

    2012-04-01

    The ether à go-go (Eag) gene encodes the voltage-gated potassium (K(+)) ion channel Kv10.1, whose function still remains unknown. As dopamine may directly affect K(+) channels, we evaluated whether a nigrostriatal dopaminergic lesion induced by the neurotoxin 6-hydroxydopamine (6-OHDA) would alter Eag1-K(+) channel expression in the rat basal ganglia and related brain regions. Male Wistar rats received a microinjection of either saline or 6-OHDA (unilaterally) into the medial forebrain bundle. The extent of the dopaminergic lesion induced by 6-OHDA was evaluated by apomorphine-induced rotational behavior and by tyrosine hydroxylase (TH) immunoreactivity. The 6-OHDA microinjection caused a partial or complete lesion of dopaminergic cells, as well as a reduction of Eag1+ cells in a manner proportional to the extent of the lesion. In addition, we observed a decrease in TH immunoreactivity in the ipsilateral striatum. In conclusion, the expression of the Eag1-K(+)-channel throughout the nigrostriatal pathway in the rat brain, its co-localization with dopaminergic cells and its reduction mirroring the extent of the lesion highlight a physiological circuitry where the functional role of this channel can be investigated. The Eag1-K(+) channel expression in dopaminergic cells suggests that these channels are part of the diversified group of ion channels that generate and maintain the electrophysiological activity pattern of dopaminergic midbrain neurons. PMID:22048886

  10. Projections from caudal ventrolateral prefrontal areas to brainstem preoculomotor structures and to Basal Ganglia and cerebellar oculomotor loops in the macaque.

    PubMed

    Borra, Elena; Gerbella, Marzio; Rozzi, Stefano; Luppino, Giuseppe

    2015-03-01

    The caudal part of the macaque ventrolateral prefrontal (VLPF) cortex hosts several distinct areas or fields--45B, 45A, 8r, caudal 46vc, and caudal 12r--connected to the frontal eye field (area 8/FEF). To assess whether these areas/fields also display subcortical projections possibly mediating a role in controlling oculomotor behavior, we examined their descending projections, based on anterograde tracer injections in each area/field, and compared them with those of area 8/FEF. All the studied areas/fields displayed projections to brainstem preoculomotor structures, precerebellar centers, and striatal sectors that are also targets of projections originating from area 8/FEF. Specifically, these projections involved: (1) the intermediate and superficial layers of the superior colliculus; (2) the mesencephalic and pontine reticular formation; (3) the dorsomedial and lateral pontine nuclei and the reticularis tegmenti pontis; and (4) the body of the caudate nucleus. Furthermore, area 45B projected also to the regions around the trochlear nucleus and to the raphe interpositus. The present data provide evidence for a role of the caudal VLPF areas/fields in controlling oculomotor behavior not only through their connections to area 8/FEF, but also in parallel through a direct access to preoculomotor brainstem structures and to the cerebellar and basal ganglia oculomotor loops. PMID:24068552

  11. An extended reinforcement learning model of basal ganglia to understand the contributions of serotonin and dopamine in risk-based decision making, reward prediction, and punishment learning

    PubMed Central

    Balasubramani, Pragathi P.; Chakravarthy, V. Srinivasa; Ravindran, Balaraman; Moustafa, Ahmed A.

    2014-01-01

    Although empirical and neural studies show that serotonin (5HT) plays many functional roles in the brain, prior computational models mostly focus on its role in behavioral inhibition. In this study, we present a model of risk based decision making in a modified Reinforcement Learning (RL)-framework. The model depicts the roles of dopamine (DA) and serotonin (5HT) in Basal Ganglia (BG). In this model, the DA signal is represented by the temporal difference error (?), while the 5HT signal is represented by a parameter (?) that controls risk prediction error. This formulation that accommodates both 5HT and DA reconciles some of the diverse roles of 5HT particularly in connection with the BG system. We apply the model to different experimental paradigms used to study the role of 5HT: (1) Risk-sensitive decision making, where 5HT controls risk assessment, (2) Temporal reward prediction, where 5HT controls time-scale of reward prediction, and (3) Reward/Punishment sensitivity, in which the punishment prediction error depends on 5HT levels. Thus the proposed integrated RL model reconciles several existing theories of 5HT and DA in the BG. PMID:24795614

  12. Seasonal change in neuron size and spacing but not neuronal recruitment in a basal ganglia nucleus in the avian song control system.

    PubMed

    Thompson, Christopher K; Brenowitz, Eliot A

    2005-01-17

    Neural plasticity in the song control system of seasonally breeding songbirds accompanies seasonal changes in singing behavior. The volume of Area X, a song control nucleus that forms a portion of the avian basal ganglia, is 75% larger in the spring than it is in the fall. The neuronal basis of the seasonal plasticity in Area X is largely unknown, however. We examined neuronal attributes of Area X in wild adult male song sparrows (Melospiza melodia) captured during the spring and the fall after being implanted for 30 days with osmotic pumps containing [3H]thymidine. We measured the volume of Area X from thionin-stained sections, and neuronal density and number, and average area of the soma from sections labeled with an antibody against Hu, a neuron-specific protein. We sampled two neuron classes: "small" neurons that were most likely striatal-like spiny neurons and "large" neurons, which most likely included pallidal-like projection neurons. We also analyzed seasonal patterns of neuronal recruitment to Area X. The average area of the soma and neuronal spacing for both neuronal classes were greater in breeding birds. There was no difference in total neuron number for both neuronal classes between seasons. The average area of the soma and density and number of newly recruited neurons did not vary across seasons. These results demonstrate that seasonal plasticity in Area X includes changes in neuron size and neuronal density, but not changes in the rate at which new neurons are recruited. PMID:15593375

  13. AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome).

    PubMed

    Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

    2014-03-01

    MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1?G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity. PMID:23756445

  14. AP1S2 is mutated in X-linked Dandy–Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome)

    PubMed Central

    Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

    2014-01-01

    MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy–Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1?G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity. PMID:23756445

  15. c-Fos immunoreactivity in prefrontal, basal ganglia and limbic areas of the rat brain after central and peripheral administration of ethanol and its metabolite acetaldehyde

    PubMed Central

    Segovia, Kristen N.; Vontell, Regina; López-Cruz, Laura; Salamone, John D.; Correa, Mercè

    2013-01-01

    Considerable evidence indicates that the metabolite of ethanol (EtOH), acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase (ADH), and also centrally by catalase. EtOH and acetaldehyde show differences in their behavioral effects depending upon the route of administration. In terms of their effects on motor activity and motivated behaviors, when administered peripherally acetaldehyde tends to be more potent than EtOH but shows very similar potency administered centrally. Since dopamine (DA) rich areas have an important role in regulating both motor activity and motivation, the present studies were undertaken to compare the effects of central (intraventricular, ICV) and peripheral (intraperitoneal, IP) administration of EtOH and acetaldehyde on a cellular marker of brain activity, c-Fos immunoreactivity, in DA innervated areas. Male Sprague-Dawley rats received an IP injection of vehicle, EtOH (0.5 or 2.5 g/kg) or acetaldehyde (0.1 or 0.5 g/kg) or an ICV injection of vehicle, EtOH or acetaldehyde (2.8 or 14.0 ?moles). IP administration of EtOH minimally induced c-Fos in some regions of the prefrontal cortex and basal ganglia, mainly at the low dose (0.5 g/kg), while IP acetaldehyde induced c-Fos in virtually all the structures studied at both doses. Acetaldehyde administered centrally increased c-Fos in all areas studied, a pattern that was very similar to EtOH. Thus, IP administered acetaldehyde was more efficacious than EtOH at inducing c-Fos expression. However, the general pattern of c-Fos induction promoted by ICV EtOH and acetaldehyde was similar. These results are consistent with the pattern observed in behavioral studies in which both substances produced the same magnitude of effect when injected centrally, and produced differences in potency after peripheral administration. PMID:23745109

  16. Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.

    PubMed

    Subramanian, Veedamali S; Marchant, Jonathan S; Said, Hamid M

    2006-11-01

    The water-soluble micronutrient thiamine is required for normal tissue growth and development in humans. Thiamine is accumulated into cells through the activity of two cell surface thiamine transporters (hTHTR1 and hTHTR2), which are differentially targeted in polarized tissues. Mutational dysfunction of hTHTR1 is associated with the clinical condition of thiamine-responsive megaloblastic anemia: the symptoms of which are alleviated by thiamine supplementation. Recently, two hTHTR2 mutants (G23V, T422A) have been discovered in clinical kindreds manifesting biotin-responsive basal ganglia disease (BBGD): the symptoms of which are alleviated by biotin administration. Why then does mutation of a specific thiamine transporter isoform precipitate a disorder correctable by exogenous biotin? To investigate the suggestion that hTHTR2 can physiologically function as a biotin transporter, we examined 1) the cell biological basis of hTHTR2 dysfunction associated with the G23V and T422A mutations and 2) the substrate specificity of hTHTR2 and these clinically relevant mutants. We show that the G23V and T422A mutants both abrogate thiamine transport activity rather than targeting of hTHTR2 to the cell surface. Furthermore, biotin accumulation was not detectable in cells overexpressing either the full length hTHTR2 or the clinically relevant hTHTR2 mutants, yet was demonstrable in the same assay using cells overexpressing the human sodium-dependent multivitamin transporter, a known biotin transporter. These results cast doubt on the most parsimonious explanation for the BBGD phenotype, namely that hTHTR2 is a physiological biotin transporter. PMID:16790503

  17. High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson’s disease

    PubMed Central

    2013-01-01

    Background It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson’s disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats. Results Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion. Conclusions These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. They provide evidence for the involvement of VGLUT2 in the modulation of BG cicuits and in particular that of thalamostriatal and thalamocortical pathways suggesting their key role in its therapeutic effects for alleviating PD motor symptoms. PMID:24308494

  18. Neuroimaging abnormalities in adults with sickle cell anemia

    PubMed Central

    Insel, Philip; Truran, Diana; Vichinsky, Elliot P.; Neumayr, Lynne D.; Armstrong, F.D.; Gold, Jeffrey I.; Kesler, Karen; Brewer, Joseph; Weiner, Michael W.

    2014-01-01

    Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = ?2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = ?3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Conclusions: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA. PMID:24523480

  19. Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia

    ERIC Educational Resources Information Center

    Brown, S.M.; Kieffaber, P.D.; Carroll, C.A.; Vohs, J.L.; Tracy, J.A.; Shekhar, A.; O'Donnell, B.F.; Steinmetz, J.E.; Hetrick, W.P.

    2005-01-01

    Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar…

  20. What are the Computations of the Cerebellum, the Basal Gangila, and the Cerebral Cortex?

    E-print Network

    Doya, Kenji

    ganglia participate in 2 #12;Cerebral Cortex Basal Ganglia Cerebellum Thalamus substantia nigra inferior olive Figure 1: Global network linking the cerebellum, the basal ganglia, and the cerebral cortex

  1. Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia.

    PubMed

    Agnati, L F; Franzen, O; Ferré, S; Leo, G; Franco, R; Fuxe, K

    2003-01-01

    Learning in neuronal networks occurs by instructions to the neurons to change their synaptic weights (i.e., efficacies). According to the present model a molecular mechanism that can contribute to change synaptic weights may be represented by multiple interactions between membrane receptors forming aggregates (receptor mosaics) via oligomerization at both pre- and post-synaptic level. These assemblies of receptors together with inter alia single receptors, adapter proteins, G-proteins and ion channels form the membrane bound part of a complex three-dimensional (3D) molecular circuit, the cytoplasmic part of which consists especially of protein kinases, protein phosphatases and phosphoproteins. It is suggested that this molecular circuit has the capability to learn and store information. Thus, engram formation will depend on the resetting of 3D molecular circuits via the formation of new receptor mosaics capable of addressing the transduction of the chemical messages impinging on the cell membrane to certain sets of G-proteins. Short-term memory occurs by a transient stabilization of the receptor mosaics producing the appropriate change in the synaptic weight. Engram consolidation (long-term memory) may involve intracellular signals that translocate to the nucleus to cause the activation of immediate early genes and subsequent formation of postulated adapter proteins which stabilize the receptor mosaics with the formation of long-lived heteromeric receptor complexes. The receptor mosaic hypothesis of the engram formation has been formulated in agreement with the Hebbian rule and gives a novel molecular basis for it by postulating that the pre-synaptic activity change in transmitter and modulator release reorganizes the receptor mosaics at post-synaptic level and subsequently at pre-synaptic level with the formation of novel 3D molecular circuits leading to a different integration of chemical signals impinging on pre- and post-synaptic membranes hence leading to a new value of the synaptic weight. Engram retrieval is brought about by the scanning of the target networks by the highly divergent arousal systems. Hence, a continuous reverberating process occurs both at the level of the neural networks as well as at the level of the 3D molecular circuits within each neuron of the network until the appropriate tuning of the synaptic weights is obtained and, subsequently, the reappearance of the engram occurs. Learning and memory in the basal ganglia is discussed in the frame of the present hypothesis. It is proposed that formation of long-term memories (consolidated receptor mosaics) in the plasma membranes of the striosomal GABA neurons may play a major role in the motivational learning of motor skills of relevance for survival. In conclusion, long-lived heteromeric receptor complexes of high order may be crucial for learning, memory and retrieval processes, where extensive reciprocal feedback loops give rise to coherent synchronized neural activity (binding) essential for a sophisticated information handling by the central nervous system. PMID:12946046

  2. Exclusion of linkage to chromosomes 14q, 2q37 and 8p21.1-q11.23 in a Serbian family with idiopathic basal ganglia calcification.

    PubMed

    Kosti?, Vladimir S; Luki?-Je?menica, Milica; Novakovi?, Ivana; Dobri?i?, Valerija; Brajkovi?, Lela; Krajinovi?, Maja; Klein, Christine; Pavlovi?, Aleksandra

    2011-09-01

    In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation. PMID:21409505

  3. Evaluation of Basal Ganglia and Thalamic Inflammation in Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection and Tourette Syndrome: A Positron Emission Tomographic (PET) Study Using 11C-[R]-PK11195.

    PubMed

    Kumar, Ajay; Williams, Mitchel T; Chugani, Harry T

    2014-08-12

    We applied PET scanning with (11)C-[R]-PK11195 (PK) to evaluate neuroinflammatory changes in basal ganglia and thalamus in children with clinically diagnosed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and Tourette syndrome. Seventeen children with PANDAS (mean age: 11.4 ± 2.6 years; 13 males), 12 with Tourette syndrome (mean age: 11.0 ± 3.0 years; 10 males), and 15 normal adults (mean age: 28.7 ± 7.9 years; 8 males) underwent dynamic PK PET imaging and binding potential, a measure of ligand-TSPO receptor (expressed by activated microglia) binding, was calculated for basal ganglia and thalamus. Binding potential values, suggesting underlying activated microglia-mediated neuroinflammation, were found to be increased in bilateral caudate and bilateral lentiform nucleus in the PANDAS group and in bilateral caudate nuclei only in the Tourette syndrome group, compared to control group. These differences in the pattern and extent of neuroinflammation also signify a possible difference in pathophysiological etiology between PANDAS and Tourette syndrome patients. PMID:25117419

  4. Convergent evidence for abnormal striatal synaptic plasticity in dystonia

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

    2010-01-01

    Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes linking etiology to pathophysiology of the disease. PMID:20005952

  5. Skeletal limb abnormalities

    MedlinePLUS

    Skeletal limb abnormalities may be due to: Cancer Genetic diseases and chromosomal abnormalities, including Marfan syndrome , Down syndrome, Apert syndrome , Basal cell nevus syndrome Improper position ...

  6. Eye movement abnormalities.

    PubMed

    Moncayo, Jorge; Bogousslavsky, Julien

    2012-01-01

    Generation and control of eye movements requires the participation of the cortex, basal ganglia, cerebellum and brainstem. The signals of this complex neural network finally converge on the ocular motoneurons of the brainstem. Infarct or hemorrhage at any level of the oculomotor system (though more frequent in the brain-stem) may give rise to a broad spectrum of eye movement abnormalities (EMAs). Consequently, neurologists and particularly stroke neurologists are routinely confronted with EMAs, some of which may be overlooked in the acute stroke setting and others that, when recognized, may have a high localizing value. The most complex EMAs are due to midbrain stroke. Horizontal gaze disorders, some of them manifesting unusual patterns, may occur in pontine stroke. Distinct varieties of nystagmus occur in cerebellar and medullary stroke. This review summarizes the most representative EMAs from the supratentorial level to the brainstem. PMID:22377853

  7. Cortico-Basal Ganglia Reward Network: Microcircuitry

    PubMed Central

    Sesack, Susan R; Grace, Anthony A

    2010-01-01

    Many of the brain's reward systems converge on the nucleus accumbens, a region richly innervated by excitatory, inhibitory, and modulatory afferents representing the circuitry necessary for selecting adaptive motivated behaviors. The ventral subiculum of the hippocampus provides contextual and spatial information, the basolateral amygdala conveys affective influence, and the prefrontal cortex provides an integrative impact on goal-directed behavior. The balance of these afferents is under the modulatory influence of dopamine neurons in the ventral tegmental area. This midbrain region receives its own complex mix of excitatory and inhibitory inputs, some of which have only recently been identified. Such afferent regulation positions the dopamine system to bias goal-directed behavior based on internal drives and environmental contingencies. Conditions that result in reward promote phasic dopamine release, which serves to maintain ongoing behavior by selectively potentiating ventral subicular drive to the accumbens. Behaviors that fail to produce an expected reward decrease dopamine transmission, which favors prefrontal cortical-driven switching to new behavioral strategies. As such, the limbic reward system is designed to optimize action plans for maximizing reward outcomes. This system can be commandeered by drugs of abuse or psychiatric disorders, resulting in inappropriate behaviors that sustain failed reward strategies. A fuller appreciation of the circuitry interconnecting the nucleus accumbens and ventral tegmental area should serve to advance discovery of new treatment options for these conditions. PMID:19675534

  8. Long-term treatment with l-DOPA and an mGlu5 receptor antagonist prevents changes in brain basal ganglia dopamine receptors, their associated signaling proteins and neuropeptides in parkinsonian monkeys.

    PubMed

    Morin, Nicolas; Jourdain, Vincent A; Morissette, Marc; Grégoire, Laurent; Di Paolo, Thérèse

    2014-04-01

    Brain glutamate overactivity is well documented in Parkinson's disease (PD) and antiglutamatergic drugs decrease L-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesias (LID); the implication of dopamine neurotransmission is not documented in this anti-LID activity. Therefore, we evaluated changes of dopamine receptors, their associated signaling proteins and neuropeptides mRNA, in normal control monkeys, in saline-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys and in L-DOPA-treated MPTP monkeys, without or with an adjunct treatment to reduce the development of LID: 2-methyl-6-(phenylethynyl)pyridine (MPEP), the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist. All de novo treatments were administered for 1 month and the animals were sacrificed thereafter. MPTP monkeys treated with l-DOPA + MPEP developed significantly less LID than MPTP monkeys treated with l-DOPA alone. [(3)H]SCH-23390 specific binding to D1 receptors of all MPTP monkeys was decreased as compared to controls in the basal ganglia and no difference was observed between all MPTP groups, while striatal D1 receptor mRNA levels remained unchanged. [(3)H]raclopride specific binding to striatal D2 receptors and mRNA levels of D2 receptors were increased in MPTP monkeys compared to controls; l-DOPA treatment reduced this binding in MPTP monkeys while it remained elevated with the l-DOPA + MPEP treatment. Striatal [(3)H]raclopride specific binding correlated positively with D2 receptor mRNA levels of all MPTP-lesioned monkeys. Striatal preproenkephalin/preprodynorphin mRNA levels and phosphorylated ERK1/2 and Akt/GSK3? levels increased only in L-DOPA-treated MPTP monkeys as compared to controls, saline treated-MPTP and l-DOPA + MPEP treated MPTP monkeys. Hence, reduction of development of LID with MPEP was associated with changes in D2 receptors, their associated signaling proteins and neuropeptides. PMID:24456747

  9. Use of a novel high-resolution magnetic resonance neurography protocol to detect abnormal dorsal root Ganglia in Sjögren patients with neuropathic pain: case series of 10 patients and review of the literature.

    PubMed

    Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C; Carrino, John; Chhabra, Avneesh

    2014-05-01

    The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional "stocking-and-glove" distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system-the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain.We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients whose neuropathic pain resolved with intravenous immunoglobulin (IVIg) therapy had improvement of MRN DRG abnormalities.We have developed a novel MRN protocol that can detect DRG abnormalities in SS patients with neuropathic pain who do not have markers of peripheral neuropathy. We found that SS patients with MRN DRG abnormalities had statistically significant, increased IENFD on skin biopsy studies, which may suggest a relationship between trophic mediators and neuropathic pain. Given that our literature review has demonstrated that many SS neuropathic pain patients do not have a neuropathy, our findings suggest an important niche for this MRN DRG technique in the evaluation of broader subsets of SS neuropathic pain patients who may not have underlying neuropathies. The improvement of MRN DRG abnormalities in patients with IVIg-induced remission of neuropathic pain suggests that our MRN protocol may be capturing reversible, immune-mediated mechanisms targeting the DRG. PMID:24797167

  10. Neural code alterations and abnormal time patterns in Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Andres, Daniela Sabrina; Cerquetti, Daniel; Merello, Marcelo

    2015-04-01

    Objective. The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson’s disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. Approach. We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. Main results. At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson’s disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. Significance. We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson’s disease.

  11. Architectonics of crayfish ganglia.

    PubMed

    Mulloney, Brian; Tschuluun, Naranzogt; Hall, Wendy M

    2003-02-15

    The central nervous system of crayfish consists of a chain of segmental ganglia that are linked by cables of intersegmental axons. Each ganglion contains a highly-ordered core of longitudinal tracts, vertical tracts, commissures, and synaptic neuropils. We review from a technical perspective the history of the description of these ganglia, and recognize four episodes of progress. Each major innovation in anatomical methods has led to new insight into the structure and function of this nervous system, and new awareness of the structural patterns that are common to the CNS of all arthropods. Ganglia in different segments of the body differ in size, and appear to differ in anatomy. From a comparison of the structures of the cores of abdominal, thoracic, and subesophageal ganglia, we argue that this apparent difference is illusory. Rather, each of these ganglia is organized on the same plan, a plan also found in insect segmental ganglia. The apparent differences follow from longitudinal compression during development and from allometric growth of particular neuropils associated with innervation of the walking legs. Different authors have described the internal organization of ganglia in different segments, so we provide a cross-reference to the nomenclatures they have introduced. We compare the locations of cell bodies of motor neurons and accessory neurons that innervate different peripheral structures, and demonstrate double-labeling of certain GABAergic peripheral inhibitory neurons. Finally, we describe the construction of digital movies of serial sections of these ganglia, and discuss their utility. PMID:12539156

  12. Neurologic abnormalities in patients with adenosine deaminase deficiency.

    PubMed

    Nofech-Mozes, Yehuda; Blaser, Susan I; Kobayashi, Jeff; Grunebaum, Eyal; Roifman, Chaim M

    2007-09-01

    Defects in adenosine deaminase enzyme cause severe immunodeficiency. Without enzyme replacement or allogeneic bone marrow transplantation, patients often suffer fatal infection in infancy. Adenosine deaminase is expressed ubiquitously; deficiency may affect various organs, including the brain. Neurologic abnormalities occur in some adenosine deaminase-deficient patients, mostly in association with infection or after bone marrow transplantation. Three cases with significant neurologic abnormalities, including hypotonia, head lag, nystagmus, difficulty in focusing gaze, seizure disorder, and moderate-severe developmental delay but with no evidence of infection or transplant-related medication toxicity are presented. Computed tomographic scans and cranial MRI revealed volume loss and abnormalities of basal ganglia and thalamus, which may reflect accelerated nerve cell death or altered stimulation of adenosine receptors. Detailed neurologic and neuroimaging evaluation should be performed for all patients with adenosine deaminase deficiency upon diagnosis, to identify potentially significant brain lesions. PMID:17765813

  13. An engineering model of lower thalamo-cortico-basal ganglionic circuit function

    E-print Network

    Lim, Eugene J. (Eugene Jungsud), 1980-

    2003-01-01

    An engineering model of lower thalamo-cortico-basal ganglionic circuit functionality was extended and tested. This model attempts to explain the circuitry of the basal ganglia, examine its functional properties, and integrate ...

  14. Cerebral abnormalities: use of calculated T1 and T2 magnetic resonance images for diagnosis

    SciTech Connect

    Mills, C.M.; Crooks, L.E.; Kaufman, L.; Brant-Zawadzki, M.

    1984-01-01

    The potential clinical importance of T1 and T2 relaxation times in distinguishing normal and pathologic tissue with magnetic resonance (MR) is discussed and clinical examples of cerebral abnormalities are given. Five patients with cerebral infarction, 15 with multiple sclerosis, two with Wilson disease, and four with tumors were imaged. Hemorrhagic and ischemic cerebrovascular accidents were distinguished using the spin echo technique. In the patients with multiple sclerosis, lesions had prolonged T1 and T2 times, but the definition of plaque was limited by spatial resolution. No abnormalities in signal intensity were seen in the patient with Wilson disease who was no longer severly disabled; abnormal increased signal intensity in the basal ganglia was found in the second patient with Wilson disease. Four tumors produced abnormal T1 and T2 relaxation times but these values alone were not sufficient for tumor characterization.

  15. A Search For Principles of Basal Ganglia Function

    E-print Network

    Anderson, Charles H.

    that they automatically select actions on the basis of past reinforcement, and the other that they compress cortical signals that tend to occur in conjunction with reinforcement. It is argued that a wide range of experi

  16. Neural representation of time in cortico-basal ganglia circuits

    E-print Network

    Jin, Dezhe

    monkeys performing a routine visuomotor task. We found that a subset of neurons exhibited time, the temporal evolution of the population activity allowed robust decoding of task time by perceptron models. We monkeys in a visually guided sequen- tial saccade task that had temporal structure but did not explicitly

  17. Synchronous Oscillations in the Basal-Ganglia-Cortical Network

    E-print Network

    -Etzion Submitted to the Senate of the Hebrew University of Jerusalem April 2009 #12;This work was carried out under), bradykinesia (slowness of movement), muscle rigidity and a tremor of 4-7 Hz. The two major subtypes/rigid dominant subtype, respectively). The major cellular event leading to PD is the death of midbrain

  18. The Basal Ganglia Mahlon R. DeLong

    E-print Network

    examination of patients with Parkinson disease, Huntington disease, and hemiballismus revealed pathological diminished movement (as in Parkinson disease) or excessive movement (as in Huntington disease). In addition changes in these subcortical nuclei. These diseases have three characteristic types of motor disturbances

  19. Genetics Home Reference: Familial idiopathic basal ganglia calcification

    MedlinePLUS

    ... in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 ... calcification ; calcinosis ; calcium ; cell ; dementia ; dystonia ; familial ; gene ; homeostasis ; idiopathic ; imaging ; inheritance ; inherited ; involuntary ; pattern of inheritance ; ...

  20. Dissociations in Processing Derivational Morphology: The Right Basal Ganglia Involvement

    ERIC Educational Resources Information Center

    Marangolo, Paola; Piras, Fabrizio

    2008-01-01

    In the neuropsychological literature, there is converging evidence for a dominant role of the left hemisphere in morphological processing. However, two right hemisphere patients were described with a clear dissociation between impaired derivational morphology and preserved inflectional processing. A recent fMRI experiment confirmed the involvement…

  1. Morphometric Brain Abnormalities in Schizophrenia in a Population-Based Sample: Relationship to Duration of Illness

    PubMed Central

    Tanskanen, Päivikki; Ridler, Khanum; Murray, Graham K.; Haapea, Marianne; Veijola, Juha M.; Jääskeläinen, Erika; Miettunen, Jouko; Jones, Peter B.; Bullmore, Edward T.; Isohanni, Matti K.

    2010-01-01

    Biased recruitment and sample selection may cause variability in neuroimaging studies. Epidemiologically principled population-based magnetic resonance imaging (MRI) studies of schizophrenia are very rare. We gathered structural MRI data on 154 subjects from the Northern Finland 1966 Birth Cohort, aged 33–35 (100 controls, 54 schizophrenia patients). Regional differences in density of gray matter, white matter, and cerebrospinal fluid (CSF) were identified between groups using nonparametric statistical analysis, and the relationship of the regional differences to duration of illness was explored. Gray matter reductions were found bilaterally in the cerebellum, thalamus, basal ganglia, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, insula, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus, cuneus, and lingual gyrus; in the left posterior cingulate, superior frontal gyrus, transverse temporal gyrus, and precuneus; and in the right postcentral gyrus. Gray matter excesses were observed bilaterally in the basal ganglia, anterior cingulate, and medial orbitofrontal cortices. There were white matter deficits in an extensive network including inter- and intrahemispheric tracts bilaterally in the frontal, temporal, parietal, and occipital lobes, subcortical structures, cerebellum, and brain stem. CSF excesses were found bilaterally in the lateral ventricles, third ventricle, interhemispheric, and left Sylvian fissure. We replicated the previous findings of structural brain abnormalities in schizophrenia on a general population level. Gray and white matter deficits were associated with duration of illness suggesting either that developmental brain deficits relate to an earlier age of onset or that brain abnormalities in schizophrenia are progressive in nature. PMID:19015212

  2. Basal cell carcinoma

    MedlinePLUS

    Basal cell skin cancer; Rodent ulcer; Skin cancer - basal cell; Cancer - skin - basal cell; Nonmelanoma skin cancer; Basal cell NMSC ... Basal cell cancer starts in the top layer of the skin called the epidermis. Most basal cell cancers occur ...

  3. Basal Cell Carcinoma

    MedlinePLUS

    ... and treatments A - D Basal cell carcinoma Basal cell carcinoma Basal cell carcinoma: This skin cancer often ... skin tissue and bone. Learn more about basal cell carcinoma: Basal cell carcinoma: Signs and symptoms Basal ...

  4. Motor Control Abnormalities in Parkinson’s Disease

    PubMed Central

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  5. Extended amygdala and basal forebrain.

    PubMed

    Alheid, George F

    2003-04-01

    The basal forebrain is a confluence of systems that are crucial to understanding some of the most important functions of the brain, including reward and punishment, learning and cognition, and feeding and reproduction. Basic to understanding this broad spectrum of behavior is untangling the interwoven functional systems in basal forebrain. This has been grounded by the appreciation that the major nearby structures, that is, amygdala and basal ganglia, provide a context for interpreting basal forebrain areas that are best viewed as extensions of either of these larger regions. The components of basal forebrain, the ventral striatopallidal system and the medial and central divisions of extended amygdala, are subcortical relays for information garnered from brain stem, thalamus, and cortical areas. With respect to the classically defined amygdala of the temporal lobe, the lateral-basolateral complex, and the superficial amygdaloid nuclei may tentatively be viewed as specialized cortical regions. Their output targets both the striatopallidal complex and the extended amygdala, with some of the most massive basal forebrain efferents originating in the basolateral amygdaloid complex. The subcortical projections of the basolateral nucleus, at least in the rat, appear to be dichotomous, with anterior (or magnocellular) portions of the nucleus preferentially targeting striatum and ventral striatum (including the core of the nucleus accumbens), while the posterior (small-celled) portions of the basolateral nucleus target the extended amygdala as well as the shell of the nucleus accumbens. This divergence represents a particular opportunity for behavioral neuroscientists analyzing basal forebrain functions. Studies exploiting the dual subcortical projection of basolateral amygdala indicate distinct functional roles for striatum versus extended amygdala. These reinforce the identification of extended amygdala as a functional-anatomical entity distinct from the striatopallidal system. PMID:12724159

  6. Widespread abnormality of the ?-aminobutyric acid-ergic system in Tourette syndrome

    PubMed Central

    Bagic, Anto; Simmons, Janine M.; Mari, Zoltan; Bonne, Omer; Xu, Ben; Kazuba, Diane; Herscovitch, Peter; Carson, Richard E.; Murphy, Dennis L.; Drevets, Wayne C.; Hallett, Mark

    2012-01-01

    Dysfunction of the ?-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive–compulsive disorder. The purpose of this study was to identify a possible dysfunction of the ?-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20?mCi of [11C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABAA receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABAA receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABAA receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics. PMID:22577221

  7. Parkinsonism caused by cavernoma located in basal ganglion

    Microsoft Academic Search

    Sibel Ertan; Gulcin Benbir; Taner Tanriverdi; Ilker Alver; Mustafa Uzan

    2005-01-01

    Deep-seated cavernoma or cavernous angioma is a very rare clinical entity, as is basal ganglia cavernoma presenting with Parkinsonism. The authors demonstrate a 56-year-old man with a cavernoma located in basal ganglion, who subsequently developed Parkinsonism. The patient refused the surgical intervention, and received L-dopa trial; however, no change in the tremor and bradykinesia was observed in spite of high

  8. Bilateral large traumatic hemorrhage of the basal ganglion

    PubMed Central

    Pandey, Nityanand; Mahapatra, Ashok; Singh, Pankaj Kumar

    2014-01-01

    Traumatic bilateral basal ganglia bleed is extremely rare. It is defined as a hemorrhagic lesion located in the basal ganglia or neighboring structures such as the internal capsule and the thalamus. This report describes a 37-year-old man who had large bilateral basal ganglia hemorrhage (BGH) with subdural hematoma and traumatic subarachnoid hemorrhage. With regards to an etiology of bilateral hemorrhage of the basal ganglia, we could not disclose any possible cause except head injury in spite of full diagnostic work-up. Our final diagnosis was bilateral traumatic BGH (TBGH). The pathomechanism of such injuries is still not clear and it is proposed to be due to shear injury to the lenticulostriate and choroidal arteries. Rather than any features of the TBGH itself, duration of coma and/or associated temporal herniation predicted slower recovery and worse outcome. Bilateral TBGH is an extremely rare entity, compatible with a favorable recovery, if not associated with damage to other cortical and subcortical structures and occurring in isolation. TBGH can be considered as a marker of poor outcome rather than its cause. The BGHs seem to be hemorrhagic contusions resulting from a shearing injury, due to high velocity impact. PMID:25685230

  9. CELL ADHESION MOLECULE CADHERIN-6 FUNCTION IN ZEBRAFISH CRANIAL AND LATERAL LINE GANGLIA DEVELOPMENT

    PubMed Central

    Liu, Q.; Dalman, M. R.; Sarmah, S.; Chen, S.; Chen, Y.; Hurlbut, A. K.; Spencer, M. A.; Pancoe, L.; Marrs, J. A.

    2015-01-01

    Cadherins regulate the vertebrate nervous system development. We previously showed that cadherin-6 message (cdh6) was strongly expressed in the majority of the embryonic zebrafish cranial and lateral line ganglia during their development. Here, we present evidence that cdh6 has specific functions during cranial and lateral line ganglia and nerve development. We analyzed the consequences of cdh6 loss-of-function on cranial ganglion and nerve differentiation in zebrafish embryos. Embryos injected with zebrafish cdh6 specific antisense morpholino oligonucleotides (MOs, which suppress gene expression during development; cdh6 morphant embryos) displayed a specific phenotype, including (i) altered shape and reduced development of a subset of the cranial and lateral line ganglia (e.g. the statoacoustic ganglion and vagal ganglion) and (ii) cranial nerves were abnormally formed. This data illustrates an important role for cdh6 in the formation of cranial ganglia and their nerves. PMID:21584906

  10. Primary Cultures of Sympathetic Ganglia

    Microsoft Academic Search

    Mary I. Johnson

    \\u000a A derivative of the neural crest, sympathetic neurons have been utilized in both in vivo and in vitro studies to approach\\u000a a number of basic questions concerning the development and function of the nervous system. The superior cervical ganglia (SCG),\\u000a and particularly the sympathetic chain, can provide significant numbers of neurons with relatively little effort in dissection,\\u000a and, with a

  11. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography

    SciTech Connect

    Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.

    1985-05-01

    Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities.

  12. Basal Cell Carcinoma (BCC)

    MedlinePLUS

    ... carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive than other types of basal ... to treat them early and with slightly more aggressive techniques. Excision – The basal cell carcinoma is cut ...

  13. Communication between neuronal somata and satellite glial cells in sensory ganglia.

    PubMed

    Huang, Li-Yen M; Gu, Yanping; Chen, Yong

    2013-10-01

    Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. "What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia?" and "how do tissue or nerve injuries affect the communication?" are the main questions addressed in this review. PMID:23918214

  14. Structural brain abnormalities in cervical dystonia

    PubMed Central

    2013-01-01

    Background Idiopathic cervical dystonia is characterized by involuntary spasms, tremors or jerks. It is not restricted to a disturbance in the basal ganglia system because non-conventional voxel-based MRI morphometry (VBM) and diffusion tensor imaging (DTI) have detected numerous regional changes in the brains of patients. In this study scans of 24 patients with cervical dystonia and 24 age-and sex-matched controls were analysed using VBM, DTI and magnetization transfer imaging (MTI) using a voxel-based approach and a region-of-interest analysis. Results were correlated with UDRS, TWSTRS and disease duration. Results We found structural alterations in the basal ganglia; thalamus; motor cortex; premotor cortex; frontal, temporal and parietal cortices; visual system; cerebellum and brainstem of the patients with dystonia. Conclusions Cervical dystonia is a multisystem disease involving several networks such as the motor, sensory and visual systems. PMID:24131497

  15. A new neurological entity manifesting as involuntary movements and dysarthria with possible abnormal copper metabolism.

    PubMed

    Tagawa, A; Ono, S; Shibata, M; Imai, T; Suzuki, M; Shimizu, N

    2001-12-01

    A few patients with an affected CNS involving abnormalities in copper metabolism have been described that do not fit any known nosological entities such as Wilson's disease or Menkes' disease. Three sporadic patients (two men and one woman) were examined with involuntary movements and dysarthria associated with abnormal concentrations of serum copper, serum ceruloplasmin, and urinary copper excretion. The onset of neurological symptoms occurred at the age of 15 to 17 years. The common clinical symptoms were involuntary movements and dysarthria. The involuntary movements included dystonia in the neck, myoclonus in the shoulder, athetosis in the neck, and rapid orobuccal movements. The dysarthria consisted of unclear, slow, and stuttering speech. Two of the three patients did not have dementia. A cousin of the female patient had been diagnosed as having Wilson's disease and had died of liver cirrhosis. Laboratory findings showed a mild reduction in serum copper and ceruloplasmin concentrations, whereas urinary copper excretion was significantly reduced in all three patients. Two of the three patients showed a high signal intensity in the basal ganglia on T2 weighted brain MRI. In conclusion, the unique findings of involuntary movements, dysarthria, and abnormal serum copper and urinary copper concentrations suggest that the three patients may constitute a new clinical entity that is distinct from either Wilson's or Menkes disease. PMID:11723201

  16. Neurogenesis in Postnatal Mouse Dorsal Root Ganglia

    Microsoft Academic Search

    Michael P. Namaka; Mike Sawchuk; Stephen C. MacDonald; Larry M. Jordan; Shawn Hochman

    2001-01-01

    Neurogenesis continues in various regions of the central nervous system (CNS) throughout life. As the mitogen basic fibroblast growth factor (bFGF) can proliferate neuronal precursors of CNS neurons in culture, and is also upregulated within adult dorsal root ganglia following axotomy, it is possible that the postnatal dorsal root ganglia contain bFGF-responsive neuronal precursors. We undertook cell culture of postnatal

  17. [Walking abnormalities in children].

    PubMed

    Segawa, Masaya

    2010-11-01

    Walking is a spontaneous movement termed locomotion that is promoted by activation of antigravity muscles by serotonergic (5HT) neurons. Development of antigravity activity follows 3 developmental epochs of the sleep-wake (S-W) cycle and is modulated by particular 5HT neurons in each epoch. Activation of antigravity activities occurs in the first epoch (around the age of 3 to 4 months) as restriction of atonia in rapid eye movement (REM) stage and development of circadian S-W cycle. These activities strengthen in the second epoch, with modulation of day-time sleep and induction of crawling around the age of 8 months and induction of walking by 1 year. Around the age of 1 year 6 months, absence of guarded walking and interlimb cordination is observed along with modulation of day-time sleep to once in the afternoon. Bipedal walking in upright position occurs in the third epoch, with development of a biphasic S-W cycle by the age of 4-5 years. Patients with infantile autism (IA), Rett syndrome (RTT), or Tourette syndrome (TS) show failure in the development of the first, second, or third epoch, respectively. Patients with IA fail to develop interlimb coordination; those with RTT, crawling and walking; and those with TS, walking in upright posture. Basic pathophysiology underlying these condition is failure in restricting atonia in REM stage; this induces dysfunction of the pedunculopontine nucleus and consequently dys- or hypofunction of the dopamine (DA) neurons. DA hypofunction in the developing brain, associated with compensatory upward regulation of the DA receptors causes psychobehavioral disorders in infancy (IA), failure in synaptogenesis in the frontal cortex and functional development of the motor and associate cortexes in late infancy through the basal ganglia (RTT), and failure in functional development of the prefrontal cortex through the basal ganglia (TS). Further, locomotion failure in early childhood causes failure in development of functional specialization of the cortex through the spinal stepping generator-fastigial nucleus-thalamus-cortex pathway. Early detection of locomotion failure and early adjustment of this condition through environmental factors can prevent the development of higher cortical dysfunction. PMID:21068458

  18. Meiotic abnormalities

    SciTech Connect

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  19. Nail abnormalities

    MedlinePLUS

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Infection: Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may cause a ...

  20. Chromosomal abnormalities

    Microsoft Academic Search

    K. Goh; R. F. Jacox; F. W. Anderson

    1980-01-01

    Cytogenetic studies from the peripheral blood of a patient with malignant lymphoma and rhematoid arthritis who was treated with intra-articular gold Au 198 revealed mosaicism with a normal female metaphase and a 43-chromosome metaphase. The abnormal cell line showed six missing normal chromosomes and three morphologically abnormal chromosomes. The trypsin-digested G-banding metaphases showed that the marker chromosomes were an isochromosome

  1. Abnormal High-Frequency Burst Firing of Cerebellar Neurons in Rapid-Onset Dystonia-Parkinsonism

    PubMed Central

    Fremont, Rachel; Calderon, D. Paola; Maleki, Sara

    2014-01-01

    Loss-of-function mutations in the ?3 isoform of the Na+/K+ ATPase (sodium pump) are responsible for rapid-onset dystonia parkinsonism (DYT12). Recently, a pharmacological model of DYT12 was generated implicating both the cerebellum and basal ganglia in the disorder. Notably, partially blocking sodium pumps in the cerebellum was necessary and sufficient for induction of dystonia. Thus, a key question that remains is how partially blocking sodium pumps in the cerebellum induces dystonia. In vivo recordings from dystonic mice revealed abnormal high-frequency bursting activity in neurons of the deep cerebellar nuclei (DCN), which comprise the bulk of cerebellar output. In the same mice, Purkinje cells, which provide strong inhibitory drive to DCN cells, also fired in a similarly erratic manner. In vitro studies demonstrated that Purkinje cells are highly sensitive to sodium pump dysfunction that alters the intrinsic pacemaking of these neurons, resulting in erratic burst firing similar to that identified in vivo. This abnormal firing abates when sodium pump function is restored and dystonia caused by partial block of sodium pumps can be similarly alleviated. These findings suggest that persistent high-frequency burst firing of cerebellar neurons caused by sodium pump dysfunction underlies dystonia in this model of DYT12. PMID:25164667

  2. Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice

    PubMed Central

    Ulu?, Aziz M.; Vo, An; Argyelan, Miklos; Tanabe, Lauren; Schiffer, Wynne K.; Dewey, Stephen; Dauer, William T.; Eidelberg, David

    2011-01-01

    The factors that determine symptom penetrance in inherited disease are poorly understood. Increasingly, magnetic resonance diffusion tensor imaging (DTI) and PET are used to separate alterations in brain structure and function that are linked to disease symptomatology from those linked to gene carrier status. One example is DYT1 dystonia, a dominantly inherited movement disorder characterized by sustained muscle contractions, postures, and/or involuntary movements. This form of dystonia is caused by a 3-bp deletion (i.e., ?E) in the TOR1A gene that encodes torsinA. Carriers of the DYT1 dystonia mutation, even if clinically nonpenetrant, exhibit abnormalities in cerebellothalamocortical (CbTC) motor pathways. However, observations in human gene carriers may be confounded by variability in genetic background and age. To address this problem, we implemented a unique multimodal imaging strategy in a congenic line of DYT1 mutant mice that contain the ?E mutation in the endogenous mouse torsinA allele (i.e., DYT1 knock-in). Heterozygous knock-in mice and littermate controls underwent microPET followed by ex vivo high-field DTI and tractographic analysis. Mutant mice, which do not display abnormal movements, exhibited significant CbTC tract changes as well as abnormalities in brainstem regions linking cerebellar and basal ganglia motor circuits highly similar to those identified in human nonmanifesting gene carriers. Moreover, metabolic activity in the sensorimotor cortex of these animals was closely correlated with individual measures of CbTC pathway integrity. These findings further link a selective brain circuit abnormality to gene carrier status and demonstrate that DYT1 mutant torsinA has similar effects in mice and humans. PMID:21464304

  3. Chromosomal abnormalities

    SciTech Connect

    Goh, K.; Jacox, R.F.; Anderson, F.W.

    1980-09-01

    Cytogenetic studies from the peripheral blood of a patient with malignant lymphoma and rhematoid arthritis who was treated with intra-articular gold Au 198 revealed mosaicism with a normal female metaphase and a 43-chromosome metaphase. The abnormal cell line showed six missing normal chromosomes and three morphologically abnormal chromosomes. The trypsin-digested G-banding metaphases showed that the marker chromosomes were an isochromosome of the long arm of chromosome 17, a translocated chromosome that involved the long arm of chromosome 4 and a chromosome 16, and a translocated chromosome that involved the long arm of chromosome 4 and a chromosome 5. It is tempting to conclude that these abnormalities were due to the gold Au 198 treatment, but we cannot exclude other possibilities.

  4. Tracheal Basal Cells

    PubMed Central

    Cole, Brook B.; Smith, Russell W.; Jenkins, Kimberly M.; Graham, Brian B.; Reynolds, Paul R.; Reynolds, Susan D.

    2010-01-01

    Analysis of lineage relationships in the naphthalene-injured tracheal epithelium demonstrated that two multipotential keratin 14–expressing cells (K14ECs) function as progenitors for Clara and ciliated cells. These K14EC were distinguished by their self-renewal capacity and were hypothesized to reside at the stem and transit amplifying tiers of a tissue-specific stem cell hierarchy. In this study, we used gene expression and histomorphometric analysis of the steady-state and naphthalene-injured trachea to evaluate the predictions of this model. We found that the steady-state tracheal epithelium is maintained by two progenitor cell pools, secretory and basal cells, and the latter progenitor pool is further divided into two subsets, keratin 14–negative and –positive. After naphthalene-mediated depletion of the secretory and ciliated cell types, the two basal cell pools coordinate to restore the epithelium. Both basal cell types up-regulate keratin 14 and generate a broadly distributed, abundant, and highly mitotic cell pool. Furthermore, basal cell proliferation is associated with generation of differentiated Clara and ciliated cells. The uniform distribution of basal cell progenitors and of their differentiated progeny leads us to propose that the hierarchical organization of tracheal reparative cells be revised to include a facultative basal cell progenitor pool. PMID:20522644

  5. Calretinin immunoreactivity in human sympathetic ganglia

    Microsoft Academic Search

    J. J. Huerta; S. Nori; M. M. Llamosas; M. T. Vázquez; E. Bronzetti; J. A. Vega

    1996-01-01

    Calretinin is an “EF-hand” calcium-binding protein involved in the maintenance of intracellular calcium ion homeostasis. This study was understaken to investigate the presence of calretinin in human lumbar paravertebral sympathetic ganglia from subjects of different ages (26–85 years) using immunohistochemical and immunoblotting methods. Calretinin-like immunoreactivity was found in a subpopulation of postganglionic sympathetic neurons, whose percentage decreased progressively with aging

  6. Basal cell carcinoma – diagnosis

    PubMed Central

    Bowszyc-Dmochowska, Monika; Strzelecka-W?klar, Daria; Da?czak-Pazdrowska, Aleksandra; Adamski, Zygmunt

    2013-01-01

    Basal cell carcinoma is the most common skin cancer in the Caucasian population. The cancer arises in sun exposed areas of the skin. The incidence of morbidity is high and it is still growing. The metastatic rate is low, but the enlarging tumor may cause severe tissue disfigurement and a poor cosmetic outcome. The diagnosis is usually clinical but there are many subtypes of this carcinoma and correct diagnosis is the clue to appropriate treatment of the lesion. The main problem in basal cell carcinoma management is the high recurrence rate. PMID:24592119

  7. Kir2 potassium channels in rat striatum are strategically localized to control basal ganglia function

    Microsoft Academic Search

    Harald Prüss; Mareike Wenzel; Dirk Eulitz; Achim Thomzig; Andreas Karschin; Rüdiger W Veh

    2003-01-01

    Parkinson’s disease is the most frequent movement disorder caused by loss of dopaminergic neurons in the midbrain. Intentions to avoid side effects of the conventional therapy should aim to identify additional targets for potential pharmacological intervention. In principle, every step of a signal transduction cascade such as presynaptic transmitter release, type and occupation of postsynaptic receptors, G protein-mediated effector mechanisms,

  8. Basal Ganglia Volumes in Children With Attention-Deficit Hyperactivity Disorder

    Microsoft Academic Search

    Elizabeth H. Aylward; Allan L. Reiss; Mark J. Reader; Harvey S. Singer; Jan E. Brown; Martha B. Denckla

    1996-01-01

    Previous research has demonstrated volume reduction of the left globus pallidus in children with the codiagnoses of Tourette syndrome and attention-deficit hyperactivity disorder (ADHD), in comparison with children who have Tourette syndrome alone and with normal controls. The purpose of this study was to determine whether children with ADHD alone also had volume reduction of the globus pallidus or other

  9. A Computational Model of Inhibitory Control in Frontal Cortex and Basal Ganglia

    ERIC Educational Resources Information Center

    Wiecki, Thomas V.; Frank, Michael J.

    2013-01-01

    Planning and executing volitional actions in the face of conflicting habitual responses is a critical aspect of human behavior. At the core of the interplay between these 2 control systems lies an override mechanism that can suppress the habitual action selection process and allow executive control to take over. Here, we construct a neural circuit…

  10. Pausing to Regroup: Thalamic Gating of Cortico-Basal Ganglia Networks

    E-print Network

    Thorn, Catherine A.

    How the cholinergic and dopaminergic systems of the striatum interact and how these interface with the massive neocortical input to the striatum are classic questions of cardinal interest to neurology and psychiatry. In ...

  11. Exhumed from thought: basal ganglia and response learning in the plus-maze.

    PubMed

    Packard, Mark G

    2009-04-12

    The plus-maze apparatus figured prominently in the historical debate between cognitive and stimulus-response habit learning theorists concerned with the fundamental question of "what" animals learn. An important feature of this task is that variants of the training procedure can be arranged to allow for an assessment of the relative use of cognitive/place or habit/response learning mechanisms. This brief review describes findings from several neurobiological studies published primarily over the past decade that have re-introduced the plus-maze to investigate the role of the dorsal striatum in learning and memory. Converging evidence from research using brain lesion, pharmacological, and molecular/genetic approaches is described supporting the hypothesis that the dorsolateral striatum plays a selective role in response learning in the plus-maze. Within a multiple systems framework of memory organization, factors that can influence the relative use of place and response learning in the plus-maze are also considered, including the nature of the visual environment, reinforcement/training parameters, and emotional state of the organism. Response learning in the plus-maze may be considered an exemplar task useful for investigating the neurobiological bases of dorsal striatal involvement in habit learning and memory. This mnemonic function of the dorsal striatum generalizes across several sensory modalities and mammalian species, including humans. PMID:19133296

  12. The effects of cues on neurons in the basal ganglia in Parkinson's disease

    E-print Network

    Brown, Emery N.

    Visual cues open a unique window to the understanding of Parkinson's disease (PD). These cues can temporarily but dramatically improve PD motor symptoms. Although details are unclear, cues are believed to suppress pathological ...

  13. Towards an executive without a homunculus: computational models of the prefrontal cortex\\/basal ganglia system

    Microsoft Academic Search

    Thomas E. Hazy; Michael J. Frank; Randall C. O'Reilly

    2007-01-01

    The prefrontal cortex (PFC) has long been thought to serve as an 'executive' that controls the selection of actions and cognitive functions more generally. However, the mechanistic basis of this executive function has not been clearly specified often amounting to a homunculus. This paper reviews recent attempts to deconstruct this homunculus by elucidating the precise computational and neural mechanisms underlying

  14. Network-level neuroplasticity in cortico-basal ganglia pathways Ann M. Graybiel*

    E-print Network

    Graybiel, Ann M.

    circuits occurs in disorders ranging from obsessive­compulsive (OC) dis- order to addiction [1­4]. A loss and compulsive beha- viours in OC disorder. In some OC-spectrum disorders, a linkage between repetitive cognitive produce severe forms of compulsive behaviour. The commonalities across this wide range of disorders

  15. Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

    E-print Network

    Crittenden, Jill R.

    The striatum is composed principally of GABAergic, medium spiny striatal projection neurons (MSNs) that can be categorized based on their gene expression, electrophysiological profiles, and input–output circuits. Major ...

  16. Glutamate-dopamine interactions in the basal ganglia: relationship to Parkinson's disease

    Microsoft Academic Search

    J. T. Greenamyre

    1993-01-01

    Summary Current antiparkinsonian therapies focus on either replacing dopamine via precursor (L-DOPA) administration, or directly stimulating postsynaptic dopamine receptors with dopamine agonists. Unfortunately, this approach is associated with numerous side effects and these drugs lose efficacy with disease progression. This article reviews recent evidence which suggests that negative modulation of glutamatergic neurotransmission has antiparkinsonian effects in a variety of rodent

  17. Functional role of the limbic system and basal ganglia in motivated behaviors

    Microsoft Academic Search

    T. Ono; H. Nishijo; H. Nishino

    2000-01-01

    It has been suggested that the cortico- and limbic-striatal systems are important in various motor functions such as motivated\\u000a behaviors. In this paper we review our previous studies to investigate neuronal mechanisms of feeding behaviors. We recorded\\u000a neuronal activity from the amygdala, caudate nucleus, globus pallidus, and substantia nigra during feeding behavior in monkeys,\\u000a and compared neuronal responses recorded from

  18. Site-specific invasion of the basal ganglia by Nocardia asteroides GUH-2

    Microsoft Academic Search

    Blaine L. Beaman; Donald Canfield; John Anderson; Brian Pate; Donald Calne

    2000-01-01

    Nocardia asteroides GUH-2 (GUH-2) invades the nigrostriatal region of the brain in mice [15]. Selective dopaminergic neuronal dropout in the\\u000a substantia nigra results in parkinsonian changes characterized by movement disorders responsive to L-dopa [15]. This is the only reported example of an experimental bacterial model for parkinsonism. Following i.v. inoculation\\u000a of GUH-2 into the non-human primate Macaca fasicularius, the nocardiae

  19. Basal Ganglia and Behaviour: Behavioural Effects of Deep Brain Stimulation in Experimental Neurological and Psychiatric Disorders

    Microsoft Academic Search

    Thibault Sesia; Sonny Tan; Rinske Vlamings; Lee Wei Lim; Veerle Visser-Vandewalle; Yasin Temel

    \\u000a The use of deep brain stimulation (DBS) to control severely disabling neurological and psychiatric conditions is an exciting\\u000a and fast emerging area of neuroscience. Deep brain stimulation has generally the same clinical effects as a lesion with respect\\u000a to the improvement of clinical disability, but has more advantages such as its adjustability and reversibility. To this day,\\u000a fundamental knowledge regarding

  20. Mini-Symposium Converging Evidence for a Fronto-Basal-Ganglia Network for

    E-print Network

    Logan, Gordon D.

    Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, 5Movement Neuroscience such as Attention Deficit Hyperactiv- ity Disorder (ADHD). The Stop signal paradigm This cognitive psychology

  1. Electrophysiology of dopamine D-1 receptors in the basal ganglia: Old facts and new perspectives

    Microsoft Academic Search

    Marco De Murtas; Antonio Pisani; Francesca Stratta; Antonello Bonci; Nicola B. Mercuri; Paolo Calabresi

    1995-01-01

    1.1. The dopamine (DA) D1-receptor family is highly represented in the mammalian brain and particularly in the nigrostriatal system, whose integrity is crucial for the execution of motor performances.2.2. In the last decade, our understanding of the electrophysiology of D1 receptors on caudate-putamen neurons has greatly improved. The effects of the activation of striatal D1 receptors were studied by extracellular

  2. Interacting cortical and basal ganglia networks underlying finding and tapping to the musical beat.

    PubMed

    Kung, Shu-Jen; Chen, Joyce L; Zatorre, Robert J; Penhune, Virginia B

    2013-03-01

    Humans are able to find and tap to the beat of musical rhythms varying in complexity from children's songs to modern jazz. Musical beat has no one-to-one relationship with auditory features-it is an abstract perceptual representation that emerges from the interaction between sensory cues and higher-level cognitive organization. Previous investigations have examined the neural basis of beat processing but have not tested the core phenomenon of finding and tapping to the musical beat. To test this, we used fMRI and had musicians find and tap to the beat of rhythms that varied from metrically simple to metrically complex-thus from a strong to a weak beat. Unlike most previous studies, we measured beat tapping performance during scanning and controlled for possible effects of scanner noise on beat perception. Results showed that beat finding and tapping recruited largely overlapping brain regions, including the superior temporal gyrus (STG), premotor cortex, and ventrolateral PFC (VLPFC). Beat tapping activity in STG and VLPFC was correlated with both perception and performance, suggesting that they are important for retrieving, selecting, and maintaining the musical beat. In contrast BG activity was similar in all conditions and was not correlated with either perception or production, suggesting that it may be involved in detecting auditory temporal regularity or in associating auditory stimuli with a motor response. Importantly, functional connectivity analyses showed that these systems interact, indicating that more basic sensorimotor mechanisms instantiated in the BG work in tandem with higher-order cognitive mechanisms in PFC. PMID:23163420

  3. Post-Stroke Apathy and Hypoperfusion in Basal Ganglia: SPECT Study

    Microsoft Academic Search

    Keiichi Onoda; Yoko Kuroda; Yasushi Yamamoto; Satoshi Abe; Hiroaki Oguro; Atsushi Nagai; Hirokazu Bokura; Shuhei Yamaguchi

    2011-01-01

    Background: Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there are few studies on regional cerebral blood flow (rCBF) in stroke patients with apathy. The present study compared rCBF between apathetic and non-apathetic patients after stroke. Methods: We recruited 102 patients with cerebral infarction within 1 month after stroke and performed neuropsychiatric assessments that included

  4. Basal Ganglia Activity in Pathological Gambling: A Fluorodeoxyglucose-Positron Emission Tomography Study

    Microsoft Academic Search

    Stefano Pallanti; M. Mehmet Haznedar; Eric Hollander; Elizabeth M. LiCalzi; Silvia Bernardi; Randall Newmark; Monte S. Buchsbaum

    2010-01-01

    Background: Pathological gambling (PG) is a disorder classified as an impulse control disorder (DSM-IV) bridging impulsive, compulsive and addictive behaviors. The striatum and thalamus are supposed to be involved in the pathophysiological substrate of these behaviors. An increased relative glucose metabolic rate (rGMR) in patients with a diagnosis of PG had previously been reported in the medial and orbitofrontal cortex.

  5. Computational studies of the role of serotonin in the basal ganglia.

    PubMed

    Reed, Michael C; Nijhout, H Frederik; Best, Janet

    2013-01-01

    It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson's disease (PD), the serotonergic projections from the dorsal raphe nucleus (DRN) release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that the effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the "balance" between the pathways to favor the indirect pathway. Originally, "balance" was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing in the two pathways too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum serves to stabilize the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson's disease progression (until late phase). There may be situations in which there are physiological reasons to "unbalance" the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task. PMID:23745108

  6. Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia

    Microsoft Academic Search

    F. Mátyás; Y. Yanovsky; K. MacKie; W. Kelsch; U. Misgeld; T. F. Freund

    2006-01-01

    Endocannabinoids, acting via type 1 cannabinoid receptors (CB1), are known to be involved in short-term synaptic plasticity via retrograde signaling. Strong depolarization of the postsynaptic neurons is followed by the endocannabinoid-mediated activation of presynaptic CB1 receptors, which suppresses GABA and\\/or glutamate release. This phenomenon is termed depolarization-induced suppression of inhibition (DSI) or excitation (DSE), respectively.Although both phenomena have been reported

  7. Basal ganglia-dependent processes in recalling learned visual-motor adaptations

    Microsoft Academic Search

    Patrick Bédard; Jerome N. Sanes

    2011-01-01

    Humans learn and remember motor skills to permit adaptation to a changing environment. During adaptation, the brain develops\\u000a new sensory–motor relationships that become stored in an internal model (IM) that may be retained for extended periods. How\\u000a the brain learns new IMs and transforms them into long-term memory remains incompletely understood since prior work has mostly\\u000a focused on the learning

  8. Congenital fibrosis of the extraocular muscles associated with cortical dysplasia and maldevelopment of the basal ganglia

    Microsoft Academic Search

    Maree P Flaherty; Padraic Grattan-Smith; Adam Steinberg; Robyn Jamieson; Elizabeth C Engle

    2001-01-01

    BackgroundCongenital fibrosis of the extraocular muscles (CFEOM) is a rare condition that has been traditionally regarded as a primary eye muscle disease. Recent studies, however, suggest that CFEOM may be the result of a primary neuropathy with secondary myopathic changes.

  9. Error Correction, the Basal Ganglia, and the Cerebellum Ph.D. Dissertation

    E-print Network

    Shadmehr, Reza

    HUNTINGTON'S DISEASE BACKGROUND ..........................................................................2 SENSORIMOTOR PROCESSING IN HUNTINGTON'S DISEASE ...............................................4 CEREBELLAR ....................................................................................................12 CHAPTER 2 - HUNTINGTON'S DISEASE BEGINS AS A DYSFUNCTION IN ERROR FEEDBACK CONTROL

  10. Intercellular communication in sensory ganglia by purinergic receptors and gap junctions: implications for chronic pain.

    PubMed

    Hanani, Menachem

    2012-12-01

    Peripheral injury can cause abnormal activity in sensory neurons, which is a major factor in chronic pain. Recent work has shown that injury induces major changes not only in sensory neurons but also in the main type of glial cells in sensory ganglia-satellite glial cells (SGCs), and that interactions between sensory neurons and SGCs contribute to neuronal activity in pain models. The main functional changes observed in SGCs after injury are an increased gap junction-mediated coupling among these cells, and augmented sensitivity to ATP. There is evidence that the augmented gap junctions contribute to neuronal hyperexcitability in pain models, but the mechanism underlying this effect is not known. The changes in SGCs described above have been found following a wide range of injuries (both axotomy and inflammation) in somatic, orofacial and visceral regions, and therefore appear to be a general feature in chronic pain. We have found that in cultures of sensory ganglia calcium signals can spread from an SGC to neighboring cells by calcium waves, which are mediated by gap junctions and ATP acting on purinergic P2 receptors. A model is proposed to explain how augmented gap junctions and greater sensitivity to ATP can combine to produce enhanced calcium waves, which can lead to neuronal excitation. Thus this simple scheme can account for several major changes in sensory ganglia that are common to a great variety of pain models. PMID:22771859

  11. Perianal Basal Cell Carcinoma

    PubMed Central

    Bulur, Isil; Boyuk, Emine; Saracoglu, Zeynep Nurhan; Arik, Deniz

    2015-01-01

    Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. Exposure to ultraviolet light is an important risk factor for BCC development and the disorder therefore develops commonly on body areas that are more exposed to sunlight, such as the face and neck. It is uncommon in the closed area of the body and quite rare in the perianal and genital regions. Herein, we report a 34-year-old patient with perianal BCC who had no additional risk factors.

  12. Future of newer basal insulin

    PubMed Central

    Madhu, S. V.; Velmurugan, M.

    2013-01-01

    Basal insulin have been developed over the years. In recent times newer analogues have been added to the armanentarium for diabetes therapy. This review specifically reviews the current status of different basal insulins PMID:23776897

  13. Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome

    Microsoft Academic Search

    Heidi Hahn; Carol Wicking; Peter G Zaphiropoulos; Mae R Gailani; Susan Shanley; Abirami Chidambaram; Igor Vorechovsky; Erika Holmberg; Anne Birgitte Unden; Susan Gillies; Kylie Negus; Ian Smyth; Carolyn Pressman; David J Leffell; Bernard Gerrard; Alisa M Goldstein; Michael Dean; Rune Toftgard; Georgia Chenevix-Trench; Brandon Wainwright; Allen E Bale

    1996-01-01

    The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety of other tumors, and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial and sporadic BCCs display loss of heterozygosity in this region, consistent with the gene being a tumor suppressor. A

  14. UNMEDULLATED FIBERS ORIGINATING IN DORSAL ROOT GANGLIA

    PubMed Central

    Gasser, Herbert S.

    1950-01-01

    The compound action potential of the unmedullated fibers arising from dorsal root ganglia, as recorded in cat skin nerves after conduction of simultaneously initiated impulses, shows among its components a temporal dispersion corresponding to velocities between 2.3 and 0.7 M.P.S. The maximum representation of the component velocities is at about 1.2 M.P.S. On both sides of the maximum the representation falls off irregularly, in such a way that groupings in the distribution produce in the action potential a configuration in which successive features appear always in the same positions at a given conduction distance. Through this demonstration of a characteristic configuration the system of the unmedullated fibers is brought into analogy with that of the medullated fibers. The unmedullated fibers originating in the dorsal root ganglia have distinctive physiological properties, among which is a large positive potential which reaches its maximum immediately after the spike and decrements to half relaxation in about 50 msec., at 37°C. The positive phases of the unit potentials in the compound action potential, owing to their duration, sum to a much greater extent than the temporally dispersed spikes; and, since they have sizes such that one equivalent to 25 per cent of the spike height would not be at the limit, in the summation process the major portion of the compound action potential is caused to be written at a potential level positive to the starting base line. The position of the spikes in the sequence can be seen in the analyses in Section III. The course of the activity in unit fibers is subject to variation in ways affecting the positive potential. Preliminary descriptions, based on orienting experiments, of how these variations are conditioned are given in Section I. Two of the findings are particularly noteworthy. One is the high sensitivity of the dimensions of the postspike positivity to temperature in the range of temperatures at which skin nerves may be expected to function, even when the environmental temperatures of an animal are moderate. The other is the high sensitivity to conditioning by previous activity. The positivity is first decreased, then replaced by a negative potential of similar duration. Reasons have been given why it is inadvisable at the present time to call the postspike potential an after-potential. A comparison has been made of the properties of the unmedullated fibers arising from dorsal root ganglia with those of fibers arising from sympathetic ganglia. The differences are so great that, in the interest of precision in designation, a division of the C group of fibers into two subgroups is indicated. It is suggested that the two subgroups be named respectively d.r.C and s.C. Measurements have been made of the diameters of the d.r.C fibers in a saphenous nerve stained with silver. Graphs showing the number of fibers at each diameter are presented in Section II. In Section III there are shown constructions, from histological data, of the action potential as it would appear, after 3 cm. of conduction, with the correlation between diameter and velocity in strict linearity. The degree of fit between the constructed and recorded potentials can be seen in Fig. 18. PMID:15428610

  15. Nerve growth factor promotes neurite outgrowth in guinea pig myenteric plexus ganglia.

    PubMed

    Mulholland, M W; Romanchuk, G; Lally, K; Simeone, D M

    1994-10-01

    Nerve growth factor (NGF) has important developmental actions in both central and peripheral nervous systems. Primary cultures of neonatal guinea pig myenteric plexus ganglia were used to examine the ability of NGF to stimulate morphological development in enteric neurons. NGF, in the presence of a serum-free medium, produced dose-dependent increases in neurite density, significant at 1 ng/ml and maximal at 100 ng/ml (4.5-fold increase vs. control). Maximum neurite length was also significantly increased at 1 ng/ml, with maximal effects at 100 ng/ml. Coincubation of NGF (50 ng/ml) with monoclonal NGF antibodies abolished increases in both neurite density (128 +/- 19 processes/mm for control, 369 +/- 19 for NGF, 183 +/- 28 for NGF+monoclonal antibodies) and neurite length. Exposure of enteric neurons to low concentrations of NGF (1 ng/ml) was also associated with increased mRNA levels for cytoskeletal genes. alpha-Tubulin mRNA levels were increased 3.9 +/- 0.7 times basal at 48 h. mRNA levels for microtubule-associated protein 2 were increased threefold at 48 h of NGF incubation. NGF demonstrates activities in cultured enteric ganglia that stimulate morphological development. PMID:7943336

  16. Odontogenic keratocysts in Nevoid basal cell carcinoma syndrome: a case report

    PubMed Central

    2009-01-01

    Nevoid basal cell carcinoma syndrome, a rare autosomal dominant disorder, comprises a number of abnormalities such as multiple nevoid basal cell carcinomas, skeletal abnormalities and multiple odontogenic keratocysts. Considering the rarity of this syndrome, we present a 12-year-old boy affected by this syndrome. He had multiple okcs, calcification of falx cerebri, bifid ribs, frontal bossing and hypertelorism. Characteristic cutaneous manifestation (nevoid basal cell carcinoma) was not present in this patient. The jaw cysts were treated with marsupialization then enucleation. The dental clinician may be the first to encounter and identify this syndrome, when the multiple cystlike radiolucencies are discovered on panoramic view. PMID:20111613

  17. Basal Cell Nevus Syndrome Showing Several Histologic Types of Basal Cell Carcinoma

    PubMed Central

    Go, Jae Wan; Kim, Shin Han; Yi, Sang Yeop

    2011-01-01

    Basal cell nevus syndrome (BCNS), or Gorlin Syndrome, is an autosomal dominant disorder, characterized by multiple developmental abnormalities and associated with germline mutations in the PTCH gene. Patients show multiple and early onset basal cell carcinomas (BCCs) in skin, odontogeniccysts in the jaw, pits on palms and soles, medulloblastoma, hypertelorism, and calcification of the falx cerebri. Clinical features of BCCs in these patients are indistinguishable from ordinary BCCs. However, some patients show variable histologic findings in subtypes of BCCs, and only one case associated with several histologic types of BCCs in the syndrome has been reported in Korea. We present a case of BCNS characterized by multiple BCCs, odontogenic keratocysts, multiple palmar pits, and calcified falx cerebri. Histopathologic findings of BCCs showed several patterns, which were nodular, superficial, and pigmented types. PMID:22028568

  18. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease

    PubMed Central

    Lammers, Nicolette M.; Sondermeijer, Brigitte M.; Twickler, Th. B. (Marcel); de Bie, Rob M.; Ackermans, Mariëtte T.; Fliers, Eric; Schuurman, P. Richard; La Fleur, Susanne E.; Serlie, Mireille J.

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans. PMID:24860415

  19. Alarin in cranial autonomic ganglia of human and rat.

    PubMed

    Schrödl, Falk; Kaser-Eichberger, Alexandra; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Bruckner, Daniela; Krefft, Karolina; Kofler, Barbara; Brandtner, Herwig; Reitsamer, Herbert A

    2015-02-01

    Extrinsic and intrinsic sources of the autonomic nervous system contribute to choroidal innervation, thus being responsible for the control of choroidal blood flow, aqueous humor production or intraocular pressure. Neuropeptides are involved in this autonomic control, and amongst those, alarin has been recently introduced. While alarin is present in intrinsic choroidal neurons, it is not clear if these are the only source of neuronal alarin in the choroid. Therefore, we here screened for the presence of alarin in human cranial autonomic ganglia, and also in rat, a species lacking intrinsic choroidal innervation. Cranial autonomic ganglia (i.e., ciliary, CIL; pterygopalatine, PPG; superior cervical, SCG; trigeminal ganglion, TRI) of human and rat were prepared for immunohistochemistry against murine and human alarin, respectively. Additionally, double staining experiments for alarin and choline acetyltransferase (ChAT), tyrosine hydroxilase (TH), substance P (SP) were performed in human and rat ganglia for unequivocal identification of ganglia. For documentation, confocal laser scanning microscopy was used, while quantitative RT-PCR was applied to confirm immunohistochemical data and to detect alarin mRNA expression. In humans, alarin-like immunoreactivity (alarin-LI) was detected in intrinsic neurons and nerve fibers of the choroidal stroma, but was lacking in CIL, PPG, SCG and TRI. In rat, alarin-LI was detected in only a minority of cranial autonomic ganglia (CIL: 3.5%; PPG: 0.4%; SCG: 1.9%; TRI: 1%). qRT-PCR confirmed the low expression level of alarin mRNA in rat ganglia. Since alarin-LI was absent in human cranial autonomic ganglia, and only present in few neurons of rat cranial autonomic ganglia, we consider it of low impact in extrinsic ocular innervation in those species. Nevertheless, it seems important for intrinsic choroidal innervation in humans, where it could serve as intrinsic choroidal marker. PMID:25497346

  20. Shape abnormalities of subcortical and ventricular structures in mild cognitive impairment and Alzheimer's disease: detecting, quantifying, and predicting.

    PubMed

    Tang, Xiaoying; Holland, Dominic; Dale, Anders M; Younes, Laurent; Miller, Michael I

    2014-08-01

    This article assesses the feasibility of using shape information to detect and quantify the subcortical and ventricular structural changes in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. We first demonstrate structural shape abnormalities in MCI and AD as compared with healthy controls (HC). Exploring the development to AD, we then divide the MCI participants into two subgroups based on longitudinal clinical information: (1) MCI patients who remained stable; (2) MCI patients who converted to AD over time. We focus on seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricles) in 754 MR scans (210 HC, 369 MCI of which 151 converted to AD over time, and 175 AD). The hippocampus and amygdala were further subsegmented based on high field 0.8 mm isotropic 7.0T scans for finer exploration. For MCI and AD, prominent ventricular expansions were detected and we found that these patients had strongest hippocampal atrophy occurring at CA1 and strongest amygdala atrophy at the basolateral complex. Mild atrophy in basal ganglia structures was also detected in MCI and AD. Stronger atrophy in the amygdala and hippocampus, and greater expansion in ventricles was observed in MCI converters, relative to those MCI who remained stable. Furthermore, we performed principal component analysis on a linear shape space of each structure. A subsequent linear discriminant analysis on the principal component values of hippocampus, amygdala, and ventricle leads to correct classification of 88% HC subjects and 86% AD subjects. PMID:24443091

  1. CHAPTER SEVEN Were Basal Primates

    E-print Network

    233 CHAPTER SEVEN Were Basal Primates Nocturnal? Evidence from Eye and Orbit Shape Callum F. Ross pattern, Charles-Dominique (1975: 86) suggested that the last common ancestor of primates "had an eye or a strepsirrhine eye. By the late 1970s, the issue of the activity pattern of basal primates was independently

  2. Abnormal Uterine Bleeding

    MedlinePLUS

    ... abnormal uterine bleeding is caused by a hormone imbalance. When hormones are the problem, doctors call the ... bleeding, or DUB. Abnormal bleeding caused by hormone imbalance is more common in teenagers or in women ...

  3. Abnormal Head Position

    MedlinePLUS

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  4. Polar basal melting on Mars

    NASA Astrophysics Data System (ADS)

    Clifford, S. M.

    1987-08-01

    The potential importance of basal melting on Mars is illustrated through the discussion of four examples: (1) the origin of the major polar reentrants, (2) the removal and storage of an ancient Martian ice sheet, (3) the mass balance of the polar terrains, and (4) the possibility of basal melting at temperate latitudes. This analysis suggests that the process of basal melting may play a key role in understanding the evolution of the Martian polar terrains and the long-term climatic behavior of water on Mars.

  5. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic therapy and topical chemotherapy. Radiotherapy should be avoided. Vitamin A analogs may play a preventive role against development of new BCCs. Life expectancy in NBCCS is not significantly altered but morbidity from complications can be substantial. Regular follow-up by a multi-specialist team (dermatologist, neurologist and odontologist) should be offered. Patients with NBCCS should strictly avoid an excessive sun exposure. PMID:19032739

  6. Immunolocalization of serotonin in Onychophora argues against segmental ganglia being an ancestral feature of arthropods

    PubMed Central

    Mayer, Georg; Harzsch, Steffen

    2007-01-01

    Background Onychophora (velvet worms) represent the most basal arthropod group and play a pivotal role in the current discussion on the evolution of nervous systems and segmentation in arthropods. Although there is a wealth of information on the immunolocalization of serotonin (5-hydroxytryptamine, 5-HT) in various euarthropods, as yet no comparable localization data are available for Onychophora. In order to understand how the onychophoran nervous system compares to that of other arthropods, we studied the distribution of serotonin-like immunoreactive neurons and histological characteristics of ventral nerve cords in Metaperipatus blainvillei (Onychophora, Peripatopsidae) and Epiperipatus biolleyi (Onychophora, Peripatidae). Results We demonstrate that paired leg nerves are the only segmental structures associated with the onychophoran nerve cord. Although the median commissures and peripheral nerves show a repeated pattern, their arrangement is independent from body segments characterized by the position of legs and associated structures. Moreover, the somata of serotonin-like immunoreactive neurons do not show any ordered arrangement in both species studied but are instead scattered throughout the entire length of each nerve cord. We observed neither a serially iterated nor a bilaterally symmetric pattern, which is in contrast to the strictly segmental arrangement of serotonergic neurons in other arthropods. Conclusion Our histological findings and immunolocalization experiments highlight the medullary organization of the onychophoran nerve cord and argue against segmental ganglia of the typical euarthropodan type being an ancestral feature of Onychophora. These results contradict a priori assumptions of segmental ganglia being an ancestral feature of arthropods and, thus, weaken the traditional Articulata hypothesis, which proposes a sistergroup relationship of Annelida and Arthropoda. PMID:17629937

  7. Phenotypic changes in satellite glial cells in cultured trigeminal ganglia.

    PubMed

    Belzer, Vitali; Shraer, Nathanael; Hanani, Menachem

    2010-11-01

    Satellite glial cells (SGCs) are specialized cells that form a tight sheath around neurons in sensory ganglia. In recent years, there is increasing interest in SGCs and they have been studied in both intact ganglia and in tissue culture. Here we studied phenotypic changes in SGCs in cultured trigeminal ganglia from adult mice, containing both neurons and SGCs, using phase optics, immunohistochemistry and time-lapse photography. Cultures were followed for up to 14 days. After isolation virtually every sensory neuron is ensheathed by SGCs, as in the intact ganglia. After one day in culture, SGCs begin to migrate away from their parent neurons, but in most cases the neurons still retain an intact glial cover. At later times in culture, there is a massive migration of SGCs away from the neurons and they undergo clear morphological changes, and at 7 days they become spindle-shaped. At one day in culture SGCs express the glial marker glutamine synthetase, and also the purinergic receptor P2X7. From day 2 in culture the glutamine synthetase expression is greatly diminished, whereas that of P2X7 is largely unchanged. We conclude that SGCs retain most of their characteristics for about 24 h after culturing, but undergo major phenotypic changes at later times. PMID:22032231

  8. Urine - abnormal color

    MedlinePLUS

    The usual color of urine is straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. ... Abnormal urine color may be caused by infection, disease, medicines, or food you eat. Cloudy or milky urine is a sign ...

  9. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

    PubMed

    Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

    2012-10-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

  10. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

    PubMed Central

    Kiran, N. K.; Tilak Raj, T. N.; Mukunda, K. S.; Rajashekar Reddy, V.

    2012-01-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

  11. Dual pathways regulate neurite outgrowth in enteric ganglia.

    PubMed

    Simeone, D M; Romanchuk, G; Mulholland, M W

    1994-10-01

    Primary cultures of guinea pig myenteric plexus ganglia were used to examine the ability of agents that activate adenylate cyclase or mimic intracellular adenosine 3',5'-cyclic monophosphate (cAMP) to stimulate morphological growth. Dose-dependent increases in neurite length and density were produced in enteric neuronal cultures by forskolin (212% of control), cholera toxin (356% of control), or the permeant cAMP analogues 8-bromoadenosine 3',5'-cyclic monophosphate and dibutyryl cAMP. (R)-p-adenosine 3',5'-cyclic monophosphorothioate, an inhibitor of cAMP-dependent kinases, blocked the growth-promoting effects of cAMP analogues but not of nerve growth factor (NGF). Activation of cAMP-dependent signaling pathways also increased production of mRNA for alpha-tubulin and microtubule-associated protein 2. Dual pathways, regulated by NGF and cAMP-dependent protein kinases, influence growth signaling in enteric ganglia. PMID:7943337

  12. The role of the amygdala and the basal ganglia in visual processing of central vs. peripheral emotional content.

    PubMed

    Almeida, Inês; van Asselen, Marieke; Castelo-Branco, Miguel

    2013-09-01

    In human cognition, most relevant stimuli, such as faces, are processed in central vision. However, it is widely believed that recognition of relevant stimuli (e.g. threatening animal faces) at peripheral locations is also important due to their survival value. Moreover, task instructions have been shown to modulate brain regions involved in threat recognition (e.g. the amygdala). In this respect it is also controversial whether tasks requiring explicit focus on stimulus threat content vs. implicit processing differently engage primitive subcortical structures involved in emotional appraisal. Here we have addressed the role of central vs. peripheral processing in the human amygdala using animal threatening vs. non-threatening face stimuli. First, a simple animal face recognition task with threatening and non-threatening animal faces, as well as non-face control stimuli, was employed in naïve subjects (implicit task). A subsequent task was then performed with the same stimulus categories (but different stimuli) in which subjects were told to explicitly detect threat signals. We found lateralized amygdala responses both to the spatial location of stimuli and to the threatening content of faces depending on the task performed: the right amygdala showed increased responses to central compared to left presented stimuli specifically during the threat detection task, while the left amygdala was better prone to discriminate threatening faces from non-facial displays during the animal face recognition task. Additionally, the right amygdala responded to faces during the threat detection task but only when centrally presented. Moreover, we have found no evidence for superior responses of the amygdala to peripheral stimuli. Importantly, we have found that striatal regions activate differentially depending on peripheral vs. central processing of threatening faces. Accordingly, peripheral processing of these stimuli activated more strongly the putaminal region, while central processing engaged mainly the caudate nucleus. We conclude that the human amygdala has a central bias for face stimuli, and that visual processing recruits different striatal regions, putaminal or caudate based, depending on the task and on whether peripheral or central visual processing is involved. PMID:23872141

  13. Integrating cortico-limbic-basal ganglia architectures for learning model-based and model-free navigation strategies

    PubMed Central

    Khamassi, Mehdi; Humphries, Mark D.

    2012-01-01

    Behavior in spatial navigation is often organized into map-based (place-driven) vs. map-free (cue-driven) strategies; behavior in operant conditioning research is often organized into goal-directed vs. habitual strategies. Here we attempt to unify the two. We review one powerful theory for distinct forms of learning during instrumental conditioning, namely model-based (maintaining a representation of the world) and model-free (reacting to immediate stimuli) learning algorithms. We extend these lines of argument to propose an alternative taxonomy for spatial navigation, showing how various previously identified strategies can be distinguished as “model-based” or “model-free” depending on the usage of information and not on the type of information (e.g., cue vs. place). We argue that identifying “model-free” learning with dorsolateral striatum and “model-based” learning with dorsomedial striatum could reconcile numerous conflicting results in the spatial navigation literature. From this perspective, we further propose that the ventral striatum plays key roles in the model-building process. We propose that the core of the ventral striatum is positioned to learn the probability of action selection for every transition between states of the world. We further review suggestions that the ventral striatal core and shell are positioned to act as “critics” contributing to the computation of a reward prediction error for model-free and model-based systems, respectively. PMID:23205006

  14. Impaired L1 and Executive Control after Left Basal Ganglia Damage in a Bilingual Basque-Spanish Person with Aphasia

    ERIC Educational Resources Information Center

    Adrover-Roig, Daniel; Galparsoro-Izagirre, Nekane; Marcotte, Karine; Ferre, Perrine; Wilson, Maximiliano A.; Ansaldo, Ana Ines

    2011-01-01

    Bilinguals must focus their attention to control competing languages. In bilingual aphasia, damage to the fronto-subcortical loop may lead to pathological language switching and mixing and the attrition of the more automatic language (usually L1). We present the case of JZ, a bilingual Basque-Spanish 53-year-old man who, after haematoma in the…

  15. Oculomotor learning revisited: a model of reinforcement learning in the basal ganglia incorporating an efference copy of motor actions

    E-print Network

    Fee, Michale S.

    In its simplest formulation, reinforcement learning is based on the idea that if an action taken in a particular context is followed by a favorable outcome, then, in the same context, the tendency to produce that action ...

  16. A novel mutation in TTC19 associated with isolated complex III deficiency, cerebellar hypoplasia, and bilateral basal ganglia lesions

    PubMed Central

    Melchionda, Laura; Damseh, Nadirah S.; Abu Libdeh, Bassam Y.; Nasca, Alessia; Elpeleg, Orly; Zanolini, Alice; Ghezzi, Daniele

    2014-01-01

    Isolated complex III (cIII) deficiency is a rare biochemical finding in mitochondrial disorders, mainly associated with mutations in mitochondrial DNA MTCYB gene, encoding cytochrome b, or in assembly factor genes (BCS1L, TTC19, UQCC2, and LYRM7), whereas mutations in nuclear genes encoding cIII structural subunits are extremely infrequent. We report here a patient, a 9 year old female born from first cousin related parents, with normal development till 18 months when she showed unsteady gait with frequent falling down, cognitive, and speech worsening. Her course deteriorated progressively. Brain MRI showed cerebellar vermis hypoplasia and bilateral lentiform nucleus high signal lesions. Now she is bed ridden with tetraparesis and severely impaired cognitive and language functions. Biochemical analysis revealed isolated cIII deficiency in muscle, and impaired respiration in fibroblasts. We identified a novel homozygous rearrangement in TTC19 (c.213_229dup), resulting in frameshift with creation of a premature termination codon (p.Gln77Argfs*30). Western blot analysis demonstrated the absence of TTC19 protein in patient’s fibroblasts, while Blue-Native Gel Electrophoresis analysis revealed the presence of cIII-specific assembly intermediates. Mutations in TTC19 have been rarely associated with mitochondrial disease to date, being described in about ten patients with heterogeneous clinical presentations, ranging from early onset encephalomyopathy to adult forms with cerebellar ataxia. Contrariwise, the biochemical defect was a common hallmark in TTC19 mutant patients, confirming the importance of TTC19 in cIII assembly/stability. Therefore, we suggest extending the TTC19 mutational screening to all patients with cIII deficiency, independently from their phenotypes. PMID:25452764

  17. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging.

    PubMed

    Wang, Dan; Li, Yan-Ying; Luo, Jian-Hua; Li, Yue-Hua

    2014-01-01

    This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50-70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60-70 and 70-80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus. PMID:24820446

  18. Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: An fMRI study

    Microsoft Academic Search

    Sule Tinaz; Haline E. Schendan; Karin Schon; Chantal E. Stern

    2006-01-01

    Semantic event sequencing is the ability to plan ahead and order meaningful events chronologically. To investigate the neural systems supporting this ability, an fMRI picture sequencing task was developed. Participants sequenced a series of four pictures presented in random order based on the temporal relationship among them. A control object discrimination task was designed to be comparable to the sequencing

  19. The structure of tonic flexor motoneurons in crayfish abdominal ganglia

    Microsoft Academic Search

    Jeffrey J. Wine; Jay E. Mittenthal; Donald Kennedy

    1974-01-01

    1.The tonic flexor motoneurons were filled with cobalt dye via the cut ends of their axons. All six physiologically defined cells were identified anatomically (Figs. 2–4).2.The cell somata are widely scattered in the ventral rind of the ganglia; three cells have ipsilateral and three cells have contralateral somata in reference to their axons; cells with contralateral somata tend to be

  20. The ganglia distributed monitoring system: design, implementation, and experience

    Microsoft Academic Search

    Matthew L. Massie; Brent N. Chun; David E. Culler

    2004-01-01

    Ganglia is a scalable distributed monitoring system for high performance computing sys- tems such as clusters and Grids. It is based on a hierarchical design targeted at federations of clusters. It relies on a multicast-based listen\\/announce protocol to monitor state within clus- ters and uses a tree of point-to-point connections amongst representative cluster nodes to fed- erate clusters and aggregate

  1. Functional properties of ryanodine receptors from rat dorsal root ganglia

    Microsoft Academic Search

    Andrew J. Lokuta; Hirochika Komai; Thomas S. McDowell; Héctor H. Valdivia

    2002-01-01

    The properties of ryanodine receptors (RyRs) from rat dorsal root ganglia (DRGs) have been studied. The density of RyRs (Bmax) determined by [3H]ryanodine binding was 63 fmol\\/mg protein with a dissociation constant (Kd) of 1.5 nM. [3H]Ryanodine binding increased with caffeine, decreased with ruthenium red and tetracaine, and was insensitive to millimolar concentrations of Mg2+ or Ca2+. DRG RyRs reconstituted

  2. Facial nerve parasympathetic preganglionic afferents to the accessory otic ganglia by way of the chorda tympani nerve in the cat

    Microsoft Academic Search

    Satoshi Kuchiiwa; T. Kuchiiwa; Satoru Nonaka; Shiro Nakagawa

    1998-01-01

    The distribution of accessory otic ganglia and connections between the ganglia and the chorda tympani nerve were investigated\\u000a in the cat in order to determine the parasympathetic preganglionic facial nerve afferents to the otic ganglia using whole\\u000a mount acetylthiocholinesterase (WATChE) histochemistry. The otic ganglia consist of a sigle main prominent ganglion and many\\u000a small accessory ganglia lying on a plexus

  3. Tooth - abnormal shape

    MedlinePLUS

    ... many different conditions. Specific diseases can affect tooth shape, tooth color, time of appearance, or absence of teeth. ... any medical conditions that may cause abnormal tooth shape? At what age ... spacing)? What other symptoms are also present? Fillings, ...

  4. Abnormal Uterine Bleeding

    MedlinePLUS

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  5. Comprehensive RNA-Seq Expression Analysis of Sensory Ganglia with a Focus on Ion Channels and GPCRs in Trigeminal Ganglia

    PubMed Central

    Manteniotis, Stavros; Lehmann, Ramona; Flegel, Caroline; Vogel, Felix; Hofreuter, Adrian; Schreiner, Benjamin S. P.; Altmüller, Janine; Becker, Christian; Schöbel, Nicole; Hatt, Hanns; Gisselmann, Günter

    2013-01-01

    The specific functions of sensory systems depend on the tissue-specific expression of genes that code for molecular sensor proteins that are necessary for stimulus detection and membrane signaling. Using the Next Generation Sequencing technique (RNA-Seq), we analyzed the complete transcriptome of the trigeminal ganglia (TG) and dorsal root ganglia (DRG) of adult mice. Focusing on genes with an expression level higher than 1 FPKM (fragments per kilobase of transcript per million mapped reads), we detected the expression of 12984 genes in the TG and 13195 in the DRG. To analyze the specific gene expression patterns of the peripheral neuronal tissues, we compared their gene expression profiles with that of the liver, brain, olfactory epithelium, and skeletal muscle. The transcriptome data of the TG and DRG were scanned for virtually all known G-protein-coupled receptors (GPCRs) as well as for ion channels. The expression profile was ranked with regard to the level and specificity for the TG. In total, we detected 106 non-olfactory GPCRs and 33 ion channels that had not been previously described as expressed in the TG. To validate the RNA-Seq data, in situ hybridization experiments were performed for several of the newly detected transcripts. To identify differences in expression profiles between the sensory ganglia, the RNA-Seq data of the TG and DRG were compared. Among the differentially expressed genes (> 1 FPKM), 65 and 117 were expressed at least 10-fold higher in the TG and DRG, respectively. Our transcriptome analysis allows a comprehensive overview of all ion channels and G protein-coupled receptors that are expressed in trigeminal ganglia and provides additional approaches for the investigation of trigeminal sensing as well as for the physiological and pathophysiological mechanisms of pain. PMID:24260241

  6. Reactive oxygen species induce procalcitonin expression in trigeminal ganglia glia

    PubMed Central

    Raddant, Ann C.; Russo, Andrew F.

    2014-01-01

    Objective To examine calcitonin gene-related peptide (CGRP) gene expression under inflammatory conditions using trigeminal ganglia organ cultures as an experimental system. These cultures have increased proinflammatory signaling that may mimic neurogenic inflammation in the migraine state. Background The trigeminal nerve sends peripheral pain signals to the central nervous system during migraine. Understanding the dynamic processes that occur within the trigeminal nerve and ganglion may provide insights into events that contribute to migraine pain. A neuropeptide of particular interest is CGRP, which can be elevated and play a causal role in migraine. However, most studies have overlooked a second splice product of the CALCA gene, which encodes calcitonin (CT), a peptide hormone involved in calcium homeostasis. Importantly, a precursor form of calcitonin called procalcitonin (proCT) can act as a partial agonist at the CGRP receptor and elevated proCT has recently been reported during migraine. Methods We used a trigeminal ganglion whole organ explant model, which has previously been demonstrated to induce pro-inflammatory agents in vitro. Quantitative PCR and immunohistochemistry were used to evaluate changes in mRNA and protein levels of CGRP and proCT. Results Whole mouse trigeminal ganglia cultured for 24 h showed a 10-fold increase in CT mRNA, with no change in CGRP mRNA. A similar effect was observed in ganglia from adult rats. ProCT immunoreactivity was localized in glial cells. Cutting the tissue blunted the increase in CT, suggesting that induction required the close environment of the intact ganglia. Consistent with this prediction, there were increased reactive oxygen species in the ganglia and the elevated CT mRNA was reduced by antioxidant treatment. Surprisingly, reactive oxygen species were increased in neurons, not glia. Conclusions These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal glia by a paracrine regulatory mechanism. We propose that this glial recruitment pathway may occur following cortical spreading depression and neurogenic inflammation to increase CGRP nociceptive actions in migraine. PMID:24512072

  7. The Human Airway Epithelial Basal Cell Transcriptome

    PubMed Central

    Wang, Rui; Zwick, Rachel K.; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G.

    2011-01-01

    Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Methodology/Principal Findings Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion/Significance The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium. PMID:21572528

  8. The Human Airway Epithelial Basal Cell Transcriptome

    Microsoft Academic Search

    Neil R. Hackett; Renat Shaykhiev; Matthew S. Walters; Rui Wang; Rachel K. Zwick; Barbara Ferris; Bradley Witover; Jacqueline Salit; Ronald G. Crystal; Melanie Koenigshoff

    2011-01-01

    BackgroundThe human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem\\/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of

  9. Expression of Cell Cycle and Apoptosis-related Proteins in Sporadic Odontogenic Keratocysts and Odontogenic Keratocysts Associated with the Nevoid Basal Cell Carcinoma Syndrome

    Microsoft Academic Search

    L. Lo Muzio; S. Staibano; G. Pannone; P. Bucci; P. F. Nocini; E. Bucci; G. De Rosa

    1999-01-01

    Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and\\/or

  10. Spinal ganglia and peripheral nerves from a patient with Tay-Sachs disease

    Microsoft Academic Search

    T. Abe; K. Ogawa; H. Fuziwara; K. Urayama; K. Nagashima

    1985-01-01

    We examined the spinal ganglia and peripheral nerves from a patient with Tay-Sachs disease, comparing the other nervous tissues morphologically and lipid-biochemically. The spinal ganglia and peripheral nerves showed numerous membranous cytoplasmic inclusion bodies (MCBs), which are characteristic of GM2-ganglioside storage in the neuronal cell bodies of the patient brains. In spinal ganglia, all neurons and satellite cells around the

  11. Motoneuron development influences dorsal root ganglia survival and Schwann cell development in a vertebrate model of spinal muscular atrophy.

    PubMed

    Hao, Le Thi; Duy, Phan Q; Jontes, James D; Beattie, Christine E

    2015-01-15

    Low levels of the survival motor neuron protein (SMN) cause the disease spinal muscular atrophy. A primary characteristic of this disease is motoneuron dysfunction and paralysis. Understanding why motoneurons are affected by low levels of SMN will lend insight into this disease and to motoneuron biology in general. Motoneurons in zebrafish smn mutants develop abnormally; however, it is unclear where Smn is needed for motoneuron development since it is a ubiquitously expressed protein. We have addressed this issue by expressing human SMN in motoneurons in zebrafish maternal-zygotic (mz) smn mutants. First, we demonstrate that SMN is present in axons, but only during the period of robust motor axon outgrowth. We also conclusively demonstrate that SMN acts cell autonomously in motoneurons for proper motoneuron development. This includes the formation of both axonal and dendritic branches. Analysis of the peripheral nervous system revealed that Schwann cells and dorsal root ganglia (DRG) neurons developed abnormally in mz-smn mutants. Schwann cells did not wrap axons tightly and had expanded nodes of Ranvier. The majority of DRG neurons had abnormally short peripheral axons and later many of them failed to divide and died. Expressing SMN just in motoneurons rescued both of these cell types showing that their failure to develop was secondary to the developmental defects in motoneurons. Driving SMN just in motoneurons did not increase survival of the animal, suggesting that SMN is needed for motoneuron development and motor circuitry, but that SMN in other cells types factors into survival. PMID:25180019

  12. Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome

    PubMed Central

    Tang, Jean Y.; Mackay-Wiggan, Julian M.; Aszterbaum, Michelle; Yauch, Robert L.; Lindgren, Joselyn; Chang, Kris; Coppola, Carol; Chanana, Anita M.; Marji, Jackleen; Bickers, David R.; Epstein, Ervin H.

    2012-01-01

    BACKGROUND Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas. METHODS We tested the anti–basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal-cell carcinomas. RESULTS In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (?65% vs. ?11%, P = 0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas. CONCLUSIONS Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of new basal-cell carcinomas in patients with the basal-cell nevus syndrome. The adverse events associated with treatment led to discontinuation in over half of treated patients. (Funded by Genentech and others; ClinicalTrials.gov number, NCT00957229.) PMID:22670904

  13. Probing ganglia dissolution and mobilization in a water-saturated porous medium using MRI

    SciTech Connect

    Johns, M.L.; Gladden, L.F.

    2000-05-01

    Magnetic resonance imaging (MRI) is used to probe the evolution of geometric characteristics such as the volume, shape, surface area, and cluster size of octanol ganglia trapped in a model porous medium, in this case a packing of spheres, as they dissolve into a mobile aqueous phase. The resulting pore-scale information is used to assess various assumptions used in existing models of the dissolution process. Dissolution of the ganglia was characterized by a reduction in the overall number of ganglia with little effect on the shape and mean of the volume distribution of the ganglia. This apparently anomalous result is explained by dissolution of the ganglia until they reach a critical size, which is dependent on the structure of the pore space, at which point they are mobilized and subsequently removed from the porous medium. The shape of the entrapped ganglia is characterized by a fractal dimension in the range 2.2--2.3, suggesting that models which assume a Euclidean geometry for the entrapped ganglia are appropriate. No significant change in the shape of entrapped ganglia is observed during dissolution. In agreement with the results of earlier workers, most hydrocarbon ganglia exist as singlets within the pore structure.

  14. Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis

    PubMed Central

    Bernardini, Nunzia; Segnani, Cristina; Ippolito, Chiara; De Giorgio, Roberto; Colucci, Rocchina; Faussone-Pellegrini, Maria Simonetta; Chiarugi, Massimo; Campani, Daniela; Castagna, Maura; Mattii, Letizia; Blandizzi, Corrado; Dolfi, Amelio

    2012-01-01

    Abstract Ulcerative colitis (UC) is an inflammatory bowel disease with alterations of colonic motility, which influence clinical symptoms. Although morpho-functional abnormalities in the enteric nervous system have been suggested, in UC patients scarce attention has been paid to possible changes in the cells that control colonic motility, including myenteric neurons, glial cells and interstitial cells of Cajal (ICC). This study evaluated the neural-glial components of myenteric ganglia and ICC in the colonic neuromuscular compartment of UC patients by quantitative immunohistochemical analysis. Full-thickness archival samples of the left colon were collected from 10 patients with UC (5 males, 5 females; age range 45–62 years) who underwent elective bowel resection. The colonic neuromuscular compartment was evaluated immunohistochemically in paraffin cross-sections. The distribution and number of neurons, glial cells and ICC were assessed by anti-HuC/D, -S100? and -c-Kit antibodies, respectively. Data were compared with findings on archival samples of normal left colon from 10 sex- and age-matched control patients, who underwent surgery for uncomplicated colon cancer. Compared to controls, patients with UC showed: (i) reduced density of myenteric HuC/D+ neurons and S100?+ glial cells, with a loss over 61% and 38%, respectively, and increased glial cell/neuron ratio; (ii) ICC decrease in the whole neuromuscular compartment. The quantitative variations of myenteric neuro-glial cells and ICC indicate considerable alterations of the colonic neuromuscular compartment in the setting of mucosal inflammation associated with UC, and provide a morphological basis for better understanding the motor abnormalities often observed in UC patients. PMID:21426484

  15. Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis.

    PubMed

    Bernardini, Nunzia; Segnani, Cristina; Ippolito, Chiara; De Giorgio, Roberto; Colucci, Rocchina; Faussone-Pellegrini, Maria Simonetta; Chiarugi, Massimo; Campani, Daniela; Castagna, Maura; Mattii, Letizia; Blandizzi, Corrado; Dolfi, Amelio

    2012-02-01

    Ulcerative colitis (UC) is an inflammatory bowel disease with alterations of colonic motility, which influence clinical symptoms. Although morpho-functional abnormalities in the enteric nervous system have been suggested, in UC patients scarce attention has been paid to possible changes in the cells that control colonic motility, including myenteric neurons, glial cells and interstitial cells of Cajal (ICC). This study evaluated the neural-glial components of myenteric ganglia and ICC in the colonic neuromuscular compartment of UC patients by quantitative immunohistochemical analysis. Full-thickness archival samples of the left colon were collected from 10 patients with UC (5 males, 5 females; age range 45-62 years) who underwent elective bowel resection. The colonic neuromuscular compartment was evaluated immunohistochemically in paraffin cross-sections. The distribution and number of neurons, glial cells and ICC were assessed by anti-HuC/D, -S100? and -c-Kit antibodies, respectively. Data were compared with findings on archival samples of normal left colon from 10 sex- and age-matched control patients, who underwent surgery for uncomplicated colon cancer. Compared to controls, patients with UC showed: (i) reduced density of myenteric HuC/D(+) neurons and S100?(+) glial cells, with a loss over 61% and 38%, respectively, and increased glial cell/neuron ratio; (ii) ICC decrease in the whole neuromuscular compartment. The quantitative variations of myenteric neuro-glial cells and ICC indicate considerable alterations of the colonic neuromuscular compartment in the setting of mucosal inflammation associated with UC, and provide a morphological basis for better understanding the motor abnormalities often observed in UC patients. PMID:21426484

  16. A review of the thoracic splanchnic nerves and celiac ganglia.

    PubMed

    Loukas, Marios; Klaassen, Zachary; Merbs, William; Tubbs, R Shane; Gielecki, Jerzy; Zurada, Anna

    2010-07-01

    Anatomical variation of the thoracic splanchnic nerves is as diverse as any structure in the body. Thoracic splanchnic nerves are derived from medial branches of the lower seven thoracic sympathetic ganglia, with the greater splanchnic nerve comprising the more cranial contributions, the lesser the middle branches, and the least splanchnic nerve usually T11 and/or T12. Much of the early anatomical research of the thoracic splanchnic nerves revolved around elucidating the nerve root level contributing to each of these nerves. The celiac plexus is a major interchange for autonomic fibers, receiving many of the thoracic splanchnic nerve fibers as they course toward the organs of the abdomen. The location of the celiac ganglia are usually described in relation to surrounding structures, and also show variation in size and general morphology. Clinically, the thoracic splanchnic nerves and celiac ganglia play a major role in pain management for upper abdominal disorders, particularly chronic pancreatitis and pancreatic cancer. Splanchnicectomy has been a treatment option since Mallet-Guy became a major proponent of the procedure in the 1940s. Splanchnic nerve dissection and thermocoagulation are two common derivatives of splanchnicectomy that are commonly used today. Celiac plexus block is also a treatment option to compliment splanchnicectomy in pain management. Endoscopic ultrasonography (EUS)-guided celiac injection and percutaneous methods of celiac plexus block have been heavily studied and are two important methods used today. For both splanchnicectomies and celiac plexus block, the innovation of ultrasonographic imaging technology has improved efficacy and accuracy of these procedures and continues to make pain management for these diseases more successful. PMID:20235178

  17. Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype

    PubMed Central

    2013-01-01

    Background Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. Methods Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. Results IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. Conclusion FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA in the tumorigenesis of triple negative, basal-like FMAs. The strong similarities in clinical behavior, morphology and IHC phenotype suggest that triple negative, basal-like FMAs may be a suitable spontaneous animal model for studying novel therapeutic approaches against human basal-like TNBC. PMID:24004841

  18. Abnormal Psychology Psychology 280

    E-print Network

    Liu, Taosheng

    1 Abnormal Psychology Psychology 280 1st Summer Session 2013 May 13June 27, 2013 Tuesday" Kalibatseva, M.A. Office: 127B Psychology Building Email: kalibats@msu.edu Phone Psychology PhD program at Michigan State University. I completed my bachelor's dual degree in psychology

  19. Abnormal Cats' Paws

    Microsoft Academic Search

    H. A. Hagen

    1887-01-01

    ABNORMITIES in cats' paws occur rather frequently in Massachusetts. They are called mitten cats, and are much in demand because they are considered to be good mousers. The first I ever saw was a male yellow tiger, whose four paws had two extra toes strongly developed. A little stray female kitten which was brought up at my house had two

  20. Abnormal Morphology Within Individuals

    Microsoft Academic Search

    MARILYN L. POLAND; KAMRAN S. MOGHISSI; PAUL T. GIBLIN; JOEL W. AGER; JANE M. OLSON

    Semen from 15 healthy volunteers was assessed for basic semen measures every 2 weeks over a 6-month period to determine the relative stability of these factors. The parameters were: sperm count, semen volume, sperm motility, and normal morphology, along with the type of abnormal morphologic forms. Basic semen measures were generally more stable than the morphologic forms. Using three samples,

  1. Monitoring Temperature and Fan Speed Using Ganglia and Winbond Chips

    SciTech Connect

    McCaffrey, Cattie; /SLAC

    2006-09-27

    Effective monitoring is essential to keep a large group of machines, like the ones at Stanford Linear Accelerator Center (SLAC), up and running. SLAC currently uses Ganglia Monitoring System to observe about 2000 machines, analyzing metrics like CPU usage and I/O rate. However, metrics essential to machine hardware health, such as temperature and fan speed, are not being monitored. Many machines have a Winbond w83782d chip which monitors three temperatures, two of which come from dual CPUs, and returns the information when the sensor command is invoked. Ganglia also provides a feature, gmetric, that allows the users to monitor their own metrics and incorporate them into the monitoring system. The programming language Perl is chosen to implement a script that invokes the sensors command, extracts the temperature and fan speed information, and calls gmetric with the appropriate arguments. Two machines were used to test the script; the two CPUs on each machine run at about 65 Celsius, which is well within the operating temperature range (The maximum safe temperature range is 77-82 Celsius for the Pentium III processors being used). Installing the script on all machines with a Winbond w83782d chip allows the SLAC Scientific Computing and Computing Services group (SCCS) to better evaluate current cooling methods.

  2. Ganglia arising from the transverse acetabular ligament: a report of two cases.

    PubMed

    Botchu, Rajesh; Esler, Colin N; Lloyd, David M; Rennie, Winston J

    2013-12-01

    Ganglia arising from the hip are rare. Its diagnosis is difficult owing to the anatomic location. A high index of suspicion and high-resolution imaging is essential to make the diagnosis. Treatment depends on the size, location, and symptoms. This report is of 2 patients with ganglia arising from the transverse acetabular ligament. PMID:24366805

  3. Behaviour of oil ganglia displaced by a surfactant solution in a porous medium

    E-print Network

    Boyer, Edmond

    L-97 Behaviour of oil ganglia displaced by a surfactant solution in a porous medium J. C. Moulu'importance relative des forces de viscosité et des forces capillaires. Abstract. 2014 The velocity of oil ganglia residual oil phase by water injection in a porous medium [1, 2]. These studies have demonstrated

  4. Her4 is necessary for establishing peripheral projections of the trigeminal ganglia in zebrafish

    Microsoft Academic Search

    Ju-Hoon So; Hang-Suk Chun; Yong-Ki Bae; Hyun-Seo Kim; Yeoll-Mae Park; Tae-Lin Huh; Ajay B. Chitnis; Cheol-Hee Kim; Sang-Yeob Yeo

    2009-01-01

    Transcripts of notch and its target genes have been detected in some differentiating neurons. However, the role of Notch in neuronal differentiation remains poorly defined. Here, we show that a subset of differentiating sensory neurons in the trigeminal ganglia express her4. Expression of her4 requires Notch signaling during neurogenesis but not during differentiation, when peripheral projections of the trigeminal ganglia

  5. Neurodegenerative effects of monopolar electrocauterization on spinal ganglia in lumbar disc surgery

    Microsoft Academic Search

    M. D. Aydin; S. Dane; C. Gundogdu; N. Gursan

    2004-01-01

    Summary Background. Monopolar electrocauterization (MEC) is widely used in spine surgery however electrical currents are hazardous for neural tissues, such as the spinal ganglia sited in the intervertebral foramina. We aimed to investigate the effects of MEC on spinal ganglia. Method. Fifteen male hybrid rabbits were included in the study. Three of the animals were used to analyze the findings

  6. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  7. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  8. Abnormal human sex chromosome constitutions

    SciTech Connect

    NONE

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  9. Airway basal cells. The "smoking gun" of chronic obstructive pulmonary disease.

    PubMed

    Crystal, Ronald G

    2014-12-15

    The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and 'omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the "smoking gun" of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

  10. Forms of Discourse in Basal Readers.

    ERIC Educational Resources Information Center

    Flood, James; Lapp, Diane

    1987-01-01

    Examined each book in 8 basal reading series (preprimers to sixth readers) to determine the variety of types of writing in these 1983 basals. Texts were examined for the number of selections representing narrative, poetry, plays, exposition, biography, hybrid writing types and for the number of pages devoted to each type of writing. (Author/NH)

  11. Contemporary Children and Basal Reading Series.

    ERIC Educational Resources Information Center

    Klebacher, Kathryn F.

    Contemporary children must deal with many family problems that children 20 years ago never had to face, including divorce, parental separation, death, working mothers, and economic status. To determine how well current basal reading series reflect the changing American family, the stories of four basal reading series for grades four, five, and six…

  12. Neurodevelopmental Abnormalities in ADHD

    PubMed Central

    Vaidya, Chandan J.

    2012-01-01

    Structural and functional imaging studies in subjects with attention deficit hyperactivity disorder (ADHD) are reviewed with the goal of gleaning information about neurodevelopmental abnormalities characterizing the disorder. Structural imaging studies, particularly those with longitudinal designs, suggest that brain maturation is delayed by a few years in ADHD. However, a maturational delay model alone is incomplete: alternate courses are suggested by differences associated with phenotypic factors, such as symptom remission/persistence and exposure to stimulant treatment. Findings from functional imaging studies point to multiple loci of abnormalities that are not limited to frontal–striatal circuitry, which is important for executive and motivational function, but also include parietal, temporal and motor cortices, and the cerebellum. However, a definitive conclusion about maturational delays or alternate trajectories cannot be drawn from this work as activation patterns are influenced by task-specific factors that may induce variable performance levels and strategies across development. In addition, no studies have implemented cross-sectional or longitudinal designs, without which the developmental origin of differences in activation cannot be inferred. Thus, current task-evoked functional imaging provides information about dynamic or state-dependent differences rather than fixed or trait-related differences. In the future, task-free functional imaging holds promise for revealing neurodevelopmental information that is minimally influenced by performance/strategic differences. Further, studies using longitudinal designs that identify sources of phenotypic heterogeneity in brain maturation and characterize the relationship between brain function and underlying structural properties are needed to provide a comprehensive view of neurodevelopmental abnormalities in ADHD. PMID:21541845

  13. Gorlin's syndrome, or nevoid basal cell carcinoma syndrome.

    PubMed Central

    Fitzpatrick, P. J.; Thompson, G. A.

    1982-01-01

    Gorlin's syndrome is a condition inherited in an autosomal dominant fashion. It involves many organs, but principally affects the skin, skeleton, and endocrine and nervous systems. The most common features are multiple nervi and basal cell carcinomas of the skin, benign jaw cysts, dyskeratotic pits in the palms and soles, rib and vertebral abnormalities, brachymetacarpalism, and calcification of the falx cerebri. In 14 patients, 4 of whom belonged to one family, the age at the time of diagnosis ranged from 11 to 63 years. Ten patients are alive, but five are severely disfigured by carcinomas. Two patients died of complications resulting from uncontrolled tumours, and two died of other cancers. New skin tumours constantly develop; small ones can be excised, but large ones require extensive surgery with or without radiotherapy. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 9 FIG. 10 FIG. 11 PMID:7116263

  14. MRI-identified abnormalities and wrist range of motion in asymptomatic versus symptomatic computer users

    PubMed Central

    2010-01-01

    Background Previous work has shown an association between restricted wrist range of motion (ROM) and upper extremity musculoskeletal disorders in computer users. We compared the prevalence of MRI-identified wrist abnormalities and wrist ROM between asymptomatic and symptomatic computer users. Methods MR images at 1.5 T of both wrists were obtained from 10 asymptomatic controls (8 F, 2 M) and 14 computer users (10 F, 4 M) with chronic wrist pain (10 bilateral; 4 right-side). Maximum wrist range of motion in flexion and radioulnar deviation was measured with an electrogoniometer. Results Extraosseous ganglia were identified in 66.6% of asymptomatic wrists and in 75% of symptomatic wrists. Intraosseous ganglia were identified in 45.8% of asymptomatic wrists and in 75% of symptomatic wrists, and were significantly (p < .05) larger in the symptomatic wrists. Distal ECU tendon instability was identified in 58.4% of both asymptomatic and symptomatic wrists. Dominant wrist flexion was significantly greater in the asymptomatic group (68.8 ± 6.7 deg.) compared to the symptomatic group (60.7 ± 7.3 deg.), p < .01. There was no significant correlation between wrist flexion and intraosseous ganglion burden (p = .09) Conclusions This appears to be the first MRI study of wrist abnormalities in computer users. This study demonstrates that a variety of wrist abnormalities are common in computer users and that only intraosseous ganglia prevalence and size differed between asymptomatic and symptomatic wrists. Flexion was restricted in the dominant wrist of the symptomatic group, but the correlation between wrist flexion and intraosseous ganglion burden did not reach significance. Flexion restriction may be an indicator of increased joint loading, and identifying the cause may help to guide preventive and therapeutic interventions. PMID:21108817

  15. Basal and 24-h C-peptide and insulin secretion rate in normal man

    Microsoft Academic Search

    Y. T. Kruszynska; P. D. Home; I. Hanning; K. G. M. M. Alberti

    1987-01-01

    Summary  An understanding of the metabolic abnormalities rising from inappropriate insulin delivery in diabetic patients demands a knowledge of 24-h and basal insulin secretion rates in normal man. We have used biosynthetic human C-peptide to determine its kinetic parameters in 10 normal subjects and applied these to measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate. Metabolic

  16. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. (Industrial Toxicology Research Centre, Lucknow (India))

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  17. Epilepsy and chromosomal abnormalities

    PubMed Central

    2010-01-01

    Background Many chromosomal abnormalities are associated with Central Nervous System (CNS) malformations and other neurological alterations, among which seizures and epilepsy. Some of these show a peculiar epileptic and EEG pattern. We describe some epileptic syndromes frequently reported in chromosomal disorders. Methods Detailed clinical assessment, electrophysiological studies, survey of the literature. Results In some of these congenital syndromes the clinical presentation and EEG anomalies seems to be quite typical, in others the manifestations appear aspecific and no strictly linked with the chromosomal imbalance. The onset of seizures is often during the neonatal period of the infancy. Conclusions A better characterization of the electro clinical patterns associated with specific chromosomal aberrations could give us a valuable key in the identification of epilepsy susceptibility of some chromosomal loci, using the new advances in molecular cytogenetics techniques - such as fluorescent in situ hybridization (FISH), subtelomeric analysis and CGH (comparative genomic hybridization) microarray. However further studies are needed to understand the mechanism of epilepsy associated with chromosomal abnormalities. PMID:20438626

  18. Frequency and Abundance of Alphaherpesvirus DNA in Human Thoracic Sympathetic Ganglia

    PubMed Central

    Rempel, April; Huntington, Jonathon; Kim, Forrest; Choe, Alexander; Gilden, Don

    2014-01-01

    Alphaherpesvirus reactivation from thoracic sympathetic ganglia (TSG) and transaxonal spread to target organs cause human visceral disease. Yet alphaherpesvirus latency in TSG has not been well characterized. In this study, quantitative PCR detected varicella-zoster virus (VZV), herpes simplex virus 1 (HSV-1), and HSV-2 DNA in 117 fresh TSG obtained postmortem from 15 subjects. VZV DNA was found in 76 (65%) ganglia from all subjects, HSV-1 DNA was found in 5 (4%) ganglia from 3 subjects, and no HSV-2 was found. PMID:24789785

  19. [Connections between neurons of sympathetic ganglia and the myenteric nerve plexus of the mammalian colon].

    PubMed

    Riakhovskaia, L V; Adamatski?, A I

    1986-10-01

    By means of retrograde transport of the fluorescent marker primulin the initial part of the sympathetic innervation of the myenteric nervous plexus of the descending colon has been characterized in cats and guinea pigs. When primulin is injected into the myenteric nervous plexus, marked neurons are revealed in the caudal mesenteric ganglion, in the celiac plexus ganglia, in the sympathetic trunk ganglia. The marked nervous populations of the extramural sympathetic ganglia differ in their form, size, number of neurons and their distribution. PMID:2432859

  20. Latent herpes simplex virus 1 infection does not induce apoptosis in human trigeminal Ganglia.

    PubMed

    Himmelein, Susanne; Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

    2015-05-15

    Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8(+) T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

  1. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    PubMed Central

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

  2. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    PubMed

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

  3. Higher diffusion in striatum and lower fractional anisotropy in white matter of methamphetamine users

    Microsoft Academic Search

    Daniel Alicata; Linda Chang; Christine Cloak; Kylie Abe; Thomas Ernst

    2009-01-01

    Methamphetamine (METH) users showed structural and chemical abnormalities on magnetic resonance (MRI) studies, particularly in the frontal and basal ganglia brain regions. Diffusion tensor imaging (DTI) may provide further insights regarding the microstructural changes in METH users. We investigated diffusion tensor measures in frontal white matter and basal ganglia of 30 adult METH users and 30 control subjects using a

  4. [Basal cell carcinoma with matrical differentiation].

    PubMed

    Goldman-Lévy, Gabrielle; Frouin, Eric; Soubeyran, Isabelle; Maury, Géraldine; Guillot, Bernard; Costes, Valérie

    2015-04-01

    Basal cell carcinoma with matrical differentiation is a very rare variant of basal cell carcinoma. To our knowledge, less than 30 cases have been reported. This tumor is composed of basaloid lobules showing a differentiation toward the pilar matrix cells. Recently, it has been demonstrated that beta-catenin would interfer with physiopathogenesis of matrical tumors, in particular pilomatricomas, but also basal cell carcinomas with matrical differentiation. This is a new case, with immunohistochemical and molecular analysis of beta-catenin, in order to explain its histogenesis. PMID:25746660

  5. A rare stapes abnormality.

    PubMed

    Kanona, Hala; Virk, Jagdeep Singh; Kumar, Gaurav; Chawda, Sanjiv; Khalil, Sherif

    2015-01-01

    The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50?dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively. PMID:25628909

  6. A Rare Stapes Abnormality

    PubMed Central

    Kanona, Hala; Virk, Jagdeep Singh; Kumar, Gaurav; Chawda, Sanjiv; Khalil, Sherif

    2015-01-01

    The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50?dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively. PMID:25628909

  7. Basal constriction : shaping the vertebrate brain

    E-print Network

    Graeden, Ellie Graham

    2011-01-01

    Organs are primarily formed from epithelia, polarized sheets of cells with an apical surface facing a lumen and basal surface resting on the underlying extracellular matrix. Cells within a sheet are joined by junctions, ...

  8. Quantitation of Latent Varicella-Zoster Virus and Herpes Simplex Virus Genomes in Human Trigeminal Ganglia

    Microsoft Academic Search

    STEPHANIE R. PEVENSTEIN; RICHARD K. WILLIAMS; DANIEL MCCHESNEY; ERIK K. MONT; JOHN E. SMIALEK; STEPHEN E. STRAUS

    1999-01-01

    Using real-time fluorescence PCR, we quantitated the numbers of copies of latent varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) genomes in 15 human trigeminal ganglia. Eight (53%) and 1 (7%) of 15 ganglia were PCR positive for HSV-1 or -2 glycoprotein G genes, with means of 2,902 6 1,082 (standard error of the

  9. Expression patterns of erythropoietin and its receptor in the developing spinal cord and dorsal root ganglia

    Microsoft Academic Search

    Wolfgang Knabe; Anna-Leena Sirén; Hannelore Ehrenreich; Hans-Jürg Kuhn

    2005-01-01

    Recombinant human erythropoietin (EPO) is neuroprotective in animal models of adult spinal cord injury, and reduces apoptosis\\u000a in adult dorsal root ganglia after spinal nerve crush. The present work demonstrates that spinal cord and dorsal root ganglia\\u000a share dynamic expression patterns of EPO and its receptor (EPOR) during development. C57Bl mice from embryonic days (E) 8\\u000a (E8) to E19 were

  10. Amino acid and protein metabolism in dorsal root ganglia of rabbits with experimental allergic neuritis

    Microsoft Academic Search

    G. K. Molnár; E. R. Korpi; H. Kalimo

    1985-01-01

    Amino acid and protein metabolism has been studied in the dorsal root ganglia of rabbits with experimental allergic neuritis\\u000a (EAN). The concentrations of a number of nonessential amino acids (glutamine, serine, aspartate, and glutamate) were reduced\\u000a in the spinal ganglia of EAN animals without any comparable change in the blood plasma. The short-term influx of glycine and\\u000a GABA was decreased

  11. Jaw mechanics in basal ceratopsia (Ornithischia, Dinosauria).

    PubMed

    Tanoue, Kyo; Grandstaff, Barbara S; You, Hai-Lu; Dodson, Peter

    2009-09-01

    Ceratopsian dinosaurs were a dominant group of herbivores in Cretaceous terrestrial ecosystems. We hypothesize that an understanding of the feeding system will provide important insight into the evolutionary success of these animals. The mandibular mechanics of eight genera of basal ceratopsians was examined to understand the variability in shape of the jaws and the early evolution of the masticatory system in Ceratopsia. Data were collected on lever arms, cranial angles and tooth row lengths. The results indicate that psittacosaurids had higher leverage at the beak and in the rostral part of the tooth row than basal neoceratopsians, but lower leverage in the caudal part of the tooth row. Although the vertebrate mandible is generally considered as a third-class lever, that of basal neoceratopsians acted as a second-class lever at the caudal part of the tooth row, as is also true in ceratopsids. When total input force from the mandibular adductor muscles on both sides of the skull is considered, the largest bite force in basal ceratopsian tooth rows was exerted in the caudal part of the tooth row at the caudal extremity of the zone with near-maximum input force. Medially positioned teeth generate higher leverage than laterally positioned teeth. The largest bite force in all basal ceratopsians is smaller than the maximum input force, a limit imposed by the morphology of the basal ceratopsian masticatory system. In ceratopsids, caudal extension of the tooth row resulted in a much larger bite force, even exceeding the maximum input force. PMID:19711460

  12. Repression of Igf1 expression by Ezh2 prevents basal cell differentiation in the developing lung.

    PubMed

    Galvis, Laura A; Holik, Aliaksei Z; Short, Kieran M; Pasquet, Julie; Lun, Aaron T L; Blewitt, Marnie E; Smyth, Ian M; Ritchie, Matthew E; Asselin-Labat, Marie-Liesse

    2015-04-15

    Epigenetic mechanisms involved in the establishment of lung epithelial cell lineage identities during development are largely unknown. Here, we explored the role of the histone methyltransferase Ezh2 during lung lineage determination. Loss of Ezh2 in the lung epithelium leads to defective lung formation and perinatal mortality. We show that Ezh2 is crucial for airway lineage specification and alveolarization. Using optical projection tomography imaging, we found that branching morphogenesis is affected in Ezh2 conditional knockout mice and the remaining bronchioles are abnormal, lacking terminally differentiated secretory club cells. Remarkably, RNA-seq analysis revealed the upregulation of basal genes in Ezh2-deficient epithelium. Three-dimensional imaging for keratin 5 further showed the unexpected presence of a layer of basal cells from the proximal airways to the distal bronchioles in E16.5 embryos. ChIP-seq analysis indicated the presence of Ezh2-mediated repressive marks on the genomic loci of some but not all basal genes, suggesting an indirect mechanism of action of Ezh2. We found that loss of Ezh2 de-represses insulin-like growth factor 1 (Igf1) expression and that modulation of IGF1 signaling ex vivo in wild-type lungs could induce basal cell differentiation. Altogether, our work reveals an unexpected role for Ezh2 in controlling basal cell fate determination in the embryonic lung endoderm, mediated in part by repression of Igf1 expression. PMID:25790853

  13. Migratory neural crest cell ?N-catenin impacts chick trigeminal ganglia formation.

    PubMed

    Wu, Chyong-Yi; Hooper, Rachel M; Han, Kyeong; Taneyhill, Lisa A

    2014-08-15

    Neural crest cells are an embryonic cell population that is crucial for proper vertebrate development. Initially localized to the dorsal neural folds, premigratory neural crest cells undergo an epithelial-to-mesenchymal transition (EMT) and migrate to their final destinations in the developing embryo. Together with epidermally-derived placode cells, neural crest cells then form the cranial sensory ganglia of the peripheral nervous system. Our prior work has shown that ?N-catenin, the neural subtype of the adherens junction ?-catenin protein, regulates cranial neural crest cell EMT by controlling premigratory neural crest cell cadherin levels. Although ?N-catenin down-regulation is critical for initial neural crest cell EMT, a potential role for ?N-catenin in later neural crest cell migration, and formation of the cranial ganglia, has not been examined. In this study, we show for the first time that migratory neural crest cells that will give rise to the cranial trigeminal ganglia express ?N-catenin and Cadherin-7. ?N-catenin loss- and gain-of-function experiments reveal effects on the migratory neural crest cell population that include subsequent defects in trigeminal ganglia assembly. Moreover, ?N-catenin perturbation in neural crest cells impacts the placode cell contribution to the trigeminal ganglia and also changes neural crest cell Cadherin-7 levels and localization. Together, these results highlight a novel function for ?N-catenin in migratory neural crest cells that form the trigeminal ganglia. PMID:24882712

  14. Effect of diabetes and aging on human sympathetic autonomic ganglia.

    PubMed Central

    Schmidt, R. E.; Plurad, S. B.; Parvin, C. A.; Roth, K. A.

    1993-01-01

    Although autonomic dysfunction frequently complicates the clinical course of patients with diabetes, relatively little is known of its underlying neuropathology. Using experimental animal models as a guide, the prevertebral superior mesenteric (SMG) and paravertebral superior cervical (SCG) sympathetic ganglia have been examined in a series of adult autopsied diabetic and non-diabetic patients of various ages using histochemical, ultrastructural, morphometric, and immunohistochemical methods. Quantitative studies demonstrated that markedly swollen argyrophilic terminal axons (neuroaxonal dystrophy) containing large numbers of disorganized neurofilaments developed in the SMG but not SCG as a function of diabetes, increasing age, and gender (males were more severely affected than females). As in experimental animals, diabetic (types I and II) patients developed histologically identical lesions prematurely and in greater numbers than age-matched nondiabetic patients. Morphometric studies showed a small but statistically significant decrease in neuronal density in the SMG but not SCG of diabetic patients. The dimensions of individual sympathetic neurons were not significantly different in aging or diabetes. The pathological lesions identified in the SMG may contribute to the autonomic dysfunction so commonly observed in diabetic patients. Images Figure 1 PMID:8317545

  15. abnormalities in infants and toddlers

    E-print Network

    Bellugi, Ursula

    Cerebellar abnormalities in infants and toddlers with Williams syndrome Wendy Jones* PhD, The Salk-mail: jones@crl.ucsd.edu One commonly observed neuroanatomical abnormality in adults with Williams syndrome children with Williams syndrome. Clinical brain MRI was examined in nine young children with Williams

  16. Chromosomal abnormalities and mental illness

    Microsoft Academic Search

    D J MacIntyre; D H R Blackwood; D J Porteous; B S Pickard; W J Muir

    2003-01-01

    Linkage studies of mental illness have provided suggestive evidence of susceptibility loci over many broad chromosomal regions. Pinpointing causative gene mutations by conventional linkage strategies alone is problematic. The breakpoints of chromosomal abnormalities occurring in patients with mental illness may be more direct pointers to the relevant gene locus. Publications that describe patients where chromosomal abnormalities co-exist with mental illness

  17. Students' reactions to abnormal psychology

    Microsoft Academic Search

    W. S. Taylor

    1932-01-01

    As a result of some concern about the effect of courses in abnormal psychology on students, a questionnaire was presented to several classes at the close of the course. The majority answering the questionnaire felt the course to be beneficial, giving evidence that the study of abnormal psychology need not be generally harmful, and may have a significant place in

  18. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  19. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  20. Intraneuronal angiotensinergic system in rat and human dorsal root ganglia

    PubMed Central

    Patil, Jaspal; Schwab, Alexander; Nussberger, Juerg; Schaffner, Thomas; Saavedra, Juan M.; Imboden, Hans

    2010-01-01

    To elucidate the local formation of angiotensin II (Ang II) in the neurons of sensory dorsal root ganglia (DRG), we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of protein renin, Ang II, Substance P and calcitonin gene-related peptide (CGRP) in the rat and human thoracic DRG. Quantitative real time PCR (qRT-PCR) studies revealed that rat DRG expressed substantial amounts of Ang-N- and ACE mRNA, while renin mRNA as well as the protein renin were untraceable. Cathepsin D-mRNA and cathepsin D-protein were detected in the rat DRG indicating the possibility of existence of pathways alternative to renin for Ang I formation. Angiotensin peptides were successfully detected with high performance liquid chromatography and radioimmunoassay in human DRG extracts. In situ hybridization in rat DRG confirmed additionally expression of Ang-N mRNA in the cytoplasm of numerous neurons. Intracellular Ang II staining could be shown in number of neurons and their processes in both the rat and human DRG. Interestingly we observed neuronal processes with angiotensinergic synapses en passant, colocalized with synaptophysin, within the DRG. In the DRG, we also identified by qRT-PCR, expression of Ang II receptor AT1A and AT2-mRNA while AT1B-mRNA was not traceable. In some neurons Substance P and CGRP were found colocalized with Ang II. The intracellular localization and colocalization of Ang II with Substance P and CGRP in the DRG neurons may indicate a participation and function of Ang II in the regulation of nociception. In conclusion, these results suggest that Ang II may be produced locally in the neurons of rat and human DRG and act as a neurotransmitter. PMID:20346377

  1. Multiple polypoid basal cell carcinomas on the perineum of a patient with basal cell nevus syndrome.

    PubMed

    Wang, Steven Q; Goldberg, Leonard H

    2007-08-01

    We present a case report of a patient with basal cell nevus syndrome (BCNS) who developed multiple polypoid basal cell carcinomas (PBCC) in the perineum. PBCC is a rare variant of nodular BCCs. Clinically, PBCCs mimic acrochordons. We recommend that the perineum, perianal, and genital areas should be included in the routine exam of patients with BCNS. PMID:17637368

  2. Topical Treatment of Basal Cell Carcinomas in Nevoid Basal Cell Carcinoma Syndrome with a Smoothened Inhibitor

    Microsoft Academic Search

    Hans Skvara; Frank Kalthoff; Josef G Meingassner; Barbara Wolff-Winiski; Heinrich Aschauer; Joseph F Kelleher; Xu Wu; Shifeng Pan; Lesanka Mickel; Christopher Schuster; Georg Stary; Ahmad Jalili; Olivier J David; Corinne Emotte; Ana Monica Costa Antunes; Kristine Rose; Jeremy Decker; Ilene Carlson; Humphrey Gardner; Anton Stuetz; Arthur P Bertolino; Georg Stingl; Menno A De Rie

    2011-01-01

    Basal cell carcinoma (BCC) is a distinctive manifestation in nevoid basal cell carcinoma syndrome (NBCCS) patients. Both inherited and acquired mutations of patched 1 (PTCH1), a tumor-suppressor gene controlling the activity of Smoothened (SMO), are the primary cause of the constitutive activation of the Hedgehog (HH) pathway, leading to the emergence of BCCs in NBCCS. LDE225, a distinct, selective antagonist

  3. Basal Cell Carcinoma in a Child

    PubMed Central

    Kuvat, Samet Vasfi; Gücin, Zuhal; Keklik, Bar??; Özyalvaçl?, Gülzade; Ba?aran, Karaca

    2011-01-01

    Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period. An 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a 3 × 4?cm diameter on his posterior scalp. Macroscopically, the lesion was excised with a 10?mm safety margin. Pathologic examination revealed a basal cell carcinoma. No symptoms or signs of a syndrome were observed both in the patient and his family. PMID:21188232

  4. Echocardiographic abnormalities following cardiac radiation

    SciTech Connect

    Perrault, D.J.; Levy, M.; Herman, J.D.; Burns, R.J.; Bar Shlomo, B.Z.; Druck, M.N.; Wu, W.Q.; McLaughlin, P.R.; Gilbert, B.W.

    1985-04-01

    Five years or more after receiving cardiac radiation, 41 patients with Hodgkin's disease and seminoma in remission were subjected to echocardiography. The abnormalities detected included pericardial thickening in 70%, thickening of the aortic and/or mitral valves in 28%, right ventricular dilatation or hypokinesis in 39%, and left ventricular dysfunction in 39%. In the 23 patients treated by an upper mantle technique with shielding, the incidence of right ventricular abnormalities and valvular thickening was significantly lower than in patients treated with modified techniques. Although no symptoms were attributable to the observed abnormalities, longer follow-up time may reveal important functional implications.

  5. Structural and functional abnormalities of the amygdala in schizophrenia.

    PubMed

    Lawrie, Stephen M; Whalley, Heather C; Job, Dominic E; Johnstone, Eve C

    2003-04-01

    Schizophrenia is characterized by delusions and hallucinations, which tend to respond to treatment with dopamine receptor blockers, and a loss of motivation and affect, which do not. Structural magnetic resonance imaging (sMRI) has convincingly demonstrated reduced volumes of the amygdala-hippocampal complex (AHC) and other limbic and paralimbic structures, on both manual tracing and automated analyses. The Edinburgh High-Risk Study (EHRS) of initially healthy adolescents with at least two affected relatives has found that AHC volumes are reduced pre-morbidly but not to schizophrenic levels, suggesting that further volume reductions may be associated with the onset of schizophrenia. AHC volumes appear to be genetically mediated in families with a dominant pattern of transmission, whereas prefrontal lobe and basal ganglia volumes are related to genetic liability to schizophrenia in the generality of high-risk subjects. Temporal lobe volumes may fall as psychotic symptoms develop, in the context of drug abuse and stress. Neuropsychological testing has also demonstrated pre-morbid impairments and symptom-related deterioration. More detailed analyses of the temporal lobe changes on sMRI and fronto-temporal dysconnectivity on fMRI are in progress. These findings are discussed with reference to other indications of pre-morbid developmental disturbance in our high-risk subjects, animal models of schizophrenia, and reliable findings from neuropathological, neuropsychological, and functional imaging studies of patients with schizophrenia. PMID:12724176

  6. Abnormal grooming activity in Dab1(scm) (scrambler) mutant mice.

    PubMed

    Strazielle, C; Lefevre, A; Jacquelin, C; Lalonde, R

    2012-07-15

    Dab1(scm) mutant mice, characterized by cell ectopias and degeneration in cerebellum, hippocampus, and neocortex, were compared to non-ataxic controls for different facets of grooming caused by brief water immersions, as well as some non-grooming behaviors. Dab1(scm) mutants were strongly affected in their quantitative functional parameters, exhibiting higher starting latencies before grooming relative to non-ataxic littermates of the A/A strain, fewer grooming bouts, and grooming components of shorter duration, with an unequal regional distribution targeting almost totally the rostral part (head washing and forelimb licking) of the animal. Only bouts of a single grooming element were preserved. The cephalocaudal order of grooming elements appeared less disorganized, mutant and control mice initiating the grooming with head washing and forelimb licking prior to licking posterior parts. However, mutants differed from controls in that all their bouts were incomplete but uninterrupted, although intergroup difference for percentage of the incorrect transitions was not significant. In contrast to grooming, Dab1(scm) mice ambulated for a longer time. During walking episodes, they exhibited more body scratching than controls, possibly to compensate for the lack of licking different body parts. In conjunction with studies with other ataxic mice, these results indicate that the cerebellar cortex affects grooming activity and is consequently involved in executing various components, but not in its sequential organization, which requires other brain regions such as cerebral cortices or basal ganglia. PMID:22561124

  7. Latency-associated transcripts of equine herpesvirus type 4 in trigeminal ganglia of naturally infected horses.

    PubMed

    Borchers, K; Wolfinger, U; Ludwig, H

    1999-08-01

    Equine herpesvirus type 4 (EHV-4) is a major respiratory pathogen of horses. Unlike most other members of the Alphaherpesvirinae, EHV-4 was regarded as non-neurotropic. Here, neural and lymphoid tissues of 17 horses have been analysed post-mortem. EHV-4 DNA was detected in 11 cases (65%) by PCR, exclusively in the trigeminal ganglia. In order to define the transcriptional activity, RNA preparations of 10 EHV-4 DNA-positive ganglia were investigated by nested RT-PCR. EHV-4-specific transcripts derived from genes 63 [herpes simplex virus type 1 (HSV-1) ICPO gene homologue] and 64 (HSV-1 ICP4 gene homologue) were detected in six trigeminal ganglia. In one other case, only gene 64-specific transcripts were present. All of the transcripts proved to be antisense orientated when a strand-specific RT-PCR was applied. Type-specific primers for gene 33 (encoding glycoprotein B) served to detect transcripts of an acute EHV-4-infection, which were found in only one of the six ganglia positive for gene 63- and gene 64-specific transcripts. Overall, these studies clearly demonstrate that EHV-4 is latent in trigeminal ganglia. PMID:10466816

  8. Position of Larval Tapeworms, Polypocephalus sp., in the Ganglia of Shrimp, Litopenaeus setiferus

    PubMed Central

    Carreon, Nadia; Faulkes, Zen

    2014-01-01

    Parasites that invade the nervous system of their hosts have perhaps the best potential to manipulate their host’s behavior, but how they manipulate the host, if they do at all, could depend on their position within the host’s nervous system. We hypothesize that parasites that live in the nervous system of their host will be randomly distributed if they exert their influence through non-specific effects (i.e., general pathology), but that their position in the nervous system will be non-random if they exert their influence by targeting specific neural circuits. We recorded the position of larval tapeworms, Polypocephalus sp., in the abdominal ganglia of white shrimp, Litopenaeus setiferus. Tapeworms are more common within ganglia than in the section of the nerve cord between ganglia, even though the nerve cord has a greater volume than the ganglia. The tapeworms are also more abundant in the periphery of the ganglia. Because most synaptic connections are within the central region of the ganglion, such positioning may represent a trade-off between controlling the nervous system and damaging it. PMID:24820854

  9. Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection

    PubMed Central

    Smith, Jeffrey M.

    2014-01-01

    Infection induces the expression of inflammatory chemokines that recruit immune cells to the site of inflammation. Whereas tissues such as the intestine and skin express unique chemokines during homeostasis, whether different tissues express distinct chemokine profiles during inflammation remains unclear. With this in mind, we performed a comprehensive screen of the chemokines expressed by two tissues (skin and sensory ganglia) infected with a common viral pathogen (herpes simplex virus type 1). After infection, the skin and ganglia showed marked differences in their expression of the family of Cxcr2 chemokine ligands. Specifically, Cxcl1/2/3, which in turn controlled neutrophil recruitment, was up-regulated in the skin but absent from the ganglia. Within the ganglia, Cxcl2 expression and subsequent neutrophil recruitment was inhibited by type I interferon (IFN). Using a combination of bone marrow chimeras and intracellular chemokine staining, we show that type I IFN acted by directly suppressing Cxcl2 expression by monocytes, abrogating their ability to recruit neutrophils to the ganglia. Overall, our findings describe a novel role for IFN in the direct, and selective, inhibition of Cxcr2 chemokine ligands, which results in the inhibition of neutrophil recruitment to neuronal tissue. PMID:24752295

  10. Basal lamina structural alterations in human asymmetric aneurismatic aorta.

    PubMed

    Cotrufo, M; De Santo, L; Della Corte, A; Di Meglio, F; Guerra, G; Quarto, C; Vitale, S; Castaldo, C; Montagnani, S

    2005-01-01

    Basal lamina (BL) is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation. We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens. We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study. We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RT-PCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin alpha2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type IV is more evident in the concavity and Tenascin in the convexity. PMID:16377578

  11. Morphometric Study of the Upper Thoracic Sympathetic Ganglia

    PubMed Central

    Lee, Sang Beom; Park, Sukh Que; Cho, Sung Jin; Choi, Soon Kwan; Bae, Hack Gun

    2011-01-01

    Objective Morphometric data for the sympathetic ganglia (SG) of the upper thoracic spine was investigated to identify the exact location of the SG in order to reduce normal tissue injury in the thoracic cavity during thoracoscopic sympathectomy. Methods In 46 specimens from 23 formalin-fixed adult cadavers, the authors measured the shortest distance from the medial margin of the T1, T2 and T3 SG to the most prominent point and medial margin of the corresponding rib heads, and to the lateral margin of the longus colli muscle. In addition, the distance between the most prominent point of the rib head and the lateral margin of longus colli muscle and the width of each SG were measured. Results The shortest distance from the medial margin of the SG to the prominent point of corresponding rib head was on average 1.9 mm on T1, 4.2 mm, and 4.1 mm on T2, T3. The distance from the medial margin of the SG to the medial margin of the corresponding rib head was 4.2 mm on T1, 5.9 mm, and 6.3 mm on T2, T3. The mean distance from the medial margin of the SG to the lateral margin of the longus colli muscle was 6.7 mm on T1, 8.8 mm, 9.9 and mm on T2, T3. The mean distance between the prominent point of the rib head and the lateral margin of the longus colli muscle was 4.8 mm on T1, 4.6 mm, and 5.9 mm on T2, T3. The mean width of SG was 6.1 mm on T1, 4.1 mm, and 3.1 mm on T2, T3. Conclusion We present morphometric data to assist in surgical planning and the localization of the upper thoracic SG during thoracoscopic sympathectomy. PMID:21892401

  12. Friedreich ataxia: metal dysmetabolism in dorsal root ganglia

    PubMed Central

    2013-01-01

    Background Friedreich ataxia (FA) causes distinctive lesions of dorsal root ganglia (DRG), including neuronal atrophy, satellite cell hyperplasia, and absorption of dying nerve cells into residual nodules. Two mechanisms may be involved: hypoplasia of DRG neurons from birth and superimposed iron (Fe)- and zinc (Zn)-mediated oxidative injury. This report presents a systematic analysis of DRG in 7 FA patients and 13 normal controls by X-ray fluorescence (XRF) of polyethylene glycol-embedded DRG; double-label confocal immunofluorescence microscopy of Zn- and Fe-related proteins; and immunohistochemistry of frataxin and the mitochondrial marker, ATP synthase F1 complex V ?-polypeptide (ATP5B). Results XRF revealed normal total Zn- and Fe-levels in the neural tissue of DRG in FA (mean ± standard deviation): Zn=5.46±2.29 ?g/ml, Fe=19.99±13.26 ?g/ml in FA; Zn=8.16±6.19 ?g/ml, Fe=23.85±12.23 ?g/ml in controls. Despite these unchanged total metal concentrations, Zn- and Fe-related proteins displayed major shifts in their cellular localization. The Zn transporter Zip14 that is normally expressed in DRG neurons and satellite cells became more prominent in hyperplastic satellite cells and residual nodules. Metallothionein 3 (MT3) stains confirmed reduction of neuronal size in FA, but MT3 expression remained low in hyperplastic satellite cells. In contrast, MT1/2 immunofluorescence was prominent in proliferating satellite cells. Neuronal ferritin immunofluorescence declined but remained strong in hyperplastic satellite cells and residual nodules. Satellite cells in FA showed a larger number of mitochondria expressing ATB5B. Frataxin immunohistochemistry in FA confirmed small neuronal sizes, irregular distribution of reaction product beneath the plasma membrane, and enhanced expression in hyperplastic satellite cells. Conclusions The pool of total cellular Zn in normal DRG equals 124.8 ?M, which is much higher than needed for the proper function of Zn ion-dependent proteins. It is likely that any disturbance of Zn buffering by Zip14 and MT3 causes mitochondrial damage and cell death. In contrast to Zn, sequestration of Fe in hyperplastic satellite cells may represent a protective mechanism. The changes in the cellular localization of Zn- and Fe-handling proteins suggest metal transfer from degenerating DRG neurons to activated satellite cells and connect neuronal metal dysmetabolism with the pathogenesis of the DRG lesion in FA. PMID:24252376

  13. Poetry Instruction: Do Basals Follow Recommended Procedures?

    ERIC Educational Resources Information Center

    Shapiro, Sheila

    To determine whether the suggested poetry teaching procedures found in the teacher manuals of sixth-grade basal readers reflect the pedagogical procedures suggested by expert opinion and research, an indepth analysis was made of a total of 106 poetry lessons in eight teacher manuals. The poetry lessons were analyzed for the purposes of determining…

  14. Middle-Ear Pressure Under Basal Conditions

    E-print Network

    Allen, Jont

    Middle-Ear Pressure Under Basal Conditions Leif Hergils, MD, Bengt Magnuson, MD, PhD \\s=b\\Spontaneous pressure changes in the middle ear were measured under bas- al conditions in ten subjects with healthy ears. Results showed that the pressure in the majority of ears remained slightly above the atmo- spheric

  15. TEMPORAL VARIABILITY IN BASAL ISOPRENE EMISSION FACTOR

    EPA Science Inventory

    Seasonal variability in basal isoprene emission factor (micrograms C /g hr or nmol/ m2 sec, leaf temperature at 30 degrees C and photosynthetically active radiation (PAR) at 1000 micromol/ m2 sec) was studied during the 1998 growing season at Duke Forest in the North Carolina Pie...

  16. Enhancing Basal Vocabulary Instruction in Kindergarten

    ERIC Educational Resources Information Center

    Lenfest, Ashleigh; Reed, Deborah K.

    2015-01-01

    To enhance the basal vocabulary instruction for kindergarten students at risk for reading difficulties, lessons provided in typical curricular materials can be supplemented with instructional elements derived from research. This article addresses how teachers can add 15 minutes of higher order instructional activities to daily reading lessons to…

  17. Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA

    E-print Network

    Lemaire, Nune

    A major physiologic sign in Parkinson disease is the occurrence of abnormal oscillations in cortico-basal ganglia circuits, which can be normalized by l-DOPA therapy. Under normal circumstances, oscillatory activity in ...

  18. Poststreptococcal dystonia with bilateral striatal enlargement: MR imaging and spectroscopic findings.

    PubMed

    Karagulle Kendi, A T; Krenzel, C; Ott, F W; Brace, J R; Norberg, S K; Kieffer, S A

    2008-08-01

    Isolated bilateral striatal necrosis is an abnormality of the basal ganglia associated with acute dystonia in children. This report describes the development of dystonic movements in a 7-year-old male patient 2 weeks after streptococcal pharyngitis. PMID:18451091

  19. Age and immune status of rhesus macaques impact simian varicella virus gene expression in sensory ganglia.

    PubMed

    Meyer, Christine; Dewane, Jesse; Kerns, Amelia; Haberthur, Kristen; Barron, Alex; Park, Byung; Messaoudi, Ilhem

    2013-08-01

    Simian varicella virus (SVV) infection of rhesus macaques (RMs) recapitulates the hallmarks of varicella-zoster virus (VZV) infection of humans, including the establishment of latency within the sensory ganglia. Various factors, including age and immune fitness, influence the outcome of primary VZV infection, as well as reactivation resulting in herpes zoster (HZ). To increase our understanding of the role of lymphocyte subsets in the establishment of viral latency, we analyzed the latent SVV transcriptome in juvenile RMs depleted of CD4 T, CD8 T, or CD20 B lymphocytes during acute infection. We have previously shown that SVV latency in sensory ganglia of nondepleted juvenile RMs is associated with a limited transcriptional profile. In contrast, CD4 depletion during primary infection resulted in the failure to establish a characteristic latent viral transcription profile in sensory ganglia, where we detected 68 out of 69 SVV-encoded open reading frames (ORFs). CD-depleted RMs displayed a latent transcriptional profile that included additional viral transcripts within the core region of the genome not detected in control RMs. The latent transcriptome of CD20-depleted RMs was comparable to the latent transcription in the sensory ganglia of control RMs. Lastly, we investigated the impact of age on the establishment of SVV latency. SVV gene expression was more active in ganglia from two aged RMs than in ganglia from juvenile RMs, with 25 of 69 SVV transcripts detected. Therefore, immune fitness at the time of infection modulates the establishment and/or maintenance of SVV latency. PMID:23698305

  20. Age and Immune Status of Rhesus Macaques Impact Simian Varicella Virus Gene Expression in Sensory Ganglia

    PubMed Central

    Meyer, Christine; Dewane, Jesse; Kerns, Amelia; Haberthur, Kristen; Barron, Alex; Park, Byung

    2013-01-01

    Simian varicella virus (SVV) infection of rhesus macaques (RMs) recapitulates the hallmarks of varicella-zoster virus (VZV) infection of humans, including the establishment of latency within the sensory ganglia. Various factors, including age and immune fitness, influence the outcome of primary VZV infection, as well as reactivation resulting in herpes zoster (HZ). To increase our understanding of the role of lymphocyte subsets in the establishment of viral latency, we analyzed the latent SVV transcriptome in juvenile RMs depleted of CD4 T, CD8 T, or CD20 B lymphocytes during acute infection. We have previously shown that SVV latency in sensory ganglia of nondepleted juvenile RMs is associated with a limited transcriptional profile. In contrast, CD4 depletion during primary infection resulted in the failure to establish a characteristic latent viral transcription profile in sensory ganglia, where we detected 68 out of 69 SVV-encoded open reading frames (ORFs). CD-depleted RMs displayed a latent transcriptional profile that included additional viral transcripts within the core region of the genome not detected in control RMs. The latent transcriptome of CD20-depleted RMs was comparable to the latent transcription in the sensory ganglia of control RMs. Lastly, we investigated the impact of age on the establishment of SVV latency. SVV gene expression was more active in ganglia from two aged RMs than in ganglia from juvenile RMs, with 25 of 69 SVV transcripts detected. Therefore, immune fitness at the time of infection modulates the establishment and/or maintenance of SVV latency. PMID:23698305

  1. ?-Spectrin Regulates the Hippo Signaling Pathway and Modulates the Basal Actin Network.

    PubMed

    Wong, Kenneth Kin Lam; Li, Wenyang; An, Yanru; Duan, Yangyang; Li, Zhuoheng; Kang, Yibin; Yan, Yan

    2015-03-01

    Emerging evidence suggests functional regulation of the Hippo pathway by the actin cytoskeleton, although the detailed molecular mechanism remains incomplete. In a genetic screen, we identified a requirement for ?-Spectrin in the posterior follicle cells for the oocyte repolarization process during Drosophila mid-oogenesis. ?-spectrin mutations lead to loss of Hippo signaling activity in the follicle cells. A similar reduction of Hippo signaling activity was observed after ?-Spectrin knockdown in mammalian cells. We further demonstrated that ?-spectrin mutations disrupt the basal actin network in follicle cells. The abnormal stress fiber-like actin structure on the basal side of follicle cells provides a likely link between the ?-spectrin mutations and the loss of the Hippo signaling activity phenotype. PMID:25589787

  2. Does varicella-zoster virus infection of the peripheral ganglia cause Chronic Fatigue Syndrome?

    PubMed

    Shapiro, Judith S

    2009-11-01

    This article posits that infection of the peripheral ganglia causes at least some cases of Chronic Fatigue Syndrome (CFS), with a neurotropic herpesvirus, particularly varicella-zoster virus (VZV), as the most likely cause of the infection. Virtually all CFS symptoms could be produced by an infection of the peripheral ganglia, with infection of the autonomic ganglia causing fatigue, postural hypotension, and sleep disturbances, and infection of the sensory ganglia causing sensory symptoms such as chronic pain. Furthermore, infections of the peripheral ganglia are known to cause long-term nerve dysfunction, which would help explain the chronic course of CFS. Herpesviruses have long been suspected as the cause of CFS; this theory has recently been supported by studies showing that administering antiherpes agents causes substantial improvement in some CFS patients. VZV is known to frequently reactivate in the peripheral ganglia of previously healthy adults and cause sudden, debilitating illness, making it a likely candidate as a cause of CFS. Moreover, many of the symptoms of CFS overlap with those of herpes zoster (shingles), with the exception that painful rash is not one of the symptoms of CFS. A model is therefore proposed in which CFS is one of the many manifestations of zoster sine herpete; that is, herpes zoster without rash. Furthermore, re-exposure to VZV in the form of chickenpox has become less common in the past few decades; without such re-exposure, immunity to VZV drops, which could explain the increased incidence of CFS. Co-infection with multiple herpesviruses is a possibility, as some CFS patients show signs of infection with other herpesviruses including Epstein-Barr, Cytomegalovirus, and HHV6. These three herpesviruses can attack immune cells, and may therefore promote neurotropic herpesvirus reactivation in the ganglia. The possibility of VZV as the causal agent in CFS has previously received almost no attention; the possibility that CFS involves infection of the peripheral ganglia has likewise been largely overlooked. This suggests that the search for a viral cause of CFS has been far from exhaustive. Several antiherpes drugs are available, as is a vaccine for VZV; more research into such agents as possible treatments for CFS is urgently needed. PMID:19520522

  3. The convergence of sympathetic preganglionic fibres on vasomotor neurones of the ganglia in lumbar sympathetic chain.

    PubMed

    Lebedev, V P; Syromiatnikov, A V; Skok, V I

    1977-04-01

    By means of intracellular recordings from the neurones of isolated L(3)-L(6) ganglia it was shown that B(1)-, B(2)- and C-preganglionic fibres widely converge on these neurones. Besides, a part of the ganglionic neurones is activated by slow-conducting C-fibres coming into the ganglia through the grey rami. Identified vasomotor neurones have the distinctive feature of preganglionic fibre convergence. Only B(2)- and C-preganglionic fibres were able to activate them, but the efficacy of the B(2)-fibre excitatory action is considerably higher. PMID:19604952

  4. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Microsoft Academic Search

    Giovanni Villa; Stefania Ceruti; Matteo Zanardelli; Giulia Magni; Luc Jasmin; Peter T Ohara; Maria P Abbracchio

    2010-01-01

    BACKGROUND: Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS). Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in

  5. The cerebral ganglia of Milnesium tardigradum Doyère (Apochela, Tardigrada): Three dimensional reconstruction and notes on their ultrastructure

    Microsoft Academic Search

    HOLGER WIEDERHÖFT; HARTMUT GREVEN

    1996-01-01

    Differential interference contrast micrographs from stretched animals, serially sectioned semi-thin and ultrathin sections revealed that the cerebral ganglia (supraoesophageal mass) of the eutardigradeMilnesium tardigradumlie above the buccal tube and adjacent tissue like a saddle. It has an anterior indentation which is penetrated by two muscles that arise from the cuticle of the forehead. The cerebral ganglia consist of lateral outer

  6. Intracerebroventricular Administration of Nerve Growth Factor Induces Gliogenesis in Sensory Ganglia, Dorsal Root, and within the Dorsal Root Entry Zone

    PubMed Central

    Schlachetzki, Johannes C. M.; Pizzo, Donald P.; Morrissette, Debbi A.; Winkler, Jürgen

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100? revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root. PMID:24738070

  7. Basal Cell Carcinoma Arising within Seborrheic Keratosis

    PubMed Central

    Yurdakul, Cüneyt; Güçer, Hasan; Sehitoglu, Ibrahim

    2014-01-01

    Malignant tumour development within a seborrheic keratosis (SK) is extremely rare. Though the most commonly developed malignant tumour is the basal cell carcinoma (BCC), other tumour types have also been reported in literature. Herein, we will report a superficial type BCC case developed within SK localized in hairy skin of a 78-year-old female patient. In immunohistochemical evaluation, diffuse positive staining with CK19 and over-expression in p53 compared with non-neoplastic areas were determined in neoplastic basaloid islands. It is always not easy to differentiate especially superficial type BCC cases from non-neoplastic epithelium of SK with histopathological evaluation. As far as this reason we believe that in difficult differentiation of these 2 lesions, in order to show the differentiation in basal epithelium, immunohistochemical evaluation may be helpful. PMID:25177624

  8. Basal Cell Carcinoma Arising within Seborrheic Keratosis.

    PubMed

    Bedir, Recep; Yurdakul, Cüneyt; Güçer, Hasan; Sehitoglu, Ibrahim

    2014-07-01

    Malignant tumour development within a seborrheic keratosis (SK) is extremely rare. Though the most commonly developed malignant tumour is the basal cell carcinoma (BCC), other tumour types have also been reported in literature. Herein, we will report a superficial type BCC case developed within SK localized in hairy skin of a 78-year-old female patient. In immunohistochemical evaluation, diffuse positive staining with CK19 and over-expression in p53 compared with non-neoplastic areas were determined in neoplastic basaloid islands. It is always not easy to differentiate especially superficial type BCC cases from non-neoplastic epithelium of SK with histopathological evaluation. As far as this reason we believe that in difficult differentiation of these 2 lesions, in order to show the differentiation in basal epithelium, immunohistochemical evaluation may be helpful. PMID:25177624

  9. The telomere repeat motif of basal Metazoa.

    PubMed

    Traut, Walther; Szczepanowski, Monika; Vítková, Magda; Opitz, Christian; Marec, Frantisek; Zrzavý, Jan

    2007-01-01

    In most eukaryotes the telomeres consist of short DNA tandem repeats and associated proteins. Telomeric repeats are added to the chromosome ends by telomerase, a specialized reverse transcriptase. We examined telomerase activity and telomere repeat sequences in representatives of basal metazoan groups. Our results show that the 'vertebrate' telomere motif (TTAGGG)( n ) is present in all basal metazoan groups, i.e. sponges, Cnidaria, Ctenophora, and Placozoa, and also in the unicellular metazoan sister group, the Choanozoa. Thus it can be considered the ancestral telomere repeat motif of Metazoa. It has been conserved from the metazoan radiation in most animal phylogenetic lineages, and replaced by other motifs-according to our present knowledge-only in two major lineages, Arthropoda and Nematoda. PMID:17385051

  10. Basal hydraulic conditions of Ice Stream B

    NASA Technical Reports Server (NTRS)

    Engelhardt, Hermann; Kamb, Barclay

    1993-01-01

    Fifteen boreholes have been drilled to the base of Ice Stream B in the vicinity of UpB Camp. The boreholes are spread over an area of about 500 x 1000 m. Several till cores were retrieved from the bottom of the 1000-m-deep holes. Laboratory tests using a simple shear box revealed a yield strength of basal till of 2 kPa. This agrees well with in-situ measurements using a shear vane. Since the average basal shear stress of Ice Stream B with a surface slope of 0.1 degree is about 20 kPa, the ice stream cannot be supported by till that weak. Additional support for this conclusion comes from the basal water pressure that has been measured in all boreholes as soon as the hot water drill reached bottom. In several boreholes, the water pressure has been continuously monitored; in two of them, over several years. The water pressure varies but stays within 1 bar of flotation where ice overburden pressure and water pressure are equal. The ratio of water and overburden pressure lies between 0.986 and 1.002. This is an extremely high value as compared to other fast-moving ice masses; e.g., Variegated Glacier in surge has a ratio of 0.8, and Columbia Glacier - a fast-moving tidewater glacier - has a ratio of 0.9. It implies that water flow under the glacier occurs in a thin film and not in conduits that would drain away water too rapidly. It also implies that basal sliding must be very effective. Water flow under the glacier was measured in a salt-injection experiment where a salt pulse was released at the bottom of a borehole while 60 m down-glacier, the electrical resistance was measured between two other boreholes. A flow velocity of 7 mm/s was obtained.

  11. Molecular Pathogenesis of Basal Cell Carcinoma

    Microsoft Academic Search

    T. Meyer

    Basal cell carcinoma (BCC) is the most frequent cancer among the white population, representing 75% of all skin cancers [1].\\u000a The incidence of BCC cases is increasing, probably because of changes of leisure activities and migration to regions with\\u000a higher solar radiation. BCCs rarely metastasize (<0.1%), and mortality rates are low; however, some tumors grow aggressively\\u000a and may cause extensive

  12. Complex patterns of abnormal heartbeats

    NASA Technical Reports Server (NTRS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

    2002-01-01

    Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

  13. Emergency and Abnormal Situations Project Emergency and Abnormal Situations

    E-print Network

    the landing gear came down... #12;10 Emergency and Abnormal Situations Issues · Checklist and Procedure-board fire and when the aircraft ditches, conducts a forced landing, or crashes is 17 minutes. The Swissair 426768 During approach...the gear failed to come down...after notifying the tower we had a `Gear

  14. Direct NK Cell-Mediated Lysis of Syngenic Dorsal Root Ganglia Neurons In Vitro1

    Microsoft Academic Search

    Eva Backstrom; Benedict J. Chambers; Krister Kristensson; Hans-Gustaf Ljunggren

    2000-01-01

    In contrast to extensive studies on the role of T and B lymphocytes in the pathogenesis of autoimmune diseases of the nervous system, little is known about NK cells and their potential role in the destruction of neural tissue. NK cells have been implicated in the selective death of sympathetic neurons resident in the superior cervical ganglia of rats after

  15. The Role of Neurotrophins in Development of Neural-Crest Cells that Become Sensory Ganglia

    Microsoft Academic Search

    Chaya Kalcheim

    1996-01-01

    A fundamental issue of neural-crest ontogeny is understanding how different types of cells are created at the right time and in the correct numbers. Sensory ganglia are among the many derivatives of the vertebrate neural crest. Their proper formation requires the regulation of several processes such as cell fate specification, proliferation, survival, and terminal differentiation. The timescale of the occurrence

  16. Identifiable Achatina giant neurones: Their localizations in ganglia, axonal pathways and pharmacological features

    Microsoft Academic Search

    Hiroshi Takeuchi; Yoko Araki; Muhammad Emaduddin; Wei Zhang; Xiao Yan Han; Thucydides L. Salunga; Shu Min Wong

    1996-01-01

    1.1. An African giant snail (Achatina fulica Férussac), originally from East Africa, is now found abundantly in tropical and subtropical regions of Asia, including Okinawa in Japan. This is one of the largest land snail species in the world. The Achatina central nervous system is composed of the buccal, cerebral and suboesophageal ganglia. The 37 giant neurones were identified in

  17. Purification and Characterization of a Cardioexcitatory Neuropeptide from the Central Ganglia of a Bivalve Mollusc

    Microsoft Academic Search

    D. A. Price; M. J. Greenberg

    1977-01-01

    We have purified a cardioexcitatory substance, previously designated peak C, from ganglia of the Sunray Venus clam, Macrocallista nimbosa. Low concentrations (10 -10M) of this substance not only excite the isolated clam heart, but also produce tonic contractions of the isolated radula protractor muscle of the whelk, Busycon contrarium. These two muscle preparations have therefore been used as a parallel

  18. Control of locomotion in marine mollusc Clione limacina II. Rhythmic neurons of pedal ganglia

    Microsoft Academic Search

    Yu. I. Arshavsky; I. N. Beloozerova; G. N. Orlovsky; Yu. V. Panchin; G. A. Pavlova

    1985-01-01

    1.Activity from neurons in isolated pedal ganglia of Clione limacina was recorded intracellularly during generation of rhythmic swimming. To map the distribution of cells in a ganglion, one of two microelectrodes was used to monitor activity of the identified neuron (1A or 2A), while the second electrode was used to penetrate successively all the visible neurons within a definite area

  19. Pathological PrP is abundant in sympathetic and sensory ganglia of hamsters fed with scrapie

    Microsoft Academic Search

    Patricia A. McBride; Michael Beekes

    1999-01-01

    Although the ultimate target of infection is the CNS, there is evidence that the peripheral nervous system (PNS) is involved in the pathogenesis of Transmissible Spongiform Encephalopathies (TSEs). We used immunocytochemistry to identify the presence of pathological accumulations of a host protein, PrP, in the CNS and PNS (sensory and autonomic ganglia) of hamsters orally infected with 263K scrapie. All

  20. Allergic airway inflammation induces the migration of dendritic cells into airway sensory ganglia

    PubMed Central

    2014-01-01

    Background A neuroimmune crosstalk between dendritic cells (DCs) and airway nerves in the lung has recently been reported. However, the presence of DCs in airway sensory ganglia under normal and allergic conditions has not been explored so far. Therefore, this study aims to investigate the localisation, distribution and proliferation of DCs in airway sensory ganglia under allergic airway inflammation. Methods Using the house dust mite (HDM) model for allergic airway inflammation BALB/c mice were exposed to HDM extract intranasally (25 ?g/50 ?l) for 5 consecutive days a week over 7 weeks. With the help of the immunohistochemistry, vagal jugular-nodose ganglia complex (JNC) sections were analysed regarding their expression of DC-markers (MHC II, CD11c, CD103), the neuronal marker PGP 9.5 and the neuropeptide calcitonin gene-related peptide (CGRP) and glutamine synthetase (GS) as a marker for satellite glia cells (SGCs). To address the original source of DCs in sensory ganglia, a proliferation experiment was also carried in this study. Results Immune cells with characteristic DC-phenotype were found to be closely located to SGCs and vagal sensory neurons under physiological conditions. The percentage of DCs in relation to neurons was significantly increased by allergic airway inflammation in comparison to the controls (HDM 51.38?±?2.38% vs. control 28.16?±?2.86%, p?ganglia, however, the proliferation rate of DCs is not significantly changed in the two treated animal groups (proliferating DCs/ total DCs: HDM 0.89?±?0.38%, vs. control 1.19?±?0.54%, p?=?0.68). Also, increased number of CGRP-positive neurons was found in JNC after allergic sensitisation and challenge (HDM 31.16?±?5.41% vs. control 7.16?±?1.53%, p?ganglia to interact with sensory neurons enhancing or protecting the allergic airway inflammation. The increase of DCs as well as CGRP-positive neurons in airway ganglia by allergic airway inflammation indicate that intraganglionic DCs and neurons expressing CGRP may contribute to the pathogenesis of bronchial asthma. To understand this neuroimmune interaction in allergic airway inflammation further functional experiments should be carried out in future studies. PMID:24980659

  1. Remodelling of the intracardiac ganglia in diabetic Goto-Kakizaki rats: an anatomical study

    PubMed Central

    2013-01-01

    Background Although cardiac autonomic neuropathy is one of major complications of diabetes mellitus (DM), anatomical data on cardiac innervation of diabetic animal models is scant and controversial. We performed this study to check whether long-term diabetic state impacts the anatomy of intracardiac ganglia in Goto-Kakizaki (GK) rats, a genetic model of type 2 DM. Methods Twelve GK rats (276?±?17 days of age; mean?±?standard error) and 13 metabolically healthy Wistar rats (262?±?5 days of age) as controls were used for this study. Blood glucose was determined using test strips, plasma insulin by radioimmunoassay. Intrinsic ganglia and nerves were visualized by acetylcholinesterase histochemistry on whole hearts. Ganglion area was measured, and the neuronal number was assessed according to ganglion area. Results The GK rats had significantly elevated blood glucose level compared to controls (11.0?±?0.6 vs. 5.9?±?0.1 mmol/l, p?ganglia, decreased total area of intracardiac ganglia (1.4?±?0.1 vs. 2.2?±?0.1 mm2, p?ganglia in GK rats is caused by a long-term diabetic state. PMID:23758627

  2. Neural basis of singing in crickets: central pattern generation in abdominal ganglia

    NASA Astrophysics Data System (ADS)

    Schöneich, Stefan; Hedwig, Berthold

    2011-12-01

    The neural mechanisms underlying cricket singing behavior have been the focus of several studies, but the central pattern generator (CPG) for singing has not been localized conclusively. To test if the abdominal ganglia contribute to the singing motor pattern and to analyze if parts of the singing CPG are located in these ganglia, we systematically truncated the abdominal nerve cord of fictively singing crickets while recording the singing motor pattern from a front-wing nerve. Severing the connectives anywhere between terminal ganglion and abdominal ganglion A3 did not preclude singing, although the motor pattern became more variable and failure-prone as more ganglia were disconnected. Singing terminated immediately and permanently after transecting the connectives between the metathoracic ganglion complex and the first unfused abdominal ganglion A3. The contribution of abdominal ganglia for singing pattern generation was confirmed by intracellular interneuron recordings and current injections. During fictive singing, an ascending interneuron with its soma and dendrite in A3 depolarized rhythmically. It spiked 10 ms before the wing-opener activity and hyperpolarized in phase with the wing-closer activity. Depolarizing current injection elicited rhythmic membrane potential oscillations and spike bursts that elicited additional syllables and reliably reset the ongoing chirp rhythm. Our results disclose that the abdominal ganglion A3 is directly involved in generating the singing motor pattern, whereas the more posterior ganglia seem to provide only stabilizing feedback to the CPG circuit. Localizing the singing CPG in the anterior abdominal neuromeres now allows analyzing its circuitry at the level of identified interneurons in subsequent studies.

  3. Food habits and the basal rate of metabolism in birds

    Microsoft Academic Search

    Brian K. McNab

    1988-01-01

    The correlation of basal rate of metabolism with various factors is examined in birds. Chief among these is body mass. As in mammals, much of the remaining variation in basal rate among birds is associated with food habits. Birds other than passerines that feed on grass, nectar, flying insects, or vertebrates generally have basal rates that are similar to mammals

  4. Chromosomal abnormalities associated with omphalocele.

    PubMed

    Chen, Chih-Ping

    2007-03-01

    Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup (3q), dup (11p), inv (11), dup (1q), del (1q), dup (4q), dup (5p), dup (6q), del (9p), dup (15q), dup(17q), Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD) such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling. PMID:17389182

  5. [A boy with nail abnormalities].

    PubMed

    Atiq, Nasirah; van Meurs, Tim

    2013-01-01

    A 12-year-old boy consulted the dermatologist for nail abnormalities. Three weeks earlier, he was treated with doxycycline 100 mg BID for 10 days because of erythema chronicum migrans. Following sun exposure, the patient had developed distal onycholysis surrounded by a hyperpigmented zone. He was diagnosed with doxycycline-induced photo-onycholysis. PMID:23838405

  6. Transcriptional abnormalities in Huntington disease

    Microsoft Academic Search

    Katharine L. Sugars; David C. Rubinsztein

    2003-01-01

    Huntington disease (HD) is caused by a CAG repeat expansion that is translated into an abnormally long polyglutamine (polyQ) tract in the huntingtin protein. The precise mechanisms leading to neurodegeneration in HD have not been fully elucidated, but alterations in gene transcription could well be involved because the activities of several nuclear proteins are compromised by the polyQ mutation. Recent

  7. Abnormalities of the optic disc

    Microsoft Academic Search

    Alfredo A. Sadun; Michelle Y. Wang

    2011-01-01

    The optic disc represents the anterior end of the optic nerve, the most forward extension of the central nervous system (CNS). The optic disc gives a rare glimpse into the CNS. Hence, diseases of the CNS are often manifested on fundus examination. Abnormalities of the optic disc may reflect eye disease (such as glaucoma), problems in development (as in various

  8. The Basal Ganglia as a Structure of Vocal Sensory-Motor Integration and Modulation of Vocal Plasticity in Mammals: Behavioral and Experimental Evidence from Tadarida brasiliensis

    E-print Network

    Tressler, Jedediah Tim

    2012-02-14

    activity of the laryngeal (Schweizer et al., 1981) and respiratory motor neurons (Saper and Loewy, 1980) respectively. Projections also synapse extensively within the reticular formation (RtF) (Mantyh, 1983; Hannig and Jurgens, 2006) and nucleus...

  9. In: Graybiel, A.M. et al., (Eds.) The Basal Ganglia VI, Kluwer Academic Publishers, Norwell, 2002 pp 641-651 Afferent Control of Nigral Dopaminergic Neurons

    E-print Network

    Tepper, James M.

    of firing. The first is that of pacemaker-like firing, characterized by very regular interspike intervals different firing modes, and the three firing patterns are best thought of as a continuum, with the pacemaker and the random pattern are not seen. Instead, virtually all dopaminergic neurons fire in the pacemaker mode

  10. Auditory observation of infant-directed speech by mothers: experience-dependent interaction between language and emotion in the basal ganglia

    PubMed Central

    Matsuda, Yoshi-Taka; Ueno, Kenichi; Cheng, Kang; Konishi, Yukuo; Mazuka, Reiko; Okanoya, Kazuo

    2014-01-01

    Adults address infants with a special speech register known as infant-directed speech (IDS), which conveys both linguistic and emotional information through its characteristic lexicon and exaggerated prosody (e.g., higher pitched, slower, and hyperarticulated). Although caregivers are known to regulate the usage of IDS (linguistic and emotional components) depending on their child’s development, the underlying neural substrates of this flexible modification are largely unknown. Here, using an auditory observation method and functional magnetic resonance imaging (fMRI) of four different groups of females, we revealed the experience-dependent influence of the emotional component on linguistic processing in the right caudate nucleus when mothers process IDS: (1) non-mothers, who do not use IDS regularly, showed no significant difference between IDS and adult-directed speech (ADS); (2) mothers with preverbal infants, who primarily use the emotional component of IDS, showed the main effect of the emotional component of IDS; (3) mothers with toddlers at the two-word stage, who use both linguistic and emotional components of IDS, showed an interaction between the linguistic and emotional components of IDS; and (4) mothers with school-age children, who use ADS rather than IDS toward their children, showed a tendency toward the main effect of ADS. The task that was most comparable to the naturalistic categories of IDS (i.e., explicit-language and implicit-emotion processing) recruited the right caudate nucleus, but it was not recruited in the control, less naturalistic condition (explicit-emotion and implicit-language processing). Our results indicate that the right caudate nucleus processes experience-and task-dependent interactions between language and emotion in mothers’ IDS. PMID:25426054

  11. Identification of target areas for deep brain stimulation in human basal ganglia substructures based on median nerve sensory evoked potential criteria

    PubMed Central

    Klostermann, F; Vesper, J; Curio, G

    2003-01-01

    Objective: In the interventional treatment of movement disorders, the thalamic ventral intermediate nucleus (VIM) and the subthalamic nucleus (STN) are the most relevant electrode targets for deep brain stimulation (DBS). This study tested the value of somatosensory evoked potentials (SEP) for the functional identification of VIM and STN. Methods: Median nerve SEP were recorded from the final stimulation electrodes targeted at STN and VIM. Throughout the stereotactic procedure SEP were recorded during short electrode stops above STN/VIM and within the presumed target areas. After digital filtering, high and low frequency SEP components were analysed separately to parameterise both the 1000 Hz SEP burst and low frequency (<100 Hz) components. Results: SEP recorded in the VIM target region could unequivocally be distinguished from SEP recorded in STN. The 1000 Hz burst signal was significantly larger in VIM than in STN without any overlap of amplitude values. In the low frequency band, a primary high amplitude negativity was obtained in VIM, contrasting with a low amplitude positivity in STN. SEP waveshapes in recordings above target positions resembled SEP obtained in STN. When entering VIM, a sharp amplitude increase was observed over a few millimetres only. Conclusions: Based on SEP criteria, the VIM target but not the STN region can be identified by typical SEP configuration changes, when penetrating the target zone. The approach is independent of the patient's cooperation and vigilance and therefore feasible in general anaesthesia. It provides an easy, reliable, and robust tool for the final assessment of electrode positions at the last instance during electrode implantation when eventual electrode revisions can easily be performed. PMID:12876229

  12. Effects of endogenous dopamine on measures of [18F]N-methylspiroperidol binding in the basal ganglia: Comparison of simulations and experimental results from PET studies in baboons

    Microsoft Academic Search

    Jean Logan; Stephen L. Dewey; Alfred P. Wolf; Joanna S. Fowler; Jonathan D. Brodie; Burton Angrist; Nora D. Volkow; S. John Gatley

    1991-01-01

    The effect of endogenous dopamine on PET measures of radioligand binding is important to the measurement of receptor density (or availability) and neurotransmitter interactions in vivo. We recently reported that pretreatment with amphetamine, a drug which stimulates dopamine release, significantly reduced NMS binding in the baboon brain as determined by the product Ak3 derived from the graphical analysis method for

  13. Astrocyte-derived nitric oxide in manganese neurotoxicity: from cellular and molecular mechanisms underlying selective neuronal vulnerability in the basal ganglia to potential therapeutic modalities

    E-print Network

    Liu, Xuhong

    2007-04-25

    enkephalin (ENK)-positive projection neurons, interneurons expressing neuronal nitric oxide synthetase (nNOS/NOS1), and choline acetyltransferase (ChAT)-expressing interneurons. Activation of surrounding astrocytes occurred with expression of inducible nitric...

  14. Metabolic GHB precursor succinate binds to gamma-hydroxybutyrate receptors: characterization of human basal ganglia areas nucleus accumbens and globus pallidus.

    PubMed

    Molnár, Tünde; Fekete, Erzsébet Kútiné; Kardos, Julianna; Simon-Trompler, Edit; Palkovits, Miklós; Emri, Zsuzsa

    2006-07-01

    Binding of the metabolic gamma-hydroxybutyrate (GHB) precursor succinate to NCS-382-sensitive [3H]GHB-labeled sites in crude synaptosomal or purified synaptic membrane fractions prepared from the human nucleus accumbens (NA), globus pallidus (GP) and rat forebrain has been shown. This site can be characterized by binding of ethyl hemisuccinate and gap-junction blockers, including carbenoxolone hemisuccinate and beta-GRA. There was no significant binding interaction between GABAB receptor ligands (CGP 55845, (R)-baclofen) and these [3H]GHB-labeled sites. GHB, NCS-382 and succinate binding profile of [3H]GHB-labeled sites in rat forebrain, human NA or GP synaptic membranes were similar. The synaptic fraction isolated from the rat forebrain was characterized by GHB binding inhibition constants: Ki,NCS-382 = 1.2 +/- 0.2 microM, Ki,GHB = 1.6 +/- 0.3 microM and Ki,SUCCINATE = 212 +/- 66 microM. In crude membranes containing mainly extrasynaptic membranes, distinct GHB and GABAB receptor sites were found in the NA. By contrast, extrasynaptic GABAB receptor sites of rat forebrain and GP were GHB- and succinate-sensitive, respectively. The heterogeneity of GABAB sites found in native membranes indicates GABAB receptor-dependent differences in GHB action. Based on these findings, we suggest that succinate (and possibly drugs available as succinate salt derivatives) can mimic some of the actions of GHB. PMID:16673403

  15. Ectopic expression of TrKA in the adult rat basal ganglia induces both nerve growth factor-dependent and -independent neuronal responses.

    PubMed

    Giannakopoulou, Dimitra; Daguin-Nerrière, Véronique; Mitsacos, Adamantia; Kouvelas, Elias D; Neveu, Isabelle; Giompres, Panagiotis; Brachet, Philippe

    2012-08-01

    Ectopic expression of tropomyosin-related kinase A (TrkA), the high-affinity receptor of nerve growth factor (NGF), has been widely used in cell culture systems to uncover its role in cell survival or death events. In contrast, little is known about the consequences of its expression in vivo. To address this question, adeno-associated virus (AAV) vectors were used to express TrkA in the substantia nigra (SN) and striatum of adult rats. Nine weeks after transfer, tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs were slightly decreased in the ipsilateral SN. This decrease was no longer significant when NGF was delivered into the striatum. There was no change of DAT binding sites or D1 or D2 receptor mRNAs and binding sites in the striatum, suggesting that ectopic TrkA exerts a limited effect on the pool of TH and DAT transcripts, without affecting overall dopamine signaling. When transferred into the striatum, TrkA transgene had no effect on the size of the cholinergic interneurons, but it exerted typical neurotrophic effects, as shown by an enlargement of the projection neurons and nitric oxide synthase (nNOS)-expressing interneurons. This trophic action was amplified by a delivery of NGF. No toxic effect of the transgene was noted. These data indicate that ectopic expression of TrkA may result in the promotion of neurotrophic effects or can influence neuronal plasticity in the absence of exogenous NGF in neuronal populations that naturally fail to respond to this factor. PMID:22419059

  16. Role of high-field intraoperative magnetic resonance imaging on a multi-image fusion-guided stereotactic biopsy of the basal ganglia: A case report.

    PubMed

    Sun, Xiang; Chen, Zhijuan; Yang, Shuyuan; Zhang, Jianning; Yue, Shuyuan; Wang, Zengguang; Yang, Weidong

    2015-01-01

    The aim of the present case study was to investigate the advantages of intraoperative magnetic resonance imaging (iMRI) on the real-time guidance and monitoring of a stereotactic biopsy. The study describes a patient with intracranial lesions, which were examined by conventional MRI and diffusion tensor imaging using a 1.5T intraoperative MRI system. The digital and pre-operative positron emission/computed tomography image data were transferred to a BrainLAB planning workstation, and a variety of images were automatically fused. The BrainLAB software was then used to reconstruct the corticospinal tract (CST) and create a three-dimensional display of the anatomical association between the CST and the brain lesions. A Leksell surgical planning workstation was used to identify the ideal target site and a reasonable needle track for the biopsy. The 1.5T iMRI was used to effectively monitor the intracranial condition during the brain biopsy procedure. Post-operatively, the original symptoms of the patient were not aggravated and no further neurological deficits were apparent. The histopathological diagnosis of non-Hodgkin's B-cell lymphoma was made. Using high-field iMRI, the multi-image fusion-guided stereotactic brain biopsy allows for a higher positive rate of biopsy and a lower incidence of complications. The approach of combining multi-image fusion images with the frame-based stereotactic biopsy may be clinically useful for intracranial lesions of deep functional areas. PMID:25435963

  17. Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control

    Microsoft Academic Search

    Catharine A. Winstanley; Christelle Baunez; David E. H. Theobald; Trevor W. Robbins

    2005-01-01

    Although the subthalamic nucleus (STN) is involved in regulating motor function, and inactivation of this structure relieves the motor symptoms in Parkinsonian patients, recent data indicate that corticosubthalamic connections are involved in both the regulation of attention and the ability to withhold from responding. Considerable evidence suggests that the neural circuitry underlying such behavioural disinhibition or impulsive action can be

  18. Calcium binding protein in the basal ganglia system of a non-mammalian vertebrate: an immunohistochemical study in the reptile Caiman crocodilus.

    PubMed

    Brauth, S E; Kitt, C A; Gerfen, C R

    1988-06-14

    In Caiman, calbindin D28K immunoreactivity (CaBP) was observed within many neurons of the substantia nigra (SN) but only in the caudal portion of the area ventralis of Tsai (AVT). A dense CaBP fiber plexus showing some regional inhomogeneity was observed in the dorsolateral portion of the telencephalic ventrolateral area (VLA). These results are consistent with previous reports that the SN and AVT project to the dorsolateral and medial portions of the VLA, and strongly support the theory that the caiman VLA contains cell populations homologous to those found in the mammalian corpus striatum. PMID:3401743

  19. Role of high-field intraoperative magnetic resonance imaging on a multi-image fusion-guided stereotactic biopsy of the basal ganglia: A case report

    PubMed Central

    SUN, XIANG; CHEN, ZHIJUAN; YANG, SHUYUAN; ZHANG, JIANNING; YUE, SHUYUAN; WANG, ZENGGUANG; YANG, WEIDONG

    2015-01-01

    The aim of the present case study was to investigate the advantages of intraoperative magnetic resonance imaging (iMRI) on the real-time guidance and monitoring of a stereotactic biopsy. The study describes a patient with intracranial lesions, which were examined by conventional MRI and diffusion tensor imaging using a 1.5T intraoperative MRI system. The digital and pre-operative positron emission/computed tomography image data were transferred to a BrainLAB planning workstation, and a variety of images were automatically fused. The BrainLAB software was then used to reconstruct the corticospinal tract (CST) and create a three-dimensional display of the anatomical association between the CST and the brain lesions. A Leksell surgical planning workstation was used to identify the ideal target site and a reasonable needle track for the biopsy. The 1.5T iMRI was used to effectively monitor the intracranial condition during the brain biopsy procedure. Post-operatively, the original symptoms of the patient were not aggravated and no further neurological deficits were apparent. The histopathological diagnosis of non-Hodgkin’s B-cell lymphoma was made. Using high-field iMRI, the multi-image fusion-guided stereotactic brain biopsy allows for a higher positive rate of biopsy and a lower incidence of complications. The approach of combining multi-image fusion images with the frame-based stereotactic biopsy may be clinically useful for intracranial lesions of deep functional areas. PMID:25435963

  20. COGNITIVE DECISION PROCESSES OFTHE BASAL GANGLIA REWARD SYSTEM 303 * M. Shatner, G. Havazelet-Heimer, A. Raz, and Hagai Bergman, Department of Physiology and the

    E-print Network

    Friedman, Nir

    signature of reward) which is modulated by the fitness of the environment to the animal predictions. A major that decision-makers are risk averse, i.e. when facing two alternatives having the same expectancy. In particular, Kahneman and Tversky (1982) have conducted several experiments to test decision making under

  1. [Developmental abnormalities and nevi of the scalp].

    PubMed

    Behle, V; Hamm, H

    2014-12-01

    Unusual congenital or early-onset skin lesions on the scalp often pose a diagnostic challenge particularly as the clinical evaluation may be hampered by dense hair growth. Thus, this paper provides a concise review on developmental abnormalities and nevi with exclusive or predominant scalp localization. Aplasia cutis congenita occurs as an isolated finding, in association with genetic syndromes, nevi and anomalies or as a consequence of intrauterine trauma and teratogens. A hairless area with a narrow surrounding rim of hypertrichosis (hair collar sign) may point to occult cranial dysraphism, especially if accompanied by further suggestive signs as port-wine stains, large hemangiomas, dimples, congenital dermoid cysts, and sinuses. Many diverse entities may hide behind cutis verticis gyrata with the primary essential form being rare and representing a diagnosis of exclusion. In contrast to former belief, benign adnexal tumors arise in a nevus sebaceus considerably more often than basal cell carcinomas and other malignant epithelial tumors. Provided that tumor development is not suspected, excision of a nevus sebaceus nevus is indicated primarily for aesthetic-psychosocial reasons. However, surgical treatment is considerably easier in small children. Nevus sebaceus may be a cutaneous marker for several complex syndromes whereas nevus psiloliparus presents almost always in connection with encephalocraniocutaneous lipomatosis. Congenital melanocytic nevi of the scalp tend toward clinical regression, so that surgical intervention in large lesions should be carefully considered. In contrast, the threshold for excision of blue nevi and other conspicuous melanocytic nevi on the scalp should be low, especially since they are difficult to monitor. PMID:25298254

  2. Tuberculous meningitis: role of CT in management and prognosis

    Microsoft Academic Search

    D P Kingsley; W A Hendrickse; B E Kendall; M Swash; V Singh

    1987-01-01

    Serial computed tomographic scans were performed during the course of tuberculous meningitis in 25 patients aged 1-70 years. Hydrocephalus rarely occurred without other abnormalities. Marked ventricular enlargement was associated with extensive basal enhancement. Basal meningeal enhancement was not a good indicator of the clinical state although marked enhancement was a risk factor for the development of basal ganglia infarction. Infarcts

  3. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  4. Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

    PubMed Central

    Kim, Ji-Hyun; Ahn, Ji-Hyun; Kim, Soo-Kyung; Lee, Dae-Ho; Kim, Hye-Soon; Shon, Ho-Sang; Jeon, Hyun-Jeong; Kim, Tae-Hwa; Cho, Yong-Wook; Kim, Jae-Taek; Han, Sung-Min; Chung, Choon-Hee; Ryu, Ohk-Hyun; Lee, Jae-Min; Lee, Soon-Hee; Kwon, Min-Jeong; Kim, Tae-kyun; Namgoong, Il-Seong; Kim, Eun-Sook; Jung, In-Kyung; Moon, Sung-Dae; Han, Je-Ho; Kim, Chong-Hwa; Cho, Eun-Hee; Kim, Ki-Young; Park, Hee-Baek; Lee, Ki-Sang; Lee, Sung-Woo; Lee, Sang-Cheol; Kang, Cheol-Min; Jeon, Byung-Sook; Song, Min-Seop; Yun, Seung-Baik; Chung, Hyung-Keun; Seong, Jong-Ho; Jeong, Jin-Yi; Cha, Bong-Yun

    2015-01-01

    Aims/Introduction Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the ?-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. Materials and Methods The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. Results Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy. Conclusions Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone. PMID:25802730

  5. Somatic loss of p53 leads to stem/progenitor cell amplification in both mammary epithelial compartments, basal and luminal.

    PubMed

    Chiche, Aurélie; Moumen, Mejdi; Petit, Valérie; Jonkers, Jos; Medina, Daniel; Deugnier, Marie-Ange; Faraldo, Marisa M; Glukhova, Marina A

    2013-09-01

    Mammary epithelium comprises a layer of luminal cells and a basal myoepithelial cell layer. Both mammary epithelial compartments, basal and luminal, contain stem and progenitor cells, but only basal cells are capable of gland regeneration upon transplantation. Aberrant expansion of stem/progenitor cell populations is considered to contribute to breast tumorigenesis. Germline deletions of p53 in humans and mice confer a predisposition to tumors, and stem cell frequency is abnormally high in the mammary epithelium of p53-deficient mice. However, it is unknown whether stem/progenitor cell amplification occurs in both, basal and luminal cell populations in p53-deficient mammary tissue. We used a conditional gene deletion approach to study the role of p53 in stem/progenitor cells residing in the mammary luminal and basal layers. Using two- and three-dimensional cell culture assays, we showed that p53 loss led to the expansion of clonogenic stem/progenitor cells in both mammary epithelial cell layers. Moreover, following p53 deletion, luminal and basal stem/progenitor cells acquired a capacity for unlimited propagation in mammosphere culture. Furthermore, limiting dilution and serial transplantation assays revealed amplification and enhanced self-renewal in the basal regenerating cell population of p53-deficient mammary epithelium. Our data suggest that the increase in stem/progenitor cell activity may be, at least, partially mediated by the Notch pathway. Taken together, these results strongly indicate that p53 restricts the propagation and self-renewal of stem/progenitor cells in both layers of the mammary epithelium providing further insight into the impact of p53 loss in breast cancerogenesis. PMID:23712598

  6. High porosity of basal till at Burroughs glacier, southeastern Alaska

    SciTech Connect

    Ronnert, L.; Mickelson, D.M. (Univ. of Wisconsin, Madison (United States))

    1992-09-01

    Debris-rich basal ice at Burroughs glacier, southeastern Alaska, has 60 vol% to 70 vol% debris. Recently deposited basal till exceeds 60 vol% sediment with 30% to almost 40% porosity. Where basal ice is very rich in debris, basal till is deposited through melt out with only slight compaction of the debris. Porosity this high in till is commonly associated with subglacially deforming and dilated sediment. However, the recently deposited basal melt-out till at Burroughs glacier has not been deformed after deposition, but has porosity values similar to tills elsewhere interpreted to be subglacially deforming and dilated in an unfrozen state. High porosity can occur in basal melt-out till deposited directly by basal melt out.

  7. Evolution of sensory structures in basal metazoa.

    PubMed

    Jacobs, Dave K; Nakanishi, Nagayasu; Yuan, David; Camara, Anthony; Nichols, Scott A; Hartenstein, Volker

    2007-11-01

    Cnidaria have traditionally been viewed as the most basal animals with complex, organ-like multicellular structures dedicated to sensory perception. However, sponges also have a surprising range of the genes required for sensory and neural functions in Bilateria. Here, we: (1) discuss "sense organ" regulatory genes, including; sine oculis, Brain 3, and eyes absent, that are expressed in cnidarian sense organs; (2) assess the sensory features of the planula, polyp, and medusa life-history stages of Cnidaria; and (3) discuss physiological and molecular data that suggest sensory and "neural" processes in sponges. We then develop arguments explaining the shared aspects of developmental regulation across sense organs and between sense organs and other structures. We focus on explanations involving divergent evolution from a common ancestral condition. In Bilateria, distinct sense-organ types share components of developmental-gene regulation. These regulators are also present in basal metazoans, suggesting evolution of multiple bilaterian organs from fewer antecedent sensory structures in a metazoan ancestor. More broadly, we hypothesize that developmental genetic similarities between sense organs and appendages may reflect descent from closely associated structures, or a composite organ, in the common ancestor of Cnidaria and Bilateria, and we argue that such similarities between bilaterian sense organs and kidneys may derive from a multifunctional aggregations of choanocyte-like cells in a metazoan ancestor. We hope these speculative arguments presented here will stimulate further discussion of these and related questions. PMID:21669752

  8. Atlas: Cartilage Abnormalities and Scores

    Microsoft Academic Search

    Hans Liebl; Thomas M. Link

    \\u000a The following chapter illustrates cartilage abnormalities and provides semiquantitative scores for these lesions. The focus\\u000a of this chapter is on the most frequently used Recht (modified Noyes and Stabler) score [1, 2] and Whole-Organ-MRI-Score (WORMS)\\u000a [3]. These scores have been used in a number of previous studies and have been found helpful in assessing the grade of cartilage\\u000a lesions, in

  9. Effect of dobutamine stress on basal septal tissue dynamics in hypertensive patients with basal septal hypertrophy.

    PubMed

    Yalçin, F; Yigit, F; Erol, T; Baltali, M; Korkmaz, M E; Müderrisoglu, H

    2006-08-01

    Left ventricular outflow tract (LVOT) obstruction has been classically observed in hypertrophic cardiomyopathy in which the LVOT obstruction is associated with asymmetric septal hypertrophy producing a systolic pressure gradient across the LVOT. Basal septal hypertrophy (BSH) with hypertension may result in dynamic LVOT obstruction as well. It was suggested that regional hypertrophy may be related to enhanced ventricular dynamics. PMID:16761028

  10. Intraperitoneal administration of AAV9-shRNA inhibits target gene expression in the dorsal root ganglia of neonatal mice

    E-print Network

    2013-01-01

    root ganglia of neonatal mice. Molecular Pain 2013 9:36.Pain 2013, 9:36 http://www.molecularpain.com/content/9/1/36 target expression in neonatalthe neonatal period, when Machida et al. Molecular Pain

  11. Long-term safety, tolerability, and efficacy of vismodegib in two patients with metastatic basal cell carcinoma and basal cell nevus syndrome.

    PubMed

    Weiss, Glen J; Tibes, Raoul; Blaydorn, Lisa; Jameson, Gayle; Downhour, Molly; White, Erica; Caro, Ivor; Von Hoff, Daniel D

    2011-10-01

    Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC. PMID:25386306

  12. Long-term safety, tolerability, and efficacy of vismodegib in two patients with metastatic basal cell carcinoma and basal cell nevus syndrome

    PubMed Central

    Weiss, Glen J.; Tibes, Raoul; Blaydorn, Lisa; Jameson, Gayle; Downhour, Molly; White, Erica; Caro, Ivor; Von Hoff, Daniel D.

    2011-01-01

    Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC. PMID:25386306

  13. Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS11 in adult mice

    Microsoft Academic Search

    John P. Rossiter; Lena Hsu; Alan C. Jackson

    2009-01-01

    The involvement of dorsal root ganglia was studied in an in vivo model of experimental rabies virus infection using the challenge\\u000a virus standard (CVS-11) strain. Dorsal root ganglia neurons infected with CVS in vitro show prolonged survival and few morphological\\u000a changes, and are commonly used to study the infection. It has been established that after peripheral inoculation of mice with

  14. Developmental patterns of caspase-3, bax and bcl-2 proteins expression in the human spinal ganglia

    Microsoft Academic Search

    Katarina Vukojevic; Dominko Carev; Damir Sapunar; Danijel Petrovic; Mirna Saraga-Babic

    2008-01-01

    The distribution of the bcl-2, bax and caspase-3 proteins was investigated in the cells of developing human spinal ganglia.\\u000a Paraffin sections of 10 human conceptuses between 5th and 9th gestational weeks were analysed morphologically, immunohistochemically\\u000a and by TUNEL-method. Cells positive to caspase-3 had brown stained nuclei or nuclear fragmentations. At earliest stages, 6%\\u000a of ganglion population were caspase-3 positive cells.

  15. [Heart-stimulating neurons in the subesophageal ganglia of the African snail Achatina fulica Férussac].

    PubMed

    Zhuravlev, V L; Kadyrov, S A; Bychkov, R E; Safonova, T A; D'iakov, A A

    1994-09-01

    5 cardiostimulating neurons belonging to 3 different functional groups were studied in visceral and right parietal ganglia of the African snail. The cell VG-1 formerly believed to be an interneuron, was shown to be a motoneuron of the heart producing the EPSPs in the myocardium. The data obtained show a considerable similarity in organization of the cardioregulating neurons system in different species of the gastropods. PMID:7536580

  16. Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

    PubMed Central

    Suadicani, Sylvia O.; Cherkas, Pavel S.; Zuckerman, Jonathan; Smith, David N.; Spray, David C.; Hanani, Menachem

    2010-01-01

    Astrocytes communicate with neurons, endothelial and other glial cells through transmission of intercellular calcium signals. Satellite glial cells (SGCs) in sensory ganglia share several properties with astrocytes, but whether this type of communication occurs between SGCs and sensory neurons has not been explored. In the present work we used cultured neurons and SGCs from mouse trigeminal ganglia to address this question. Focal electrical or mechanical stimulation of single neurons in trigeminal ganglion cultures increased intracellular calcium concentration in these cells and triggered calcium elevations in adjacent glial cells. Similar to neurons, SGCs responded to mechanical stimulation with increase in cytosolic calcium that spread to the adjacent neuron and neighboring glial cells. Calcium signaling from SGCs to neurons and among SGCs was diminished in the presence of the broad-spectrum P2 receptor antagonist suramin (50 µM) or in the presence of the gap junction blocker carbenoxolone (100 µM), whereas signaling from neurons to SGCs was reduced by suramin, but not by carbenoxolone. Following induction of submandibular inflammation by Complete Freund’s Adjuvant injection, the amplitude of signaling among SGCs and from SGCs to neuron was increased, whereas the amplitude from neuron to SGCs was reduced. These results indicate for the first time the presence of bidirectional calcium signaling between neurons and SGCs in sensory ganglia cultures, which is mediated by the activation of purinergic P2 receptors, and to some extent by gap junctions. Furthermore, the results indicate that not only sensory neurons, but also SGCs release ATP. This form of intercellular calcium signaling likely plays key roles in the modulation of neuronal activity within sensory ganglia in normal and pathological states. PMID:19891813

  17. Quantitative reduction of the perineuronal glial sheath in the spinal ganglia of aged rabbits

    Microsoft Academic Search

    Ennio Pannese; Carla Martinelli; Patrizia Sartori

    1996-01-01

    We carried out morphometric studies, using the electron microscope, on the nerve cell bodies and the enveloping satellite\\u000a cell sheaths from spinal ganglia of young adult and aged rabbits. We found that the volume ratio between the satellite cell\\u000a sheaths and the related nerve cell bodies was significantly smaller in the aged animals. It is known that satellite cells\\u000a play

  18. Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts

    Microsoft Academic Search

    L. Zerboni; M. Reichelt; A. Arvin

    \\u000a Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster.\\u000a VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis\\u000a by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which\\u000a to examine VZV neurotropism. Experimental

  19. Pain-related mediators underlie incision-induced mechanical nociception in the dorsal root ganglia

    PubMed Central

    Yuan, Xiuhong; Liu, Xiangyan; Tang, Qiuping; Deng, Yunlong

    2013-01-01

    Approximately 50–70% of patients experience incision-induced mechanical nociception after surgery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether interleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical nociception remains uncertain. In this study, forty rats were divided randomly into the incision surgery (n = 32) and sham surgery (n = 8) groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group received anesthesia, but not an incision. Von Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord (L3–5) showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons (diameter < 20 ?m and 20–40 ?m) and satellite cells in the dorsal root ganglia of the spinal cord (L3–5) in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons (diameter > 40 ?m) at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by incision surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to mechanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by incision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws. PMID:25206654

  20. Satellite glial cells in dorsal root ganglia are activated in streptozotocin-treated rodents

    PubMed Central

    Hanani, Menachem; Blum, Erez; Liu, Shuangmei; Peng, Lichao; Liang, Shangdong

    2014-01-01

    Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ-treatment the number of neurons surrounded with GFAP-positive SGCs in dorsal root ganglia increased 4-fold in mice and 5-fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2-fold in STZ-treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target. PMID:25312986