Sample records for abnormal basal ganglia

  1. Abnormal microstructures of the basal ganglia in schizophrenia revealed by diffusion tensor imaging.

    PubMed

    Hashimoto, Ryota; Mori, Takeyuki; Nemoto, Kiyotaka; Moriguchi, Yoshiya; Noguchi, Hiroko; Nakabayashi, Tetsuo; Hori, Hiroaki; Harada, Seiichi; Kunugi, Hiroshi; Saitoh, Osamu; Ohnishi, Takashi

    2009-01-01

    There has been a hypothesis that deficits in the basal ganglia-thalamic system may play an important role in the dysfunctional goal-directed behaviour in schizophrenia. By using diffusion tensor imaging, we measured fractional anisotropy (FA) values in the basal ganglia-thalamic system in 42 schizophrenics and 42 matched controls to investigate microstructural tissue alterations in the basal ganglia-thalamic system in schizophrenia. Schizophrenics had significantly lower FA values in the bilateral globus pallidus and left thalamus compared to controls, suggesting that schizophrenics might have microstructural abnormalities in globus pallidus and thalamus. These data support the notion that myelination abnormalities in basal ganglia-thalamic system are related to the pathophysiology of schizophrenia. PMID:19253093

  2. Role of movement in long-term basal ganglia changes: implications for abnormal motor responses.

    PubMed

    Simola, Nicola; Morelli, Micaela; Frazzitta, Giuseppe; Frau, Lucia

    2013-01-01

    Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson's disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management. PMID:24167489

  3. Role of movement in long-term basal ganglia changes: implications for abnormal motor responses

    PubMed Central

    Simola, Nicola; Morelli, Micaela; Frazzitta, Giuseppe; Frau, Lucia

    2013-01-01

    Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson’s disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management. PMID:24167489

  4. Imaging basal ganglia function

    PubMed Central

    BROOKS, DAVID J.

    2000-01-01

    In this review, the value of functional imaging for providing insight into the role of the basal ganglia in motor control is reviewed. Brain activation findings in normal subjects and Parkinson's disease patients are examined and evidence supporting the existence for functionally independent distributed basal ganglia-frontal loops is presented. It is argued that the basal ganglia probably act to focus and filter cortical output, optimising the running of motor programs. PMID:10923986

  5. Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1?/? Mice

    PubMed Central

    Lim, Soo-Yeon; Mah, Won

    2015-01-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2–3 months old) and juvenile (4 weeks old) Git1?/? mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in Git1?/? mice. PMID:25997734

  6. Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1 (-/-) Mice.

    PubMed

    Lim, Soo-Yeon; Mah, Won

    2015-06-30

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2-3 months old) and juvenile (4 weeks old) Git1 (-/-) mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in Git1 (-/-) mice. PMID:25997734

  7. Neuropsychiatry of the basal ganglia

    PubMed Central

    Ring, H; Serra-Mestres, J

    2002-01-01

    This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are important links between parts of the brain that have classically been considered to be related to emotional functioning and brain regions previously considered to have largely motor functions. The basal ganglia have a role in the development and integration of psychomotor behaviours, involving motor functions, memory and attentional mechanisms, and reward processes. PMID:11784818

  8. [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

  9. 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's disease. In addition, the basal ganglia have been implicated in a range of neuropsychiatric disorders, and basal ganglia function is disrupted in addictive states. The basal ganglia are also thought to have

  10. Basal ganglia echogenicity in tauopathies.

    PubMed

    Sadowski, Krzysztof; Serafin-Król, Ma?gorzata; Szlachta, Karol; Friedman, Andrzej

    2015-06-01

    Accumulating data confirm the usefulness of transcranial sonography (TCS) in the diagnosis of Parkinson's disease. The relevance of basal ganglia abnormalities depicted by TCS in atypical parkinsonian syndromes still needs further assessment. In the present study, 20 patients with progressive supranuclear palsy (PSP) and 13 patients with corticobasal syndrome (CBS) were studied with the use of transcranial sonography. Echogenicity of the substantia nigra (SN) and lenticular nucleus (LN) were assessed. 0/20 patients with PSP and 8/12 (66.6 %) patients with CBS were characterized with SN hyperechogenicity. LN hyperechogenicity was observed in 9/20 patients diagnosed with PSP and 0/11 of CBS patients. The combination of SN isoechogenicity and LN hyperechogenicity reached 100 % sensitivity and positive predictive value for the diagnosis of PSP. The results of this study point out that CBS has to be taken into consideration when SN hyperechogenicity is depicted in a patient with parkinsonian syndrome. Normal echogenicity of the SN coexisting with LN hyperechogenicity practically excludes CBS. PMID:25204278

  11. [Motor control by the basal ganglia].

    PubMed

    Takakusaki, Kaoru

    2009-06-01

    The cerebral cortex controls cognitive and voluntary process of movements. The brainstem and spinal cord are involved in the execution of innately acquired motor patterns such as postural reflexes, muscle tone regulation and locomotion. Cortico-reticular projections arising from the motor cortical areas contribute to the postural control that precedes the voluntary movement process. The basal ganglia cooperatively regulates the activities of the cerebral cortex and the brainstem-spinal cord by its strong inhibitory and dis-inhibitory effects upon these target structures so that goal-directed movements could be appropriately performed. We propose that basal ganglia disfunction, including the abnormality in the dopaminergic projection system, may disturb the cooperative regulation, resulting in motor deficiencies expressed in basal diseases. PMID:19618841

  12. 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…

  13. Behavioral abnormalities and circuit defects in the basal ganglia of a mouse model of 16p11.2 deletion syndrome.

    PubMed

    Portmann, Thomas; Yang, Mu; Mao, Rong; Panagiotakos, Georgia; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L; Grueter, Brad A; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L; Zhengqui, Zhou; Miller, Michael A; Lerch, Jason P; Henkelman, R Mark; Shamloo, Mehrdad; Malenka, Robert C; Crawley, Jacqueline N; Dolmetsch, Ricardo E

    2014-05-22

    A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. PMID:24794428

  14. Functional Neuroanatomy of the Basal Ganglia

    PubMed Central

    Lanciego, José L.; Luquin, Natasha; Obeso, José A.

    2012-01-01

    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field. PMID:23071379

  15. Action, time and the basal ganglia

    PubMed Central

    Yin, Henry H.

    2014-01-01

    The ability to control the speed of movement is compromised in neurological disorders involving the basal ganglia, a set of subcortical cerebral nuclei that receive prominent dopaminergic projections from the midbrain. For example, bradykinesia, slowness of movement, is a major symptom of Parkinson's disease, whereas rapid tics are observed in patients with Tourette syndrome. Recent experimental work has also implicated dopamine (DA) and the basal ganglia in action timing. Here, I advance the hypothesis that the basal ganglia control the rate of change in kinaesthetic perceptual variables. In particular, the sensorimotor cortico-basal ganglia network implements a feedback circuit for the control of movement velocity. By modulating activity in this network, DA can change the gain of velocity reference signals. The lack of DA thus reduces the output of the velocity control system which specifies the rate of change in body configurations, slowing the transition from one body configuration to another. PMID:24446506

  16. Computer Modeling in Basal Ganglia Disorders

    Microsoft Academic Search

    José Luis Contreras-Vidal

    The last two decades have witnessed an increasing interest in the use of computational modeling and mathematical analysis\\u000a as tools to unravel the complex neural mechanisms and computational algorithms underlying the function of the basal ganglia\\u000a and related structures under normal and neurological conditions (1–3). Computational modeling of basal ganglia disorders has until recently been focused on Parkinson’s disease (PD),

  17. THE BASAL GANGLIA: FOCUSED SELECTION AND INHIBITION OF COMPETING MOTOR PROGRAMS

    Microsoft Academic Search

    JONATHAN W MINK

    1996-01-01

    The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these abnormalities. However, it has not

  18. Basal Ganglia calcification in mitochondrial disorders.

    PubMed

    Finsterer, Josef; Kopsa, Wolfgang

    2005-09-01

    Though basal ganglia calcification (BGC) has been recognized as a feature of mitochondriopathy, little is known about its frequency in a larger cohort. The aim of this work was to assess the frequency of BGC, type and frequency of clinical and additional imaging central-nervous-system (CNS) abnormalities and of non-CNS abnormalities in mitochondriopathy patients with BGC. Retrospectively reviewed were the records of all mitochondriopathy patients in whom BGC was found on cerebral CT during 10 years. Among those who underwent cerebral CT, thirty-six, 24 women, 12 men, aged 33-93 years, showed BGC. The most frequent clinical CNS manifestations in these patients were epilepsy (n = 9), Parkinson syndrome (n = 9), dementia (n = 7), dysarthria (n = 5), spasticity (n = 4), tremor (n = 4), or stroke (n = 4). Additional cerebral CT-findings were atrophy (n = 10), lacunas (n = 6), leucaraiosis (n = 6), focal gliosis (n = 4), or stroke (n = 1). MR imaging, carried out in 12 patients, confirmed BGC in one. The 36 patients presented with involvement of the CNS (n = 32), endocrine system (n = 29), peripheral nervous system (n = 28), heart (n = 23), inner ear (n = 16), eyes (n = 15), guts (n = 11), blood (n = 9), kidney (n = 2), or dermis (n = 2). BGC occurs in one sixth of non-selected patients with mitochondriopathy and is associated with clinical and imaging CNS abnormalities and multisystem disease in the majority of them. PMID:16167199

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

    E-print Network

    Graybiel, Ann M.

    of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute in disease states affecting the basal ganglia. q 2004 Published by Elsevier Ltd. Keywords: Basal ganglia is part of the habit-forming system of the mammalian brain, and that abnormal activation of striatal

  20. GABAergic output of the basal ganglia

    Microsoft Academic Search

    O. Hikosaka

    2007-01-01

    Using GABAergic outputs from the SNr or GPi, the basal ganglia exert inhibitory control over several motor areas in the brainstem which in turn control the central pattern generators for the basic motor repertoire including eye–head orientation, locomotion, mouth movements, and vocalization. These movements are by default kept suppressed by tonic rapid firing of SNr\\/GPi neurons, but can be released

  1. 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.

  2. Cysticercosis lesions in basal ganglia are common but clinically silent.

    PubMed

    Cosentino, Carlos; Velez, Miriam; Torres, Luis; Garcia, Hector H

    2002-01-01

    Movement disorders due to basal ganglia involvement by neurocysticercosis are rarely seen. To evaluate the frequency of basal ganglia location of cysticercotic cysts and its clinical manifestations, baseline MRI scans of 120 consecutive patients with active neurocysticercosis were reviewed and the presence and number of active cysticercosis lesions (viable cysts or enhancing lesions) in the basal ganglia were recorded and correlated with demographic and clinical data. Basal ganglia involvement was found in 32 cases (26.7%). The frequency of lesions in basal ganglia was related to the total number of lesions, ranging from 5% of patients with a single cysticerci, to 60% in patients with more than five parasites. Putamen and caudate nuclei were the most frequent sites of lesions. No significant difference between both hemispheres was observed. Basal ganglia localization is common in neurocysticercosis but it is rarely associated with clinical manifestations. PMID:11792479

  3. Functional changes of the basal ganglia circuitry in Parkinson's disease

    Microsoft Academic Search

    Fabio Blandini; Giuseppe Nappi; Cristina Tassorelli; Emilia Martignoni

    2000-01-01

    The basal ganglia circuitry processes the signals that flow from the cortex, allowing the correct execution of voluntary movements. In Parkinson's disease, the degeneration of dopaminergic neurons of the substantia nigra pars compacta triggers a cascade of functional changes affecting the whole basal ganglia network. The most relevant alterations affect the output nuclei of the circuit, the medial globus pallidus

  4. Metabotropic glutamate receptors in the basal ganglia motor circuit

    Microsoft Academic Search

    Giuseppe Battaglia; Michael J. Marino; Ferdinando Nicoletti; P. Jeffrey Conn

    2005-01-01

    In recent years there have been tremendous advances in our understanding of the circuitry of the basal ganglia and our ability to predict the behavioural effects of specific cellular changes in this circuit on voluntary movement. These advances, combined with a new understanding of the rich distribution and diverse physiological roles of metabotropic glutamate receptors in the basal ganglia, indicate

  5. 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

  6. Basal Ganglia Volume and Shape in Children With Attention Deficit Hyperactivity Disorder

    PubMed Central

    Qiu, Anqi; Crocetti, Deana; Adler, Marcy; Mahone, E. Mark; Denckla, Martha B.; Miller, Michael I.; Mostofsky, Stewart H.

    2010-01-01

    Objective Volumetric abnormalities of basal ganglia have been associated with attention deficit hyperactivity disorder (ADHD), especially in boys. To specify localization of these abnormalities, large deformation diffeomorphic metric mapping (LDDMM) was used to examine the effects of ADHD, sex, and their interaction on basal ganglia shapes. Method The basal ganglia (caudate, putamen, globus pallidus) were manually delineated on magnetic resonance imaging from 66 typically developing children (35 boys) and 47 children (27 boys) with ADHD. LDDMM mappings from 35 typically developing children were used to generate basal ganglia templates. Shape variations of each structure relative to the template were modeled for each subject as a random field using Laplace-Beltrami basis functions in the template coordinates. Linear regression was used to examine group differences in volumes and shapes of the basal ganglia. Results Boys with ADHD showed significantly smaller basal ganglia volumes compared with typically developing boys, and LDDMM revealed the groups remarkably differed in basal ganglia shapes. Volume compression was seen bilaterally in the caudate head and body and anterior putamen as well as in the left anterior globus pallidus and right ventral putamen. Volume expansion was most pronounced in the posterior putamen. No volume or shape differences were revealed in girls with ADHD. Conclusions The shape compression pattern of basal ganglia in boys with ADHD suggests that ADHD-associated deviations from typical brain development involve multiple frontal-subcortical control loops, including circuits with premotor, oculomotor, and prefrontal cortices. Further investigations employing brain-behavior analyses will help to discern the task-dependent contributions of these circuits to impaired response control that is characteristic of ADHD. PMID:19015232

  7. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

    Chen, Christopher H.; Fremont, Rachel; Arteaga-Bracho, Eduardo E.; Khodakhah, Kamran

    2014-01-01

    The graceful, purposeful motion of our body is an engineering feat which remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. Here we show in mice that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway. Under physiological conditions this short latency pathway is capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition this pathway relays aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  8. Neural Representation of Time in Cortico-basal Ganglia Circuits

    E-print Network

    Jin, Dezhe Z.

    Encoding time is universally required for learning and structuring motor and cognitive actions, but how the brain keeps track of time is still not understood. We searched for time representations in cortico-basal ganglia ...

  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. Cognitive-motor interactions of the basal ganglia in development.

    PubMed

    Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

  11. Reassessing Models of Basal Ganglia Function and Dysfunction

    PubMed Central

    Nelson, Alexandra B.; Kreitzer, Anatol C.

    2015-01-01

    The basal ganglia are a series of interconnected subcortical nuclei. The function and dysfunction of these nuclei has been studied intensively as it pertains to motor control, but more recently our knowledge of these functions has broadened to include prominent roles in cognition and affective control. This review will summarize historical models of basal ganglia function, findings which have supported or conflicted with these models, and emphasize recent work in animals and humans directly testing the hypotheses generated by these models. PMID:25032493

  12. Risk Factors for Silent Cerebral Infarcts in Subcortical White Matter and Basal Ganglia

    Microsoft Academic Search

    Toshiyuki Uehara; Masayasu Tabuchi; Etsuro Mori

    Background and Purpose—The purpose of this study was to clarify whether the relevant risk factors for silent cerebral infarcts (SCIs) in subcortical white matter (WM) are different from those in the basal ganglia (BG). Methods—Subjects of this study were 219 adults without a history of stroke or transient ischemic attack and without any abnormality on a neurological examination who consecutively

  13. Basal ganglia calcification in BB/E rats with diabetes.

    PubMed

    Lammie, G A; Kelly, P A T; Baird, J D; Smith, W; Chatterjee, S; Frier, B M; Strachan, M W J

    2005-01-01

    Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline. PMID:15639413

  14. ARCHIVAL REPORT Impaired Prefrontal-Basal Ganglia Functional

    E-print Network

    ARCHIVAL REPORT Impaired Prefrontal-Basal Ganglia Functional Connectivity and Substantia Nigra-evoked hyperactivity of the substantia nigra that occurred in association with prefrontal and striatal hypoactivity, substantia nigra T wo cornerstones of our emerging understanding of schizo- phrenia are the role of excess

  15. Is Broca's Area Part of a Basal Ganglia Thalamocortical Circuit?

    Microsoft Academic Search

    Michael T. Ullman

    2006-01-01

    The cortex constituting Broca's area does not exist in isolation. Rather, like other cortical regions, Broca's area is connected to other brain structures, which likely play closely related functional roles. This paper focuses on the basal ganglia, a set of subcortical structures that project through topographically organized “channels” via the thalamus to different frontal regions. It is hypothesized that the

  16. Hypersexuality and Stroke: A Role for the Basal Ganglia?

    Microsoft Academic Search

    Richard B. Libman; Elzbieta J. Wirkowski

    1996-01-01

    Hyposexuality after stroke has been frequently observed, but hypersexuality as a sequela of stroke has been less commonly documented. Damage to limbic structures, especially in the temporal lobes, has been thought to play a crucial role in this clinical syndrome. The possible importance of the basal ganglia in the production of hypersexuality has been infrequently recognized despite numerous connections with

  17. Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidium in basal ganglia circuitry

    Microsoft Academic Search

    André Parent; Lili-Naz Hazrati

    1995-01-01

    The subthalamic nucleus and the external pallidum (GPe) are classically viewed as part of the so-called indirect pathway, which acts in concert with the direct pathway. The direct and indirect pathways form the conceptual framework of the anatomical and functional organization of the basal ganglia. A review of recent data regarding the connections of the subthalamic nucleus and the GPe

  18. Basal Ganglia Plus Insula Damage Yields Stronger Disruption of Smoking Addiction Than Basal Ganglia Damage Alone

    PubMed Central

    2014-01-01

    Introduction: The main objective of this study was to elucidate the importance of the basal ganglia (BG) and insula (INS) for nicotine addiction and smoking behavior. Methods: We used a lesion study examining the effects of BG and INS damage on changes in smoking behavior and nicotine dependence over time in a prospective manner. We studied whether combined BG and INS damage yields more substantial disruption of smoking and nicotine dependence than damage to the BG alone and compared with damage to other brain regions outside the BG and INS (brain-damaged comparison [BDC] group). We obtained neuroanatomical and behavioral data for 63 neurological patients with stroke at 1 month after onset and at 3-, 6-, and 12-month follow-ups. All patients were smokers at lesion onset. Results: The BG and BG + INS groups had significantly higher and more sustained rates of smoking cessation than patients with damage elsewhere. By 12 months after onset, only 14.3% of the patients in the BDC group were classified as nonsmokers. In the BG group, 37% were not smoking by the 12-month follow-up, and in the BG + INS group, smoking cessation was even more pronounced, as 75% of this group was not smoking at the 12-month epoch. Conclusions: The findings show that damage to the BG alone can cause disruption of smoking addiction, and when BG damage is combined with INS damage, the disruption increases. The latter finding is consistent with the proposal that the INS has a key role in smoking addiction. PMID:24169814

  19. Cerebellar networks with the cerebral cortex and basal ganglia

    PubMed Central

    Bostan, Andreea C.; Dum, Richard P.; Strick, Peter L.

    2013-01-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent results from neuroanatomical, behavioral and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that the output from the cerebellum reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, indicating that the two subcortical structures are part of a densely interconnected network. Altogether, these results provide the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  20. The vestibular-basal ganglia connection: balancing motor control.

    PubMed

    Stiles, Lucy; Smith, Paul F

    2015-02-01

    Connections between the vestibular system and the basal ganglia have been sporadically studied over the last century. Electrophysiological studies of field potentials in animals have shown that most areas of the striatum respond to electrical vestibular stimulation while human studies isolated responses to vestibular stimulation to the putamen of the striatum. Protein studies have shown inconsistent results regarding changes in receptor levels of a number of receptor types. Recent tracer studies identified a pathway between the vestibular nucleus and the striatum via the thalamus, completely bypassing the cortex. Vestibular sensory input is represented in the part of the striatum - the dorsolateral striatum - where fibres from the sensorimotor areas terminate. It is therefore possible that vestibular signals are used together with other sensorimotor inputs in the striatum for body and limb control. The combination of electrophysiological results, changes in protein levels and tracer studies have led to the idea that the dorsolateral striatum is likely to be the main input area for vestibular signals in the basal ganglia and these will have an influence on motor control. This may have clinical implications in the treatment of basal ganglia disorders and other movement disorders. PMID:25498858

  1. Echogenicity of basal ganglia structures in different Huntington's disease phenotypes.

    PubMed

    Saft, Carsten; Hoffmann, Rainer; Strassburger-Krogias, Katrin; Lücke, Thomas; Meves, Saskia H; Ellrichmann, Gisa; Krogias, Christos

    2015-06-01

    In Huntington's disease (HD), a neurodegenerative-inherited disease, chorea as the typical kind of movement disorder is described. Beside chorea, however, all other kinds of movement disturbances, such as bradykinesia, dystonia, tremor or myoclonus can occur. Aim of the current study was to investigate alterations in the echogenicity of basal ganglia structures in different Huntington's disease phenotypes. 47 patients with manifest and genetically confirmed HD were recruited. All participants underwent a thorough neurological examination. According to a previously described method, classification into predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes was performed depending on subscores of the Unified Huntington's Disease Rating Scale. In addition, findings in juvenile HD were compared to adult HD. Transcranial sonography was performed by investigators blinded to clinical classification. There were no significant differences in basal ganglia echogenicities between the three phenotypes. Size of echogenic area of substantia nigra (SN) correlated positively with CAG repeat and bradykinesia subscore, and negatively with age of onset and chorea subscore. Comparing juvenile and adult HD subtypes, SN hyperechogenicity was significantly more often detectable in the juvenile form (100 vs. 29.3 %, p = 0.002). Regarding echogenicity of caudate or lentiform nuclei, no significant differences were detected. HD patients with the juvenile variant exhibit marked hyperechogenicity of substantia nigra. No significant differences in basal ganglia echogenicities between predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes were detected. PMID:25503829

  2. Correlation transfer from basal ganglia to thalamus in Parkinson's disease

    PubMed Central

    Pamela, Reitsma; Brent, Doiron; Jonathan, Rubin

    2011-01-01

    Spike trains from neurons in the basal ganglia of parkinsonian primates show increased pairwise correlations, oscillatory activity, and burst rate compared to those from neurons recorded during normal brain activity. However, it is not known how these changes affect the behavior of downstream thalamic neurons. To understand how patterns of basal ganglia population activity may affect thalamic spike statistics, we study pairs of model thalamocortical (TC) relay neurons receiving correlated inhibitory input from the internal segment of the globus pallidus (GPi), a primary output nucleus of the basal ganglia. We observe that the strength of correlations of TC neuron spike trains increases with the GPi correlation level, and bursty firing patterns such as those seen in the parkinsonian GPi allow for stronger transfer of correlations than do firing patterns found under normal conditions. We also show that the T-current in the TC neurons does not significantly affect correlation transfer, despite its pronounced effects on spiking. Oscillatory firing patterns in GPi are shown to affect the timescale at which correlations are best transferred through the system. To explain this last result, we analytically compute the spike count correlation coefficient for oscillatory cases in a reduced point process model. Our analysis indicates that the dependence of the timescale of correlation transfer is robust to different levels of input spike and rate correlations and arises due to differences in instantaneous spike correlations, even when the long timescale rhythmic modulations of neurons are identical. Overall, these results show that parkinsonian firing patterns in GPi do affect the transfer of correlations to the thalamus. PMID:22355287

  3. Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence

    PubMed Central

    Wang, Tiebin; Jing, Wei; Xia, Yang; Xu, Peng; Luo, Cheng; Valdes-Sosa, Pedro A.; Yao, Dezhong

    2014-01-01

    Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. PMID:24626189

  4. 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

  5. Basal ganglia-premotor dysfunction during movement imagination in writer's cramp.

    PubMed

    Castrop, Florian; Dresel, Christian; Hennenlotter, Andreas; Zimmer, Claus; Haslinger, Bernhard

    2012-09-15

    The pathophysiology of idiopathic focal hand dystonia (writer's cramp) is characterized by deficient inhibitory basal ganglia function and altered cortical sensorimotor processing. To explore if this is already a primary finding in dystonia for internal movement simulation independent of dystonic motor output or abnormal sensory input, we investigated the neural correlates of movement imagination and observation in patients with writer's cramp. Event-related fMRI was applied during kinesthetic motor imagery of drawing simple geometric figures (imagination task) and passively observing videos of hands drawing identical figures (observation task). Compared with healthy controls, patients with writer's cramp showed deficient activation of the left primary sensorimotor cortex, mesial and left dorsal premotor cortex, bilateral putamen, and bilateral thalamus during motor imagery. No significant signal differences between both groups were found during the observation task. We conclude that internal movement simulation and planning as tested during imagination of hand movements appear to be dysfunctional in patients with writer's cramp, whereas visual signal processing and observation-induced activation are unaffected. Deficient basal ganglia-premotor activation could be a correlate of impaired basal ganglia inhibition and focusing during the selection of motor programs in dystonia. This finding seems to be an intrinsic deficit, as it is found during motor imagery in the absence of dystonic symptoms. PMID:22328061

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

    Microsoft Academic Search

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

    2010-01-01

    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

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

    Microsoft Academic Search

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

    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

  8. Neural circuits and topographic organization of the basal ganglia and related regions

    Microsoft Academic Search

    Katsuma Nakano

    2000-01-01

    The present review was attempted to analyze the multiple channels of basal ganglia-thalamocortical connections, and the connections of their related nuclei. The prefrontal and motor areas consist of a number of modules, which seem to provide multiple subloops of the basal ganglia-thalamocortical connections in subhuman primates. There may be a great degree of convergence of the limbic, associative and motor

  9. Motor sequences and the basal ganglia: Kinematics, not habits

    PubMed Central

    Desmurget, Michel; Turner, Robert S.

    2010-01-01

    Despite a lack of definitive evidence, it is frequently proposed that the Basal Ganglia (BG) motor circuit plays a critical role in the storage and execution of movement sequences (or motor habits). To test this hypothesis directly, we inactivated the sensorimotor territory of the globus pallidus internus (sGPi, the main BG motor output) in two monkeys trained to perform overlearned and random sequences of four out-and-back reaching movements directed to visual targets. Infusion of muscimol (a GABAA agonist) into sGPi caused dysmetria and slowing of individual movements, but these impairments were virtually identical for overlearned and random sequences. The fluid predictive execution of learned sequences and the animals’ tendency to reproduce the sequence pattern in random trials was preserved following pallidal blockade. These results suggest the BG motor circuit contributes to motor execution, but not to motor sequencing or the storage of overlearned serial skills. PMID:20519543

  10. Basal Ganglia MR Relaxometry in Obsessive-Compulsive Disorder: T2 Depends Upon Age of Symptom Onset

    PubMed Central

    Hubbard, Emily; Hassenstab, Jason; Yip, Agustin; Vymazal, Josef; Herynek, Vit; Giedd, Jay; Murphy, Dennis L.; Greenberg, Benjamin D.

    2010-01-01

    Dysfunction in circuits linking frontal cortex and basal ganglia (BG) is strongly implicated in obsessive-compulsive disorder (OCD). On MRI studies, neuropsychiatric disorders with known BG pathology have abnormally short T2 relaxation values (a putative biomarker of elevated iron) in this region. We asked if BG T2 values are abnormal in OCD. We measured volume and T2 and T1 relaxation rates in BG of 32 adults with OCD and 33 matched controls. There were no group differences in volume or T1 values in caudate, putamen, or globus pallidus (GP). The OCD group had lower T2 values (suggesting higher iron content) in the right GP, with a trend in the same direction for the left GP. This effect was driven by patients whose OCD symptoms began from around adolescence to early adulthood. The results suggest a possible relationship between age of OCD onset and iron deposition in the basal ganglia. PMID:20503112

  11. Parallel basal ganglia circuits for voluntary and automatic behaviour to reach rewards.

    PubMed

    Kim, Hyoung F; Hikosaka, Okihide

    2015-07-01

    The basal ganglia control body movements, value processing and decision-making. Many studies have shown that the inputs and outputs of each basal ganglia structure are topographically organized, which suggests that the basal ganglia consist of separate circuits that serve distinct functions. A notable example is the circuits that originate from the rostral (head) and caudal (tail) regions of the caudate nucleus, both of which target the superior colliculus. These two caudate regions encode the reward values of visual objects differently: flexible (short-term) values by the caudate head and stable (long-term) values by the caudate tail. These value signals in the caudate guide the orienting of gaze differently: voluntary saccades by the caudate head circuit and automatic saccades by the caudate tail circuit. Moreover, separate groups of dopamine neurons innervate the caudate head and tail and may selectively guide the flexible and stable learning/memory in the caudate regions. Studies focusing on manual handling of objects also suggest that rostrocaudally separated circuits in the basal ganglia control the action differently. These results suggest that the basal ganglia contain parallel circuits for two steps of goal-directed behaviour: finding valuable objects and manipulating the valuable objects. These parallel circuits may underlie voluntary behaviour and automatic skills, enabling animals (including humans) to adapt to both volatile and stable environments. This understanding of the functions and mechanisms of the basal ganglia parallel circuits may inform the differential diagnosis and treatment of basal ganglia disorders. PMID:25981958

  12. Genetic screening and functional characterization of PDGFRB mutations associated with basal ganglia calcification of unknown etiology.

    PubMed

    Sanchez-Contreras, Monica; Baker, Matthew C; Finch, NiCole A; Nicholson, Alexandra; Wojtas, Aleksandra; Wszolek, Zbigniew K; Ross, Owen A; Dickson, Dennis W; Rademakers, Rosa

    2014-08-01

    Three causal genes for idiopathic basal ganglia calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet-derived growth factor receptor family type ?, and PDGFB, encoding PDGF-B, the specific ligand of PDGFR?, were found implicating the PDGF-B/PDGFR? pathway in abnormal brain calcification. In this study, we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFR? and two previously reported mutants, p.L658P and p.R987W PDGFR? in cell culture. We show that, in response to PDGF-BB stimulation, the p.L658P mutation completely suppresses PDGFR? autophosphorylation, whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC. PMID:24796542

  13. Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia

    PubMed Central

    Stoessl, A. Jon; Lehericy, Stephane; Strafella, Antonio P.

    2015-01-01

    Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson’s disease from healthy controls, and show great promise for differentiation between Parkinson’s disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson’s disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson’s disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression. PMID:24954673

  14. 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

  15. Cytokine Effects on the Basal Ganglia and Dopamine Function: the Subcortical Source of Inflammatory Malaise

    PubMed Central

    Felger, Jennifer C.; Miller, Andrew H.

    2012-01-01

    Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. PMID:23000204

  16. A spiking neural network based on the basal ganglia functional anatomy.

    PubMed

    Baladron, Javier; Hamker, Fred H

    2015-07-01

    We introduce a spiking neural network of the basal ganglia capable of learning stimulus-action associations. We model learning in the three major basal ganglia pathways, direct, indirect and hyperdirect, by spike time dependent learning and considering the amount of dopamine available (reward). Moreover, we allow to learn a cortico-thalamic pathway that bypasses the basal ganglia. As a result the system develops new functionalities for the different basal ganglia pathways: The direct pathway selects actions by disinhibiting the thalamus, the hyperdirect one suppresses alternatives and the indirect pathway learns to inhibit common mistakes. Numerical experiments show that the system is capable of learning sets of either deterministic or stochastic rules. PMID:25863288

  17. The Basal Ganglia within a Cognitive System in Birds and Mammals

    PubMed Central

    Petkov, Christopher I.; Jarvis, Erich D.

    2015-01-01

    The primate basal ganglia are fundamental to the Ackermann and colleagues’ proposal. However, primates and rodents are models for human cognitive functions involving basal-ganglia circuits and links between striatal function and vocal communication come from songbirds. We suggest that the proposal is better integrated in cognitive and/or motor theories on spoken language origins and with more analogous nonhuman animal models. PMID:25514958

  18. High affinity serotonin binding sites in human brain: a comparison of cerebral cortex and basal ganglia

    Microsoft Academic Search

    A. J. Cross I; P. Slater

    1989-01-01

    Summary The high-affinity binding of3H-serotonin and3H-DP-AT was studied in membrane preparations and tissue sections of cerebral cortex and basal ganglia of human brain. In tissue sections,3H-serotonin bound to sites present at high density in the cerebral cortex, hippocampus and basal ganglia.3HDPAT bound predominantly to the outer layers of the cerebral cortex and the hippocampus, no significant binding was observed in

  19. Prospects for cannabinoid therapies in basal ganglia disorders.

    PubMed

    Fernández-Ruiz, Javier; Moreno-Martet, Miguel; Rodríguez-Cueto, Carmen; Palomo-Garo, Cristina; Gómez-Cańas, María; Valdeolivas, Sara; Guaza, Carmen; Romero, Julián; Guzmán, Manuel; Mechoulam, Raphael; Ramos, José A

    2011-08-01

    Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like ?(9) -tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB(1) and CB(2) receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB(2) receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB(2) receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB(2) receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB(2) receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB(2) receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation. PMID:21545415

  20. 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.

  1. Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease

    PubMed Central

    Rolinski, Michal; Griffanti, Ludovica; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.L.; Wilcock, Gordon K.; Filippini, Nicola; Zamboni, Giovanna; Hu, Michele T.M.; Mackay, Clare E.

    2015-01-01

    Resting state functional MRI (rs-fMRI) has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD). In order to assess whether changes within the basal ganglia network (BGN) are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD). Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease. PMID:26106536

  2. The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry

    Microsoft Academic Search

    D Joel; I Weiner

    1997-01-01

    The current view of basal ganglia organization holds that functionally corresponding subregions of the frontal cortex, basal ganglia and thalamus form several parallel segregated basal ganglia-thalamocortical circuits. In addition, this view states that striatal output reaches the basal ganglia output nuclei (the substantia nigra pars reticulata (SNR) and the internal segment of the globus pallidus (GPi)) via a `direct' pathway,

  3. Bilateral basal ganglia calcification and recurrent generalized seizures as initial presentation of idiopathic hypoparathyroidism in an infant

    PubMed Central

    Bhat, Manzoor Ahmad; Laway, Bashir Ahmad; Mustafa, Farhat

    2015-01-01

    Pathological calcification of basal ganglia has been encountered in children since long back and is associated with various disease entities both acute and chronic. Idiopathic hypoparathyroidism is an important cause of basal ganglia calcification and can account for up to 73.8% of cases. The pathogenesis of basal ganglia calcification in hypoparathyroidism is not clear, however, a high calcium-phosphorus product and poor calcium control are believed to be directly related to calcification. Besides, a direct correlation is seen with the duration of hypocalcemia; the critical duration being ?4 years. In the presented patient, basal ganglia calcification was seen at a very young age of 6 months. To best of our knowledge, this is probably the youngest case of bilateral basal ganglia calcification in idiopathic hypoparathyroidism in literature. This suggests that besides duration of hypocalcemia, certain genetic factors and the intrauterine milieu may have a role in the pathogenesis of basal ganglia calcification.

  4. 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

  5. Do basal Ganglia amplify willed action by stochastic resonance? A model.

    PubMed

    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

  6. 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

  7. An entropy-based model for basal ganglia dysfunctions in movement disorders.

    PubMed

    Darbin, Olivier; Dees, Daniel; Martino, Anthony; Adams, Elizabeth; Naritoku, Dean

    2013-01-01

    During this last decade, nonlinear analyses have been used to characterize the irregularity that exists in the neuronal data stream of the basal ganglia. In comparison to linear parameters for disparity (i.e., rate, standard deviation, and oscillatory activities), nonlinear analyses focus on complex patterns that are composed of groups of interspike intervals with matching lengths but not necessarily contiguous in the data stream. In light of recent animal and clinical studies, we present a review and commentary on the basal ganglia neuronal entropy in the context of movement disorders. PMID:23762856

  8. 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…

  9. 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…

  10. Importing the Computational Neuroscience Toolbox into Neuro-Evolution--Application to Basal Ganglia

    E-print Network

    Paris-Sud XI, Université de

    Importing the Computational Neuroscience Toolbox into Neuro-Evolution--Application to Basal Ganglia, France ABSTRACT Neuro-evolution and computational neuroscience are two sci- entific domains that produce provide well-defined bench- marks for neuro-evolution. To support these claims, a method to evolve

  11. 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

  12. Basal Ganglia Volume Is Associated with Aerobic Fitness in Preadolescent Children

    Microsoft Academic Search

    Laura Chaddock; Kirk I. Erickson; Ruchika Shaurya Prakash; Matt VanPatter; Michelle W. Voss; Matthew B. Pontifex; Lauren B. Raine; Charles H. Hillman; Arthur F. Kramer

    2010-01-01

    The present investigation is the first to explore the association between childhood aerobic fitness and basal ganglia structure and function. Rodent research has revealed that exercise influences the striatum by increasing dopamine signaling and angiogenesis. In children, higher aerobic fitness levels are associated with greater hippocampal volumes, superior performance on tasks of attentional and interference control, and elevated event-related brain

  13. Analysis of five cases with neurogenic stuttering following brain injury in the basal ganglia

    Microsoft Academic Search

    Tetsuo Tani; Yasujiro Sakai

    2011-01-01

    This study examined stuttering patterns in five patients with basal ganglia injury. None of the patients had a history of developmental stuttering. Four patients were right-handed; one patient was ambidextrous. Stuttering tests administered to patients assessed sentence repetition, reading aloud, explanations of a comic strip, and conversation. Accessory behaviors such as facial grimaces, associated movements of the limbs, and avoidance

  14. The disrupted basal ganglia and behavioural control: an integrative cross-domain perspective of spontaneous stereotypy.

    PubMed

    McBride, Sebastian D; Parker, Matthew O

    2015-01-01

    Spontaneous stereotypic behaviour (SB) is common in many captive animal species, as well as in humans with some severe psychiatric disorders, and is often cited as being related to general basal ganglia dysfunction. Despite this assertion, there is little in the literature examining SB specifically in terms of the basal ganglia mechanics. In this review, we attempt to fill this gap by offering an integrative, cross-domain perspective of SB by linking what we currently understand about the SB phenotype with the ever-growing literature on the anatomy and functionality of the basal ganglia. After outlining current models of SB from different theoretical perspectives, we offer a broad but detailed overview of normally functioning basal ganglia mechanics, and attempt to link this with current neurophysiological evidence related to spontaneous SB. Based on this we present an empirically derived theoretical framework, which proposes that SB is the result of a dysfunctional action selection system that may reflect dysregulation of excitatory (direct) and inhibitory (indirect and hyperdirect) pathways as well as alterations in mechanisms of behavioural switching. This approach also suggests behaviours that specifically become stereotypic may reflect inbuilt low selection threshold behavioural sequences associated with early development and the species-specific ethogram or, low threshold behavioural sequences that are the result of stress-induced dopamine exposure at the time of performance. PMID:25052167

  15. 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…

  16. 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

  17. On a basal ganglia role in learning and rehearsing visual–motor associations

    Microsoft Academic Search

    Patrick Bédard; Jerome N. Sanes

    2009-01-01

    Fronto-striatal circuitry interacts with the midbrain dopaminergic system to mediate the learning of stimulus–response associations, and these associations often guide everyday actions, but the precise role of these circuits in forming and consolidating rules remains uncertain. A means to examine basal ganglia circuit contributions to associative motor learning is to examine these process in a lesion model system, such as

  18. Basal ganglia network by constrained spherical deconvolution: a possible cortico-pallidal pathway?

    PubMed

    Milardi, Demetrio; Gaeta, Michele; Marino, Silvia; Arrigo, Alessandro; Vaccarino, Gianluigi; Mormina, Enricomaria; Rizzo, Giuseppina; Milazzo, Carmelo; Finocchio, Giovanni; Baglieri, Annalisa; Anastasi, Giuseppe; Quartarone, Angelo

    2015-03-01

    In the recent past, basal ganglia circuitry was simplified as represented by the direct and indirect pathways and by hyperdirect pathways. Based on data from animal studies, we hypothesized a fourth pathway, the cortico-pallidal, pathway, that complements the hyperdirect pathway to the subthalamus. Ten normal brains were analyzed by using the high angular resolution diffusion imaging-constrained spherical deconvolution (CSD)-based technique. The study was performed with a 3T magnetic resonance imaging (MRI) scanner (Achieva, Philips Healthcare, Best, Netherlands); by using a 32-channel SENSE head coil. We showed that CSD is a powerful technique that allows a fine evaluation of both the long and small tracts between cortex and basal ganglia, including direct, indirect, and hyperdirect pathways. In addition, a pathway directly connecting the cortex to the globus pallidus was seen. Our results confirm that the CSD tractography is a valuable technique allowing a reliable reconstruction of small- and long-fiber pathways in brain regions with multiple fiber orientations, such as basal ganglia. This could open a future scenario in which CSD could be used to focally target with deep brain stimulation (DBS) the small bundles within the basal ganglia loops. PMID:25156805

  19. 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

  20. Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X

    PubMed Central

    Haesler, Sebastian; Rochefort, Christelle; Georgi, Benjamin; Licznerski, Pawel; Osten, Pavel; Scharff, Constance

    2007-01-01

    The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2. PMID:18052609

  1. Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue.

    PubMed

    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

  2. Switching from automatic to controlled behavior: cortico-basal ganglia mechanisms

    PubMed Central

    Hikosaka, Okihide; Isoda, Masaki

    2010-01-01

    Although we carry out most daily tasks nearly automatically, it is occasionally necessary to change a routine if something changes in our environment and the behavior becomes inappropriate. Such behavioral switching can occur either retroactively based on error feedback or proactively by detecting a contextual cue. Recent imaging and electrophysiological data in humans and monkeys have suggested that the frontal cortical areas play executive roles in behavioral switching. The anterior cingulate cortex acts retroactively and the pre-supplementary motor area acts proactively to enable behavioral switching. The lateral prefrontal cortex reconfigures cognitive processes constituting the switched behavior. The subthalamic nucleus and the striatum in the basal ganglia mediate these cortical signals to achieve behavioral switching. We discuss how breaking a routine to allow more adaptive behavior requires a fine-tuned recruitment of the frontal cortical-basal ganglia neural network. PMID:20181509

  3. Biotin-responsive Basal Ganglia disease: a treatable differential diagnosis of leigh syndrome.

    PubMed

    Distelmaier, Felix; Huppke, Peter; Pieperhoff, Peter; Amunts, Katrin; Schaper, Jörg; Morava, Eva; Mayatepek, Ertan; Kohlhase, Jürgen; Karenfort, Michael

    2014-01-01

    Biotin-responsive basal ganglia disease (BBGD) is an autosomal recessive disorder, which is caused by mutations in the SLC19A3 gene. BBGD typically causes (sub)acute episodes with encephalopathy and subsequent neurological deterioration. If untreated, the clinical course may be fatal. Our report on a 6-year-old child with BBGD highlights that the disease is a crucial differential diagnosis of Leigh syndrome. Therefore, biotin and thiamine treatment is recommended for any patient with symmetrical basal ganglia lesions and neurological symptoms until BBGD is excluded. In addition, we exemplify that deformation-field-based morphometry of brain magnetic resonance images constitutes a novel quantitative tool, which might be very useful to monitor disease course and therapeutic effects in neurometabolic disorders. PMID:24166474

  4. Evidence for a causal inverse model in an avian cortico-basal ganglia circuit

    PubMed Central

    Giret, Nicolas; Kornfeld, Joergen; Ganguli, Surya; Hahnloser, Richard H. R.

    2014-01-01

    Learning by imitation is fundamental to both communication and social behavior and requires the conversion of complex, nonlinear sensory codes for perception into similarly complex motor codes for generating action. To understand the neural substrates underlying this conversion, we study sensorimotor transformations in songbird cortical output neurons of a basal-ganglia pathway involved in song learning. Despite the complexity of sensory and motor codes, we find a simple, temporally specific, causal correspondence between them. Sensory neural responses to song playback mirror motor-related activity recorded during singing, with a temporal offset of roughly 40 ms, in agreement with short feedback loop delays estimated using electrical and auditory stimulation. Such matching of mirroring offsets and loop delays is consistent with a recent Hebbian theory of motor learning and suggests that cortico-basal ganglia pathways could support motor control via causal inverse models that can invert the rich correspondence between motor exploration and sensory feedback. PMID:24711417

  5. 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.

  6. Neuropsychological and 18FDG-PET studies in a family with idiopathic basal ganglia calcifications

    Microsoft Academic Search

    Isabelle Le Ber; Rose-Marie Marié; Benoît Chabot; Catherine Lalevée; Gilles-Louis Defer

    2007-01-01

    Idiopathic basal ganglia calcification (FIBGC) is a rare autosomal dominant neurodegenerative disease, the main clinical signs of which are parkinsonism, cognitive deterioration and\\/or psychiatric troubles. Familial forms are rare. The underlying basis is not known. We performed detailed neurological, neuropsychological, brain CT scans and MRI evaluations in 15 patients of a large FIBGC family. Three patients also underwent a 18FDG-PET

  7. Oscillatory activity in the human basal ganglia: more than just beta, more than just Parkinson's disease.

    PubMed

    Alegre, Manuel; Valencia, Miguel

    2013-10-01

    The implantation of deep brain stimulators in different structures of the basal ganglia to treat neurological and psychiatric diseases has allowed the recording of local field potential activity in these structures. The analysis of these signals has helped our understanding of basal ganglia physiology in health and disease. However, there remain some major challenges and questions for the future. In a recent work, Tan et al. (Tan, H., Pogosyan, A., Anam, A., Foltynie, T., Limousin, P., Zrinzo, L., et al. 2013. Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease. Exp. Neurol. 240,122-129) take profit of these recordings to study the changes in subthalamic oscillatory activity during the hold and release phases of a grasping paradigm, and correlate the changes in different frequency bands with performance parameters. They found that beta activity was related to the release phase, while force maintenance related most to theta and gamma/HFO activity. There was no significant effect of the motor state of the patient on this latter association. These findings suggest that the alterations in the oscillatory activity of the basal ganglia in Parkinson's disease are not limited to the beta band, and they involve aspects different from movement preparation and initiation. Additionally, these results highlight the usefulness of the combination of well-designed paradigms with recordings in off and on motor states (in Parkinson's disease), or in different pathologies, in order to understand not only the pathophysiology of the diseases affecting the patients, but also the normal physiology of the basal ganglia. PMID:23764499

  8. Hypomyelination with atrophy of the basal ganglia and cerebellum: further delineation of the phenotype and genotype-phenotype correlation.

    PubMed

    Hamilton, Eline M; Polder, Emiel; Vanderver, Adeline; Naidu, Sakkubai; Schiffmann, Raphael; Fisher, Kate; Raguž, Ana Boban; Blumkin, Luba; van Berkel, Carola G M; Waisfisz, Quinten; Simons, Cas; Taft, Ryan J; Abbink, Truus E M; Wolf, Nicole I; van der Knaap, Marjo S

    2014-07-01

    Hypomyelination with atrophy of the basal ganglia and cerebellum is a rare leukoencephalopathy that was identified using magnetic resonance imaging in 2002. In 2013, whole exome sequencing of 11 patients with the disease revealed that they all had the same de novo mutation in TUBB4A, which encodes tubulin ?-4A. We investigated the mutation spectrum in a cohort of 42 patients and the relationship between genotype and phenotype. Patients were selected on the basis of clinical and magnetic resonance imaging abnormalities that are indicative of hypomyelination with atrophy of the basal ganglia and cerebellum. Genetic testing and a clinical inventory were performed, and sequential magnetic resonance images were evaluated using a standard protocol. The heterozygous TUBB4A mutation observed in the first 11 patients was the most common (25 patients). Additionally, 13 other heterozygous mutations were identified, located in different structural domains of tubulin ?-4A. We confirmed that the mutations were de novo in all but three patients. In two of these three cases we lacked parental DNA and in one the mutation was also found in the mother, most likely due to mosaicism. Patients showed a phenotypic continuum ranging from neonatal to childhood disease onset, normal to delayed early development and slow to more rapid neurological deterioration. Neurological symptomatology consisted of extrapyramidal movement abnormalities, spasticity, ataxia, cognitive deficit and sometimes epilepsy. Three patients died and the oldest living patient was 29 years of age. The patients' magnetic resonance images showed an absent or disappearing putamen, variable cerebellar atrophy and highly variable cerebral atrophy. Apart from hypomyelination, myelin loss was evident in several cases. Three severely affected patients had similar, somewhat atypical magnetic resonance image abnormalities. The study results were strongly suggestive of a genotype-phenotype correlation. The 25 patients with the common c.745G>A mutation generally had a less rapidly progressive disease course than the 17 cases with other TUBB4A mutations. Overall, this work demonstrates that the distinctive magnetic resonance imaging pattern for hypomyelination with atrophy of the basal ganglia and cerebellum defines a homogeneous clinical phenotype of variable severity. Patients almost invariably have prominent extrapyramidal movement abnormalities, which are rarely seen in patients with hypomyelination of different origin. A dominant TUBB4A mutation is also associated with dystonia type 4, in which magnetic resonance images of the brain seem normal. It is highly likely that there is a disease continuum associated with TUBB4A mutations, of which hypomyelination with atrophy of the basal ganglia and cerebellum and dystonia type 4 are the extremes. This would indicate that extrapyramidal movement abnormalities constitute the core feature of the disease spectrum related to dominant TUBB4A mutations and that all other features are variable. PMID:24785942

  9. Dlx-2 homeobox gene controls neuronal differentiation in primary cultures of developing basal ganglia

    Microsoft Academic Search

    Min Dingz; Laurence Robel; Alaina J. James; David D. Eisenstat; James F. Leckman; John L. R. Rubenstein; Flora M. Vaccarino

    1997-01-01

    Homeodomain-containing genes of theDlx family are expressed in the developing basal ganglia. To investigate the role ofDlx genes during development, we studied their cellular localization in primary cultures of embryonic basal telencephalon, and\\u000a examined the changes in cellular phenotypes resulting from blockade ofDlx-2 expression. Cells containingDlx-1, Dlx-2, andDlx-5 mRNAs are immature cells of the neuronal lineage expressing the microtubule-associated proteins

  10. Anti-basal ganglia antibodies: a possible diagnostic utility in idiopathic movement disorders?

    PubMed Central

    Church, A; Dale, R; Giovannoni, G

    2004-01-01

    Background: The spectrum of post-streptococcal brain disorders includes chorea, tics, and dystonia. The proposed mediators of disease are anti-basal ganglia (neuronal) antibodies (ABGA). Aim: To evaluate ABGA as a potential diagnostic marker in a cohort of UK post-streptococcal movement disorders. Methods: Forty UK children presenting with movement disorders associated with streptococcal infection were recruited. ABGA was measured using ELISA and Western immunoblotting. To determine ABGA specificity and sensitivity, children with neurological diseases (n = 100), children with uncomplicated streptococcal infection (n = 40), and children with autoimmune disease (n = 50) were enrolled as controls. Results: The mean ELISA result was increased in the post-streptococcal movement disorder group compared to all controls and derived a sensitivity of 82.4% and specificity of 79%. The Western immunoblotting method to detect ABGA derived a sensitivity and specificity of 92.5% and 94.7% respectively. There was common binding to basal ganglia antigens of 40, 45, and 60 kDa. Immunofluorescence localised the antibody binding to basal ganglia neurones. Conclusion: ABGA appears to be a potentially useful diagnostic marker in post-streptococcal neurological disorders. Western immunoblotting appears to be the preferred method due to good sensitivity and specificity and the ability to test several samples at once. PMID:15210488

  11. 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

  12. 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

  13. 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

  14. Balancing the basal ganglia circuitry: A possible new role for dopamine D2 receptors in health and disease.

    PubMed

    Cazorla, Maxime; Kang, Un Jung; Kellendonk, Christoph

    2015-06-01

    Current therapies for treating movement disorders such as Parkinson's disease are effective but limited by undesirable and intractable side effects. Developing more effective therapies will require better understanding of what causes basal ganglia dysregulation and why medication-induced side effects develop. Although basal ganglia have been extensively studied in the last decades, its circuit anatomy is very complex, and significant controversy exists as to how the interplay of different basal ganglia nuclei process motor information and output. We have recently identified the importance of an underappreciated collateral projection that bridges the striatal output direct pathway with the indirect pathway. These bridging collaterals are extremely plastic in the adult brain and are involved in the regulation of motor balance. Our findings add a new angle to the classical model of basal ganglia circuitry that could be exploited for the development of new therapies against movement disorders. In this Scientific Perspective, we describe the function of bridging collaterals and other recent discoveries that challenge the simplicity of the classical basal ganglia circuit model. We then discuss the potential implication of bridging collaterals in the pathophysiology of Parkinson's disease and schizophrenia. Because dopamine D2 receptors and striatal neuron excitability have been found to regulate the density of bridging collaterals, we propose that targeting these projections downstream of D2 receptors could be a possible strategy for the treatment of basal ganglia disorders. © 2015 International Parkinson and Movement Disorder Society. PMID:26018615

  15. Neural representation of a target auditory memory in a cortico-basal ganglia pathway.

    PubMed

    Achiro, Jennifer M; Bottjer, Sarah W

    2013-09-01

    Vocal learning in songbirds, like speech acquisition in humans, entails a period of sensorimotor integration during which vocalizations are evaluated via auditory feedback and progressively refined to achieve an imitation of memorized vocal sounds. This process requires the brain to compare feedback of current vocal behavior to a memory of target vocal sounds. We report the discovery of two distinct populations of neurons in a cortico-basal ganglia circuit of juvenile songbirds (zebra finches, Taeniopygia guttata) during vocal learning: (1) one in which neurons are selectively tuned to memorized sounds and (2) another in which neurons are selectively tuned to self-produced vocalizations. These results suggest that neurons tuned to learned vocal sounds encode a memory of those target sounds, whereas neurons tuned to self-produced vocalizations encode a representation of current vocal sounds. The presence of neurons tuned to memorized sounds is limited to early stages of sensorimotor integration: after learning, the incidence of neurons encoding memorized vocal sounds was greatly diminished. In contrast to this circuit, neurons known to drive vocal behavior through a parallel cortico-basal ganglia pathway show little selective tuning until late in learning. One interpretation of these data is that representations of current and target vocal sounds in the shell circuit are used to compare ongoing patterns of vocal feedback to memorized sounds, whereas the parallel core circuit has a motor-related role in learning. Such a functional subdivision is similar to mammalian cortico-basal ganglia pathways in which associative-limbic circuits mediate goal-directed responses, whereas sensorimotor circuits support motor aspects of learning. PMID:24005299

  16. The basal ganglia in perceptual timing: Timing performance in Multiple System Atrophy and Huntington's disease?

    PubMed Central

    Cope, Thomas E.; Grube, Manon; Singh, Baldev; Burn, David J.; Griffiths, Timothy D.

    2014-01-01

    The timing of perceptual events depends on an anatomically and functionally connected network comprising basal ganglia, cerebellum, pre-frontal cortex and supplementary motor area. Recent studies demonstrate the cerebellum to be involved in absolute, duration-based timing, but not in relative timing based on a regular beat. Conversely, functional involvement of the striatum is observed in relative timing, but its role in absolute timing is unclear. This work tests the specific role of the basal ganglia in the perceptual timing of auditory events. It aims to distinguish the hypothesised unified model of time perception (Teki, Grube, & Griffiths, 2012), in which the striatum is a mandatory component for all timing tasks, from a modular system in which they subserve relative timing, with absolute timing processed by the cerebellum. Test groups comprised individuals with Multiple System Atrophy, a disorder in which similar pathology can produce clinical deficits associated with dysfunction of the cerebellum (MSA-C, n=8) or striatum (MSA-P, n=10), and early symptomatic Huntington's disease (HD, n=14). Individuals with chronic autoimmune peripheral neuropathy (n=11) acted as controls. Six adaptive tasks were carried out to assess perceptual thresholds for absolute timing through duration discrimination for sub- and supra-second time intervals, and relative timing through the detection of beat-based regularity and irregularity, detection of a delay within an isochronous sequence, and the discrimination of sequences with metrical structure. All three patient groups exhibited impairments in performance in comparison with the control group for all tasks, and severity of impairment was significantly correlated with disease progression. No differences were demonstrated between MSA-C and MSA-P, and the most severe impairments were observed in those with HD. The data support an obligatory role for the basal ganglia in all tested timing tasks, both absolute and relative, as predicted by the unified model. The results are not compatible with models of a brain timing network based upon independent modules. PMID:24135486

  17. Neural Representation of a Target Auditory Memory in a Cortico-Basal Ganglia Pathway

    PubMed Central

    Bottjer, Sarah W.

    2013-01-01

    Vocal learning in songbirds, like speech acquisition in humans, entails a period of sensorimotor integration during which vocalizations are evaluated via auditory feedback and progressively refined to achieve an imitation of memorized vocal sounds. This process requires the brain to compare feedback of current vocal behavior to a memory of target vocal sounds. We report the discovery of two distinct populations of neurons in a cortico-basal ganglia circuit of juvenile songbirds (zebra finches, Taeniopygia guttata) during vocal learning: (1) one in which neurons are selectively tuned to memorized sounds and (2) another in which neurons are selectively tuned to self-produced vocalizations. These results suggest that neurons tuned to learned vocal sounds encode a memory of those target sounds, whereas neurons tuned to self-produced vocalizations encode a representation of current vocal sounds. The presence of neurons tuned to memorized sounds is limited to early stages of sensorimotor integration: after learning, the incidence of neurons encoding memorized vocal sounds was greatly diminished. In contrast to this circuit, neurons known to drive vocal behavior through a parallel cortico-basal ganglia pathway show little selective tuning until late in learning. One interpretation of these data is that representations of current and target vocal sounds in the shell circuit are used to compare ongoing patterns of vocal feedback to memorized sounds, whereas the parallel core circuit has a motor-related role in learning. Such a functional subdivision is similar to mammalian cortico-basal ganglia pathways in which associative-limbic circuits mediate goal-directed responses, whereas sensorimotor circuits support motor aspects of learning. PMID:24005299

  18. Dyskinesia associated with hyperglycemia and basal ganglia hyperintensity: report of a rare diabetic complication.

    PubMed

    Taboada, Giselle F; Lima, Giovanna A B; Castro, José E C; Liberato, Bernardo

    2013-03-01

    The syndrome of dyskinesia associated with hyperglycemia and basal ganglia hyperintensity on T1 - weighted MR images is rare and most often affects elderly patients with type 2 diabetes. We report a case of a 79 year-old female patient who presented to the ED with a 12 h history of a left sided hemichoreoathetosis. Laboratory results revealed pronounced nonketotic hyperglycemia [27 mmol/L (486 mg/dL); HbA1c 140 mmol/mol (15 %)] and brain MRI showed bilateral T1 hyperintensity in the basal ganglia, more noticeable on the right side. One week before she had been admitted with a diagnosis of transient ischemic attack consisting in left hemiparesthesia, also with nonketotic hyperglycemia [38.9 mmol/L (700 mg/dL)] and was discharged home with partial correction of her metabolic disturbance. The movement disorder did not improve with adequate glycemic control so haloperidol was started. Six weeks later she was seen on an outpatient basis. She still had minimal residual involuntary movements of the left arm and leg. Laboratory exams revealed a well controlled diabetes mellitus [glycemia 6.0 mmol/L (109 mg/dL), HbA1c 57 mmol/mol (7.4 %)]. In conclusion, the syndrome of dyskinesia associated to hyperglycemia and hyperintensity in the basal ganglia on T1 - weighted MR images is a rare, intriguing and yet incompletely understood complication of diabetes mellitus. The increasing number of reported cases may help to better understand its peculiarities such as the existence of a clear clinical radiological dissociation and to unveil pathophysiological aspects. We suggest the possibility that the metabolic disturbances unmask a previous established asymptomatic striatum vasculopathy. PMID:23154926

  19. Identifying the Basal Ganglia Network Model Markers for Medication-Induced Impulsivity in Parkinson's Disease Patients

    PubMed Central

    Balasubramani, Pragathi Priyadharsini; Chakravarthy, V. Srinivasa; Ali, Manal; Ravindran, Balaraman; Moustafa, Ahmed A.

    2015-01-01

    Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its impairment in PD. The results presented here not only show that computational modelling can be used as a valuable tool for understanding and interpreting clinical data, but they also show that computational modeling has the potential to become an invaluable tool to predict the onset of behavioral changes during disease progression. PMID:26042675

  20. Identifying the Basal Ganglia network model markers for medication-induced impulsivity in Parkinson's disease patients.

    PubMed

    Balasubramani, Pragathi Priyadharsini; Chakravarthy, V Srinivasa; Ali, Manal; Ravindran, Balaraman; Moustafa, Ahmed A

    2015-01-01

    Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its impairment in PD. The results presented here not only show that computational modelling can be used as a valuable tool for understanding and interpreting clinical data, but they also show that computational modeling has the potential to become an invaluable tool to predict the onset of behavioral changes during disease progression. PMID:26042675

  1. 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

  2. [A role of the basal ganglia in the occurrence of visual hallucinations (a hypothetical mechanism)].

    PubMed

    Sil'kis, I G

    2005-01-01

    A hypothetical mechanism of the basal ganglia involvement in visual hallucinations is proposed. According to this mechanism, hallucination is the result of modulation of the efficacy of corticostriatal synaptic inputs and changes in spiny cell activity due to the rise of striatal dopamine concentration (or due to other reasons). These changes cause an inhibition of neurons in the substantia nigra pars reticulata and subsequent disinhibition of neurons in the superior colliculus and pedunculopontine nucleus (including its cholinergic cells). In the absence of afferentation from the retina this disinhibition leads to activation of neurons in the lateral geniculate nucleus, pulvinar and other thalamic nuclei projecting to the primary and highest visual cortical areas, prefrontal cortex, and also back to the striatum. Hallucinations as conscious visual patterns are the result of selection of signals circulating in several interconnected loops each of which includes one of above mentioned neocortical areas, one of thalamic nuclei, limbic and one of visual areas of the basal ganglia, superior colliculus and/or pedunculopontine nucleus. According to our model, cannabinoids, opioids and ketamine may lead to hallucinations due to their promotional role in the LTD of cortical inputs to GABAergic spiny cells of striatal striosomes projecting to dopaminergic neurons, disinhibition of the lasts, and increase in striatal dopamine concentration. PMID:16316020

  3. 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

  4. Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia

    SciTech Connect

    Weiner, D.M. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA) Howard Hughes Medical Inst., Bethesda, MD (USA)); Levey, A.I. (National Inst. of Neurological Disorders and Stroke, Bethesda, MD (USA) Johns Hopkins Univ., Baltimore, MD (USA)); Brann, M.R. (National Inst. of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1990-09-01

    Within the basal ganglia, acetylcholine and dopamine play a central role in the extrapyramidal control of motor function. The physiologic effects of these neurotransmitters are mediated by a diversity of receptor subtypes, several of which have now been cloned. Muscarinic acetylcholine receptors are encoded by five genes (m1-m5), and of the two known dopamine receptor subtypes (D1 and D2) the D2 receptor gene has been characterized. To gain insight into the physiological roles of each of these receptor subtypes, the authors prepared oligodeoxynucleotide probes to localize receptor subtype mRNAs within the rat striatum and substantia nigra by in situ hybridization histochemistry. Within the striatum, three muscarinic (m1, m2, m4) receptor mRNAs and the D2 receptor mRNA were detected. The m1 mRNA was expressed in most neurons; the m2 mRNA, in neurons which were both very large and rare; and the m4 and D2 mRNAs, in 40-50% of the neurons, one-third of which express both mRNAs. Within the substantia nigra, pars compacta, only the m5 and D2 mRNAs were detected, and most neurons expressed both mRNAs. These data provide anatomical evidence for the identity of the receptor subtypes which mediate the diverse effects of muscarinic and dopaminergic drugs on basal ganglia function.

  5. 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.

  6. fMRI of cocaine self-administration in macaques reveals functional inhibition of basal ganglia.

    PubMed

    Mandeville, Joseph B; Choi, Ji-Kyung; Jarraya, Bechir; Rosen, Bruce R; Jenkins, Bruce G; Vanduffel, Wim

    2011-05-01

    Disparities in cocaine-induced neurochemical and metabolic responses between human beings and rodents motivate the use of non-human primates (NHP) to model consequences of repeated cocaine exposure in human subjects. To characterize the functional response to cocaine infusion in NHP brain, we employed contrast-enhanced fMRI during both non-contingent injection of drug and self-administration of cocaine in the magnet. Cocaine robustly decreased cerebral blood volume (CBV) throughout basal ganglia and motor/pre-motor cortex and produced subtle functional inhibition of prefrontal cortex. No brain regions exhibited significant elevation of CBV in response to cocaine challenge. Theses effects in NHP brain are opposite in sign to the cocaine-induced fMRI response in rats, but consistent with previous measurements in NHP based on glucose metabolism. Because the striatal ratio of D2 to D1 receptors is larger in human beings and NHP than rats, we hypothesize that the inhibitory effects of D2 receptor binding dominate the functional response in primates, whereas excitatory D1 receptor stimulation predominates in the rat. If the NHP accurately models the human response to cocaine, downregulation of D2 receptors in human cocaine-abusing populations can be expected to blunt cocaine-induced functional responses, contributing to the weak and variable fMRI responses reported in human basal ganglia following cocaine infusion. PMID:21307843

  7. DISCONNECTION OF A BASAL GANGLIA CIRCUIT IN JUVENILE SONGBIRDS ATTENUATES THE SPECTRAL DIFFERENTIATION OF SONG SYLLABLES

    PubMed Central

    Elliott, Kevin C.; Wu, Wei; Bertram, Richard; Johnson, Frank

    2014-01-01

    Similar to language acquisition by human infants, juvenile male zebra finches (Taeniopygia guttata) imitate an adult (tutor) song by transitioning from repetitive production of one or two undifferentiated protosyllables to the sequential production of a larger and spectrally heterogeneous set of syllables. The primary motor region that controls learned song is driven by a confluence of input from two pre-motor pathways: a posterior pathway that encodes the adult song syllables and an anterior pathway that includes a basal ganglia-thalamo-cortical circuit. Like mammalian motor-learning systems, the songbird basal ganglia (BG) circuit is thought to be necessary for shaping juvenile vocal behavior (undifferentiated protosyllables) towards specific targets (the tutor’s song syllables). Here, we tested the hypothesis that anterior pathway activity contributes to the process of protosyllable differentiation. Bilateral ablation of LMAN (lateral magnocellular nucleus of the anterior nidopallium) was used to disconnect BG circuitry at ages prior to protosyllable production and differentiation. Comparison to surgical controls revealed that protosyllables fail to differentiate in birds that received juvenile LMAN ablation – the adult songs of birds with >80% bilateral LMAN ablation consisted of only one or two syllables produced with the repetitive form and spectral structure that characterizes undifferentiated protosyllables in normal juveniles. Our findings support a role for BG circuitry in shaping juvenile vocal behavior towards the acoustic structure of the tutor song and suggest that posterior pathway function remains in an immature ‘default’ state when developmental interaction with the anterior pathway is reduced or eliminated. PMID:24218118

  8. Using a hybrid neuron in physiologically inspired models of the basal ganglia

    PubMed Central

    Thibeault, Corey M.; Srinivasa, Narayan

    2013-01-01

    Our current understanding of the basal ganglia (BG) has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the BG, however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the BG, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation (DBS). The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under DBS. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of DBS and the latter allowing for the efficient simulation of larger more comprehensive networks. PMID:23847524

  9. New Roles for the External Globus Pallidus in Basal Ganglia Circuits and Behavior

    PubMed Central

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

    2014-01-01

    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

  10. The basal ganglia is necessary for learning spectral, but not temporal features of birdsong

    PubMed Central

    Ali, Farhan; Fantana, Antoniu L.; Burak, Yoram; Ölveczky, Bence P.

    2013-01-01

    Executing a motor skill requires the brain to control which muscles to activate at what times. How these aspects of control - motor implementation and timing - are acquired, and whether the learning processes underlying them differ, is not well understood. To address this we used a reinforcement learning paradigm to independently manipulate both spectral and temporal features of birdsong, a complex learned motor sequence, while recording and perturbing activity in underlying circuits. Our results uncovered a striking dissociation in how neural circuits underlie learning in the two domains. The basal ganglia was required for modifying spectral, but not temporal structure. This functional dissociation extended to the descending motor pathway, where recordings from a premotor cortex analogue nucleus reflected changes to temporal, but not spectral structure. Our results reveal a strategy in which the nervous system employs different and largely independent circuits to learn distinct aspects of a motor skill. PMID:24075977

  11. Basal ganglia circuit loops, dopamine and motivation: A review and enquiry.

    PubMed

    Ikemoto, Satoshi; Yang, Chen; Tan, Aaron

    2015-09-01

    Dopamine neurons located in the midbrain play a role in motivation that regulates approach behavior (approach motivation). In addition, activation and inactivation of dopamine neurons regulate mood and induce reward and aversion, respectively. Accumulating evidence suggests that such motivational role of dopamine neurons is not limited to those located in the ventral tegmental area, but also in the substantia nigra. The present paper reviews previous rodent work concerning dopamine's role in approach motivation and the connectivity of dopamine neurons, and proposes two working models: One concerns the relationship between extracellular dopamine concentration and approach motivation. High, moderate and low concentrations of extracellular dopamine induce euphoric, seeking and aversive states, respectively. The other concerns circuit loops involving the cerebral cortex, basal ganglia, thalamus, epithalamus, and midbrain through which dopaminergic activity alters approach motivation. These models should help to generate hypothesis-driven research and provide insights for understanding altered states associated with drugs of abuse and affective disorders. PMID:25907747

  12. Post-traumatic basal ganglia haemorrhage in a child with primary central nervous system lymphoma.

    PubMed

    Jankowski, Pawel P; Levy, Michael L; Crawford, John Ross

    2013-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare tumour of childhood with 15-20 cases reported yearly in North America. We present a case of a 13-year-old boy diagnosed with PCNSL who presented more than one-and-a-half years post-treatment with high dose cytosine arabinoside and methotrexate with a right-sided basal ganglia haemorrhage on MRI following a concussion while playing organised football against medical advice. There was no evidence of an underlying vascular malformation or recurrent disease by MRI, cerebrospinal fluid analysis or positron emission tomography computed tomography (PET-CT). However, 6 months post-injury he presented with asymptomatic disease recurrence of the frontal lobe. Our case reports an unusual MRI pattern of post-traumatic injury in a child previously treated for PCNSL that would support a recommendation for the avoidance of contact sports in this population. PMID:23904430

  13. The cortico-basal ganglia integrative network: the role of the thalamus

    PubMed Central

    Haber, Suzanne N.; Calzavara, Roberta

    2015-01-01

    The thalamus is a critical component of the frontal cortical-basal ganglia-thalamic circuits that mediate motivation and emotional drive, planning and cognition for the development and expression of goal-directed behaviors. Each functional region of the frontal cortex is connected with specific areas of each basal ganglia (BG) structure and of the thalamus. In addition, the thalamus sends a massive, topographically organized projection directly to the striatum. Tract-tracing and physiological experiments have indicated a general topographic organization of the cortical-BG-thalamic loops and supported a model of BG function based on parallel and segregated pathways. However, the learning and execution of appropriate behavioral responses require integration of inputs related to emotional, cognitive, and motor cortical functions. Our recent data indicate that integration may occur via non-reciprocal connections between the striatum and substantia nigra and within “hot spots” of convergence between cortico-striatal projections from different functional regions. Similarly, integration may exist in the thalamus. There are non-reciprocal connections between the thalamus and cortex via thalamocortical projections that terminate in the superficial and deep cortical layers. These terminals can influence different functional cortical areas that, in turn, project to the striatum and back to the thalamus. In addition, a non-reciprocal corticothalamic projection terminates in thalamic regions that are parts of other circuits. Finally, ‘hot spots’ of convergence between terminals from different cortical regions may also occur in the thalamus as is seen in the striatum. Thus, via several different pathways, the thalamus may serve as an important center of integration of networks that underlie the ability to modulate behaviors. PMID:18950692

  14. 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; Castańeda, 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

  15. SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia.

    PubMed

    Baker, Matt; Strongosky, Audrey J; Sanchez-Contreras, Monica Y; Yang, Shan; Ferguson, Will; Calne, Donald B; Calne, Susan; Stoessl, A Jon; Allanson, Judith E; Broderick, Daniel F; Hutton, Michael L; Dickson, Dennis W; Ross, Owen A; Wszolek, Zbigniew K; Rademakers, Rosa

    2014-03-01

    Idiopathic basal ganglia calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and TaqMan copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in two of the 27 cases of IBGC (7 %). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. TaqMan copy number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256-bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia-related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early onset dystonia in this family. The identification of an SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated. PMID:24135862

  16. Basal ganglia volume is associated with aerobic fitness in preadolescent children.

    PubMed

    Chaddock, Laura; Erickson, Kirk I; Prakash, Ruchika Shaurya; VanPatter, Matt; Voss, Michelle W; Pontifex, Matthew B; Raine, Lauren B; Hillman, Charles H; Kramer, Arthur F

    2010-08-01

    The present investigation is the first to explore the association between childhood aerobic fitness and basal ganglia structure and function. Rodent research has revealed that exercise influences the striatum by increasing dopamine signaling and angiogenesis. In children, higher aerobic fitness levels are associated with greater hippocampal volumes, superior performance on tasks of attentional and interference control, and elevated event-related brain potential indices of executive function. The present study used magnetic resonance imaging to investigate if higher-fit and lower-fit 9- and 10-year-old children exhibited differential volumes of other subcortical brain regions, specifically the basal ganglia involved in attentional control. The relationship between aerobic fitness, dorsal and ventral striatum volumes and performance on an attention and inhibition Eriksen flanker task was also examined. The results indicated that higher-fit children showed superior flanker task performance compared to lower-fit children. Higher-fit children also showed greater volumes of the dorsal striatum, and dorsal striatum volume was negatively associated with behavioral interference. The results support the claim that the dorsal striatum is involved in cognitive control and response resolution and that these cognitive processes vary as a function of aerobic fitness. No relationship was found between aerobic fitness, the volume of the ventral striatum and flanker performance. The findings suggest that increased childhood aerobic fitness is associated with greater dorsal striatal volumes and that this is related to enhanced cognitive control. Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle during childhood has important public health and educational implications. PMID:20693803

  17. Creative cognition and the brain: dissociations between frontal, parietal-temporal and basal ganglia groups.

    PubMed

    Abraham, Anna; Beudt, Susan; Ott, Derek V M; Yves von Cramon, D

    2012-10-30

    The objective of the study was to investigate creativity in relation to brain function by assessing creative thinking in various neurological populations. Several measures were employed to assess different facets of creative thinking in clinical groups with frontal lobe, basal ganglia or parietal-temporal lesions relative to matched healthy control participants. The frontal group was subdivided into frontolateral, frontopolar and frontal-extensive groups. Hierarchical regression analyses were employed to assess the significance levels associated with the effects after accounting for IQ differences between the groups. Findings were only considered noteworthy if they at least suggested the presence of a strong trend and were accompanied by medium to large effect sizes. The parietal-temporal and frontolateral groups revealed poorer overall performance with the former demonstrating problems with fluency related measures, whereas the latter were also less proficient at producing original responses. In contrast, the basal ganglia and frontopolar groups demonstrated superior performance in the ability to overcome the constraints imposed by salient semantic distractors when generating creative responses. In summary, the dissociations in the findings reveal the selective involvement of different brain regions in diverse aspects of creativity. Lesion location posed selective limitations on the ability to generate original responses in different contexts, but not on the ability to generate relevant responses, which was compromised in most patient groups. The noteworthy findings from this exploratory study of enhanced performance in specific aspects of creative cognition following brain damage are discussed with reference to the generic idea that superior creative ability can result from altered brain function. PMID:22982590

  18. Efferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes.

    PubMed

    Martinez-Marcos, Alino; Ubeda-Bańon, Isabel; Lanuza, Enrique; Halpern, Mimi

    2005-05-01

    The olfactostriatum is a portion of the basal ganglia of snakes that receives substantial vomeronasal afferents through projections from the nucleus sphericus. In a preceding article, the olfactostriatum of garter snakes (Thamnophis sirtalis) was characterized on the basis of chemoarchitecture (distribution of serotonin, neuropeptide Y and tyrosine hydroxylase) and pattern of afferent connections [Martinez-Marcos, A., Ubeda-Banon, I., Lanuza, E., Halpern, M., 2005. Chemoarchitecture and afferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes. J. Chem. Neuroanat. 29, 49-69]. In the present study, its efferent connections have been investigated. The olfactostriatum projects to the main and accessory olfactory bulbs, lateral cortex, septal complex, ventral pallidum, external, ventral anterior and dorsolateral amygdalae, bed nucleus of the stria terminalis, preoptic area, lateral posterior hypothalamic nucleus, ventral tegmental area, substantia nigra and raphe nuclei. Tracer injections in the nucleus accumbens proper, a structure closely associated with the olfactostriatum, result in a similar pattern of efferent connections with the exception of those reaching the main and accessory olfactory bulbs, lateral cortex, external, ventral anterior and dorsolateral amygdalae and bed nucleus of the stria terminalis. These data, therefore, help to characterize the olfactostriatum, an apparently specialized area of the nucleus accumbens. Double labeling experiments after tracer injections in the nucleus sphericus and the lateral posterior hypothalamic nucleus demonstrate a pathway between these two structures through the olfactostriatum. Injections in the olfactostriatum and in the medial amygdala show parallel projections to the lateral posterior hypothalamic nucleus. Since this hypothalamic nucleus has been previously described as projecting to the hypoglossal nucleus, both, the medial amygdala and the olfactostriatum may mediate vomeronasal influence on tongue-flick behavior. PMID:15820623

  19. 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

  20. Basal ganglia calcification induced by excitotoxicity: an experimental model characterised by electron microscopy and X-ray microanalysis

    Microsoft Academic Search

    Nicole Mahy; Alberto Prats; Alberto Riveros; Noemí Andrés; Fabián Bernal

    1999-01-01

    Activation of glutamate receptors induces an excitotoxic neurodegenerative process characterised in some brain areas by the\\u000a formation of calcium precipitates. To examine the pathogenesis of basal ganglia calcification (BGC), an improved procedure\\u000a of X-ray microanalysis was used to study experimental excitotoxic calcification in the rat. Three weeks after injection of\\u000a ibotenic acid (IBO) in the rat basal forebrain, calcified inclusions

  1. Basal Ganglia Structures Differentially Contribute to Verbal Fluency: Evidence from Human Immunodeficiency Virus (HIV)-Infected Adults

    ERIC Educational Resources Information Center

    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.

    2012-01-01

    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…

  2. Structural differences in basal ganglia of elite running versus martial arts athletes: a diffusion tensor imaging study.

    PubMed

    Chang, Yu-Kai; Tsai, Jack Han-Chao; Wang, Chun-Chih; Chang, Erik Chihhung

    2015-07-01

    The aim of this study was to use diffusion tensor imaging (DTI) to characterize and compare microscopic differences in white matter integrity in the basal ganglia between elite professional athletes specializing in running and martial arts. Thirty-three young adults with sport-related skills as elite professional runners (n = 11) or elite professional martial artists (n = 11) were recruited and compared with non-athletic and healthy controls (n = 11). All participants underwent health- and skill-related physical fitness assessments. Fractional anisotropy (FA) and mean diffusivity (MD), the primary indices derived from DTI, were computed for five regions of interest in the bilateral basal ganglia, including the caudate nucleus, putamen, globus pallidus internal segment (GPi), globus pallidus external segment (GPe), and subthalamic nucleus. Results revealed that both athletic groups demonstrated better physical fitness indices compared with their control counterparts, with the running group exhibiting the highest cardiovascular fitness and the martial arts group exhibiting the highest muscular endurance and flexibility. With respect to the basal ganglia, both athletic groups showed significantly lower FA and marginally higher MD values in the GPi compared with the healthy control group. These findings suggest that professional sport or motor skill training is associated with changes in white matter integrity in specific regions of the basal ganglia, although these positive changes did not appear to depend on the type of sport-related motor skill being practiced. PMID:25929552

  3. 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

  4. 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

  5. Biomimetic race model of the loop between the superior colliculus and the basal ganglia: Subcortical selection of saccade targets.

    PubMed

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

    2015-07-01

    The superior colliculus, a laminar structure involved in the retinotopic mapping of the visual field, plays a cardinal role in several cortical and subcortical pathways of the saccadic system. Although the selection of saccade targets has long been thought to be mainly the product of cortical processes, a growing body of evidence hints at the implication of the superior colliculus in selection processes independent from cortical inputs, capable of producing saccades at latencies incompatible with the cortical pathways. This selection ability could be produced firstly by the lateral connections between the neurons of its maps, and secondly by its interactions with the midbrain basal ganglia, already renowned for their role in decision making. We propose a biomimetic population-coded race model of selection based on a dynamic tecto-basal loop that reproduces the observed ability of the superior colliculus to stochastically select between similar stimuli. Our model's selection accuracy depends on the discriminability of the target and the distractors. Our model also offers an explanation for the phenomenon of Remote Distractor Effect based on the lateral connectivity within the basal ganglia circuitry rather than on lateral inhibitions within the collicular maps. Finally, we propose a role for the intermediate layers of the superior colliculus, as stochastic integrators dynamically gated by the selective disinhibition of the basal ganglia channels that is consistent with the recorded activity profiles of these neurons. PMID:25884111

  6. Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training.

    PubMed

    Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-01-01

    Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training. PMID:26035693

  7. Focal basal ganglia lesions are associated with impairments in reward-based reversal learning.

    PubMed

    Bellebaum, Christian; Koch, Benno; Schwarz, Michael; Daum, Irene

    2008-03-01

    The basal ganglia (BG) are thought to play a key role in learning from feedback, with mesencephalic dopamine neurons coding errors in reward prediction, thereby mediating information processing in the BG and the prefrontal cortex. In the present study, reward-based learning was assessed in patients with focal BG lesions, by studying outcome-based acquisition and reversal of stimulus-stimulus associations with different reward magnitudes in two probabilistic learning tasks. Eleven patients with selective BG lesions (three females) and 18 healthy control subjects (six females) participated in this study. Two cognitive transfer tasks provided a measure of declarative learning strategy application. On the group level, BG patients showed deficits in reversal learning, with dorsal striatum lesion patients being most severely affected. While basic mechanisms of learning from feedback such as the processing of different reward magnitudes appeared to be intact, patients needed more trials than controls to learn a second reward-based task, suggesting reduced carry-over effects in learning. A patient with a bilateral BG lesion showed better performance than controls on most learning tasks, applying a compensatory declarative learning strategy. The results are discussed in terms of the implication of different BG subregions in different aspects of learning from feedback. PMID:18263624

  8. Secondary insults and outcomes in patients with hypertensive basal ganglia hemorrhage.

    PubMed

    Fei, Z; Zhang, X; Song, S J

    2005-01-01

    This study was designed to monitor secondary insults and their impact on outcomes of patients with hypertensive basal ganglia hemorrhage (HBGH). One hundred and twelve patients with HBGH (male 73, female 39) of age 42 +/- 8 years (range from 38 to 57 years) were studied. Operations included craniotomy or trephination drainage with urokinase thrombolysis. Conventional therapies were also given to the patients including the administration of mannitol, crystalloid and colloid solution. In the meantime, blood pressure (MAP), temperature (T) and SaO2 and other parameters were recorded in the intensive care unit. The ICP values were recorded, and the early clinical outcome was assessed upon discharge according to Glasgow Outcome Scale. Cerebral Perfusion Pressure was calculated as CPP = MAP-MICP. Outcomes in the group without secondary insults were better than that in the group with secondary insults (P < 0.01). No unfavorable outcomes were found in the 59 cases managed by ultra-early surgery whereas 36.1% of the cases operated after 6 hours of onset had unfavorable outcomes. It is concluded that the high incident rate of secondary insults in HICH patients influences outcome. Ultra-early surgery may also contribute to improved quality of survival. PMID:16463862

  9. 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

  10. Disconnecting force from money: effects of basal ganglia damage on incentive motivation.

    PubMed

    Schmidt, Liane; d'Arc, Baudouin Forgeot; Lafargue, Gilles; Galanaud, Damien; Czernecki, Virginie; Grabli, David; Schüpbach, Michael; Hartmann, Andreas; Lévy, Richard; Dubois, Bruno; Pessiglione, Mathias

    2008-05-01

    Bilateral basal ganglia lesions have been reported to induce a particular form of apathy, termed auto-activation deficit (AAD), principally defined as a loss of self-driven behaviour that is reversible with external stimulation. We hypothesized that AAD reflects a dysfunction of incentive motivation, a process that translates an expected reward (or goal) into behavioural activation. To investigate this hypothesis, we designed a behavioural paradigm contrasting an instructed (externally driven) task, in which subjects have to produce different levels of force by squeezing a hand grip, to an incentive (self-driven) task, in which subjects can win, depending on their hand grip force, different amounts of money. Skin conductance was simultaneously measured to index affective evaluation of monetary incentives. Thirteen AAD patients with bilateral striato-pallidal lesions were compared to thirteen unmedicated patients with Parkinson's; disease (PD), which is characterized by striatal dopamine depletion and regularly associated with apathy. AAD patients did not differ from PD patients in terms of grip force response to external instructions or skin conductance response to monetary incentives. However, unlike PD patients, they failed to distinguish between monetary incentives in their grip force. We conclude that bilateral striato-pallidal damage specifically disconnects motor output from affective evaluation of potential rewards. PMID:18344560

  11. Indirect basal ganglia pathway mediation of repetitive behavior: attenuation by adenosine receptor agonists.

    PubMed

    Tanimura, Yoko; Vaziri, Sasha; Lewis, Mark H

    2010-06-26

    Repetitive behaviors are diagnostic for autism and common in related neurodevelopmental disorders. Despite their clinical importance, underlying mechanisms associated with the expression of these behaviors remain poorly understood. Our lab has previously shown that the rates of spontaneous stereotypy in deer mice (Peromyscus maniculatus) were negatively correlated with enkephalin content, a marker of striatopallidal but not striatonigral neurons. To investigate further the role of the indirect basal ganglia pathway, we examined neuronal activation of the subthalamic nucleus (STN) using cytochrome oxidase (CO) histochemistry in high- and low-stereotypy mice. CO activity in STN was significantly lower in high-stereotypy mice and negatively correlated with the frequency of stereotypy. In addition, exposure to environmental enrichment, which attenuated stereotypy, normalized the activity of STN. Co-administration of the adenosine A(2A) receptor agonist CGS21680 and the A(1) receptor agonist CPA attenuated stereotypy dose-dependently. The significant reduction associated with the lowest dose of the drug combination tested was due to its effects on mice with lower baseline levels of stereotypy. Higher doses of the drug combination were required to show robust behavioral effects, and presumably requisite activation of the indirect pathway, in high-stereotypy mice. These findings support that decreased indirect pathway activity is linked to the expression of high levels of stereotypy in deer mice and that striatal A(1) and A(2A) receptors may provide promising therapeutic targets for the treatment of repetitive behaviors in neurodevelopmental disorders. PMID:20178817

  12. Idiopathic basal ganglia calcification-associated PDGFRB mutations impair the receptor signalling

    PubMed Central

    Arts, Florence A; Velghe, Amélie I; Stevens, Monique; Renauld, Jean-Christophe; Essaghir, Ahmed; Demoulin, Jean-Baptiste

    2015-01-01

    Platelet-derived growth factors (PDGF) bind to two related receptor tyrosine kinases, which are encoded by the PDGFRA and PDGFRB genes. Recently, heterozygous PDGFRB mutations have been described in patients diagnosed with idiopathic basal ganglia calcification (IBGC or Fahr disease), a rare inherited neurological disorder. The goal of the present study was to determine whether these mutations had a positive or negative impact on the PDGFRB activity. We first showed that the E1071V mutant behaved like wild-type PDGFRB and may represent a polymorphism unrelated to IBGC. In contrast, the L658P mutant had no kinase activity and failed to activate any of the pathways normally stimulated by PDGF. The R987W mutant activated Akt and MAP kinases but did not induce the phosphorylation of signal transducer and activator of transcription 3 (STAT3) after PDGF stimulation. Phosphorylation of phospholipase C? was also decreased. Finally, we showed that the R987W mutant was more rapidly degraded upon PDGF binding compared to wild-type PDGFRB. In conclusion, PDGFRB mutations associated with IBGC impair the receptor signalling. PDGFRB loss of function in IBGC is consistent with recently described inactivating mutations in the PDGF-B ligand. These results raise concerns about the long-term safety of PDGF receptor inhibition by drugs such as imatinib. PMID:25292412

  13. 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. PMID:25730121

  14. 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

  15. Hemichorea improved by carotid artery stenting in a 73-year-old man with hypoperfusion of the basal ganglia.

    PubMed

    Kodera, Yuka; Nakayama, Taira; Yutani, Sachiko; Uesugi, Tsuyoshi; Ohnuki, Youichi; Takizawa, Shunya

    2015-01-01

    A 73-year-old man presented with continuous hemichoreic movement of right arm and leg and with dyskinesia in his tongue. Magnetic resonance image (MRI) showed no ischemic lesion within the basal ganglia, but magnetic resonance angiography (MRA) and carotid duplex ultrasonography showed the left internal carotid occlusion and 80% stenosis in the right common carotid artery. Tc-99m-ECD-SPECT showed hypoperfusion of the frontal lobe, temporal lobe, parietal lobe, basal ganglia and thalamus. A trial of haloperidol had no effect; therefore, the right carotid artery stenting was performed. Hypoperfusion in the left internal carotid artery area was improved by cross flow from the right side, and his hemichorea gradually improved. This result supports the notion that hypoperfusion-related hemichorea may occur, even in the absence of cerebral ischemia. PMID:26028201

  16. Rare co-occurrence of dural arteriovenous fistula and arteriovenous malformation with bilateral subcortical and basal ganglia calcification.

    PubMed

    Sayani, Raza; Khan, Zahid Anwar; Tanveer-ul-Haq; Hamid, Rana Shoaib; Azeemuddin, Muhammed

    2012-06-01

    The present study describes the imaging findings in a patient with dural arteriovenous fistula (AVR) and arteriovenous malformation (AVM) with bilateral subcortical and basal ganglia calcification. A 29 year old male patient presented with chief complaint of recent onset of generalized tonic clonic seizures and mild disorientation. The imaging studies on MCT demonstrated diffuse, symmetric calcification in the bilateral basal ganglia and subcortical white matter. MR imaging and angiography revealed AVM in parietooccipital region with supply predominantly from left posterior cerebral and middle cerebral arteries. Multiple dural feeders from meningeal branches of occipital and superficial temporal branches of bilateral external carotid and right internal carotid arteries. Calcification is proposed to be due to chronic reflux into the parenchymal veins or vascular steal phenomenon. This rare co-occurrence of subcortical calcification in a patient with a dural AVF and AVM is being reported. PMID:22755350

  17. 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

  18. Age-related changes of the functional architecture of the cortico-basal ganglia circuitry during motor task execution.

    PubMed

    Marchand, William R; Lee, James N; Suchy, Yana; Garn, Cheryl; Johnson, Susanna; Wood, Nicole; Chelune, Gordon

    2011-03-01

    Normal human aging is associated with declining motor control and function. It is thought that dysfunction of the cortico-basal ganglia circuitry may contribute to age-related sensorimotor impairment, however the underlying mechanisms are poorly characterized. The aim of this study was to enhance our understanding of age-related changes in the functional architecture of these circuits. Fifty-nine subjects, consisting of a young, middle and old group, were studied using functional MRI and a motor activation paradigm. Functional connectivity analyses and examination of correlations of connectivity strength with performance on the activation task as well as neurocognitive tasks completed outside of magnet were conducted. Results indicated that increasing age is associated with changes in the functional architecture of the cortico-basal ganglia circuitry. Connectivity strength increased between subcortical nuclei and cortical motor and sensory regions but no changes were found between subcortical components of the circuitry. Further, increased connectivity was correlated with poorer performance on a neurocognitive task independently of age. This result suggests that increased connectivity reflects a decline in brain function rather than a compensatory process. These findings advance our understanding of the normal aging process. Further, the methods employed will likely be useful for future studies aimed at disambiguating age-related versus illness progression changes associated with neuropsychiatric disorders that involve the cortico-basal ganglia circuitry. PMID:21167945

  19. How do the basal ganglia contribute to categorization? Their role in generalization, response selection, and learning via feedback

    PubMed Central

    Seger, Carol A.

    2008-01-01

    This article examines how independent corticostriatal loops linking basal ganglia with cerebral cortex contribute to visual categorization. The first aspect of categorization discussed is the role of the visual corticostriatal loop, which connects the visual cortex and the body/tail of the caudate, in mapping visual stimuli to categories, including evaluating the degree to which this loop may generalize across individual category members. The second aspect of categorization discussed is the selection of appropriate actions or behaviors on the basis of category membership, and the role of the visual corticostriatal loop output and the motor corticostriatal loop, which connects motor planning areas with the putamen, in action selection. The third aspect of categorization discussed is how categories are learned with the aid of feedback linked dopaminergic projections to the basal ganglia. These projections underlie corticostriatal synaptic plasticity across the basal ganglia, and also serve as input to the executive and motivational corticostriatal loops that play a role in strategic use of feedback. PMID:17919725

  20. 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

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

    PubMed

    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

  2. Basal ganglia contribution to rule expectancy and temporal predictability in speech.

    PubMed

    Kotz, Sonja A; Schmidt-Kassow, Maren

    2015-07-01

    The current work set out to answer three questions: (1) Are reported syntactic deficits in patients with structural damage to the basal ganglia (BG) in the cortico-striato-thalamo-cortical systems (CSTCS) the result of a syntax specific computational deficit or are they potentially a consequence of a generalized timing deficit? (2) Do BG patients suffer from a simple beat perception deficit in speech comparable to the one reported in music? (3) Can regular speech meter (i.e., a pattern of beats induced by the regular alteration of stressed and unstressed syllable accents) ameliorate the computation of syntactically marked information by making speech events temporally predictable and salient? The latter 'remediation' hypothesis would predict that when speech events (i.e., those that are syntactically marked) are metrically aligned to the syllabic accent structure, the computation of syntactic information is facilitated or in the case of patients ameliorated. During continuous EEG measurement nineteen patients with focal BG lesions and matched healthy controls listened to metrically regular and syntactically well-formed sentences and metrically well-formed sentences that either violated syntactic expectancy, metrical expectancy, or both. While healthy controls showed an expected P600 response in the event-related brain potential (ERP) to all expectancy violations, BG patients showed overall comparable P600 responses to all, but the metrical expectancy violation. These results confirm that (1) BG patients suffer from a simple beat perception deficit in speech and (2) regular speech meter ameliorates the computation of syntactically marked information in the speech signal. We propose that a domain general sensorimotor cerebello-thalamo-cortical system (CTCS), involved in event-based temporal processing, engages in the remediation of dysfunctional cortico-striato-thalamo-cortical timing that affects the timely computation of linguistic (i.e., syntax) information in the speech signal. PMID:25863903

  3. A spiking Basal Ganglia model of synchrony, exploration and decision making

    PubMed Central

    Mandali, Alekhya; Rengaswamy, Maithreye; Chakravarthy, V. Srinivasa; Moustafa, Ahmed A.

    2015-01-01

    To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either “explore” or “exploit” or “not to take any action” for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration. In this study we build a spiking network model to relate exploration to synchrony levels in the BG (which are a neural marker for tremor in Parkinson's disease). Key BG nuclei such as the Sub Thalamic Nucleus (STN), Globus Pallidus externus (GPe) and Globus Pallidus internus (GPi) were modeled as Izhikevich spiking neurons whereas the Striatal output was modeled as Poisson spikes. The model is cast in reinforcement learning framework with the dopamine signal representing reward prediction error. We apply the model to two decision making tasks: a binary action selection task (similar to one used by Humphries et al., 2006) and an n-armed bandit task (Bourdaud et al., 2008). The model shows that exploration levels could be controlled by STN's lateral connection strength which also influenced the synchrony levels in the STN-GPe circuit. An increase in STN's lateral strength led to a decrease in exploration which can be thought as the possible explanation for reduced exploratory levels in Parkinson's patients. Our simulations also show that on complete removal of IP, the model exhibits only Go and No-Go behaviors, thereby demonstrating the crucial role of IP in exploration. Our model provides a unified account for synchronization, action section, and explorative behavior. PMID:26074761

  4. A spiking Basal Ganglia model of synchrony, exploration and decision making.

    PubMed

    Mandali, Alekhya; Rengaswamy, Maithreye; Chakravarthy, V Srinivasa; Moustafa, Ahmed A

    2015-01-01

    To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either "explore" or "exploit" or "not to take any action" for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration. In this study we build a spiking network model to relate exploration to synchrony levels in the BG (which are a neural marker for tremor in Parkinson's disease). Key BG nuclei such as the Sub Thalamic Nucleus (STN), Globus Pallidus externus (GPe) and Globus Pallidus internus (GPi) were modeled as Izhikevich spiking neurons whereas the Striatal output was modeled as Poisson spikes. The model is cast in reinforcement learning framework with the dopamine signal representing reward prediction error. We apply the model to two decision making tasks: a binary action selection task (similar to one used by Humphries et al., 2006) and an n-armed bandit task (Bourdaud et al., 2008). The model shows that exploration levels could be controlled by STN's lateral connection strength which also influenced the synchrony levels in the STN-GPe circuit. An increase in STN's lateral strength led to a decrease in exploration which can be thought as the possible explanation for reduced exploratory levels in Parkinson's patients. Our simulations also show that on complete removal of IP, the model exhibits only Go and No-Go behaviors, thereby demonstrating the crucial role of IP in exploration. Our model provides a unified account for synchronization, action section, and explorative behavior. PMID:26074761

  5. Motor thalamus integration of cortical, cerebellar and basal ganglia information: implications for normal and parkinsonian conditions

    PubMed Central

    Bosch-Bouju, Clémentine; Hyland, Brian I.; Parr-Brownlie, Louise C.

    2013-01-01

    Motor thalamus (Mthal) is implicated in the control of movement because it is strategically located between motor areas of the cerebral cortex and motor-related subcortical structures, such as the cerebellum and basal ganglia (BG). The role of BG and cerebellum in motor control has been extensively studied but how Mthal processes inputs from these two networks is unclear. Specifically, there is considerable debate about the role of BG inputs on Mthal activity. This review summarizes anatomical and physiological knowledge of the Mthal and its afferents and reviews current theories of Mthal function by discussing the impact of cortical, BG and cerebellar inputs on Mthal activity. One view is that Mthal activity in BG and cerebellar-receiving territories is primarily “driven” by glutamatergic inputs from the cortex or cerebellum, respectively, whereas BG inputs are modulatory and do not strongly determine Mthal activity. This theory is steeped in the assumption that the Mthal processes information in the same way as sensory thalamus, through interactions of modulatory inputs with a single driver input. Another view, from BG models, is that BG exert primary control on the BG-receiving Mthal so it effectively relays information from BG to cortex. We propose a new “super-integrator” theory where each Mthal territory processes multiple driver or driver-like inputs (cortex and BG, cortex and cerebellum), which are the result of considerable integrative processing. Thus, BG and cerebellar Mthal territories assimilate motivational and proprioceptive motor information previously integrated in cortico-BG and cortico-cerebellar networks, respectively, to develop sophisticated motor signals that are transmitted in parallel pathways to cortical areas for optimal generation of motor programmes. Finally, we briefly review the pathophysiological changes that occur in the BG in parkinsonism and generate testable hypotheses about how these may affect processing of inputs in the Mthal. PMID:24273509

  6. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia

    PubMed Central

    Kawasaki, Hiroaki; Springett, Gregory M.; Toki, Shinichiro; Canales, Juan J.; Harlan, Patricia; Blumenstiel, Justin P.; Chen, Emy J.; Bany, I. Amy; Mochizuki, Naoki; Ashbacher, Amy; Matsuda, Michiyuki; Housman, David E.; Graybiel, Ann M.

    1998-01-01

    Ras proteins, key regulators of growth, differentiation, and malignant transformation, recently have been implicated in synaptic function and region-specific learning and memory functions in the brain. Rap proteins, members of the Ras small G protein superfamily, can inhibit Ras signaling through the Ras/Raf-1/mitogen-activated protein (MAP) kinase pathway or, through B-Raf, can activate MAP kinase. Rap and Ras proteins both can be activated through guanine nucleotide exchange factors (GEFs). Many Ras GEFs, but to date only one Rap GEF, have been identified. We now report the cloning of a brain-enriched gene, CalDAG-GEFI, which has substrate specificity for Rap1A, dual binding domains for calcium (Ca2+) and diacylglycerol (DAG), and enriched expression in brain basal ganglia pathways and their axon-terminal regions. Expression of CalDAG-GEFI activates Rap1A and inhibits Ras-dependent activation of the Erk/MAP kinase cascade in 293T cells. Ca2+ ionophore and phorbol ester strongly and additively enhance this Rap1A activation. By contrast, CalDAG-GEFII, a second CalDAG-GEF family member that we cloned and found identical to RasGRP [Ebinu, J. O., Bottorff, D. A., Chan, E. Y. W., Stang, S. L., Dunn, R. J. & Stone, J. C. (1998) Science 280, 1082–1088], exhibits a different brain expression pattern and fails to activate Rap1A, but activates H-Ras, R-Ras, and the Erk/MAP kinase cascade under Ca2+ and DAG modulation. We propose that CalDAG-GEF proteins have a critical neuronal function in determining the relative activation of Ras and Rap1 signaling induced by Ca2+ and DAG mobilization. The expression of CalDAG-GEFI and CalDAG-GEFII in hematopoietic organs suggests that such control may have broad significance in Ras/Rap regulation of normal and malignant states. PMID:9789079

  7. Developmental Changes in the Organization of Functional Connections between the Basal Ganglia and Cerebral Cortex

    PubMed Central

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

    2014-01-01

    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

  8. Rule-based categorization deficits in focal basal ganglia lesion and Parkinson's disease patients.

    PubMed

    Ell, Shawn W; Weinstein, Andrea; Ivry, Richard B

    2010-08-01

    Patients with basal ganglia (BG) pathology are consistently found to be impaired on rule-based category learning tasks in which learning is thought to depend upon the use of an explicit, hypothesis-guided strategy. The factors that influence this impairment remain unclear. Moreover, it remains unknown if the impairments observed in patients with degenerative disorders such as Parkinson's disease (PD) are also observed in those with focal BG lesions. In the present study, we tested patients with either focal BG lesions or PD on two categorization tasks that varied in terms of their demands on selective attention and working memory. Individuals with focal BG lesions were impaired on the task in which working memory demand was high and performed similarly to healthy controls on the task in which selective-attention demand was high. In contrast, individuals with PD were impaired on both tasks, and accuracy rates did not differ between on and off medication states for a subset of patients who were also tested after abstaining from dopaminergic medication. Quantitative, model-based analyses attributed the performance deficit for both groups in the task with high working memory demand to the utilization of suboptimal strategies, whereas the PD-specific impairment on the task with high selective-attention demand was driven by the inconsistent use of an optimal strategy. These data suggest that the demands on selective attention and working memory affect the presence of impairment in patients with focal BG lesions and the nature of the impairment in patients with PD. PMID:20600196

  9. 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

  10. [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

  11. Association between the basal ganglia and large-scale brain networks in epilepsy.

    PubMed

    Rektor, Ivan; Tom?ík, Jan; Mikl, Michal; Mare?ek, Radek; Brázdil, Milan; Rektorová, Irena

    2013-04-01

    Epilepsy may affect connectivity between the putamen and cortex even during the resting state. Putamen is part of the basal ganglia resting state network (BG-RSN) which is anti-correlated with the default mode network (DMN) in healthy subjects. Therefore, we aimed at studying the functional brain connectivity (FC) of the putamen with the cortical areas engaged in the DMN as well as with the primary somatomotor cortex which is a cortical region engaged in the BG-RSN. We compared the data obtained in patients with epilepsy with that in healthy controls (HC). Functional magnetic resonance imaging (fMRI) was performed in 10 HC and 24 patients with epilepsy: 14 patients with extratemporal epilepsy (PE) and 10 patients with temporal epilepsy (PT). Resting state fMRI data was obtained using the 1.5 T Siemens Symphony scanner. The Group ICA of fMRI Toolbox (GIFT) program was used for independent component analysis. The component representing the DMN was chosen according to a spatial correlation with a mask typical for DMN. The FC between the putamen and the primary somatomotor cortex was studied to assess the connectivity of the putamen within the BG-RSN. A second-level analysis was calculated to evaluate differences among the groups using SPM software. In patients with epilepsy as compared to HC, the magnitude of anti-correlation between the putamen and brain regions engaged in the DMN was significantly lower. In fact, the correlation changed the connectivity direction from negative in HC to positive in PE and PT. The disturbed FC of the BG in patients with epilepsy as compared with HC was further illustrated by a significant decrease in connectivity between the left/right putamen and the left/right somatomotor cortex, i.e. between regions that are engaged in the BG-RSN. The FC between the putamen and the cortex is disturbed in patients with epilepsy. This may reflect an altered function of the BG in epilepsy. PMID:23400553

  12. The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood.

    PubMed

    Manza, Peter; Zhang, Sheng; Hu, Sien; Chao, Herta H; Leung, Hoi-Chung; Li, Chiang-shan R

    2015-02-15

    The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49 years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the "task-positive" network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction. PMID:25514518

  13. Impaired L1 and executive control after left basal ganglia damage in a bilingual Basque-Spanish person with aphasia.

    PubMed

    Adrover-Roig, Daniel; Galparsoro-Izagirre, Nekane; Marcotte, Karine; Ferré, Perrine; Wilson, Maximiliano A; Inés Ansaldo, Ana

    2011-06-01

    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 left basal ganglia, presented with executive deficits and aphasia, characterised by more impaired language processing in Basque, his L1. Assessment with the Bilingual Aphasia Test revealed impaired spontaneous and automatic speech production and speech rate in L1, as well as impaired L2-to-L1 sentence translation. Later observation led to the assessment of verbal and non-verbal executive control, which allowed JZ's impaired performance on language tasks to be related to executive dysfunction. In line with previous research, we report the significant attrition of L1 following damage to the left basal ganglia, reported for the first time in a Basque-Spanish bilingual. Implications for models of declarative and procedural memory are discussed. PMID:21453016

  14. Blood-nerve barrier: distribution of anionic sites on the endothelial plasma membrane and basal lamina of dorsal root ganglia.

    PubMed

    Bush, M S; Reid, A R; Allt, G

    1991-09-01

    Previous investigations of the blood-nerve barrier have correlated the greater permeability of ganglionic endoneurial vessels, compared to those of nerve trunks, with the presence of fenestrations and open intercellular junctions. Recent studies have demonstrated reduced endothelial cell surface charge in blood vessels showing greater permeability. To determine the distribution of anionic sites on the plasma membranes and basal laminae of endothelial cells in dorsal root ganglia, cationic colloidal gold and cationic ferritin were used. Electron microscopy revealed the existence of endothelial microdomains with differing labelling densities. Labelling indicated that caveolar and fenestral diaphragms and basal laminae are highly anionic at physiological pH, luminal plasma membranes and endothelial processes are moderately charged and abluminal plasma membranes are weakly anionic. Tracers did not occur in caveolae or cytoplasmic vesicles. In vitro tracer experiments at pH values of 7.3, 5.0, 3.5 and 2.0 indicated that the anionic charge on the various endothelial domains was contributed by chemical groups with differing pKa values. In summary, the labelling of ganglionic and sciatic nerve vessels was similar except for the heavy labelling of diaphragms in a minority of endoneurial vessels in ganglia. This difference is likely to account in part for the greater permeability of ganglionic endoneurial vessels. The results are discussed with regard to the blood-nerve and -brain barriers and vascular permeability in other tissues and a comparison made between the ultrastructure and anionic microdomains of epi-, peri- and endoneurial vessels of dorsal root ganglia and sciatic nerves. PMID:1960538

  15. The effects of the acute administration of low-dosage ethanol on the phasic neurochemical oscillations of the basal ganglia.

    PubMed

    Noori, H R

    2012-09-01

    The effects of the acute ethanol consumption on the brain's neurochemistry are largely studied at the synaptic level. Here, the acute action of low dosages of ethanol, in terms of the inhibition of the glutamatergic system through antagonizing the N-methyl-D-aspartate receptors, on the neurochemical oscillations along the neurocircuitry of the basal ganglia is investigated by mathematical models. Substantial alterations in the dynamical behaviour of the neurochemical oscillations after single administration of low dosages of ethanol have been observed. Significant dynamical changes in the gamma-aminobutyric acid and glutamate systems along the subthalamic-pallidal feedback loop and the dopamine system of the striatal complex suggest new perspectives in the understanding of the ethanol-induced motor dysfunctions. PMID:21543550

  16. Nurture versus nature: long-term impact of forced right-handedness on structure of pericentral cortex and basal ganglia.

    PubMed

    Klöppel, Stefan; Mangin, Jean-Francois; Vongerichten, Anna; Frackowiak, Richard S J; Siebner, Hartwig R

    2010-03-01

    Does a conflict between inborn motor preferences and educational standards during childhood impact the structure of the adult human brain? To examine this issue, we acquired high-resolution T1-weighted magnetic resonance scans of the whole brain in adult "converted" left-handers who had been forced as children to become dextral writers. Analysis of sulcal surfaces revealed that consistent right- and left-handers showed an interhemispheric asymmetry in the surface area of the central sulcus with a greater surface contralateral to the dominant hand. This pattern was reversed in the converted group who showed a larger surface of the central sulcus in their left, nondominant hemisphere, indicating plasticity of the primary sensorimotor cortex caused by forced use of the nondominant hand. Voxel-based morphometry showed a reduction of gray matter volume in the middle part of the left putamen in converted left-handers relative to both consistently handed groups. A similar trend was found in the right putamen. Converted subjects with at least one left-handed first-degree relative showed a correlation between the acquired right-hand advantage for writing and the structural changes in putamen and pericentral cortex. Our results show that a specific environmental challenge during childhood can shape the macroscopic structure of the human basal ganglia. The smaller than normal putaminal volume differs markedly from previously reported enlargement of cortical gray matter associated with skill acquisition. This indicates a differential response of the basal ganglia to early environmental challenges, possibly related to processes of pruning during motor development. PMID:20203186

  17. 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…

  18. Temporal Coupling with Cortex Distinguishes Spontaneous Neuronal Activities in Identified Basal Ganglia-Recipient and Cerebellar-Recipient Zones of the Motor Thalamus

    PubMed Central

    Nakamura, Kouichi C.; Sharott, Andrew; Magill, Peter J.

    2014-01-01

    Neurons of the motor thalamus mediate basal ganglia and cerebellar influences on cortical activity. To elucidate the net result of ?-aminobutyric acid-releasing or glutamatergic bombardment of the motor thalamus by basal ganglia or cerebellar afferents, respectively, we recorded the spontaneous activities of thalamocortical neurons in distinct identified “input zones” in anesthetized rats during defined cortical activity states. Unexpectedly, the mean rates and brain state dependencies of the firing of neurons in basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) were matched during slow-wave activity (SWA) and cortical activation. However, neurons were distinguished during SWA by their firing regularities, low-threshold spike bursts and, more strikingly, by the temporal coupling of their activities to ongoing cortical oscillations. The firing of neurons across the BZ was stronger and more precisely phase-locked to cortical slow (?1 Hz) oscillations, although both neuron groups preferentially fired at the same phase. In contrast, neurons in BZ and CZ fired at different phases of cortical spindles (7–12 Hz), but with similar strengths of coupled firing. Thus, firing rates do not reflect the predicted inhibitory–excitatory imbalance across the motor thalamus, and input zone-specific temporal coding through oscillatory synchronization with the cortex could partly mediate the different roles of basal ganglia and cerebellum in behavior. PMID:23042738

  19. Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and co-localization with the metabotropic glutamate receptor 5 in the striatum

    E-print Network

    Hall, Randy A

    localization in the monkey basal ganglia Associate Editor: Paul Sawchenko Keywords: mGluR5, Parkinson's Disease for the treatment of Parkinson's Disease and other neurological disorders. In rodents, the therapeutic efficacy of A neuromodulator that binds to at least four known G-protein- coupled receptors in the brain (A1, A2A, A2B, and A3

  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. 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

  2. Temporal Changes of CB1 Cannabinoid Receptor in the Basal Ganglia as a Possible Structure-Specific Plasticity Process in 6-OHDA Lesioned Rats

    PubMed Central

    Chaves-Kirsten, Gabriela P.; Mazucanti, Caio H. Y.; Real, Caroline C.; Souza, Bruna M.; Britto, Luiz R. G.; Torrăo, Andréa S.

    2013-01-01

    The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson’s Disease (PD). Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP), internal globus pallidus (IGP) and substantia nigra pars reticulata (SNpr) of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH), parvalbumin, calbindin and glutamic acid decarboxylase (GAD) expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model. PMID:24116178

  3. Expression and localisation of CYP2D enzymes in rat basal ganglia

    Microsoft Academic Search

    Andrew G Riedl; Paul M Watts; Robert J Edwards; Timothy Schulz-Utermoehl; Alan R Boobis; Peter Jenner; C. David Marsden

    1999-01-01

    P450 enzymes in the CYP2D subfamily have been suggested to contribute to the susceptibility of individuals in developing Parkinson's disease. We have used specific anti-peptide antisera and peroxidase immunohistochemistry to investigate the expression of CYP2D enzymes in the rat brain and some possible factors that may affect their regulation. In male Wistar rats, CYP2D1 was not detected in the basal

  4. Model-based analysis and control of a network of basal ganglia spiking neurons in the normal and Parkinsonian states

    NASA Astrophysics Data System (ADS)

    Liu, Jianbo; Khalil, Hassan K.; Oweiss, Karim G.

    2011-08-01

    Controlling the spatiotemporal firing pattern of an intricately connected network of neurons through microstimulation is highly desirable in many applications. We investigated in this paper the feasibility of using a model-based approach to the analysis and control of a basal ganglia (BG) network model of Hodgkin-Huxley (HH) spiking neurons through microstimulation. Detailed analysis of this network model suggests that it can reproduce the experimentally observed characteristics of BG neurons under a normal and a pathological Parkinsonian state. A simplified neuronal firing rate model, identified from the detailed HH network model, is shown to capture the essential network dynamics. Mathematical analysis of the simplified model reveals the presence of a systematic relationship between the network's structure and its dynamic response to spatiotemporally patterned microstimulation. We show that both the network synaptic organization and the local mechanism of microstimulation can impose tight constraints on the possible spatiotemporal firing patterns that can be generated by the microstimulated network, which may hinder the effectiveness of microstimulation to achieve a desired objective under certain conditions. Finally, we demonstrate that the feedback control design aided by the mathematical analysis of the simplified model is indeed effective in driving the BG network in the normal and Parskinsonian states to follow a prescribed spatiotemporal firing pattern. We further show that the rhythmic/oscillatory patterns that characterize a dopamine-depleted BG network can be suppressed as a direct consequence of controlling the spatiotemporal pattern of a subpopulation of the output Globus Pallidus internalis (GPi) neurons in the network. This work may provide plausible explanations for the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's disease and pave the way towards a model-based, network level analysis and closed-loop control and optimization of DBS parameters, among many other applications. Based on 'Model-based spatiotemporal analysis and control of a network of spiking basal ganglia neurons' by Liu J, Khalil H K and Oweiss K G 2011 in the Proceedings of the 5th IEEE EMBS Conference on Neural Engineering.

  5. 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

  6. 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

  7. The basal ganglia and inhibitory mechanisms in response selection: evidence from subliminal priming of motor responses in Parkinson's disease.

    PubMed

    Seiss, Ellen; Praamstra, Peter

    2004-02-01

    Subliminal response priming was used to investigate inhibitory control processes relevant to response selection impairments in Parkinson's disease. Using a backward masking technique, covert activation of left- or right-hand responses was induced without subjects consciously perceiving the stimuli (right- or left-pointing arrows). The masked priming stimuli were followed by visible arrow stimuli, instructing for a left- or right-hand response, at a delay (interstimulus interval, ISI) of 0 or 100 ms. Motor cortex activation was recorded by means of the electroencephalographic lateralized readiness potential (LRP). Parkinson's disease patients (n = 12) were compared with age-matched controls (n = 12) and young controls (n = 10). In young controls, the ISI = 100 ms task effectively invoked inhibition of the subliminally primed responses, as demonstrated by a reversal of prime-target compatibility effects compared with the ISI = 0 ms task. This reversal implied that there was a so-called negative compatibility effect with faster responses and fewer errors when prime and target arrows pointed in opposite directions than when they required the same response. This negative compatibility effect turned into a positive compatibility effect in Parkinson's disease patients, while age-matched controls produced intermediate values. Together, these results support the view that response selection involves competitive, mutually inhibitory interactions between response alternatives, influenced by basal ganglia-thalamocortical mechanisms. As indicated by the reduced inhibition of partially activated responses, Parkinson's disease and, to a lesser degree, normal ageing affect the efficiency of these inhibitory interactions. PMID:14645146

  8. A Computational Model of Basal Ganglia and its Role in Memory Retrieval in Rewarded Visual Memory Tasks

    PubMed Central

    Vitay, Julien; Hamker, Fred H.

    2009-01-01

    Visual working memory (WM) tasks involve a network of cortical areas such as inferotemporal, medial temporal and prefrontal cortices. We suggest here to investigate the role of the basal ganglia (BG) in the learning of delayed rewarded tasks through the selective gating of thalamocortical loops. We designed a computational model of the visual loop linking the perirhinal cortex, the BG and the thalamus, biased by sustained representations in prefrontal cortex. This model learns concurrently different delayed rewarded tasks that require to maintain a visual cue and to associate it to itself or to another visual object to obtain reward. The retrieval of visual information is achieved through thalamic stimulation of the perirhinal cortex. The input structure of the BG, the striatum, learns to represent visual information based on its association to reward, while the output structure, the substantia nigra pars reticulata, learns to link striatal representations to the disinhibition of the correct thalamocortical loop. In parallel, a dopaminergic cell learns to associate striatal representations to reward and modulates learning of connections within the BG. The model provides testable predictions about the behavior of several areas during such tasks, while providing a new functional organization of learning within the BG, putting emphasis on the learning of the striatonigral connections as well as the lateral connections within the substantia nigra pars reticulata. It suggests that the learning of visual WM tasks is achieved rapidly in the BG and used as a teacher for feedback connections from prefrontal cortex to posterior cortices. PMID:20725505

  9. One View of the Current State of Understanding in Basal Ganglia Pathophysiology and What is Needed for the Future

    PubMed Central

    Montgomery, Erwin B.

    2011-01-01

    Deep Brain Stimulation (DBS), arguably, is the most dramatic development in movement disorders since the levodopa for Parkinson’s disease. Yet, its mechanisms of action of DBS are unknown. However, DBS related research already has demonstrated that current concepts of basal ganglia pathophysiology are wrong. Specifically, the notion that over-activity of the globus pallidus interna causes parkinsonism, the basis for the most current theories, is no longer tenable. The development of any new theory will be aided by an understanding of how current theories are wrong and why have these flawed theories persist. Many of the problems of current theories are more matters of inference, assumptions, presumptions, and the accepted level of ambiguity than they are of fact. Consequently, it is imperative that these issues be addressed. Just as the inappropriate use of a tool or method is grounds for criticism, methods of reasoning are tools that can be used inappropriately and should be subject to discussion just as misuse of any other tool. Thorough criticism can provide very important lesions though the process could be mistaken as harsh or personal; neither is the case here. At the least, such analyzes can point to potential pitfalls that could be avoided in the development of new theories. As will be discussed, theories are important for the development of therapies but perhaps most important, for the acceptance of new therapies, as was the case for the recent resurgence of interest in surgical therapies. PMID:24868387

  10. An Avian Basal Ganglia-Forebrain Circuit Contributes Differentially to Syllable Versus Sequence Variability of Adult Bengalese Finch Song

    PubMed Central

    Hampton, Cara M.; Sakata, Jon T.; Brainard, Michael S.

    2009-01-01

    Behavioral variability is important for motor skill learning but continues to be present and actively regulated even in well-learned behaviors. In adult songbirds, two types of song variability can persist and are modulated by social context: variability in syllable structure and variability in syllable sequencing. The degree to which the control of both types of adult variability is shared or distinct remains unknown. The output of a basal ganglia-forebrain circuit, LMAN (the lateral magnocellular nucleus of the anterior nidopallium), has been implicated in song variability. For example, in adult zebra finches, neurons in LMAN actively control the variability of syllable structure. It is unclear, however, whether LMAN contributes to variability in adult syllable sequencing because sequence variability in adult zebra finch song is minimal. In contrast, Bengalese finches retain variability in both syllable structure and syllable sequencing into adulthood. We analyzed the effects of LMAN lesions on the variability of syllable structure and sequencing and on the social modulation of these forms of variability in adult Bengalese finches. We found that lesions of LMAN significantly reduced the variability of syllable structure but not of syllable sequencing. We also found that LMAN lesions eliminated the social modulation of the variability of syllable structure but did not detect significant effects on the modulation of sequence variability. These results show that LMAN contributes differentially to syllable versus sequence variability of adult song and suggest that these forms of variability are regulated by distinct neural pathways. PMID:19357331

  11. Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging.

    PubMed

    O'Sullivan, R L; Rauch, S L; Breiter, H C; Grachev, I D; Baer, L; Kennedy, D N; Keuthen, N J; Savage, C R; Manzo, P A; Caviness, V S; Jenike, M A

    1997-07-01

    A morphometric magnetic resonance imaging (MRI) study compared volumes of brain structures in 10 female subjects with trichotillomania (repetitive hair-pulling) versus 10 normal controls matched for sex, age, handedness, and education. Three-dimensional MRI scans were blindly normalized and segmented using well-characterized semiautomated intensity and differential contour algorithms by signal intensity-frequency histograms. Consistent with one a priori hypothesis, left putamen volume was found to be significantly smaller in trichotillomania subjects as compared with normal matched controls. This is the first report of a structural brain abnormality in trichotillomania. Results are discussed in terms of putative relationships between trichotillomania, Tourette's syndrome, and obsessive-compulsive disorder. PMID:9193740

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

    PubMed

    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

  13. 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

  14. Loss of cannabinoid CB 1 receptors in the basal ganglia in the late akinetic phase of rats with experimental Huntington’s disease

    Microsoft Academic Search

    Isabel Lastres-Becker; María Gómez; Rosario de Miguel; José A. Ramos; Javier Fernández-Ruiz

    2002-01-01

    We have recently examined the status of the endocannabinoid transmission in the basal ganglia in Huntington’s disease (HD)\\u000a using a rat model generated by bilateral intrastriatal injections of 3-nitropropionic acid (3-NP). In these previous studies,\\u000a we focused on the early phase of hyperactivity that occurs 1–2 weeks after the lesion, comparable to early grades of the human\\u000a disease, while in

  15. Common Features of Neural Activity during Singing and Sleep Periods in a Basal Ganglia Nucleus Critical for Vocal Learning in a Juvenile Songbird

    PubMed Central

    Yanagihara, Shin; Hessler, Neal A.

    2011-01-01

    Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase. PMID:21991379

  16. Transsylvian-Transinsular Approach for Deep-Seated Basal Ganglia Hemorrhage: An Experience at a Single Institution

    PubMed Central

    Kim, Seung Hwan; Kim, Hae Yu; Lee, Sun-il

    2015-01-01

    Objective Treatment of spontaneous intracerebral hemorrhage (ICH) remains controversial. However, an extensive hemorrhage with a poor mental status is suitable for surgical evacuation. Our experience with the transsylvian-transinsular (TS-TI) microsurgical approach for deep-seated basal ganglia (BG) ICH was investigated. Material and Methods A retrospective review was conducted on 86 patients with BG ICH who underwent an operation at the Department of Neurosurgery of our Hospital from September 2011 to October 2014. Thirteen patients underwent craniotomy and the TS-TI microsurgical approach for hematoma evacuation. Twenty-seven patients underwent conventional craniotomy with the trans-cortical transtemporal (TC-TT) approach, and 46 patients underwent a burrhole operation and hematoma drainage using a frameless stereotaxic device (ST). Results The average age distribution was similar. The preoperative Glasgow coma scale (GCS) was similar for the TC-TT and TS-TI groups. The pre-operative hematoma levels were higher in the TC-TT (109.4 ± 48.6 mL) and TS-TI (96.0 ± 39.0 mL) groups than in the ST group (46.5 ± 23.5 mL). The hematoma removal rate was 77% in the TC-TT group, 88% in the TS-TI group, and 34% in the ST group. The mean maintenance period of a hematoma catheter was 3.6 days in the ST group. The clinical outcome showed correlation with the preoperative neurological symptoms. Conclusion The TS-TI group was superior to the TC-TT group for evacuation of an intracerebral hematoma.

  17. Cortico-basal ganglia networks subserving goal-directed behavior mediated by conditional visuo-goal association

    PubMed Central

    Hoshi, Eiji

    2013-01-01

    Action is often executed according to information provided by a visual signal. As this type of behavior integrates two distinct neural representations, perception and action, it has been thought that identification of the neural mechanisms underlying this process will yield deeper insights into the principles underpinning goal-directed behavior. Based on a framework derived from conditional visuomotor association, prior studies have identified neural mechanisms in the dorsal premotor cortex (PMd), dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), and basal ganglia (BG). However, applications resting solely on this conceptualization encounter problems related to generalization and flexibility, essential processes in executive function, because the association mode involves a direct one-to-one mapping of each visual signal onto a particular action. To overcome this problem, we extend this conceptualization and postulate a more general framework, conditional visuo-goal association. According to this new framework, the visual signal identifies an abstract behavioral goal, and an action is subsequently selected and executed to meet this goal. Neuronal activity recorded from the four key areas of the brains of monkeys performing a task involving conditional visuo-goal association revealed three major mechanisms underlying this process. First, visual-object signals are represented primarily in the vlPFC and BG. Second, all four areas are involved in initially determining the goals based on the visual signals, with the PMd and dlPFC playing major roles in maintaining the salience of the goals. Third, the cortical areas play major roles in specifying action, whereas the role of the BG in this process is restrictive. These new lines of evidence reveal that the four areas involved in conditional visuomotor association contribute to goal-directed behavior mediated by conditional visuo-goal association in an area-dependent manner. PMID:24155692

  18. Endocannabinoids mediate synaptic plasticity at glutamatergic synapses on spiny neurons within a basal ganglia nucleus necessary for song learning

    PubMed Central

    Thompson, John A.

    2011-01-01

    Activation of type 1 cannabinoid receptors (CB1R) in many central nervous system structures induces both short- and long-term changes in synaptic transmission. Within mammalian striatum, endocannabinoids (eCB) are one of several mechanisms that induce synaptic plasticity at glutamatergic terminals onto medium spiny neurons. Striatal synaptic plasticity may contribute a critical component of adaptive motor coordination and procedural learning. Songbirds are advantageous for studying the neural mechanisms of motor learning because they possess a neural pathway necessary for song learning and adult song plasticity that includes a striato-pallidal nucleus, area X (homologous to a portion of mammalian basal ganglia). Recent findings suggest that eCBs contribute to vocal development. For example, dense CB1R expression in song control nuclei peaks around the closure of the sensori-motor integration phase of song development. Also, systemic administration of a CB1R agonist during vocal development impairs song learning. Here we test whether activation of CB1R alters excitatory synaptic input on spiny neurons in area X of adult male zebra finches. Application of the CB1R agonist WIN55212–2 decreased excitatory postsynaptic current (EPSC) amplitude; that decrease was blocked by the CB1R antagonist AM251. Guided by eCB experiments in mammalian striatum, we tested and verified that at least two mechanisms indirectly activate CB1Rs through eCBs in area X. First, activation of group I metabotropic glutamate receptors with the agonist 3,5-dihydroxyphenylglycine (DHPG) induced a CB1R-mediated reduction in EPSC amplitude. Second, we observed that a 10 s postsynaptic depolarization induced a calcium-mediated, eCB-dependent decrease in synaptic strength that resisted rescue with late CB1R blockade. Together, these results show that eCB modulation occurs at inputs to area X spiny neurons and could influence motor learning and production. PMID:21177997

  19. Striatal dopamine modulates basal ganglia output and regulates social context-dependent behavioral variability through D1 receptors

    PubMed Central

    Leblois, Arthur; Wendel, Benjamin J.; Perkel, David J

    2010-01-01

    Cortico–basal ganglia (BG) circuits are thought to promote the acquisition of motor skills through reinforcement learning. In songbirds, a specialized portion of the BG is responsible for song learning and plasticity. This circuit generates song variability that underlies vocal experimentation in young birds and modulates song variability depending on the social context in adult birds. When male birds sing in the presence of a female, a social context associated with decreased BG-induced song variability, the extracellular dopamine (DA) level is increased in the avian BG nucleus Area X. These results suggest that DA could trigger song variability changes through its action in Area X. Consistent with this hypothesis, we report that DA delivered to Area X weakens the output signal of the avian cortico-BG circuit. Acting through D1 receptors, DA reduced responses in Area X to song playback and to electrical stimulation of its afferent cortical nucleus HVC. Specifically, DA reduced the response to direct excitatory input and decreased firing variability in Area X pallidal neurons, which provide the output to the thalamus. As a consequence, DA delivery in Area X also decreased responses to song playback in the cortical output nucleus of the BG loop, the lateral magnocellular nucleus of the anterior nidopallium (LMAN). Further, interfering with D1 receptor transmission in Area X abolished social context-related changes in song variability. In conclusion, we propose that DA acts on D1 receptors in Area X to modulate the BG output signal and trigger changes in song variability. PMID:20410125

  20. Basal ganglia dysfunction

    MedlinePLUS

    ... 71. Lang AE. Parkinsonism. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... AE. Other movement disorders. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  1. 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

  2. [A role of dopamine-dependent activity reorganizations in the cortico-basal ganglia-thalamocortical loops in visual attention (hypothetical mechanism)].

    PubMed

    Sil'kis, I G

    2007-01-01

    A mechanism of attention is proposed according to which its influence on visual processing is switched on by release of dopamine into the striatum. A dopamine release during involuntary attention is promoted by visual activation of striatonigral cells via the thalamus and subsequent disinhibition through the basal ganglia of the superior colliculus. A dopamine release during voluntary attention is promoted by activation of prefrontal cortex. The strengthening of responses of neocortical neurons to attended stimulus, and suppression of responses to other stimuli is the result of opposite modulatory action of dopamine on the efficacy of strong and weak corticostriatal inputs. This leads to changes in the output basal ganglia signals ("attentional filter") that exert disinhibitory and inhibitory influence (via the thalamus) on neocortical cells that initially were strongly and weakly activated by a stimulus, respectively. From proposed mechanism follows, that attention modulates only those components of responses of cortical neurons which latency exceeds the latency of reactions of dopaminergic cells (80-100 ms). PMID:18064906

  3. Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.

    PubMed

    Haroon, Ebrahim; Felger, Jennifer C; Woolwine, Bobbi J; Chen, Xiangchuan; Parekh, Samir; Spivey, James R; Hu, Xiaoping P; Miller, Andrew H

    2015-05-01

    Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate turnover by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit 1) and after 4weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly greater increase in glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior. PMID:25500218

  4. Differentiation of sCJD and vCJD forms by automated analysis of basal ganglia intensity distribution in multisequence MRI of the brain-definition and evaluation of new MRI-based ratios

    Microsoft Academic Search

    Marius George Linguraru; Nicholas Ayache; Eric Bardinet; Miguel Ángel González Ballester; Damien Galanaud; Stéphane Haďk; Baptiste Faucheux; J.-J. Hauw; Patrick Cozzone; Didier Dormont; Jean-philippe Brandel

    2006-01-01

    We present a method for the analysis of basal ganglia (including the thalamus) for accurate detection of human spongiform encephalopathy in multisequence magnetic resonance imaging (MRI) of the brain. One common feature of most forms of prion protein diseases is the appearance of hyperintensities in the deep grey matter area of the brain in T2-weighted magnetic resonance (MR) images. We

  5. Int J Comput Assist Radiol Surg . Author manuscript Automated segmentation of basal ganglia and deep brain structures in MRI

    E-print Network

    Paris-Sud XI, Université de

    Int J Comput Assist Radiol Surg . Author manuscript Page /1 12 Automated segmentation of basal, VISAGES : Vision Action et Gestion d Informations en Sant1 ' é INSERM : U746 , CNRS : UMR6074 , INRIA,' and less frequently to dystonia that is a syndrome of sustained muscle contractions producing writhing

  6. Differential gene expression for glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase in basal ganglia, thalamus, and hypothalamus of the monkey

    SciTech Connect

    Benson, D.L.; Isackson, P.J.; Hendry, S.H.; Jones, E.G. (Department of Anatomy, University of California, Irvine (USA))

    1991-06-01

    In situ hybridization histochemistry, using cRNA probes, revealed a complementarity in the distributions of cells in the basal ganglia, basal nucleus of Meynert, thalamus, hypothalamus, and rostral part of the midbrain that showed gene expression for glutamic acid decarboxylase (GAD) or the alpha-subunit of type II calcium-calmodulin-dependent protein kinase (CAM II kinase-alpha). Cells in certain nuclei such as the thalamic reticular nucleus, globus pallidus, and pars reticulata of the substantia nigra show GAD gene expression only; others in nuclei such as the basal nucleus of Meynert, medial mamillary nuclei, and ventromedial hypothalamic nuclei show CAM II kinase-alpha gene expression only. A few nuclei, for example, the pars compacta of the substantia nigra and the greater part of the subthalamic nucleus, display gene expression for neither GAD nor CAM II kinase-alpha. In other nuclei, notably those of the dorsal thalamus, and possibly in the striatum, GAD- and CAM II kinase-expressing cells appear to form two separate populations that, in most thalamic nuclei, together account for the total cell population. In situ hybridization reveals large amounts of CAM II kinase-alpha mRNA in the neuropil of most nuclei containing CAM II kinase-alpha-positive cells, suggesting its association with dendritic polyribosomes. The message may thus be translated at those sites, close to the synapses with which the protein is associated. The in situ hybridization results, coupled with those from immunocytochemical staining for CAM II kinase-alpha protein, indicate that CAM II kinase-alpha is commonly found in certain non-GABAergic afferent fiber systems but is not necessarily present in the postsynaptic cells on which they terminate. It appears to be absent from most GABAergic fiber systems but can be present in the cells on which they terminate.

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

    PubMed

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

    2013-08-01

    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 after local inflammation of the rat lumbar sensory ganglia. In normal dorsal root ganglion (DRG), quantitative polymerase chain reaction 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 mediated primarily by myelinated A fiber sensory neurons. PMID:23622763

  8. Hypothalamic and basal ganglia projections to the posterior thalamus: Possible role in modulation of migraine headache and photophobia

    PubMed Central

    Kagan, Ruth; Kainz, Vanessa; Burstein, Rami; Noseda, Rodrigo

    2013-01-01

    Migraine attacks are typically described as unilateral, throbbing pain that is usually accompanied by nausea, vomiting, and exaggerated sensitivities to light, noise and smell. The headache phase of a migraine attack is mediated by activation of the trigeminovascular pathway; a nociceptive pathway that originates in the meninges and carries pain signals through meningeal nociceptors to the spinal trigeminal nucleus and from there to the cortex through relay neurons in the thalamus. Recent studies in our lab have identified a population of trigeminovascular neurons in the posterior (Po) and lateral posterior (LP) thalamic nuclei that may be involved in the perception of whole-body allodynia (abnormal skin sensitivity) and photophobia (abnormal sensitivity to light) during migraine. The purpose of the current study was to identify sub-cortical areas that are in position to directly regulate the activity of these thalamic trigeminovascular neurons. Such process begins with anatomical mapping of neuronal projections to the posterior thalamus of the rat by performing discrete injections of the retrograde tracer Fluorogold into the Po/LP region. Such injections yielded retrogradely labeled neurons in the nucleus of the diagonal band of Broca, the dopaminergic cells group A11/A13, the ventromedial and ventral tuberomamillary nuclei of the hypothalamus. We also found that some of these neurons contain acetylcholine, dopamine, cholecystokinin and histamine, respectively. Accordingly, we speculate that these forebrain/hypothalamic projections to Po and LP may play a role in those migraine attacks triggered by disrupted sleep, skipping meals and emotional reactions. PMID:23806720

  9. 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

  10. 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 Deurwaerdčre, 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

  11. Memory, Mood, Dopamine, and Serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Lesioned Mouse Model of Basal Ganglia Injury

    PubMed Central

    Vu?kovi?, Marta G.; Wood, Ruth I.; Holschneider, Daniel P.; Abernathy, Avery; Togasaki, Daniel M.; Smith, Alexsandra; Petzinger, Giselle M.; Jakowec, Michael W.

    2012-01-01

    The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as a model of basal ganglia injury and Parkinson’s disease. The present study investigated the effects of MPTP-induced lesioning on associative memory, conditioned fear, and affective behavior. Male C57BL/6 mice were administered saline or MPTP and separate groups were evaluated at either 7 or 30 days post-lesioning. In the social transmission of food preference test, mice showed a significant decrease in preference for familiar food 30 days post-MPTP compared to controls. Mice at both 7 and 30 days post-MPTP-lesioning had increased fear extinction compared to controls. HPLC analysis of tissues homogenates showed dopamine and serotonin were depleted in the striatum, frontal cortex, and amygdala. No changes in anxiety or depression were detected by the tail suspension, sucrose preference, light-dark preference, or hole-board tests. In conclusion, acute MPTP-lesioning regimen in mice causes impairments in associative memory and conditioned fear, no mood changes, and depletion of dopamine and serotonin throughout the brain. PMID:18718537

  12. 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, Mercč

    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

  13. 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

  14. 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

  15. Expression of c-fos mRNA in the basal ganglia associated with contingent tolerance to amphetamine-induced hypophagia.

    PubMed

    Bachand, Kimberlee D; Guthrie, Kathleen M; Wolgin, David L

    2009-03-17

    Tolerance to the hypophagic effect of psychostimulants is contingent on having access to food while intoxicated. Rats given chronic injections of such drugs with access to food learn to suppress stereotyped movements, which interfere with feeding. In contrast, controls given the drug after food access do not learn to suppress stereotypy and, therefore, do not become tolerant. To determine the role of the basal ganglia in this phenomenon, we used in situ hybridization to measure the expression of c-fos mRNA, a marker for neural activation, in the brains of tolerant and nontolerant rats. Rats given chronic amphetamine injections prior to food access learned to suppress stereotyped movements, whereas yoked controls given the drug after feeding did not. Following an acute injection of amphetamine, both of these groups had higher levels of c-fos mRNA than saline-treated controls throughout the striatum, in the nucleus accumbens core, the ventral pallidum and layers V-VI of the motor cortex. In contrast, tolerant rats, which had learned to suppress stereotypy, had higher levels of c-fos mRNA than both amphetamine- and saline-treated controls in the entopeduncular nucleus, globus pallidus, subthalamic nucleus, pedunculopontine nucleus, nucleus accumbens shell, olfactory tubercle, somatosensory cortex, and layers II-IV of motor cortex. These data suggest that the learned suppression of amphetamine-induced stereotypy involves the activation of dorsal striatal pathways previously implicated in response selection as well as the ventral striatum, long implicated in appetitive motivation and reinforcement. PMID:19084559

  16. Characterization and distribution of (125I)epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain

    SciTech Connect

    Joyce, J.N.; Janowsky, A.; Neve, K.A. (Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia (USA))

    1991-06-01

    The distribution and pharmacology of the binding of {sup 125}I-epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain is described in human brain. Saturation analysis of the binding of {sup 125}I-epidepride to membranes derived from striatum and regions of cortex demonstrated similar Kd values (34 and 28-33 pM, respectively) but differing maximum density of binding site values (152 and 3-8 fmol/mg of protein, respectively). The pharmacological profile of binding in cortex was also similar to striatum (epidepride greater than spiperone greater than butaclamol = flupenthixol greater than clozapine) except that an additional low-affinity site, blocked by the alpha-2 adrenergic antagonist idazoxan, was present in cortex. Quantification by autoradiography also demonstrated the greatest binding in the basal ganglia, with the striatum exhibiting greater binding than the pallidal complex or midbrain regions. For the pallidum, binding in the external segment was higher than the internal segment. Within the midbrain the binding of {sup 125}I-epidepride correlated well with the known distribution of DA-containing cell bodies, with the substantia nigra (pars compacta and pars lateralis) and ventral tegmental area (A10) higher than area A8 and central gray. Binding in frontal and parietal cortex was highest in the internal layers (layers V and VI). Temporal cortex showed a 2-fold higher density of binding than other cortical regions and a trilaminar pattern; binding was greater in the external (layers I and II) and internal layers than in the middle layers (III and IV). This pattern changed in the parahippocampal complex. Within the lateral occipitotemporal cortex, binding was densest in layers I to III and very low in layers IV to VI, but binding was almost nonexistent in the adjacent entorhinal cortex.

  17. Selected Gray Matter Volumes and Gender but Not Basal Ganglia nor Cerebellum Gyri Discriminate Left Versus Right Cerebral Hemispheres: Multivariate Analyses in human Brains at 3T.

    PubMed

    Roldan-Valadez, Ernesto; Suarez-May, Marcela A; Favila, Rafael; Aguilar-Castańeda, Erika; Rios, Camilo

    2015-07-01

    Interest in the lateralization of the human brain is evident through a multidisciplinary number of scientific studies. Understanding volumetric brain asymmetries allows the distinction between normal development stages and behavior, as well as brain diseases. We aimed to evaluate volumetric asymmetries in order to select the best gyri able to classify right- versus left cerebral hemispheres. A cross-sectional study performed in 47 right-handed young-adults healthy volunteers. SPM-based software performed brain segmentation, automatic labeling and volumetric analyses for 54 regions involving the cerebral lobes, basal ganglia and cerebellum from each cerebral hemisphere. Multivariate discriminant analysis (DA) allowed the assembling of a predictive model. DA revealed one discriminant function that significantly differentiated left vs. right cerebral hemispheres: Wilks' ??=?0.008, ?(2) (9)?=?238.837, P?

  18. Expression of c-fos mRNA in the Basal Ganglia Associated with Contingent Tolerance to Amphetamine-Induced Hypophagia

    PubMed Central

    Bachand, Kimberlee D.; Guthrie, Kathleen M.; Wolgin, David L.

    2009-01-01

    Tolerance to the hypophagic effect of psychostimulants is contingent on having access to food while intoxicated. Rats given chronic injections of such drugs with access to food learn to suppress stereotyped movements, which interfere with feeding. In contrast, controls given the drug after food access do not learn to suppress stereotypy and, therefore, do not become tolerant. To determine the role of the basal ganglia in this phenomenon, we used in situ hybridization to measure the expression of c-fos mRNA, a marker for neural activation, in the brains of tolerant and nontolerant rats. Rats given chronic amphetamine injections prior to food access learned to suppress stereotyped movements, whereas yoked controls given the drug after feeding did not. Following an acute injection of amphetamine, both of these groups had higher levels of c-fos mRNA than saline-treated controls throughout the striatum, in the nucleus accumbens core, the ventral pallidum and layers V–VI of the motor cortex. In contrast, tolerant rats, which had learned to suppress stereotypy, had higher levels of c-fos mRNA than both amphetamine- and saline-treated controls in the entopeduncular nucleus, globus pallidus, subthalamic nucleus, pedunculopontine nucleus, nucleus accumbens shell, olfactory tubercle, somatosensory cortex, and layers II–IV of motor cortex. These data suggest that the learned suppression of amphetamine-induced stereotypy involves the activation of dorsal striatal pathways previously implicated in response selection as well as the ventral striatum, long implicated in appetitive motivation and reinforcement. PMID:19084559

  19. Prior MDMA (Ecstasy) use is associated with increased basal ganglia–thalamocortical circuit activation during motor task performance in humans: An fMRI study

    PubMed Central

    Karageorgiou, John; Dietrich, Mary S.; Charboneau, Evonne J.; Woodward, Neil D.; Blackford, Jennifer U.; Salomon, Ronald M.; Cowan, Ronald L.

    2009-01-01

    MDMA (3,4-methylenedioxymethamphetamine; Ecstasy) is a popular recreational drug that produces long-lasting serotonin (5-HT) neurotoxicity consisting of reductions in markers for 5-HT axons. 5-HT innervates cortical and subcortical brain regions mediating motor function, predicting that MDMA users will have altered motor system neurophysiology. We used functional magnetic resonance imaging (fMRI) to assay motor task performance-associated brain activation changes in MDMA and non-MDMA users. 24 subjects (14 MDMA users and 10 controls) performed an event-related motor tapping task (1, 2 or 4 taps) during fMRI at 3 T. Motor regions of interest were used to measure percent signal change (PSC) and percent activated voxels (PAV) in bilateral motor cortex, sensory cortex, supplementary motor area (SMA), caudate, putamen, pallidum and thalamus. We used SPM5 to measure brain activation via three methods: T-maps, PSC and PAV. There was no statistically significant difference in reaction time between the two groups. For the Tap 4 condition, MDMA users had more activation than controls in the right SMA for T-score (p = 0.02), PSC (p = 0.04) and PAV (p = 0.03). Lifetime episodes of MDMA use were positively correlated with PSC for the Tap 4 condition on the right for putamen and pallidum; with PAV in the right motor and sensory cortex and bilateral thalamus. In conclusion, we found a group difference in the right SMA and positive dose–response association between lifetime exposure to MDMA and signal magnitude and extent in several brain regions. This evidence is consistent with MDMA-induced alterations in basal ganglia–thalamocortical circuit neurophysiology and is potentially secondary to neurotoxic effects on 5-HT signaling. Further studies examining behavioral correlates and the specific neurophysiological basis of the observed findings are warranted. PMID:19264142

  20. 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

  1. A network model of basal ganglia for understanding the roles of dopamine and serotonin in reward-punishment-risk based decision making

    PubMed Central

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

    2015-01-01

    There is significant evidence that in addition to reward-punishment based decision making, the Basal Ganglia (BG) contributes to risk-based decision making (Balasubramani et al., 2014). Despite this evidence, little is known about the computational principles and neural correlates of risk computation in this subcortical system. We have previously proposed a reinforcement learning (RL)-based model of the BG that simulates the interactions between dopamine (DA) and serotonin (5HT) in a diverse set of experimental studies including reward, punishment and risk based decision making (Balasubramani et al., 2014). Starting with the classical idea that the activity of mesencephalic DA represents reward prediction error, the model posits that serotoninergic activity in the striatum controls risk-prediction error. Our prior model of the BG was an abstract model that did not incorporate anatomical and cellular-level data. In this work, we expand the earlier model into a detailed network model of the BG and demonstrate the joint contributions of DA-5HT in risk and reward-punishment sensitivity. At the core of the proposed network model is the following insight regarding cellular correlates of value and risk computation. Just as DA D1 receptor (D1R) expressing medium spiny neurons (MSNs) of the striatum were thought to be the neural substrates for value computation, we propose that DA D1R and D2R co-expressing MSNs are capable of computing risk. Though the existence of MSNs that co-express D1R and D2R are reported by various experimental studies, prior existing computational models did not include them. Ours is the first model that accounts for the computational possibilities of these co-expressing D1R-D2R MSNs, and describes how DA and 5HT mediate activity in these classes of neurons (D1R-, D2R-, D1R-D2R- MSNs). Starting from the assumption that 5HT modulates all MSNs, our study predicts significant modulatory effects of 5HT on D2R and co-expressing D1R-D2R MSNs which in turn explains the multifarious functions of 5HT in the BG. The experiments simulated in the present study relates 5HT to risk sensitivity and reward-punishment learning. Furthermore, our model is shown to capture reward-punishment and risk based decision making impairment in Parkinson's Disease (PD). The model predicts that optimizing 5HT levels along with DA medications might be essential for improving the patients' reward-punishment learning deficits.

  2. 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

  3. 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

  4. 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…

  5. 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

    2015-05-01

    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

  6. Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis

    Microsoft Academic Search

    Eun Yeon Joo; Seung Bong Hong; Woo Suk Tae; Jee Hyun Kim; Sun Jung Han; Dae Won Seo; Kyung-Han Lee; Myoung-Hee Kim; Seunghwan Kim; Mann Hyung Lee; Byung Tae Kim

    2005-01-01

    Purpose: Previous cerebral blood flow and glucose metabolism studies suggest that the basal ganglia or thalamus is involved in the pathogenesis of paroxysmal kinesigenic choreoathetosis (PKC). However, the under- lying cerebral abnormalities in idiopathic PKC have not been elucidated. To localise cerebral perfusion abnormal- ities in PKC, we performed interictal brain perfusion 99m Tc-ethylcysteinate dimer (ECD) single-photon emis- sion computed

  7. 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

  8. Cortico-Basal Ganglia Reward Network: Microcircuitry

    Microsoft Academic Search

    Susan R Sesack; Anthony A Grace; AA Grace

    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

  9. 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

  10. Abnormal apical-to-basal transport of dietary ovalbumin by secretory IgA stimulates a mucosal Th1 response.

    PubMed

    Abed, J; Lebreton, C; Champier, G; Cuvillier, A; Cogné, M; Meresse, B; Dugave, C; Garfa-Traoré, M; Corthésy, B; Cerf-Bensussan, N; Heyman, M

    2014-03-01

    In celiac disease, enhanced permeability to gliadin peptides can result from their apico-basal transport by secretory immunoglobulin A1 (SIgA1) binding to the CD71 receptor ectopically expressed at the gut epithelial surface. Herein, we have established a mouse model in which there is apico-basal transport of the model antigen ovalbumin (OVA) by specific SIgA1 and have analyzed local T-cell activation. Transgenic DO11.10 mice were grafted with a hybridoma-secreting OVA-specific humanized IgA1, which could bind mouse CD71 and which were released in the intestinal lumen as SIgA. CD71 expression was induced at the gut apical surface by treating the mice with tyrphostin A8. Following gavage of the mice with OVA, OVA-specific CD4? T cells isolated from the mesenteric lymph nodes displayed higher expression of the activation marker CD69 and produced more interferon gamma in mice bearing the hybridoma-secreting OVA-specific IgA1, than in ungrafted mice or in mice grafted with an irrelevant hybridoma. These results indicate that the protective role of SIgA1 might be jeopardized in human pathological conditions associated with ectopic expression of CD71 at the gut surface. PMID:23839063

  11. 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

  12. 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 ...

  13. 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.

  14. Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye

    Microsoft Academic Search

    Nicola A. Grzeschik; Nancy Amin; Julie Secombe; Anthony M. Brumby; Helena E. Richardson

    2007-01-01

    In homozygous mutants of Drosophila lethal-2-giant larvae (lgl), tissues lose apico-basal cell polarity and exhibit ectopic proliferation. Here, we use clonal analysis in the developing eye to investigate the effect of lgl null mutations in the context of surrounding wild-type tissue. lgl? clones in the larval eye disc exhibit ectopic expression of the G1–S regulator, Cyclin E, and ectopic proliferation,

  15. Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye.

    PubMed

    Grzeschik, Nicola A; Amin, Nancy; Secombe, Julie; Brumby, Anthony M; Richardson, Helena E

    2007-11-01

    In homozygous mutants of Drosophila lethal-2-giant larvae (lgl), tissues lose apico-basal cell polarity and exhibit ectopic proliferation. Here, we use clonal analysis in the developing eye to investigate the effect of lgl null mutations in the context of surrounding wild-type tissue. lgl- clones in the larval eye disc exhibit ectopic expression of the G1-S regulator, Cyclin E, and ectopic proliferation, but do not lose apico-basal cell polarity. Decreasing the perdurance of Lgl protein in larval eye disc clones, by forcing extra proliferation of lgl- tissue (using a Minute background), leads to a loss in cell polarity and to more extreme ectopic cell proliferation. Later in development at the pupal stage, lgl mutant photoreceptor cells show aberrant apico-basal cell polarity, but this is not associated with ectopic proliferation, presumably because cells are differentiated. Thus in a clonal context, the ectopic proliferation and cell polarity defects of lgl- mutants are separable. Furthermore, lgl- mosaic eye discs have alterations in the normal patterns of apoptosis: in larval discs some lgl- and wild-type cells at the clonal boundary undergo apoptosis and are excluded from the epithelia, but apoptosis is decreased elsewhere in the disc, and in pupal retinas lgl- tissue shows less apoptosis. PMID:17870065

  16. Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye

    PubMed Central

    Grzeschik, Nicola A.; Amin, Nancy; Secombe, Julie; Brumby, Anthony M.; Richardson, Helena E.

    2010-01-01

    In homozygous mutants of Drosophila lethal-2-giant larvae (lgl), tissues lose apico-basal cell polarity and exhibit ectopic proliferation. Here, we use clonal analysis in the developing eye to investigate the effect of lgl null mutations in the context of surrounding wild-type tissue. lgl? clones in the larval eye disc exhibit ectopic expression of the G1-S regulator, Cyclin E, and ectopic proliferation, but do not lose apico-basal cell polarity. Decreasing the perdurance of Lgl protein in larval eye disc clones, by forcing extra proliferation of lgl? tissue (using a Minute background), leads to a loss in cell polarity and to more extreme ectopic cell proliferation. Later in development at the pupal stage, lgl mutant photoreceptor cells show aberrant apico-basal cell polarity, but this is not associated with ectopic proliferation, presumably because cells are differentiated. Thus in a clonal context, the ectopic proliferation and cell polarity defects of lgl? mutants are separable. Furthermore, lgl? mosaic eye discs have alterations in the normal patterns of apoptosis: in larval discs some lgl? and wild-type cells at the clonal boundary undergo apoptosis and are excluded from the epithelia, but apoptosis is decreased elsewhere in the disc, and in pupal retinas lgl? tissue shows less apoptosis. PMID:17870065

  17. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in treating neurodegenerative disorders.

  18. Genetics Home Reference: Familial idiopathic basal ganglia calcification

    MedlinePLUS

    ... the front of the brain are involved in reasoning, planning, judgment, and problem-solving. The regions of ... more about genetic testing , particularly the difference between clinical tests and research tests . To locate a healthcare ...

  19. Dissociating Hippocampal versus Basal Ganglia Contributions to Learning and Transfer

    E-print Network

    Shohamy, Daphna

    Parkinson's disease, and healthy controls, using an ``acquired equivalence'' associative learning task, but not the hippocampus, play a critical role in stimulus­response- based habit learning (e.g., White, 1997; Knowlton for learning simple stimulus­response-based learning, it does appear to be critical for some forms of more

  20. Basal Ganglia Engagement during Feedback Processing after a Substantial Delay

    PubMed Central

    Dobryakova, Ekaterina; Tricomi, Elizabeth

    2013-01-01

    The striatum has been shown to play an important role in learning from performance-related feedback that is presented shortly after each response. However, less is known about the neural mechanisms supporting learning from feedback that is substantially delayed from the original response. Since the consequences of one’s actions often do not become known until after a delay, it is important to understand whether delayed feedback can produce neural responses similar to those elicited by immediate feedback presentation. We investigated this issue by using functional magnetic resonance imaging (fMRI) as participants performed a paired-associate learning task with 180 distinct trials. Feedback indicating response accuracy was presented immediately, after a delay of 25 minutes, or not at all. Both immediate and delayed feedback led to significant gains in accuracy on a post-test, relative to no feedback. Replicating previous work, we found that the caudate nuclei showed greater activation for positive feedback than negative feedback when the feedback was presented immediately. In addition, delayed feedback also led to differential caudate activity to positive versus negative feedback. Delayed negative feedback also produced significant activation of the putamen and globus pallidus (the lentiform nucleus), relative to no feedback and delayed positive feedback. This suggests that the caudate nucleus is sensitive to the affective nature of feedback, across different timescales, while the lentiform nucleus may be particularly involved in processing the information carried by negative feedback after a substantial delay. PMID:23817894

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

    MedlinePLUS

    ... facial palsy), paralysis of the eye muscles (external ophthalmoplegia), difficulty chewing or swallowing (dysphagia), and slurred speech. ... inherited ; injury ; involuntary ; metabolism ; motor ; nervous system ; neurological ; ... prevalence ; protein ; psychomotor ; quadriparesis ; recessive ; seizure ; syndrome ; ...

  2. RESEARCH ARTICLE Basal ganglia-dependent processes in recalling learned

    E-print Network

    Patrick Be´dard · Jerome N. Sanes Received: 17 August 2010 / Accepted: 17 January 2011 / Published online al. 2009), and arbitrary stimulus­response associations (Be´dard and Sanes 2009; Grol et al. 2006 would participate as learning progresses through automaticity (Doyon et al. P. Be´dard Á J. N. Sanes

  3. Information processing in the different Basal Ganglia sub regions

    E-print Network

    of "Doctor of Philosophy" by Avital Adler Submitted to the Senate of the Hebrew University of Jerusalem for the degree of "Doctor of Philosophy" by Avital Adler Submitted to the Senate of the Hebrew University

  4. Abnormal Bursting as a Pathophysiological Mechanism in Parkinson's Disease

    PubMed Central

    Lobb, CJ

    2014-01-01

    Despite remarkable advances in Parkinson's disease (PD) research, the pathophysiological mechanisms causing motor dysfunction remain unclear, possibly delaying the advent of new and improved therapies. Several such mechanisms have been proposed including changes in neuronal firing rates, the emergence of pathological oscillatory activity, increased neural synchronization, and abnormal bursting. This review focuses specifically on the role of abnormal bursting of basal ganglia neurons in PD, where a burst is a physiologically-relevant, transient increase in neuronal firing over some reference period or activity. After reviewing current methods for how bursts are detected and what the functional role of bursts may be under normal conditions, existing studies are reviewed that suggest that bursting is abnormally increased in PD and that this increases with worsening disease. Finally, the influence of therapeutic approaches for PD such as dopamine-replacement therapy with levodopa or dopamine agonists, lesions, or deep brain stimulation on bursting is discussed. Although there is insufficient evidence to conclude that increased bursting causes motor dysfunction in PD, current evidence suggests that targeted investigations into the role of bursting in PD may be warranted. PMID:24729952

  5. 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.

  6. 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

  7. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    Microsoft Academic Search

    Lorenzo Lo Muzio

    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

  8. 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

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

    PubMed Central

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

    2001-01-01

    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

  10. Congenital Abnormalities

    MedlinePLUS

    ... and may develop serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal ... Detecting Genetic Abnormalities Prenatal Genetic Counseling Children with Down Syndrome: Health Care Information for Families Last Updated 5/ ...

  11. The effects of neonatal basal forebrain lesions oncognition : towards understanding the developmental roleof the cholinergic basal forebrain

    Microsoft Academic Search

    Joanne Berger-Sweeney

    1998-01-01

    Abnormal development of the cholinergic basal forebrain has been implicated innumerous developmental disabilities such as Rett Syndrome and Down Syndrome. This reviewsummarizes recent data using two rodent animal models that involve interrupting cholinergic basalforebrain projections on postnatal day 1 and postnatal day 7 when basal forebrain fibers arebeginning to innervate their neocortical and hippocampal targets, respectively. In one model,electrolytic lesions

  12. Nail abnormalities

    MedlinePLUS

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... of the nail bed from the nail plate (onycholysis). Severe illness or surgery may cause horizontal depressions ...

  13. Exogenous silver in dorsal root ganglia, peripheral nerve, enteric ganglia, and adrenal medulla

    Microsoft Academic Search

    J. Rungby

    1986-01-01

    Following intraperitoneal (i.p.) or oral administration of silver salts, the anatomic distribution of silver in the peripheral nervous system (PNS) has been studied. The structures examined were dorsal root ganglia, peripheral nerve (N. ischiadicus), enteric ganglia, and adrenal medulla.

  14. Cardiac neurones of autonomic ganglia.

    PubMed

    Wallis, D; Watson, A H; Mo, N

    1996-09-01

    The properties of the postganglionic sympathetic neurones supplying the heart and arising in the stellate and adjacent paravertebral ganglia of various species are discussed with respect to their location, morphology, synaptic input and membrane characteristics. Results from our laboratory on the morphology of rat stellate neurones projecting to the heart were obtained either by intracellular injection of hexammine cobaltic (III) chloride or by retrograde labelling of cells using cobalt-lysine complex. Intracellular recordings were made from cells using electrodes filled either with potassium chloride plus hexammine cobaltic chloride or potassium acetate. Neurones which projected axons into cardiac nerve branches arising from the stellate ganglion were termed putative cardiac neurones, because of the possibility that some supply pulmonary targets. Putative cardiac neurones had unbranched axons and were ovoid or polygonal in shape, but showed considerable variation in soma size and in the complexity of dendritic trees. The mean two-dimensional surface area was 463 microns2 and the mean number of primary dendrites was seven. Other studies have found that the morphology of rat stellate ganglion neurones is similar to that of superior cervical ganglion cells. However, in strains of rat displaying spontaneous hypertension, dendritic length may be increased. Histochemical studies do not, as yet, seem to have demonstrated a distinctive neurochemical profile for stellate cardiac neurones, but various types of peptide-containing intraganglionic nerve fibres have been identified in the guinea pig. In our electrophysiological studies, putative cardiac neurones were found to receive a complex presynaptic input arising from the caudal sympathetic trunk and from T1 and T2 thoracic rami. In addition, 16% of cardiac neurones received a synaptic input from the cardiac nerve. The properties of postganglionic parasympathetic neurones distributed in the cardiac plexus and termed intrinsic cardiac neurones are discussed, including the results of studies on cultures of these neurones. PMID:8873060

  15. Abnormal high-frequency burst firing of cerebellar neurons in rapid-onset dystonia-parkinsonism.

    PubMed

    Fremont, Rachel; Calderon, D Paola; Maleki, Sara; Khodakhah, Kamran

    2014-08-27

    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

  16. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation.

    PubMed

    Israelashvili, Michal; Loewenstern, Yocheved; Bar-Gad, Izhar

    2015-07-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  17. 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

  18. 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.

  19. Cerebellar abnormalities in Huntington's disease: a role in motor and psychiatric impairment?

    PubMed

    Rees, Elin M; Farmer, Ruth; Cole, James H; Haider, Salman; Durr, Alexandra; Landwehrmeyer, Bernhard; Scahill, Rachael I; Tabrizi, Sarah J; Hobbs, Nicola Z

    2014-11-01

    The cerebellum has received limited attention in Huntington's disease (HD), despite signs of possible cerebellar dysfunction, including motor incoordination and impaired gait, which are currently attributed to basal ganglia atrophy and disrupted fronto-striatal circuits. This study is the first to investigate a potential contribution of macro- and microstructural cerebellar damage to clinical manifestations of HD. T1- and diffusion-weighted 3T magnetic resonance imaging (MRI) scans were obtained from 12 controls and 22 early-stage HD participants. Manual delineation and voxel-based morphometry were used to assess between-group differences in cerebellar volume, and diffusion metrics were compared between groups within the cerebellar gray and white matter. Associations between these imaging measures and clinical scores were examined within the HD group. Reduced paravermal volume was detected in HD compared with controls using voxel-based morphometry (P?abnormalities were detected in both cerebellar gray matter and white matter. Smaller cerebellar volumes, although not significantly reduced, were significantly associated with impaired gait and psychiatric morbidity and of borderline significance with pronate/supinate-hand task performance. Abnormal cerebellar diffusion was associated with increased total motor score, impaired saccade initiation, tandem walking, and timed finger tapping. In conclusion, atrophy of the paravermis, possibly encompassing the cerebellar nuclei, and microstructural abnormalities within the cerebellum may contribute to HD neuropathology. Aberrant cerebellar diffusion and reduced cerebellar volume together associate with impaired motor function and increased psychiatric symptoms in stage I HD, potentially implicating the cerebellum more centrally in HD presentation than previously recognized. PMID:25123926

  20. White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients

    PubMed Central

    Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Stone, Taylor; Smith, J. Keith; Hall, Colin; Bullitt, Elizabeth; Shen, Dinggang; Lin, Weili

    2015-01-01

    HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter. PMID:19376246

  1. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    PubMed

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy. PMID:7699389

  2. Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence.

    PubMed

    Ersche, Karen D; Barnes, Anna; Jones, P Simon; Morein-Zamir, Sharon; Robbins, Trevor W; Bullmore, Edward T

    2011-07-01

    A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n?=?60) with data on healthy volunteers (n?=?60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption. PMID:21690575

  3. Inhibition of Smoothened Signaling Prevents Ultraviolet B-Induced Basal Cell Carcinomas through Regulation of Fas Expression and Apoptosis

    Microsoft Academic Search

    Mohammad Athar; Chengxin Li; Xiuwei Tang; Sumin Chi; Xiaoli Zhang; Arianna L. Kim; Stephen K. Tyring; Levy Kopelovich; Jennifer Hebert; Ervin H. Epstein Jr; David R. Bickers; Jingwu Xie

    2004-01-01

    Abnormal activation of the hedgehog-signaling pathway is the pivotal abnormality driving the growth of basal cell carcinomas (BCCs), the most common type of human cancer. Antagonists of this pathway such as cyclopamine may therefore be useful for treatment of basal cell carcino- mas and other hedgehog-driven tumors. We report here that chronic oral administration of cyclopamine dramatically reduces (66%) UVB-

  4. [Endometriosis and basal temperature].

    PubMed

    Köhler, G; Lober, R

    1988-01-01

    Basal body temperature of 168 cycles have been measured in 20 infertile women (age 21-31 years) with endometriosis. There were 10.1% anovulatory cycles, and in 22.5% of the 151 biphasic cycles the hyperthermic phase lasted less than 11 days. A late decline of basal body temperature after the onset of menstruation was recorded in 34.5% and may be only limitedly indicative of endometriosis. In 64.9% of all cycles basal body temperature was somewhat elevated and/or proved one or more temperature peaks in the follicular phase. Perhaps this may be indicative of endometriosis. Nevertheless the so-called endocrinologic infertility requires endoscopy for accurate diagnosis. PMID:3394441

  5. Proton MR Spectroscopy of Mitochondrial Diseases: Analysis of Brain Metabolic Abnormalities and Their Possible Diagnostic Relevance

    Microsoft Academic Search

    M. Cristina Bianchi; Michela Tosetti; Roberta Battini; Maria L. Manca; Michelangelo Mancuso; Giovanni Cioni; Raffaello Canapicchi; Gabriele Siciliano

    of 1H MR spectroscopy in the clinical evaluation of these disorders. METHODS: In 15 patients (11 adults, four children) with mitochondrial diseases, localized MR spectra were obtained at short TEs in cerebellar white matter, paratrigonal white matter, and parieto-occipital cortex that appeared normal on MR images. Additional spectra of basal ganglia and cortical gray matter structural lesions were obtained in

  6. 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

  7. A Rap Guanine Nucleotide Exchange Factor Enriched Highly in the Basal Ganglia

    Microsoft Academic Search

    Hiroaki Kawasaki; Gregory M. Springett; Shinichiro Toki; Juan J. Canales; Patricia Harlan; Justin P. Blumenstiel; Emy J. Chen; I. Amy Bany; Naoki Mochizuki; Amy Ashbacher; Michiyuki Matsuda; David E. Housman; Ann M. Graybiel

    1998-01-01

    Ras proteins, key regulators of growth, differentiation, and malignant transformation, recently have been implicated in synaptic function and region-specific learning and memory functions in the brain. Rap proteins, members of the Ras small G protein superfamily, can inhibit Ras signaling through the Ras\\/Raf-1\\/mitogen-activated protein (MAP) kinase pathway or, through B-Raf, can activate MAP kinase. Rap and Ras proteins both can

  8. Coupled Nonparametric Shape and Moment-Based Intershape Pose Priors for Multiple Basal Ganglia Structure Segmentation

    Microsoft Academic Search

    Mustafa Gökhan Uzunbas; Octavian Soldea; Devrim Unay; Müjdat Çetin; Gözde B. Ünal; Aytül Erçil; Ahmet Ekin

    2010-01-01

    This paper presents a new active contour-based, statistical method for simultaneous volumetric segmentation of multiple subcortical structures in the brain. In biological tissues, such as the human brain, neighboring structures exhibit co-dependencies which can aid in segmentation, if properly analyzed and modeled. Motivated by this observation, we formulate the segmentation problem as a maximum a posteriori estimation problem, in which

  9. The role of the pedunculopontine region in basal-ganglia mechanisms of akinesia

    Microsoft Academic Search

    L. E. Munro-Davies; J. Winter; T. Z. Aziz; J. F. Stein

    1999-01-01

    The akinesia of Parkinsonism is relieved by pallidotomy and subthalamic nucleotomy, but not by thalamotomy. Therefore, this\\u000a disabling symptom probably depends upon connections other than the pallidal-thalamocortical tracts, possibly efferents of\\u000a the medial pallidum descending to the upper brainstem. We have previously demonstrated akinesia in the normal monkey following\\u000a radiofrequency lesioning in the region of the pedunculopontine nucleus (PPN), one

  10. ccsd-00016414,version1-3Jan2006 Contracting model of the basal ganglia

    E-print Network

    Paris-Sud XI, Université de

    of interconnected subcortical nu- clei, involved in numerous processes, from motor functions to cognitive ones (Mink, and they thus have been proposed to constitute the neural substrate of action selection (Mink, 1996; Krotopov of the BIBA project funded by the European Com- munity, grant IST-2001-32115 is acknowledged. competing

  11. 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.

  12. SYSTEMS NEUROSCIENCE Normal Basal gaNglia movemeNt-related activity

    E-print Network

    Bar-Gad, Izhar

    .,1991a; Mink and Thach,1991a; Turner andAnderson,1997). Later studies found that some BG neurons also not to a single movement parameter, but rather to combinations of motor and contextual features (Mink and Thach, and similarly, closely located neurons often encode different behavioral parameters (DeLong et al., 1985; Mink

  13. How do the basal ganglia and cerebellum gain access to the cortical motor areas?

    PubMed

    Strick, P L

    1985-01-01

    We have used retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase to examine the origin of the thalamic input to the two premotor areas with the densest projections to the motor cortex. These are: arcuate premotor area (APA) and the supplementary motor area (SMA). Retrograde transport demonstrated that the two premotor areas and the motor cortex each receive thalamic input from separate, cytoarchitectonically well-defined subdivisions of the ventrolateral thalamus. According to the nomenclature of Olszewski (1952), input to the APA originates largely from area X; input to the SMA originates largely from the pars oralis subdivision of the nucleus ventralis lateralis (VLo); and that to the motor cortex is largely from the pars oralis subdivision of the nucleus ventralis posterior lateralis (VPLo). These observations, when combined with prior studies on the termination of various subcortical efferents in the thalamus, lead to the following scheme of projections: rostral portions of the deep cerebellar nuclei project to motor cortex via VPLo, caudal portions of the deep cerebellar nuclei project to the APA via area X; and the globus pallidus projects to the SMA via VLo. Thus each thalamocortical pathway is associated with a distinct subcortical input. PMID:3913443

  14. Hyporesponsive Reward Anticipation in the Basal Ganglia following Severe Institutional Deprivation Early in Life

    ERIC Educational Resources Information Center

    Mehta, Mitul A.; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C. R.; Sonuga-Barke, Edmund

    2010-01-01

    Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous…

  15. Structural analysis of the basal ganglia in schizophrenia Daniel Mamah a,, Lei Wang a

    E-print Network

    , Washington University Medical School, St. Louis, United States b Department of Neurology, Washington University Medical School, St. Louis, United States c Mallinckrodt Department of Radiology, Washington University Medical School, St. Louis, United States Received 4 May 2006; received in revised form 21 August

  16. Atypical developmental venous anomaly associated with contrast enhancement and hyperperfusion in the surrounding basal ganglia

    PubMed Central

    Solak, Aynur; Genc, Berhan; Bilgic, Nalan

    2015-01-01

    Developmental venous anomalies (DVAs) are the most common type of cerebral vascular malformations. They are generally accepted as variants of venous development and frequently identified incidentally, particularly on contrast-enhanced MR imaging. Most of the DVAs do not affect the integrity of the surrounding parenchyma. This article discusses an atypical DVA which is associated with contrast enhancement and increased perfusion within the drainage territory of the DVA, probably due to anomalous venous drainage. These unusual perfusion patterns of the DVAs should be differentiated from other entities such as hypervascular brain tumors or ischemia with hemodynamical changes which have different clinical management. PMID:26029651

  17. Defining the Intercommissural Plane and Stereotactic Coordinates for the Basal Ganglia in the Göttingen Minipig Brain

    Microsoft Academic Search

    Frederikke Rosendal; M. Mallar Chakravarty; Niels Sunde; Anders Rodell; Kristjana Y. Jonsdottir; Michael Pedersen; Carsten Bjarkam; Jens Christian Sřrensen

    2010-01-01

    The intercommissural line joining the anterior and posterior commissures defines stereotactic coordinate systems used in functional neurosurgical procedures. Such coordinate systems are generally accepted in humans and nonhuman primate experimental settings and provide high stereotactic precision and reproducibility. The ethical concern surrounding the use of nonhuman primates has motivated and helped popularize the use of the Göttingen minipig as an

  18. 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 ...

  19. Adenosine A2A Receptor in the Monkey Basal Ganglia: Ultrastructural Localization and Colocalization With

    E-print Network

    Hall, Randy A

    , including Parkinson's disease (PD; Pinna, 2009), drug addiction (Brown and Short, 2008), sleep disorders) is a potential drug target for the treatment of Parkinson's disease and other neurological disorders. In rodents TERMS: mGluR5; Parkinson's disease; primate; immunogold; globus pallidus; substantia nigra; putamen

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

    E-print Network

    condition. Using the method of partial spectra, we demonstrate that temporal correlations in the discharge variable that represents the mean discharge rate of neurons in that nucleus, and focuses on the gross in these mean discharge rates. It posits that the death of midbrain dopaminergic neurons that occurs in PD

  1. Severity of Dysfluency Correlates with Basal Ganglia Activity in Persistent Developmental Stuttering

    ERIC Educational Resources Information Center

    Giraud, Anne-Lise; Neumann, Katrin; Bachoud-Levi, Anne-Catherine; von Gudenberg, Alexander W.; Euler, Harald A.; Lanfermann, Heinrich; Preibisch, Christine

    2008-01-01

    Previous studies suggest that anatomical anomalies [Foundas, A. L., Bollich, A. M., Corey, D. M., Hurley, M., & Heilman, K. M. (2001). "Anomalous anatomy of speech-language areas in adults with persistent developmental stuttering." "Neurology," 57, 207-215; Foundas, A. L., Corey, D. M., Angeles, V., Bollich, A. M., Crabtree-Hartman, E., & Heilman,…

  2. Probing basal ganglia functions by saccade eye Masayuki Watanabe1,2,3

    E-print Network

    Munoz, Douglas Perry

    , such as Parkinson's disease (Bergman et al., 1998; Obeso et al., 2000) and schizophrenia (Carlsson & Carlsson, 1990 derived from neurophysiological experiments in behaving monkeys by taking advantage of homologies

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

    E-print Network

    Bar-Gad, Izhar

    Available online 31 July 2012 Keywords: Transcranial magnetic stimulation (TMS) Parkinson's disease Primate. Introduction Parkinsonism is associated with altered neurophysiological activi- ty throughout the cortico in Parkinsonism Hadass Tischler a , Anan Moran a , Katya Belelovsky a , Maya Bronfeld a , Alon Korngreen a

  4. The role of the basal ganglia in learning and memory: Insight from Parkinson's Karin Foerde

    E-print Network

    Foerde, Karin

    of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions of memory are supported by different brain structures. A focus of research within this frame- work the organization of memory in the brain. It has led to major advances in understanding the role of the medial

  5. Life beyond the Basal.

    ERIC Educational Resources Information Center

    Grey, Jeanne; Carbone, Carole

    1987-01-01

    Reading is a tool for learning. The goal for the teaching of reading must be to produce lovers of reading. A holistic approach should replace exclusive dependence on basal readers. Effective methods are the following: (1) language experience approach; (2) word banks; (3) pattern books; (4) sustained silent reading; and (5) directed…

  6. Synaptic ultrastructural alterations anticipate the development of neuroaxonal dystrophy in sympathetic ganglia of aged and diabetic mice.

    PubMed

    Schmidt, Robert E; Parvin, Curtis A; Green, Karen G

    2008-12-01

    Neuroaxonal dystrophy, a distinctive axonopathy characterized by marked enlargement of distal axons, is the hallmark pathologic alteration in aged and diabetic human prevertebral sympathetic ganglia and in corresponding rodent models. Neuroaxonal dystrophy is thought to represent the abnormal outcome of cycles of synaptic degeneration and regeneration; a systematic study of identified axon terminals in aged and diabetic prevertebral ganglia, however, has not previously been performed. We examined the initial changes that develop in presynaptic and postsynaptic elements in sympathetic ganglia of aged and diabetic mice and found numerous synaptic changes involving both presynaptic and postsynaptic elements. Early alterations in presynaptic axon terminal size, vesicle content, and morphology culminate in the development of anastomosing membranous tubulovesicular aggregates, accumulation of autophagosomes, and amorphous debris that form a continuum with progressively larger classically dystrophic swellings. Dendritic changes consist of the development of swellings composed of delicate tubulovesicular elements and mitochondriopathy characterized by increased numbers of small mitochondria and, exclusively in aged ganglia, megamitochondria. These results support the hypothesis that neuroaxonal dystrophy results from progressive changes in presynaptic axon terminals that likely involve membrane dynamics and which are accompanied by distinctive changes in postsynaptic dendritic elements. PMID:19018240

  7. 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

  8. Activation of Expression of Hedgehog Target Genes in Basal Cell Carcinomas

    Microsoft Academic Search

    Jeannette M Bonifas; Sally Pennypacker; Pao-Tien Chuang; Andrew P McMahon; Mickey Williams; Arnon Rosenthal; Frederic J de Sauvage; Ervin H Epstein

    2001-01-01

    Mutations in hedgehog signaling pathway genes, especially PTC1 and SMO, are pivotal to the development of basal cell carcinomas. The study of basal cell carcinoma gene expression not only may elucidate mechanisms by which hedgehog signaling abnormalities produce aberrant tumor cell behavior but also can provide data on in vivo hedgehog target gene control in humans. We have found, in

  9. Heme oxygenase-1, heme oxygenase-2 and biliverdin reductase in peripheral ganglia from rat, expression and plasticity

    Microsoft Academic Search

    S. Magnusson; J. Ekström; E. Elmér; M. Kanje; L. Ny; P. Alm

    1999-01-01

    The expression of inducible and constitutive heme oxygenase and biliverdin reductase was studied in normal and cultured peripheral ganglia from adult rats, using immunocytochemistry and in situ hybridization. Dramatic changes were induced by one to two days' culturing of dorsal root ganglia, nodose ganglia, otic ganglia, sphenopalatine ganglia and superior cervical ganglia. An up-regulation of inducible heme oxygenase was found

  10. Retroactions Between Basal Hydrology and Basal Sliding from Numerical Experiments

    NASA Astrophysics Data System (ADS)

    Gagliardini, O.; Passalacqua, O.; Werder, M. A.

    2014-12-01

    The basal sliding of glaciers is modulated by the presence of basal water and more precisely its pressure. On one hand, where the basal water pressure increases, the ice friction on the bedrock is reduced and the basal sliding velocity increases. On an other hand, an increase of basal sliding will influence the development of the basal hydrology systems. These processes leads to non-steady ice velocities and have a seasonal or even diurnal signature. In this study, a basal hydrology model is coupled with an ice flow model through a water pressure dependent friction law. The basal hydrology model includes an inefficient cavity-type water sheet and a network of efficient discrete channels. Both systems are connected and evolve in time in response to the water inputs. Ice flow is modelled either solving the full-Stokes equations or the shallow shelf approximation. Basal hydrology and ice flow are connected through a Coulomb type friction law which depends on the basal water pressure. The equations of both ice flow and hydrology are implemented in the open source, finite element, ice sheet / ice flow model Elmer/Ice. The coupling of basal hydrology and ice flow is studied for different glacier geometries and external forcing having different amplitude and temporal signatures. The classically used one way coupling, where only the hydrology influence the ice flow, is compared to a two way coupling where both hydrology and ice flow interact in a fully coupled way.

  11. 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

  12. 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. PMID:25848349

  13. 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

  14. The chelonian spinal nerve ganglia are a conglomerate of the spinal nerve ganglia proper and the sympathetic ganglia.

    PubMed

    Kadota, Tetsuo; Nakano, Masato; Atobe, Yoshitoshi; Goris, Richard C; Funakoshi, Kengo

    2009-01-01

    A tyrosine hydroxylase-immunoreactive cell mass is found in the caudal portion of the dorsal nerve ganglion of the red-eared slider, Trachemys scripta elegans. The ganglion appears as a flat oval structure in the horizontal plane, where the major axis runs latero-medially, and the minor axis rostro-caudally in the ventral view. A communicating branch to the sympathetic chain diverges from the top of each tubercle which lies on the caudo-lateral side of the ganglion. A tyrosine hydroxylase- immunoreactive cell mass is located in this tubercle. This cell mass exists in both sexes. Tyrosine hydroxylase-immunoreactive cells, that contain Nissl bodies in cytoplasm and are enveloped by the satellite cells, are multipolar and their neural processes are distributed in a distal direction into the spinal nerve. The range of distribution of the synapsin I-immunoreactive structures is limited to the tyrosine hydroxylase-immunoreactive cell mass. The chelonian dorsal spinal nerve ganglia are a conglomerate of the spinal nerve ganglion proper and the sympathetic ganglion. PMID:19468213

  15. Neural Stem Cells in Drosophila: Molecular Genetic Mechanisms Underlying Normal Neural Proliferation and Abnormal Brain Tumor Formation

    PubMed Central

    Saini, Nidhi; Reichert, Heinrich

    2012-01-01

    Neural stem cells in Drosophila are currently one of the best model systems for understanding stem cell biology during normal development and during abnormal development of stem cell-derived brain tumors. In Drosophila brain development, the proliferative activity of neural stem cells called neuroblasts gives rise to both the optic lobe and the central brain ganglia, and asymmetric cell divisions are key features of this proliferation. The molecular mechanisms that underlie the asymmetric cell divisions by which these neuroblasts self-renew and generate lineages of differentiating progeny have been studied extensively and involve two major protein complexes, the apical complex which maintains polarity and controls spindle orientation and the basal complex which is comprised of cell fate determinants and their adaptors that are segregated into the differentiating daughter cells during mitosis. Recent molecular genetic work has established Drosophila neuroblasts as a model for neural stem cell-derived tumors in which perturbation of key molecular mechanisms that control neuroblast proliferation and the asymmetric segregation of cell fate determinants lead to brain tumor formation. Identification of novel candidate genes that control neuroblast self-renewal and differentiation as well as functional analysis of these genes in normal and tumorigenic conditions in a tissue-specific manner is now possible through genome-wide transgenic RNAi screens. These cellular and molecular findings in Drosophila are likely to provide valuable genetic links for analyzing mammalian neural stem cells and tumor biology. PMID:22737173

  16. 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

  17. Abnormal functional connectivity between motor cortex and pedunculopontine nucleus following chronic dopamine depletion

    PubMed Central

    Valencia, Miguel; Chavez, Mario; Artieda, Julio; Bolam, J. Paul

    2013-01-01

    The activity of the basal ganglia is altered in Parkinson's disease (PD) as a consequence of the degeneration of dopamine neurons in the substantia nigra pars compacta. This results in aberrant discharge patterns and expression of exaggerated oscillatory activity across the basal ganglia circuit. Altered activity has also been reported in some of the targets of the basal ganglia, including the pedunculopontine nucleus (PPN), possibly due to its close interconnectivity with most regions of the basal ganglia. However, the nature of the involvement of the PPN in the pathophysiology of PD has not been fully elucidated. Here, we recorded local field potentials in the motor cortex and the PPN in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD under urethane anesthesia. By means of linear and nonlinear statistics, we analyzed the synchrony between the motor cortex and the PPN and the delay in the interaction between these two structures. We observed the presence of coherent activity between the cortex and the PPN in low (5–15 Hz)- and high (25–35 Hz)-frequency bands during episodes of cortical activation. In each case, the cortex led the PPN. Dopamine depletion strengthened the interaction of the low-frequency activities by increasing the coherence specifically in the theta and alpha ranges and reduced the delay of the interaction in the gamma band. Our data show that cortical inputs play a determinant role in leading the coherent activity with the PPN and support the involvement of the PPN in the pathophysiology of PD. PMID:24174651

  18. Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging

    PubMed Central

    Müller-Vahl, Kirsten R; Kaufmann, Jörn; Grosskreutz, Julian; Dengler, Reinhard; Emrich, Hinderk M; Peschel, Thomas

    2009-01-01

    Background Pathophysiological evidence suggests an involvement of fronto-striatal circuits in Tourette syndrome (TS). To identify TS related abnormalities in gray and white matter we used optimized voxel-based morphometry (VBM) and magnetization transfer imaging (MTI) which are more sensitive to tissue alterations than conventional MRI and provide a quantitative measure of macrostructural integrity. Methods Volumetric high-resolution anatomical T1-weighted MRI and MTI were acquired in 19 adult, unmedicated male TS patients without co-morbidities and 20 age- and sex-matched controls on a 1.5 Tesla neuro-optimized GE scanner. Images were pre-processed and analyzed using an optimized version of VBM in SPM2. Results Using VBM, TS patients showed significant decreases in gray matter volumes in prefrontal areas, the anterior cingulate gyrus, sensorimotor areas, left caudate nucleus and left postcentral gyrus. Decreases in white matter volumes were detected in the right inferior frontal gyrus, the left superior frontal gyrus and the anterior corpus callosum. Increases were found in the left middle frontal gyrus and left sensorimotor areas. In MTI, white matter reductions were seen in the right medial frontal gyrus, the inferior frontal gyrus bilaterally and the right cingulate gyrus. Tic severity was negatively correlated with orbitofrontal structures, the right cingulate gyrus and parts of the parietal-temporal-occipital association cortex bilaterally. Conclusion Our MRI in vivo neuropathological findings using two sensitive and unbiased techniques support the hypothesis that alterations in frontostriatal circuitries underlie TS pathology. We suggest that anomalous frontal lobe association and projection fiber bundles cause disinhibition of the cingulate gyrus and abnormal basal ganglia function. PMID:19435502

  19. 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.

  20. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and

    E-print Network

    Richner, Heinz

    Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity testosterone/corticosterone ratio. They also exhibit hyperactivity in the amygdala under both basal conditions. Alterations in the connectivity between the orbitofrontal cortex and the amygdala were linked

  1. Functional networks in motor sequence learning: abnormal topographies in Parkinson's disease.

    PubMed

    Nakamura, T; Ghilardi, M F; Mentis, M; Dhawan, V; Fukuda, M; Hacking, A; Moeller, J R; Ghez, C; Eidelberg, D

    2001-01-01

    We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's disease (PD) using 15O-water (H2 15O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning-related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical activation compensating for abnormalities in basal ganglia function. PMID:11198104

  2. CYTOLOGICAL STUDIES OF ORGANOTYPIC CULTURES OF RAT DORSAL ROOT GANGLIA FOLLOWING X-IRRADIATION IN VITRO

    PubMed Central

    Masurovsky, Edmund B.; Bunge, Mary Bartlett; Bunge, Richard P.

    1967-01-01

    Long-term organotypic cultures of rat dorsal root ganglia were exposed to a single 40 kR dose of 184 kvp X-rays and studied in the living and fixed states by light or electron microscopy at 1–14 day intervals thereafter. Within the first 4 days following irradiation, over 30% of the neurons display chromatolytic reactions (eccentric nuclei, peripheral dispersal of Nissl substance, central granular zone) as well as abnormal nucleolar changes and dissociation of ribosomes from endoplasmic reticulum cisternae. Some satellite cells undergo retraction or acute degeneration, leaving only basement membrane to cover the neuron in these areas. 8 days after irradiation, neurons also exhibit (a) areas in which ribosomes are substantially reduced, (b) regions of cytoplasmic sequestration, (c) extensive vacuolization of granular endoplasmic reticulum and Golgi complex, and (d) diversely altered mitochondria (including the presence of ribosome-like particles or association with abnormal glycogen and lipid deposits). Nucleolar components become altered or reoriented and may form abnormal projections and ringlike configurations. Sizeable areas of the neuronal soma are now denuded of satellite cells; underlying these areas, nerve processes are found abnormally invaginated into the neuronal cytoplasm. By the 14th day following irradiation, most neurons display marked degenerative changes including extensive regions of ribosome depletion, sequestration, vacuolization, autolysis, and, in some areas, swirls of filaments, myelin figures, and heterogeneous dense bodies. These observations demonstrate that X-irradiation produces profound cytopathological changes in nervous tissue isolated from the host and that many of these changes resemble the effects of radiation on nervous tissue in vivo. PMID:10976234

  3. A dorsal root ganglia cell line derived from trisomy 16 fetal mice, a model for Down syndrome.

    PubMed

    Allen, David D; Cárdenas, Ana María; Arriagada, Christian; Bennett, Lori B; García, Carlos J; Caviedes, Raúl; Rapoport, Stanley I; Caviedes, Pablo

    2002-03-25

    We have established two immortalized cell lines from dorsal root ganglia of normal (G4b) and trisomy 16 mice (GT1), a model for Down syndrome. By immunohistochemistry, both cell lines exhibit neuronal traits and lack glial markers. GTl cells exhibited greater [3H]choline uptake than G4b cells. K+ and nicotine-mediated acetylcholine release was greater in GT1 cells. Basal intracellular Ca2+ concentration ([Ca2+]i) was significantly lower in GTl cells. More GTl cells responded to neurotransmitters with a transient [Ca2+]i increase compared to G4b cells, but both cell types showed similar amplitudes of [Ca2+]i responses. The results show that both cell lines retain neuronal characteristics and respond to specific neurotransmitter stimuli. Altered GT1 cell responses could be related to neuronal pathophysiology in Down's syndrome. PMID:11930168

  4. Teachers Reflect Standards in Basals

    ERIC Educational Resources Information Center

    Gewertz, Catherine

    2012-01-01

    Dozens of teachers and literacy specialists from across the country hunkered down in Baltimore at round tables, with laptops, pens, and paper, intent on rewriting the collections that wield tremendous influence over the way millions of U.S. children learn literacy skills: the big-name basal readers. Hailing from 18 school districts in 11 states,…

  5. The Code, Connectionism, and Basals.

    ERIC Educational Resources Information Center

    Murphy, Sharon

    1991-01-01

    Examines computer modeling of the reading process and the instructional technology of basals, the two pillars of Marilyn Adams text, "Beginning to Read: Thinking and Learning about Print." Explains why the author believes Adams is fundamentally wrong in her theoretical approach to reading instruction. (MG)

  6. 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

  7. Immunoprevention of Basal Cell Carcinomas with Recombinant Hedgehog-interacting Protein

    Microsoft Academic Search

    Annika Vogt; Pao-Tien Chuang; Jennifer Hebert; Jimmy Hwang; Ying Lu; Levy Kopelovich; Mohammad Athar; David R. Bickers; Ervin H. Epstein

    2006-01-01

    Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog- interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1 ? \\/ ? mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels

  8. 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

  9. 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

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

    Microsoft Academic Search

    D Caparros-Lefebvre; A Destée; H Petit

    1997-01-01

    BACKGROUNDStriatal 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.METHODSBetween 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

  11. ACCEPTED MANUSCRIPT The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia

    E-print Network

    Eddy, Sean

    ACCEPTED MANUSCRIPT output The inhibitory microcircuit of the substantia nigra provides feedback and biomedical research from eLife. #12;1 1 2 3 4 5 6 7 8 9 The inhibitory microcircuit of the substantia nigra circuits. Here we show that feedback via axon39 collaterals of substantia nigra projection neurons control

  12. The effect of cystic cavities on deep brain stimulation in the basal ganglia: a simulation-based study

    NASA Astrophysics Data System (ADS)

    Ĺström, Mattias; Johansson, Johannes D.; Hariz, Marwan I.; Eriksson, Ola; Wĺrdell, Karin

    2006-06-01

    Although the therapeutic effect of deep brain stimulation (DBS) is well recognized, a fundamental understanding of the mechanisms responsible is still not known. In this study finite element method (FEM) modelling and simulation was used in order to study relative changes of the electrical field extension surrounding a monopolar DBS electrode positioned in grey matter. Due to the frequently appearing cystic cavities in the DBS-target globus pallidus internus, a nucleus of grey matter with and without a cerebrospinal fluid filled cystic cavity was modelled. The position, size and shape of the cyst were altered in relation to the electrode. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between grey and white matters. The cyst increased the radial extension and changed the shape of the electrical field substantially. The position, size and shape of the cyst were the main influencing factors. We suggest that cystic cavities in the DBS-target may result in closely related unexpected structures or neural fibre bundles being stimulated and could be one of the reasons for suboptimal clinical effects or stimulation-induced side effects.

  13. Handbook of Basal Ganglia Structure and Function Copyright 2010 Elsevier B.V. All rights reserved.2010

    E-print Network

    Tepper, James M.

    . LTS Neurons A. Synaptic Connectivity V. Calretinin Interneurons VI. Other GABAergic Interneurons that identify the other types of striatal GABA interneurons, i.e., calretinin, nitric oxide synthase (NOS

  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. Chemoarchitecture and afferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes.

    PubMed

    Martinez-Marcos, Alino; Ubeda-Bańon, Isabel; Lanuza, Enrique; Halpern, Mimi

    2005-01-01

    The olfactostriatum, a portion of the striatal complex of snakes, is the major tertiary vomeronasal structure in the ophidian brain, receiving substantial afferents from the nucleus sphericus, the primary target of accessory olfactory bulb efferents. In the present study, we have characterized the olfactostriatum of garter snakes (Thamnophis sirtalis) on the basis of chemoarchitecture (distribution of serotonin, neuropeptide Y and tyrosine hydroxylase) and hodology (afferent connections). The olfactostriatum is densely immunoreactive for serotonin and neuropeptide Y and shows moderate-to-weak immunoreactivity for tyrosine hydroxylase. In addition to afferents from the nucleus sphericus, the olfactostriatum receives inputs from the dorsal and lateral cortices, nucleus of the accessory olfactory tract, external and dorsolateral amygdalae, dorsomedial thalamic nucleus, ventral tegmental area and raphe nuclei. Double labeling experiments demonstrated that the distribution of serotonin and neuropeptide Y in this area almost completely overlaps the terminal field of projections from the nucleus sphericus. Also, serotonergic and dopaminergic innervation of the olfactostriatum likely arise, respectively, from the raphe nuclei and the ventral tegmental area, whereas local circuit neurons originate the neuropeptide Y immunoreactivity. These results indicate that the olfactostriatum of snakes could be a portion of the nucleus accumbens, with features characteristic of the accumbens shell, devoted to processing vomeronasal information. Comparative data suggest that a similar structure is present in the ventral striatum of amphibians and mammals. PMID:15589701

  16. Neurophysiological changes in the primate basal ganglia following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced

    E-print Network

    Bar-Gad, Izhar

    Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel Abstract Parkinson's disease (PD. Introduction Parkinson's disease (PD) is a neurodegenerative disorder that impairs primarily motor skills James Parkinson, after which the disease was later termed. He described the symptoms as "Involuntary

  17. 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

  18. 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

  19. 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

  20. Purification and culture of adult rat dorsal root ganglia neurons.

    PubMed

    Delree, P; Leprince, P; Schoenen, J; Moonen, G

    1989-06-01

    To study the trophic requirements of adult rat dorsal root ganglia neurons (DRG) in vitro, we developed a purification procedure that yields highly enriched neuronal cultures. Forty to fifty ganglia are dissected from the spinal column of an adult rat. After enzymatic and mechanical dissociation of the ganglia, myelin debris are eliminated by centrifugation on a Percoll gradient. The resulting cell suspension is layered onto a nylon mesh with a pore size of 10 microns. Most of the neurons, the diameter of which ranged from 17 microns to greater than 100 microns, are retained on the upper surface of the sieve; most of the non-neuronal cells with a caliber of less than 10 microns after trypsinization go through it. Recovery of neurons is achieved by reversing the mesh onto a Petri dish containing culture medium. Neurons to non-neurons ratio is 1 to 10 in the initial cell suspension and 1 to 1 after separation. When these purified neurons are seeded at a density of 3,000 neurons/cm2 in 6 mm polyornithine-laminin (PORN-LAM) coated wells, neuronal survival (assessed by the ability to extend neurites), measured after 48 hr of culture, is very low (from 0 to 16%). Addition of nerve growth factor (NGF) does not improve neuronal survival. However, when neurons are cultured in the presence of medium conditioned (CM) by astrocytes or Schwann cells, 60-80% of the seeded, dye-excluding neurons survive. So, purified adult DRG neurons require for their short-term survival and regeneration in culture, a trophic support that is present in conditioned medium from PNS or CNS glia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2754765

  1. 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

  2. Beta and gamma frequency-range abnormalities in parkinsonian patients under cognitive sensorimotor task.

    PubMed

    Dushanova, Juliana; Philipova, Dolja; Nikolova, Gloria

    2010-06-15

    Parkinson's disease (PD) is a neurodegenerative disorder caused by a disruption of dopaminergic neurotransmission in the basal ganglia. Some of PD clinical symptoms are suggested to stem directly from the excessive synchrony between the basal ganglia and cortical circuits. Our present investigation explores the functional relationships between event-related desynchronization/synchronization (ERD/ERS) of beta and gamma band activity for idiopathic non-demented Parkinson's patients (PP) and control subjects (CS) during auditory discrimination tasks between two tone types (LT: 800 Hz, HT: 1000 Hz) within two post-stimulus intervals of 0-250 and 250-600 ms. Beta1 (13-20 Hz) ERD was found for both groups within both intervals more expressed in CS except for frontal beta1 synchronization in CS during the second interval. Beta2 (20-32 Hz) ERD was revealed in CS after both tones during both post-stimulus intervals. Beta2 ERS was only observed in PP. The most prominent beta2 ERS followed HT during the second interval. Gamma frequency (32-50 Hz) ERD was found in both groups except for fronto-parietal ERS for PP during the first interval after LT. During the second interval, either tone, we found prominent ERS for PP and ERD for CS everywhere except for a frontal ERS after HT. Deviations of the beta and gamma ERD/ERS for the PP compared with CS during the sensorimotor and cognitive processing are a clear evidence for disturbances in the temporal and regional integration of these frequency components and the relationships between cortical and the basal ganglia circuits in parkinsonism. PMID:20392453

  3. Basal norepinephrine in depersonalization disorder.

    PubMed

    Simeon, Daphne; Guralnik, Orna; Knutelska, Margaret; Yehuda, Rachel; Schmeidler, James

    2003-11-01

    In contrast to the noradrenergic dysregulation described in PTSD, little is known regarding noradrenergic function in dissociative disorders. The purpose of this preliminary study was to investigate basal norepinephrine in depersonalization disorder (DPD). Nine subjects with DSM-IV DPD, without lifetime PTSD, were compared to nine healthy comparison (HC) subjects. Norepinephrine was measured via 24-h urine collection and three serial plasma determinations. Groups did not differ significantly in plasma norepinephrine levels. Compared to the HC group, the DPD group demonstrated significantly higher urinary norepinephrine, only prior to covarying for anxiety. The DPD group also demonstrated a highly significant inverse correlation between urinary norepinephrine and depersonalization severity (r=-0.88). Norepinephrine and cortisol levels (reported in a prior study) were not intercorrelated. We concluded that although dissociation accompanied by anxiety was associated with heightened noradrenergic tone, there was a marked basal norepinephrine decline with increasing severity of dissociation. The findings are in concordance with the few reports on autonomic blunting in dissociation and merit further investigation. PMID:14572626

  4. Renal abnormalities in leprosy.

    PubMed

    Kirsztajn, G M; Nishida, S K; Silva, M S; Ajzen, H; Pereira, A B

    1993-01-01

    We have evaluated laboratory and clinical manifestations of renal disease in 96 patients with leprosy, looking for a sensitive and early marker for detection and possibly follow-up of nephropathy in these patients. Microscopic hematuria was observed in 21.9% of the cases (with dysmorphic erythrocytes in 71.4% of them). Abnormal microalbuminuria and urinary beta 2-microglobulin were found in 15.8 and 19.8% of the cases, respectively. We have observed a high frequency of hematuria, abnormal microalbuminuria and elevation of urinary beta 2-microglobulin in these patients still with normal serum creatinine. PMID:8289988

  5. 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

  6. The Properties and Connections of Nerve Cells in Leech Ganglia Maintained in Culture

    Microsoft Academic Search

    S. Miyazaki; J. G. Nicholls

    1976-01-01

    Segmental ganglia of the central nervous system of the leech were maintained in culture medium outside the animal for several weeks at 16 degrees C, and electrical recordings made from identified sensory and motor nerve cells. Ganglia were isolated and cultured singly, in chains and connected to the skin and muscles they normally innervate. Such preparations are suitable for a

  7. Temporal lobe abnormalities in dementia and depression: a study using high resolution single photon emission tomography and magnetic resonance imaging

    PubMed Central

    Ebmeier, K.; Prentice, N.; Ryman, A.; Halloran, E.; Rimmington, J; Best, J.; Goodwin, G.

    1997-01-01

    OBJECTIVES—Perfusion SPECT and MRI were used to test the hypothesis that late onset depression is associated with brain abnormalities.?METHODS—Forty depressed patients (DSM-III-R major depressive episode, not demented at two year follow up) were recruited who were either drug free, or on a stable dose of antidepressants for at least three weeks, as well as 22 demented patients (DSM-IIIR and NINCDS/ADRDA criteria for probable Alzheimer's disease). Patients were imaged at rest with a high resolution single slice 12 detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-exametazime (HM-PAO). Temporal lobe templates were fitted with brains pitched by 20°-30°. A subgroup of 41 patients (22 depressed) were also scanned using a Siemens Magnetron 1.0 Tesla magnetic resonance imager, using a FLAIR imaging sequence for the assessment of white matter hyperintensities, and a Turbo FLASH sequence for the measurement of medial temporal lobe width.?RESULTS—Demented patients showed reduced perfusion, particularly in the left temporoparietal cortex. In these regions of interest, patients with late onset depression tended to have perfusion values intermediate between patients with early onset depression and demented patients. Differences in changes in white matter between demented and early and late onset depressive patients did not reach conventional levels of significance. Temporal lobe width differed between demented and depressed patients, but not between early and late onset depressed patients. Perfusion and temporal lobe width were not associated, but reductions of perfusion were associated with periventricular white matter changes. Mini mental state examination scores were associated with temporal perfusion in demented patients and with changes in deep white matter in depressed patients. Finally, severity of depressive symptoms was associated with decreased perfusion in frontotemporal and basal ganglia regions of interest.?CONCLUSION—A cumulative effect of duration of illness on regional cerebral perfusion could not be confirmed. Late onset depression may show more abnormalities of deep white matter and of left temporoparietal perfusion than early onset depression, but the underlying pathology remains to be established.?? PMID:9408100

  8. Morphological and Electrophysiological Characteristics of Noncholinergic Basal

    E-print Network

    Tepper, James M.

    pallidum and substantia innominata were recorded extracellularly, labeled juxtacellularly with biocytin acetyltransferase; GABA; biocytin; juxtacellular labeling The magnocellular basal forebrain cholinergic system has

  9. Molecular analysis of neurogenic placode development in a basal ray-finned fish

    PubMed Central

    Modrell, Melinda S.; Buckley, David; Baker, Clare V.H.

    2014-01-01

    Neurogenic placodes are transient, thickened patches of embryonic vertebrate head ectoderm that give rise to the paired peripheral sense organs and most neurons in cranial sensory ganglia. We present the first analysis of gene expression during neurogenic placode development in a basal actinopterygian (ray-finned fish), the North American paddlefish (Polyodon spathula). Pax3 expression in the profundal placode confirms its homology with the ophthalmic trigeminal placode of amniotes. We report the conservation of expression of Pax2 and Pax8 in the otic and/or epibranchial placodes, Phox2b in epibranchial placode-derived neurons, Sox3 during epibranchial and lateral line placode development, and NeuroD in developing cranial sensory ganglia. We identify Sox3 as a novel marker for developing fields of electrosensory ampullary organs and for ampullary organs themselves. Sox3 is also the first molecular marker for actinopterygian ampullary organs. This is consistent with, though does not prove, a lateral line placode origin for actinopterygian ampullary organs. PMID:21381180

  10. Molecular analysis of neurogenic placode development in a basal ray-finned fish.

    PubMed

    Modrell, Melinda S; Buckley, David; Baker, Clare V H

    2011-04-01

    Neurogenic placodes are transient, thickened patches of embryonic vertebrate head ectoderm that give rise to the paired peripheral sense organs and most neurons in cranial sensory ganglia. We present the first analysis of gene expression during neurogenic placode development in a basal actinopterygian (ray-finned fish), the North American paddlefish (Polyodon spathula). Pax3 expression in the profundal placode confirms its homology with the ophthalmic trigeminal placode of amniotes. We report the conservation of expression of Pax2 and Pax8 in the otic and/or epibranchial placodes, Phox2b in epibranchial placode-derived neurons, Sox3 during epibranchial and lateral line placode development, and NeuroD in developing cranial sensory ganglia. We identify Sox3 as a novel marker for developing fields of electrosensory ampullary organs and for ampullary organs themselves. Sox3 is also the first molecular marker for actinopterygian ampullary organs. This is consistent with, though does not prove, a lateral line placode origin for actinopterygian ampullary organs. PMID:21381180

  11. Ice Sheet Stratigraphy Can Constrain Basal Slip

    NASA Astrophysics Data System (ADS)

    Wolovick, M.; Creyts, T. T.; Buck, W. R.; Bell, R. E.

    2014-12-01

    Basal slip is an important component of ice sheet mass flux and dynamics. Basal slip varies over time due to variations in basal temperature, water pressure, and sediment cover. All of these factors can create coherent patterns of basal slip that migrate over time. Our knowledge of the spatial variability in basal slip comes from inversions of driving stress, ice thickness, and surface velocity, but these inversions contain no information about temporal variability. We do not know if the patterns in slip revealed by those inversions move over time. While englacial stratigraphy has classically been used to constrain surface accumulation and geothermal flux, it is also sensitive to horizontal gradients in basal slip. Here we show that englacial stratigraphy can constrain the velocity of basal slip patterns. Englacial stratigraphy responds strongly to patterns of basal slip that move downstream over time close to the ice sheet velocity. In previous work, we used a thermomechanical model to discover that thermally controlled slip patterns migrate downstream and create stratigraphic structures, but we were unable to directly control the pattern velocity, as that arose naturally out of the model physics. Here, we use a kinematic flowline model that allows us to directly control pattern velocity, and thus is applicable to a wide variety of slip mechanisms in addition to basal temperature. We find that the largest and most intricate stratigraphic structures develop when the pattern moves at the column-average ice velocity. Patterns that move slower than the column-average ice velocity produce overturned stratigraphy in the lower part of the ice sheet, while patterns moving at the column-average eventually cause the entire ice sheet to overturn if they persist long enough. Based on these forward models, we develop an interpretive guide for deducing moving patterns in basal slip from ice sheet internal layers. Ice sheet internal stratigraphy represents a potentially vast untapped source of information on basal sliding.

  12. Introduction Sismicit profonde et frottement basal

    E-print Network

    Paris-Sud XI, Université de

    Introduction Sismicité profonde et frottement basal Inuence du jökulhlaup sur la sismicité Laboratoire de Géophysique Interne et Tectonophysique Université de Savoie, Chambéry, France Le Bourget du Lac profonde et frottement basal Inuence du jökulhlaup sur la sismicité Corrélation de bruit au glacier d

  13. Exercises to Improve Gait Abnormalities

    MedlinePLUS

    ... Home About Goals Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  14. 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.

  15. Abnormal ionization in sonoluminescence

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%–70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  16. 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

  17. Abnormal Cerebrovascular Reactivity in Patients with Parkinson's Disease

    PubMed Central

    Camargo, Carlos Henrique Ferreira; Martins, Eduardo Antunes; Lange, Marcos Christiano; Hoffmann, Henrique Alvaro; Luciano, Jissa Jeanete; Young Blood, Marcelo Rezende; Schafranski, Marcelo Derbli; Ferro, Marcelo Machado; Miyoshi, Edmar

    2015-01-01

    Background. Orthostatic hypotension (OH) is an important nonmotor manifestation of Parkinson's disease (PD). Changes in cerebrovascular reactivity may contribute to this manifestation and can be monitored using transcranial Doppler. Objective. To identify possible changes in cerebrovascular reactivity in patients with OH. Methods. Twenty-two individuals were selected and divided into three groups: with and without OH and controls. Transcranial Doppler was used to assess basal mean blood flow velocity, postapnea mean blood flow velocity, percentage increase in mean blood flow velocity, and cerebrovascular reactivity as measured by the breath-holding index. Results. PD patients had lower values of basal velocity (p = 0.019), postapnea velocity (p = 0.0015), percentage increase in velocity (p = 0.039), and breath-holding index (p = 0.04) than the controls. Patients with OH had higher values of basal velocity (p = 0.09) and postapnea velocity (p = 0.19) but lower values of percentage increase in velocity (p = 0.22) and breath-holding index (p = 0.32) than patients without OH. Conclusions. PD patients present with abnormalities in a compensatory mechanism that regulates cerebral blood flow. OH could be an indicator of these abnormalities.

  18. A case of Sturge-Weber syndrome with peculiar venous abnormalities

    Microsoft Academic Search

    Kenzo Hamano; Misako Ito; Kei Inai; Tadao Nose; Hitoshi Takita

    1993-01-01

    A case of Sturge-Weber syndrome with poor filling of the deep cerebral venous system is reported. Usually in this syndrome, enlargement of the internal cerebral, basal Rosenthal, deep medullary, and subependymal veins is revealed by angiography. The abnormality of the deep cerebral venous system in this case corresponded to diffuse faint calcification of the right parietal parenchyma. This was accompanied

  19. 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

  20. The abnormal fontanel.

    PubMed

    Kiesler, Joseph; Ricer, Rick

    2003-06-15

    The diagnosis of an abnormal fontanel requires an understanding of the wide variation of normal. At birth, an infant has six fontanels. The anterior fontanel is the largest and most important for clinical evaluation. The average size of the anterior fontanel is 2.1 cm, and the median time of closure is 13.8 months. The most common causes of a large anterior fontanel or delayed fontanel closure are achondroplasia, hypothyroidism, Down syndrome, increased intracranial pressure, and rickets. A bulging anterior fontanel can be a result of increased intracranial pressure or intracranial and extracranial tumors, and a sunken fontanel usually is a sign of dehydration. A physical examination helps the physician determine which imaging modality, such as plain films, ultrasonography, computed tomographic scan, or magnetic resonance imaging, to use for diagnosis. PMID:12825844

  1. Neurotensin receptor 1 immunoreactivity in the peripheral ganglia and carotid body

    PubMed Central

    Porzionato, A.; Macchi, V.; Amagliani, A.; Castagliuolo, I.; Parenti, A.; De Caro, R.

    2009-01-01

    In the present study we investigated, through immunohistochemistry, the presence and location of neurotensin receptor 1 (NTR1) in the peripheral ganglia and carotid body of 16 humans and 5 rats. In both humans and rats, NTR1 immunostained ganglion cells were found in superior cervical ganglia (57.4±11.6% and 72.4±11.4%, respectively, p<0.05), enteric ganglia (51.9±10.4% and 64.6±6.1%, p<0.05), sensory ganglia (69.2±10.7% and 73.0±13.1%, p>0.05) and parasympathetic ganglia (52.1±14.1% and 59.4±14.0%, p>0.05), supporting a modulatory role for NT in these ganglia. Positivity was also detected in 45.6±9.2% and 50.8±6.8% of human and rat type I glomic cells, respectively, whereas type II cells were negative. Our findings suggest that NT produced by type I cells acts in an autocrine or paracrine way on the same cell type, playing a modulatory role on chemoception.

  2. Haem degradation in abnormal haemoglobins.

    PubMed Central

    Brown, S B; Docherty, J C

    1978-01-01

    The coupled oxidation of certain abnormal haemoglobins leads to different bile-pigment isomer distributions from that of normal haemoglobin. The isomer pattern may be correlated with the structure of the abnormal haemoglobin in the neighbourhood of the haem pocket. This is support for haem degradation by an intramolecular reaction. PMID:708385

  3. 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.

  4. Functional organization of crayfish abdominal ganglia. III. Swimmeret motor neurons.

    PubMed

    Mulloney, B; Hall, W M

    2000-04-01

    Swimmerets are limbs on several segments of the crayfish abdomen that are used for forward swimming and other behaviors. We present evidence that the functional modules demonstrated previously in physiological experiments are reflected in the morphological disposition of swimmeret motor neurons. The single nerve that innervates each swimmeret divides into two branches that separately contain the axons of power-stroke and return-stroke motor neurons. We used Co(++) or biocytin to backfill the entire pool of neurons that innervated a swimmeret, or functional subsets whose axons occurred in particular branches. Each filled cell body extended a single neurite that projected first to the Lateral Neuropil (LN), and there branched to form dendritic structures and its axon. All the motor neurons that innervated one swimmeret had cell bodies located in the ganglion from which their axons emerged, and the cell bodies of all but two of these neurons were located ipsilateral to their swimmeret. Counts of cell bodies filled from selected peripheral branches revealed about 35 power-stroke motor neurons and 35 return-stroke motor neurons. The cell bodies of these two types were segregated into different clusters within the ganglion, but both types sent their neurites into the ipsilateral LN and had their principle branches in this neuropil. We saw no significant differences in the numbers or distributions of these motor neurons in ganglia A2 through A5. These anatomical features are consistent with the physiological evidence that each swimmeret is controlled by its own neural module, which drives the alternating bursts of impulses in power-stroke and return-stroke motor neurons. We propose that the LN is the site of the synaptic circuit that generates this pattern. PMID:10723001

  5. Constraining basal hydrology with model inversions of basal friction using new InSAR surface velocities.

    NASA Astrophysics Data System (ADS)

    Larour, E.; Rignot, E.; Seroussi, H.; Morlighem, M.

    2012-04-01

    Constraining ice flow models for continental ice sheets such as Antarctica or Greenland can be difficult, especially regarding the specification of basal friction at the ice/bed interface. Historically, two approches have been taken: 1) model the basal hydrology of the ice sheet, and relate the resulting basal water pressure to the basal drag coefficient and 2) invert for the basal drag coefficient using InSAR surface velocities, and infer the resulting basal hydrology. Here, we use both approaches within the Ice Sheet System Model (ISSM), the JPL/UCI developed ice flow model, for which we have developed a new hydrological model based on LeBrocq et al, 2009. We compare this model against a large scale inversion of Antarctica's basal drag coefficient using new InSAR surface velocities from Rignot et al 2011. We discuss the potential for this model to improve constraints on basal friction evolution, and implications for projections of ice flow dynamics in a changing climate. We also discuss relevance for calibrating thermal models of Antarctica. This work was performed at the California Institute of Technology's Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration's Cryosphere Science Program.

  6. Constraining basal hydrology with model inversions of basal friction using new InSAR surface velocities.

    NASA Astrophysics Data System (ADS)

    Larour, E. Y.; Rignot, E. J.; Seroussi, H. L.; Morlighem, M.

    2011-12-01

    Constraining ice flow models for continental ice sheets such as Antarctica or Greenland can be difficult, especially regarding the specification of basal friction at the ice/bed interface. Historically, two approches have been taken: 1) model the basal hydrology of the ice sheet, and relate the resulting basal water pressure to the basal drag coefficient and 2) invert for the basal drag coefficient using InSAR surface velocities, and infer the resulting basal hydrology. Here, we use both approaches within the Ice Sheet System Model (ISSM), the JPL/UCI developed ice flow model, for which we develop a new hydrological model based on Johnson et al 2002. We compare this model against a massive inversion of Antarctica's basal drag coefficient using new InSAR surface velocities from Rignot et al 2011. We discuss the potential for this model to improve constraints on basal friction evolution, and implications for projections of ice flow dynamics in a changing climate. This work was performed at the California Institute of Technology's Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration's Cryosphere Science Program.

  7. P2X7 receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia.

    PubMed

    Liu, Shuangmei; Shi, Qingming; Zhu, Qicheng; Zou, Ting; Li, Guilin; Huang, An; Wu, Bing; Peng, Lichao; Song, Miaomiao; Wu, Qin; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Lv, Qiulan; Zou, Lifang; Zhang, Xi; Ying, Mofeng; Li, Guodong; Liang, Shangdong

    2015-06-01

    Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint "Dachangshu" and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor. PMID:25527178

  8. 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

  9. 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

  10. Position of larval tapeworms, Polypocephalus sp., in the ganglia of shrimp, Litopenaeus setiferus.

    PubMed

    Carreon, Nadia; Faulkes, Zen

    2014-07-01

    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

  11. 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 ...

  12. Chromosomal abnormalities in human sperm

    SciTech Connect

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

  13. A Genome-Wide Screen to Identify Transcription Factors Expressed in Pelvic Ganglia of the Lower Urinary Tract

    PubMed Central

    Wiese, Carrie B.; Ireland, Sara; Fleming, Nicole L.; Yu, Jing; Valerius, M. Todd; Georgas, Kylie; Chiu, Han Sheng; Brennan, Jane; Armstrong, Jane; Little, Melissa H.; McMahon, Andrew P.; Southard-Smith, E. Michelle

    2012-01-01

    Relative positions of neurons within mature murine pelvic ganglia based on expression of neurotransmitters have been described. However the spatial organization of developing innervation in the murine urogenital tract (UGT) and the gene networks that regulate specification and maturation of neurons within the pelvic ganglia of the lower urinary tract (LUT) are unknown. We used whole-mount immunohistochemistry and histochemical stains to localize neural elements in 15.5?days post coitus (dpc) fetal mice. To identify potential regulatory factors expressed in pelvic ganglia, we surveyed expression patterns for known or probable transcription factors (TF) annotated in the mouse genome by screening a whole-mount in situ hybridization library of fetal UGTs. Of the 155 genes detected in pelvic ganglia, 88 encode TFs based on the presence of predicted DNA-binding domains. Neural crest (NC)-derived progenitors within the LUT were labeled by Sox10, a well-known regulator of NC development. Genes identified were categorized based on patterns of restricted expression in pelvic ganglia, pelvic ganglia and urethral epithelium, or pelvic ganglia and urethral mesenchyme. Gene expression patterns and the distribution of Sox10+, Phox2b+, Hu+, and PGP9.5+ cells within developing ganglia suggest previously unrecognized regional segregation of Sox10+ progenitors and differentiating neurons in early development of pelvic ganglia. Reverse transcription-PCR of pelvic ganglia RNA from fetal and post-natal stages demonstrated that multiple TFs maintain post-natal expression, although Pax3 is extinguished before weaning. Our analysis identifies multiple potential regulatory genes including TFs that may participate in segregation of discrete lineages within pelvic ganglia. The genes identified here are attractive candidate disease genes that may now be further investigated for their roles in malformation syndromes or in LUT dysfunction. PMID:22988430

  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. Le Crtac terminal et le Palocne basal

    E-print Network

    Paris-Sud XI, Université de

    Le Crétacé terminal et le Paléocčne basal de l'Europe nord-occidentale* The end Cretaceous that Cretaceous sedimentation in northwest Europe continued until the end ofthe Maastrichtian. Following the end-Maastrichtian regression. marked by a period qfkarst- ification, northwest Europe was affected by two successive

  16. Basal Textbooks and the Social Studies

    ERIC Educational Resources Information Center

    Ediger, Marlow

    2010-01-01

    Basal textbooks are rather popular for social studies teachers to use in the classroom setting. There are selected reasons for this occurring. They do provide beginning and new teachers a framework for ongoing lessons and units of study. The accompanying Manual provides suggestions for learning activities for learners to pursue. Evaluation…

  17. ?-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

  18. Emergency and Abnormal Situations Project

    E-print Network

    --------------------------------------------------------Context Dependent Manufacturers Regulatory Agencies Company (Management, Dispatch, Maintenance) Flight and Cabin Crews ATC #12;Economic and Regulatory Pressures Philosophies Emergency and Abnormal Situations Project Taxonomy of the Domain Economic and Regulatory Pressures Pertaining to Dealing with and Training

  19. Anatomy of giant serotonin-containing neurones in the cerebral ganglia of Helix pomatia and Limax maximus

    Microsoft Academic Search

    V. W. Pentreath; N. N. Osborne; G. A. Cottrell

    1973-01-01

    There is a giant serotonin-containing neurone (GSC) in each cerebral ganglion of Helix pomatia and Limax maximus. In Helix, presynaptic endings of the GSCs are located in the buccal ganglia and peripheral musculature. Dense-cored vesicles of mean diameter 100 nm were observed in the perikarya and the axon branches of the GSCs within the cerebral ganglia. Evidence is presented which

  20. 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.

  1. Kidney transplantation in abnormal bladder

    PubMed Central

    Mishra, Shashi K.; Muthu, V.; Rajapurkar, Mohan M.; Desai, Mahesh R.

    2007-01-01

    Structural urologic abnormalities resulting in dysfunctional lower urinary tract leading to end stage renal disease may constitute 15% patients in the adult population and up to 20-30% in the pediatric population. A patient with an abnormal bladder, who is approaching end stage renal disease, needs careful evaluation of the lower urinary tract to plan the most satisfactory technical approach to the transplant procedure. Past experience of different authors can give an insight into the management and outcome of these patients. This review revisits the current literature available on transplantation in abnormal bladder and summarizes the clinical approach towards handling this group of difficult transplant patients. We add on our experience as we discuss the various issues. The outcome of renal transplant in abnormal bladder is not adversely affected when done in a reconstructed bladder. Correct preoperative evaluation, certain technical modification during transplant and postoperative care is mandatory to avoid complications. Knowledge of the abnormal bladder should allow successful transplantation with good outcome. PMID:19718334

  2. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

    PubMed Central

    Flegel, Caroline; Schöbel, Nicole; Altmüller, Janine; Becker, Christian; Tannapfel, Andrea; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq) to conduct the first expression analysis of human trigeminal ganglia (TG) and dorsal root ganglia (DRG). We analyzed the data with a focus on G-protein coupled receptors (GPCRs) and ion channels, which are (potentially) involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP) channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs) with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues. PMID:26070209

  3. The Anterograde Transport of Rabies Virus in Rat Sensory Dorsal Root Ganglia Neurons

    Microsoft Academic Search

    HENRI TSIANG; ERIK LYCKE; PIERRE-EMMANUEL CECCALDI; ALAIN ERMINE; XAVIER HIRARDOT

    1989-01-01

    SUMMARY We have previously described the capacity of neurites extending from cultured rat sensory dorsal root ganglia (DRG) neurons to transport rabies virus through axoplasm in the retrograde direction. Here we report the infection of cultured neurons derived from the DRG and the subsequent anterograde transport of rabies virus from the infected cell somas through the extending neurites to its

  4. 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

  5. Endogenous neurokinins facilitate synaptic transmission in guinea pig airway parasympathetic ganglia.

    PubMed

    Canning, Brendan J; Reynolds, Sandra M; Anukwu, Linus U; Kajekar, Radhika; Myers, Allen C

    2002-08-01

    Neurokinin-containing nerve fibers were localized to guinea pig airway parasympathetic ganglia in control tissues but not in tissues pretreated with capsaicin. The purpose of the present study was to determine whether neurokinins, released during axonal reflexes or after antidromic afferent nerve stimulation, modulate ganglionic synaptic neurotransmission. The neurokinin type 3 (NK(3)) receptor antagonists SB-223412 and SR-142801 inhibited vagally mediated cholinergic contractions of bronchi in vitro at stimulation voltages threshold for preganglionic nerve activation but had no effect on vagally mediated contractions evoked at optimal voltage or field stimulation-induced contractions. Intracellular recordings from the ganglia neurons revealed that capsaicin-sensitive nerve stimulation potentiated subsequent preganglionic nerve-evoked fast excitatory postsynaptic potentials. This effect was mimicked by the NK(3) receptor agonist senktide analog and blocked by SB-223412. In situ, senktide analog markedly increased baseline tracheal cholinergic tone, an effect that was reversed by atropine and prevented by vagotomy or SB-223412. Comparable effects of intravenous senktide analog on pulmonary insufflation pressure were observed. These data highlight the important integrative role played by parasympathetic ganglia and indicate that activation of NK(3) receptors in airway ganglia by endogenous neurokinins facilitates synaptic neurotransmission. PMID:12121843

  6. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.

    PubMed

    Flegel, Caroline; Schöbel, Nicole; Altmüller, Janine; Becker, Christian; Tannapfel, Andrea; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq) to conduct the first expression analysis of human trigeminal ganglia (TG) and dorsal root ganglia (DRG). We analyzed the data with a focus on G-protein coupled receptors (GPCRs) and ion channels, which are (potentially) involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP) channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs) with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues. PMID:26070209

  7. Differential expression of P2X receptors on neurons from different parasympathetic ganglia

    E-print Network

    Burnstock, Geoffrey

    of sphenopalatine and submandibular ganglia responded. Lowering pH potentiated ATP responses in neurons from all cervical ganglion (Reekie and Burnstock, 1994) and guinea-pig coeliac ganglion (Khakh et al., 1995) respond neu- rons, ATP evoked an inward current, and acidification to pH 6.2 increased the response amplitude

  8. Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral glucose utilization

    SciTech Connect

    Engber, T.M.; Susel, Z.; Kuo, S.; Chase, T.N. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1990-12-01

    The effect of chronic levodopa administration on the functional activity of the basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The rates of local cerebral glucose utilization were studied under basal conditions as well as in response to challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100 mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an osmotic pump or intermittently by twice-daily injections. Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula. In control (lesioned and treated chronically with saline) rats, the D1 agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and 56%, respectively. Both continuous and intermittent levodopa blunted the SKF 38393-induced elevation in glucose metabolism in the substantia nigra pars reticulata, while intermittent levodopa also attenuated the increase in the entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not increase glucose utilization in any brain region in control animals; following intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64% in the subthalamic nucleus and by 39% in the deep layers of the superior colliculus on the ipsilateral side.

  9. 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

  10. Optimizing Reduction in Basal Hyperglucagonaemia to Repair Defective Glucagon Counterregulation in Insulin Deficiency

    PubMed Central

    Farhy, Leon S.; McCall, Anthony L.

    2012-01-01

    In health, the pancreatic islet cells work as a network with highly coordinated signals over time to balance glycaemia within a narrow range. In type 1 diabetes (T1DM), with autoimmune destruction of the ?-cells, lack of insulin is considered the primary abnormality and is the primary therapy target. However, replacing insulin alone does not achieve adequate glucose control and recent studies have focused on controlling the endogenous glucagon release as well. In T1DM, glucagon secretion is disordered but not absolutely deficient; it may be excessive postprandially yet it is characteristically insufficient and delayed in response to hypoglycaemia. We review our system-level analysis of the pancreatic endocrine network mechanisms of glucagon counterregulation (GCR) and their dysregulation in T1DM and focus on possible use of ?-cell inhibitors (ACI) to manipulate the glucagon axis to repair the defective GCR. Our results indicate that the GCR abnormalities are of “network origin”. The lack of ?-cell signalling is the primary deficiency which contributes to two separate network abnormalities: (i) absence of a ?-cell switch-off trigger and (ii) increase intraislet basal glucagon. A strategy to repair these abnormalities with ACI is proposed which could achieve better control of glycaemia with reduced hypoglycaemia risk. PMID:21824267

  11. Novel inhibitors of basal glucose transport as potential anticancer agents

    Microsoft Academic Search

    Weihe Zhang; Yi Liu; Xiaozhuo Chen; Stephen C. Bergmeier

    2010-01-01

    Cancer cells commonly show increased levels of glucose uptake and dependence. A potential strategy for the treatment of cancer may be the inhibition of basal glucose transport. We report here the synthesis of a small library of polyphenolic esters that inhibit basal glucose transport in H1299 lung and other cancer cells. These basal glucose transport inhibitors also inhibit cancer cell

  12. 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

  13. 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

  14. The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans

    PubMed Central

    2008-01-01

    Background Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBF?, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals. Results In this study, we detect and characterize the hitherto unexplored Runx/CBF? genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBF?-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBF? dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBF? are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors. Conclusion These results reveal that Runx and CBF? likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBF?-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians. PMID:18681949

  15. 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...

  16. The Albin-DeLong `box and arrow' model has long been the accepted standard model for the basal ganglia network.

    E-print Network

    Bar-Gad, Izhar

    Parkinson's disease SNc substantia nigra pars compacta SNr substantia nigra pars reticulata STN subthalamic] and the substantia nigra, pars reticulata [SNr], for simplicity referred to hereafter as GPi). The BG control -- via

  17. 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

    oxide synthase (iNOS/NOS2) and production of nitric oxide (NO)/peroxynitrite (ONOO-). Activated astrocytes were detected primarily near the microvasculature in both the striatum and globus pallidus (GP). It is suggested that Mn exposure may damage...

  18. Preliminary Findings of Antistreptococcal Antibody Titers and Basal Ganglia Volumes in Tic, Obsessive-compulsive, and Attention-Deficit\\/Hyperactivity Disorders

    Microsoft Academic Search

    Bradley S. Peterson; James F. Leckman; Daniel Tucker; Lawrence Scahill; Lawrence Staib; Heping Zhang; Robert King; Donald J. Cohen; John C. Gore; Paul Lombroso

    2000-01-01

    Background: Previous studies have provided prelimi- nary serological evidence supporting the theory that symp- toms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported as- sociations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also un- known whether streptococcal infection is associated in

  19. 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

    ........................................................... 91 1 CHAPTER I INTRODUCTION Vocalization requires the complex coordination of multiple respiratory, laryngeal and supralaryngeal motor units. The neural mechanisms underlying vocal motor control are poorly understood in mammalian... 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...

  20. 5HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

    Microsoft Academic Search

    Franz X Vollenweider; Peter Vontobel; Daniel Hell; Klaus L Leenders

    1999-01-01

    The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine

  1. Selective localisation of P450 enzymes and NADPH-P450 oxidoreductase in rat basal ganglia using anti-peptide antisera

    Microsoft Academic Search

    Andrew G Riedl; Paul M Watts; Robert J Edwards; Alan R Boobis; Peter Jenner; C. David Marsden

    1996-01-01

    Environmental or endogenous toxins may cause nigral cell death in Parkinson's disease (PD) due to altered expression of P450 enzymes. In rat brain, immunohistochemistry using anti-peptide antisera showed NADPH-P450 oxidoreductase and CYP2B1\\/2 in various hypothalamic nuclei and CYP1A1 in the globus pallidus, but neither enzyme was expressed in substantia nigra. No specific immunoreactivity to CYP2D1 or CYP3A1 was found in

  2. 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

  3. Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis

    PubMed Central

    Wu, Tong; Wang, Xudong; Li, Jing; Song, Xiuzhen; Wang, Ying; Wang, Yunfeng; Zhang, Lei; Li, Ziyao; Tian, Jiawei

    2015-01-01

    Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC), and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of these pathways. Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer. PMID:26126114

  4. [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

  5. Postural Abnormalities: An Individualized Program.

    ERIC Educational Resources Information Center

    Vodola, Thomas M.

    As one of the components of the Project ACTIVE (All Children Totally Involved Exercising) Teacher Training Model Kit, the manual is designed to enable the educator to organize, conduct, and evaluate individualized-personalized programs for children in grades 4 through 12 with postural abnormalities. An introductory chapter covers definitions and…

  6. [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

  7. Steganography with Least Histogram Abnormality

    Microsoft Academic Search

    Xinpeng Zhang; Shuozhong Wang; Kaiwen Zhang

    2003-01-01

    A novel steganographic scheme is proposed which avoids asymmetry inherent in conventional LSB embedding techniques so that abnormality in the image histogram is kept minimum. The proposed technique is capable of re- sisting the ?2 test and RS analysis, as well as a new steganalytic method named GPC analysis as introduced in this paper. In the described steganographic tech- nique,

  8. Basal cell carcinomas: attack of the hedgehog

    PubMed Central

    Epstein, Ervin H.

    2015-01-01

    Basal cell carcinomas (BCCs) were essentially a molecular ‘black box’ until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours. PMID:18813320

  9. Epidemiology of basal-like breast cancer

    Microsoft Academic Search

    Robert C. Millikan; Beth Newman; Chiu-Kit Tse; Patricia G. Moorman; Kathleen Conway; Lisa V. Smith; Miriam H. Labbok; Joseph Geradts; Jeannette T. Bensen; Susan Jackson; Sarah Nyante; Chad Livasy; Lisa Carey; H. Shelton Earp; Charles M. Perou

    2008-01-01

    Risk factors for the newly identified “intrinsic” breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal\\u000a growth factor receptor 2-positive\\/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based,\\u000a case–control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive\\u000a and in situ breast cancer, and case subtypes were compared

  10. 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

  11. Effects of equine grass sickness on sympathetic neurons in prevertebral and paravertebral ganglia.

    PubMed

    Shotton, H R; Lincoln, J; McGorum, B C

    2011-07-01

    Acute equine grass sickness (EGS) is a fatal disease of horses that is thought to be due to ingestion of a neurotoxic agent causing extensive damage to autonomic neurons. The aim of this study was to compare the effects of EGS on neurons in two sympathetic ganglia, the paravertebral cranial cervical ganglion (CCG) and the prevertebral coeliac/cranial mesenteric ganglion (CG/CMG). Specimens from horses with EGS and controls were obtained post mortem and processed using single and double immunofluorescence labelling for PGP 9.5 and HuC/HuD (pan-neuronal markers), TUNEL and caspase 3 (markers for apoptosis), vasoactive intestinal polypeptide (VIP) and galanin (markers of the cell body response to injury following axotomy or exposure to sympathetic neurotoxins) and tyrosine hydroxylase (TH, marker for noradrenaline synthesis). In control horses, all neurons contained PGP 9.5 and HuC/HuD. There was a significant loss of PGP 9.5 and HuC/HuD expression in samples from horses with EGS that occurred to a greater extent in the CG/CMG than the CCG. The number of caspase 3-positive neurons increased significantly in both ganglia, but TUNEL staining of sympathetic neurons was only significantly increased in the CG/CMG in EGS. No VIP was observed in any ganglia; however, there was a significant increase in galanin-positive neurons in both ganglia in EGS. In the CCG, there was a significant shift towards increased fluorescence intensity for TH, possibly indicating an initial accumulation of TH within the cell body. In contrast, TH fluorescence intensity was significantly reduced in the CG/CMG in EGS correlating with the greater loss of neurons. These results demonstrate that EGS can induce a cell body response that is similar to the response of sympathetic neurons to a chemical neurotoxin. EGS also causes loss of sympathetic neurons, some of which occurs via apoptosis. Changes were more marked in the CG/CMG than the CCG indicating that the prevertebral ganglia were affected earlier than the paravertebral ganglia in the pathological process and had undergone greater neurodegeneration. PMID:21457994

  12. Abnormal Red Cell Structure and Function in Neuroacanthocytosis

    PubMed Central

    Cluitmans, Judith C. A.; Tomelleri, Carlo; Yapici, Zuhal; Dinkla, Sip; Bovee-Geurts, Petra; Chokkalingam, Venkatachalam; De Franceschi, Lucia; Brock, Roland; Bosman, Giel J. G. C. M.

    2015-01-01

    Background Panthothenate kinase-associated neurodegeneration (PKAN) belongs to a group of hereditary neurodegenerative disorders known as neuroacanthocytosis (NA). This genetically heterogeneous group of diseases is characterized by degeneration of neurons in the basal ganglia and by the presence of deformed red blood cells with thorny protrusions, acanthocytes, in the circulation. Objective The goal of our study is to elucidate the molecular mechanisms underlying this aberrant red cell morphology and the corresponding functional consequences. This could shed light on the etiology of the neurodegeneration. Methods We performed a qualitative and semi-quantitative morphological, immunofluorescent, biochemical and functional analysis of the red cells of several patients with PKAN and, for the first time, of the red cells of their family members. Results We show that the blood of patients with PKAN contains not only variable numbers of acanthocytes, but also a wide range of other misshapen red cells. Immunofluorescent and immunoblot analyses suggest an altered membrane organization, rather than quantitative changes in protein expression. Strikingly, these changes are not limited to the red blood cells of PKAN patients, but are also present in the red cells of heterozygous carriers without neurological problems. Furthermore, changes are not only present in acanthocytes, but also in other red cells, including discocytes. The patients’ cells, however, are more fragile, as observed in a spleen-mimicking device. Conclusion These morphological, molecular and functional characteristics of red cells in patients with PKAN and their family members offer new tools for diagnosis and present a window into the pathophysiology of neuroacanthocytosis. PMID:25933379

  13. 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

  14. Cadmium effect on the structure of supra- and subpharyngeal ganglia and the neurosecretory processes in earthworm Dendrobaena veneta (Rosa).

    PubMed

    Siekierska, Ewa

    2003-01-01

    Cadmium effects on the supra- and subpharyngeal ganglia, neurosecretion and RNA content in the neurosecretory cells were tested in earthworms Dendrobaena veneta exposed to 10 and 50 mg Cd kg(-1) in soil after 20 days of the experiment. Accumulation of cadmium in the ganglia of nervous system was also measured using AAS method. Cadmium was accumulated in the nervous system. The accumulated amount was proportional to Cd soil concentration and the exposure time. A considerable fall in neurosecretion and RNA content in the neurosecretory cells and neurosecretion in the neuropile (the axons) of both tested ganglia was induced by 50 mg Cd kg(-1). It seemed that neurosecretion synthesis and its axonal transport could be suppressed. Cadmium caused degenerative changes as vacuolization of the neurosecretory cells and neuropile in both tested ganglia. PMID:12860099

  15. Mastoid abnormalities in down syndrome

    Microsoft Academic Search

    R. B. J. Glass; D. K. Yousefzadeh; N. J. Roizen

    1989-01-01

    Hearing loss and otitis media are commonly associated with Down syndrome. Hypoplasia of the mastoids is seen in many affected\\u000a children and sclerosis of mastoid bones is not uncommon in Down syndrome. Awareness and early recognition of mastoid abnormality\\u000a may lead to appropriate and timely therapy, thereby preserving the child’s hearing or compensating for hearing loss; factors\\u000a which are important

  16. Infertile mares with chromosome abnormalities

    Microsoft Academic Search

    I. A. Stewart-Scott

    1988-01-01

    Chromosomal abnormalities have been detected in five mares identified by their poor reproductive performance. All had small gonads and absent or irregular oestrous cycles. One mare was 65, XXX, two were 64, XY sex-reversal females and two were sex chromosome mosaics with karyotypes of 63, XO\\/64, XX\\/64, XY and 63, XO\\/64, XX respectively. This report supports the suggestion made in

  17. 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

  18. Ovarian Steroidogenic Abnormalities in PCOS

    Microsoft Academic Search

    Jessica K. Wickenheisser; Jan M. McAllister

    Androgen excess, theca, granulosa, polycystic ovary syndrome, steroidogenesis, folliculogenesis, estrogen, insulin sensitivity,\\u000a signaling defect. Polycystic ovary syndrome (PCOS) is a common, clinically heterogeneous disorder that affects approximately\\u000a 6–10% of premenopausal women [1, 2]. Hyperandrogenemia is the biochemical hallmark of PCOS. Reproductive and endocrine abnormalities\\u000a include disordered gonadotropin secretion, oligomenorrhea and anovulatory infertility, and endometrial hyperplasia. Obesity,\\u000a hirsutism, acne, and alopecia

  19. Expression of peptides, nitric oxide synthase and NPY receptor in trigeminal and nodose ganglia after nerve lesions

    Microsoft Academic Search

    Xu Zhang; Ru-Rong Ji; Jan Arvidsson; Jan M. Lundberg; Tamas Bartfai; Katarina Bedecs; Tomas Hökfelt

    1996-01-01

    Using immunohistochemistry and in situ hybridization, the expression of galanin (GAL)\\/galanin message associated peptide (GMAP)-, neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)\\/peptide histidine isoleucine (PHI)- and nitric oxide synthase (NOS)-like immunoreactivities and mRNAs, and NPY receptor mRNA was studied in normal trigeminal and nodose ganglia and 14 and 42 days after peripheral axotomy. In normal trigeminal ganglia about 11% of

  20. 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

  1. Sodium dependency of GABA uptake into glial cells in bullfrog sympathetic ganglia

    Microsoft Academic Search

    Saeko Sakai; Junko Tasaka; Tsuneo Tosaka I

    1990-01-01

    The kinetics of sodium dependency of GABA uptake by satellite glial cells was studied in bullfrog sympathetic ganglia. GABA uptake followed simple Michaelis-Menten kinetics at all sodium concentrations tested. Increasing external sodium concentration increased bothKm andVmax for GABA uptake, with an increase in theVmax\\/Km ratio. The initial rate of uptake as a function of the sodium concentration exhibited sigmoid shape

  2. Detection of Caprine Herpesvirus 1 in Sacral Ganglia of Latently Infected Goats by PCR

    PubMed Central

    Tempesta, Maria; Pratelli, Annamaria; Greco, Grazia; Martella, Vito; Buonavoglia, Canio

    1999-01-01

    A study of the latency of caprine herpesvirus 1 (CpHV.1) was carried out with four latently infected goats. Three goats were treated with dexamethasone and euthanized after 4 and 6 days. PCR and virus isolation allowed us to detect CpHV.1 only in the third and fourth sacral ganglia of the two animals euthanized 6 days after the start of treatment. PMID:10203533

  3. Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury

    Microsoft Academic Search

    J. Frederick; M. E. Buck; D. J. Matson; D. N. Cortright

    2007-01-01

    Thermosensitive TRP channels display unique thermal responses, suggesting distinct roles mediating sensory transmission of temperature. However, whether relative expression of these channels in dorsal root ganglia (DRG) is altered in nerve injury is unknown. We developed a multiplex ribonuclease protection assay (RPA) to quantify rat TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8 RNA levels in DRG. We used the multiplex

  4. Differential contribution of Neurog1 and Neurog2 on the formation of cranial ganglia along the anterior-posterior axis

    PubMed Central

    Takano-Maruyama, Masumi; Chen, Yiju; Gaufo, Gary O.

    2012-01-01

    SUMMARY The neural crest (NC) and placode are transient neurogenic cell populations that give rise to cranial ganglia of the vertebrate head. The formation of the anterior NC- and placode-derived ganglia has been shown to depend on the single activity of either Neurog1 or Neurog2. The requirement of the more posterior cranial ganglia on Neurog1 and Neurog2 is unknown. Here we show that the formation of the NC-derived parasympathetic otic ganglia, and placode-derived visceral sensory petrosal and nodose ganglia are dependent on the redundant activities of Neurog1 and Neurog2. Tamoxifen-inducible Cre lineage labeling of Neurog1 and Neurog2 show a dynamic spatiotemporal expression profile in both NC and epibranchial placode that correlates with the phenotypes of the Neurog-mutant embryos. Our data, together with previous studies, suggest that the formation of cranial ganglia along the anterior-posterior axis is dependent on the dynamic spatiotemporal activities of Neurog1 and/or Neurog2 in both NC and epibranchial placode. PMID:22102600

  5. Stem cells from wildtype and Friedreich's ataxia mice present similar neuroprotective properties in dorsal root ganglia cells.

    PubMed

    Jones, Jonathan; Estirado, Alicia; Redondo, Carolina; Martinez, Salvador

    2013-01-01

    Many neurodegenerative disorders share a common susceptibility to oxidative stress, including Alzheimer's, Parkinson Disease, Huntington Disease and Friedreich's ataxia. In a previous work, we proved that stem cell-conditioned medium increased the survival of cells isolated from Friedreich's ataxia patients, when submitted to oxidative stress. The aim of the present work is to confirm this same effect in dorsal root ganglia cells isolated from YG8 mice, a mouse model of Friedreich's ataxia. In this disorder, the neurons of the dorsal root ganglia are the first to degenerate. Also, in this work we cultured mesenchymal stem cells isolated from YG8 mice, in order to compare them with their wildtype counterpart. To this end, dorsal root ganglia primary cultures isolated from YG8 mice were exposed to oxidative stress and cultured with conditioned medium from either wildtype or YG8 stem cells. As a result, the conditioned medium increased the survival of the dorsal root ganglia cells. This coincided with an increase in oxidative stress-related markers and frataxin expression levels. BDNF, NT3 and NT4 trophic factors were detected in the conditioned medium of both wild-type and YG8 stem cells, all which bind to the various neuronal cell types present in the dorsal root ganglia. No differences were observed in the stem cells isolated from wildtype and YG8 mice. The results presented confirm the possibility that autologous stem cell transplantation may be a viable therapeutic approach in protecting dorsal root ganglia neurons of Friedreich's ataxia patients. PMID:23671637

  6. 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

  7. Combining Registration and Abnormality Detection in Mammography

    E-print Network

    Desolneux, Agnès

    Combining Registration and Abnormality Detection in Mammography Mohamed Hachama, Agn`es Desolneux (e.g. lesions) in mammography are solved separately, although the solutions of these problems 2006 #12;Combining Registration and Abnormality Detection in Mammography 179 The definition

  8. The dermatoscopic universe of basal cell carcinoma

    PubMed Central

    Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Specchio, Francesca; Raucci, Margaritha; Zalaudek, Iris

    2014-01-01

    Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC. PMID:25126452

  9. Radiation-induced basal cell carcinoma

    PubMed Central

    Zargari, Omid

    2015-01-01

    Background: The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. A variety of cancers including basal cell carcinoma (BCC) are seen years after this treatment. Objective: We sought to determine the clinical characteristics of BCCs among irradiated patients. Methods: The clinical records of all patients with BCC in a clinic in north of Iran were reviewed. Results: Of the 58 cases of BCC, 29 had positive history for radiotherapy in their childhood. Multiple BCCs were seen in 79.3% and 10.3% of patients with history and without history of radiotherapy, respectively. Conclusions: X-ray radiation is still a major etiologic factor in developing BCC in northern Iran. Patients with positive history for radiotherapy have higher rate of recurrence.

  10. Abnormal Supranuclear Eye Movements in the Child

    Microsoft Academic Search

    Lorraine Cassidy; David Taylor; Christopher Harris

    2000-01-01

    Abnormal eye movements in the infant or young child can be congenital or acquired. They may be a result of abnormal early visual development or a sign of underlying neurologic or neuromuscular disease. It is important to be able to detect these abnormalities and to distinguish them from normal but immature eye movements. The spectrum of disease in children differs

  11. Site-Specific Basal Body Duplication in Chlamydomonas

    PubMed Central

    O’Toole, Eileen T.; Dutcher, Susan K.

    2014-01-01

    Correct centriole/basal body positioning is required for numerous biological processes, yet how the cell establishes this positioning is poorly understood. Analysis of centriolar/basal body duplication provides a key to understanding basal body positioning and function. Chlamydomonas basal bodies contain structural features that enable specific triplet microtubules to be specified. Electron tomography of cultures enriched in mitotic cells allowed us to follow basal body duplication and identify a specific triplet at which duplication occurs. Probasal bodies elongate in prophase, assemble transitional fibers (TF) and are segregated with a mature basal body near the poles of the mitotic spindle. A ring of nine-singlet microtubules is initiated at metaphase, orthogonal to triplet eight. At telophase/cytokinesis, triplet microtubule blades assemble first at the distal end, rather than at the proximal cartwheel. The cartwheel undergoes significant changes in length during duplication, which provides further support for its scaffolding role. The uni1-1 mutant contains short basal bodies with reduced or absent TF and defective transition zones, suggesting that the UNI1 gene product is important for coordinated probasal body elongation and maturation. We suggest that this site-specific basal body duplication ensures the correct positioning of the basal body to generate landmarks for intracellular patterning in the next generation. PMID:24166861

  12. Basal bodies exhibit polarized positioning in zebrafish cone photoreceptors

    PubMed Central

    Ramsey, Michelle; Perkins, Brian D.

    2012-01-01

    The asymmetric positioning of basal bodies, and therefore cilia, is often critical for proper cilia function. This planar polarity is critical for motile cilia function but has not been extensively investigated for non-motile cilia or for sensory cilia such as vertebrate photoreceptors. Zebrafish photoreceptors form an organized mosaic ideal for investigating cilia positioning. We report that in the adult retina, the basal bodies of red, green-, and blue-sensitive cone photoreceptors localized asymmetrically on the cell edge nearest to the optic nerve. In contrast, no patterning was seen in the basal bodies of ultraviolet-sensitive cones or in rod photoreceptors. The asymmetric localization of basal bodies was consistent in all regions of the adult retina. Basal body patterning was unaffected in the cones of the XOPS-mCFP transgenic line, which lacks rod photoreceptors. Finally, the adult pattern was not seen in 7 day post fertilization (dpf) larvae as basal bodies were randomly distributed in all the photoreceptor subtypes. These results establish the asymmetrical localization of basal bodies in red-, green-, and blue-sensitive cones in adult zebrafish retinas but not in larvae. This pattern suggests an active cellular mechanism regulated the positioning of basal bodies after the transition to the adult mosaic and that rods do not seem to be necessary for the patterning of cone basal bodies. PMID:23171982

  13. Complex-Value Coherence Mapping Reveals Novel Abnormal Resting-State Functional Connectivity Networks in Task-Specific Focal Hand Dystonia

    PubMed Central

    Hinkley, Leighton B. N.; Sekihara, Kensuke; Owen, Julia P.; Westlake, Kelly P.; Byl, Nancy N.; Nagarajan, Srikantan S.

    2013-01-01

    Resting-state imaging designs are powerful in modeling functional networks in movement disorders because they eliminate task performance related confounds. However, the most common metric for quantifying functional connectivity, i.e., bivariate magnitude coherence (Coh), can sometimes be contaminated by spurious correlations in blood-oxygen level dependent (BOLD) signal due to smoothing and seed blur, thereby limiting the identification of true interactions between neighboring neural populations. Here, we apply a novel functional connectivity metric., i.e., imaginary coherence (ICoh), to BOLD fMRI data in healthy individuals and patients with task-specific focal hand dystonia (tspFHD), in addition to the traditional magnitude Coh metric. We reconstructed resting-state sensorimotor, basal ganglia, and default-mode networks using both Coh and ICoh. We demonstrate that indeed the ICoh metric eliminates spatial blur around seed placement and reflects slightly different networks from Coh. We then identified significant reductions in resting-state connectivity within both the sensorimotor and basal ganglia networks in patients with tspFHD, primarily in the hemisphere contralateral to the affected hand. Collectively, these findings direct our attention to the fact that multiple networks are decoupled in tspFHD that can be unraveled by different functional connectivity metrics, and that this aberrant communication contributes to clinical deficits in the disorder. PMID:24133480

  14. Nonosseous abnormalities on bone scans.

    PubMed

    Loutfi, Issa; Collier, B David; Mohammed, Ahmed M

    2003-09-01

    Although bone scanning is a test primarily concerned with skeletal abnormalities, important nonosseous findings are occasionally present on the images. To gauge the significance of such nonosseous uptake and, in particular, to determine whether these findings contain useful diagnostic information, the technical and medical staff in nuclear medicine must recognize the various patterns of nonbony uptake and understand their causes. The objectives of this article are to demonstrate the appearances of nonosseous uptake on bone scans, to categorize the forms of soft-tissue uptake, to emphasize technical artifacts leading to soft-tissue uptake, and to highlight the clinical significance of pathologic soft-tissue uptake. PMID:12968045

  15. Foot abnormalities of wild birds

    USGS Publications Warehouse

    Herman, C.M.; Locke, L.N.; Clark, G.M.

    1962-01-01

    The various foot abnormalities that occur in birds, including pox, scaly-leg, bumble-foot, ergotism and freezing are reviewed. In addition, our findings at the Patuxent Wildlife Research Center include pox from dove, mockingbird, cowbird, grackle and several species of sparrows. Scaly-leg has been particularly prevalent on icterids. Bumble foot has been observed in a whistling swan and in a group of captive woodcock. Ergotism is reported from a series of captive Canada geese from North Dakota. Several drug treatments recommended by others are presented.

  16. Abnormalities of the erythrocyte membrane.

    PubMed

    Gallagher, Patrick G

    2013-12-01

    Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy. PMID:24237975

  17. Pathology Case Study: Sensory Abnormalities

    NSDL National Science Digital Library

    Duggal, Neil

    The Department of Pathology at the University of Pittsburgh Medical Center has compiled a wide range of pathology case studies to aid students and instructors in the medical/health science field. This particular case focuses on a 30-year-old man with a history of focal numbness, bladder and bowel dysfunction, and progressive sensory abnormalities. The patientâ??s history, images from an MRI, microscopic images of a specimen collected during his laminectomy, and final diagnosis are provided in this case for your review. Students will find this resource especially helpful, as it provides experience with patient history, lab results, and diagnostics.

  18. Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma?

    PubMed Central

    Mehta, Karaninder S.; Mahajan, Vikram K.; Chauhan, Pushpinder S.; Sharma, Anju Lath; Sharma, Vikas; Abhinav, C.; Khatri, Gayatri; Prabha, Neel; Sharma, Saurabh; Negi, Muninder

    2012-01-01

    Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenous cisplatin (50?mg) and 5-florouracil (5-FU, 750?mg) on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest. PMID:23304569

  19. Educational Content of Basal Reading Texts: Implications for Comprehension Instruction.

    ERIC Educational Resources Information Center

    Schmidt, William H.; And Others

    To explore the issue of educational content in basal readers, a study analyzed 34 basal reading textbooks, representing eight of the most commonly used series in American elementary education. Educational content was defined and categorized along three dimensions: subject matter, function, and ethos. The subject matter component covered theories,…

  20. Effects of aging on basal fat oxidation in obese humans

    Microsoft Academic Search

    Thomas P. J. Solomon; Christine M. Marchetti; Raj K. Krishnan; Frank Gonzalez; John P. Kirwan

    2008-01-01

    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO2max) were measured in 10 older (age, 60 ± 4 years; mean ± SEM) and 10 younger (age, 35 ± 4

  1. Paleoenvironmental analysis of thrombolites in the basal Purbeck Formation

    E-print Network

    Wilson, Mark A.

    Paleoenvironmental analysis of thrombolites in the basal Purbeck Formation (Upper Jurassic the basal Purbeck Formation (Upper Jurassic) on the Isle of Portland, southern England, are described upright and for some time after they fell, a period of a few hundred years. This suggests a relatively

  2. Phylogenetic Context and Basal Metazoan Model Systems1

    Microsoft Academic Search

    ALLEN G. COLLINS; S. MCFADDEN; BERND SCHIERWATER

    2005-01-01

    SYNOPSIS. In comparative studies using model organisms, extant taxa are often referred to as basal. The term suggests that such taxa are descendants of lineages that diverged early in the history of some larger taxon. By this usage, the basal metazoans comprise just four phyla (Placozoa, Porifera, Cnidaria, and Cten- ophora) and the large clade Bilateria. We advise against this

  3. Volcanic Landslide Basal Friction as Measured by Seismic Waves

    Microsoft Academic Search

    E. E. Brodsky; E. Gordeev

    2002-01-01

    The long runout of large landslides, and therefore apparently low basal friction, has long been a subject of intense debate. Volcanic landslides have even longer runouts than other avalanches, perhaps due to the importance of hot gases as a driving force or basal lubricant. We invert seismic data from the March 30, 1956 Bezymianny, Russia for an equivalent force source.

  4. New basal cell carcinoma susceptibility loci.

    PubMed

    Stacey, Simon N; Helgason, Hannes; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexř, Bjřrn A; Tjřnneland, Anne; Overvad, Kim; Jonasson, Jon G; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T; Halldorsson, Bjarni V; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I; Gudbjartsson, Daniel F; Olafsson, Jon H; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  5. Pine Island Glacier - local flow mechanisms and basal sliding

    NASA Astrophysics Data System (ADS)

    Wilkens, N. M.; Kleiner, T.; Humbert, A.

    2013-12-01

    Pine Island Glacier is a fast moving outlet glacier in the West Antarctic Ice Sheet. Several tributaries feeding the central ice stream characterise the flow field structure of this glacier. In the past decades the glacier has shown acceleration, thinning and a significant grounding line retreat. These ongoing processes are coinciding with a concentrated mass loss in the area around Pine Island Glacier, the Amundsen Sea Embayment. The area is of additional interest due to its retrograde bed slope. The postulated instability of the setting turns the glacier into an even more suitable object for modelling studies. One major challenge encountered when modelling the flow field of Pine Island Glacier is to reproduce the locally varying flow pattern, with its many tributaries. Commonly this difficulty is overcome by inversion for parameters controlling basal sliding. Our study is aimed at connecting basal sliding again to physical parameters. To achieve this we conduct experiments of Pine Island Glacier with the diagnostic 3D full-Stokes model COMice. The model is thermo-mechanically coupled and implemented with the commercial finite-element package COMSOL Multiphysics©. We use remotely sensed surface velocity data to validate our results. In a first step, the model is used to identify dominant local mechanisms that drive the flow of the different tributaries. We identify connections between the basal topography, the basal temperature, the driving stress and the basal roughness distribution. The thus gained information is used to confine basal sliding. Areas with similar qualitative characteristics are identified, and constant-sliding assumptions made for those. Additionally, the basal roughness distribution is matched onto a basal sliding parameter. This way the sliding law is again brought closer to its original meaning. Our results are important for prognostic model experiments, as we connect basal sliding to locally varying basal properties, which might lead to different responses of the tributaries to altered external forcing.

  6. Laboratory Validation of a Screening Model: Exploring the Interplay between Dissolution and Degradation Rates in Ganglia-Dominated Source Zones

    NASA Astrophysics Data System (ADS)

    Phelan, T. J.; Abriola, L. M.; Gibson, J. L.; Smits, K. M.; Christ, J.

    2013-12-01

    In-situ bioremediation is a widely applied treatment technology for source zones contaminated with dense non-aqueous phase liquids (DNAPLs). It is both economical and reasonably efficient for long-term management and closure of contaminated sites. A number of laboratory studies have demonstrated enhancement in chlorinated ethene dissolution rates due to the presence of dehalogenating microorganisms, which may lead to increased mass removal rates and shorter cleanup times. Previous modeling efforts have suggested this dissolution enhancement can be a factor of 10 or more when the contaminant is located in high saturation DNAPL pools. Yet, laboratory studies with DNAPL trapped as ganglia have suggested dissolution enhancement is often less than 10. This presentation investigates the interplay between dissolution and degradation rates in ganglia-contaminated source zones using a one-dimensional, simplified, steady-state, analytical solution to the advection-dispersion-reaction equation. A linear driving force model is employed to simulate ganglia dissolution. Degradation kinetics are approximated as zero- or first-order. Model predictions are independently compared to laboratory data available in the literature. Results indicate that dissolution enhancement predictions in ganglia-dominated source zones are often much less than those predicted assuming high saturation pools, suggesting that the presented model is a better tool for estimating bioenhanced dissolution in ganglia-contaminated regions. Furthermore, this screening model provides a remarkably good prediction of laboratory results and could provide practitioners with a useful tool for estimating the extent to which bioenhanced dissolution may aid in site closure strategies.

  7. Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate.

    PubMed Central

    Coen, D M; Kosz-Vnenchak, M; Jacobson, J G; Leib, D A; Bogard, C L; Schaffer, P A; Tyler, K L; Knipe, D M

    1989-01-01

    Herpes simplex virus infection of mammalian hosts involves lytic replication at a primary site, such as the cornea, translocation by axonal transport to sensory ganglia and replication, and latent infection at a secondary site, ganglionic neurons. The virus-encoded thymidine kinase, which is a target for antiviral drugs such as acyclovir, is not essential for lytic replication yet evidently is required at the secondary site for replication and some phase of latent infection. To determine the specific stage in viral pathogenesis at which this enzyme is required, we constructed virus deletion mutants that were acyclovir resistant and exhibited no detectable thymidine kinase activity. After corneal inoculation of mice, the mutants replicated to high titers in the eye but were severely impaired for acute replication in trigeminal ganglia and failed to reactivate from ganglia upon cocultivation with permissive cells. Nevertheless, latency-associated transcripts were expressed in neuronal nuclei of ganglia from mutant-infected mice and superinfection of the ganglia with a second virus rescued the latent mutant virus. Thus, contrary to a widely accepted hypothesis, the thymidine kinase-negative mutants established latent infections, implying that neither thymidine kinase activity nor ganglionic replication is necessary for establishment of latency. Rather, thymidine kinase appears to be necessary for reactivation from latency. These results suggest that acyclovir-resistant viruses could establish latent infections in clinical settings and have implications for the use of genetically engineered herpesviruses to deliver foreign genes to neurons. Images PMID:2543985

  8. Laboratory Assessment of a Screening Model: Exploring the Coupling between Dissolution and Degradation Rates in Ganglia-Dominated Source Zones

    NASA Astrophysics Data System (ADS)

    Phelan, T. J.; Abriola, L. M.; Gibson, J. L.; Smits, K. M.; Christ, J.

    2014-12-01

    In-situ bioremediation is a widely applied treatment technology for source zones contaminated with dense non-aqueous phase liquids (DNAPLs). It is both economical and reasonably efficient for long-term management and closure of contaminated sites. A number of laboratory studies have demonstrated enhancement in chlorinated ethene dissolution rates due to the presence of dehalogenating microorganisms, which may lead to increased mass removal rates and shorter cleanup times. Previous modeling efforts have suggested this dissolution enhancement can be a factor of 10 or more when the contaminant is located in high saturation DNAPL pools. Yet, laboratory studies with DNAPL trapped as ganglia have suggested dissolution enhancement is often less than 10. This presentation investigates the interplay between dissolution and degradation rates in ganglia-contaminated source zones using a one-dimensional, simplified, steady-state, analytical solution to the advection-dispersion-reaction equation. A linear driving force model is employed to simulate ganglia dissolution. Degradation kinetics are approximated as zero- or first-order. Model predictions are independently compared to laboratory data available in the literature. Results indicate that dissolution enhancement predictions in ganglia-dominated source zones are often much less than those predicted assuming high saturation pools, suggesting that the presented model is a better tool for estimating bioenhanced dissolution in ganglia-contaminated regions. Furthermore, this screening model provides a remarkably good prediction of laboratory results and could provide practitioners with a useful tool for estimating the extent to which bioenhanced dissolution may aid in site closure strategies.

  9. Neurochemical characterization of extrinsic nerves in myenteric ganglia of the guinea pig distal colon.

    PubMed

    Chen, Bao Nan; Sharrad, Dale F; Hibberd, Timothy J; Zagorodnyuk, Vladimir P; Costa, Marcello; Brookes, Simon J H

    2015-04-01

    Extrinsic nerves to the gut influence the absorption of water and electrolytes and expulsion of waste contents, largely via regulation of enteric neural circuits; they also contribute to control of blood flow. The distal colon is innervated by extrinsic sympathetic and parasympathetic efferent and spinal afferent neurons, via axons in colonic nerve trunks. In the present study, biotinamide tracing of colonic nerves was combined with immunohistochemical labeling for markers of sympathetic, parasympathetic, and spinal afferent neurons to quantify their relative contribution to the extrinsic innervation. Calcitonin gene-related peptide, vesicular acetylcholine transporter, and tyrosine hydroxylase, which selectively label spinal afferent, parasympathetic, and sympathetic axons, respectively, were detected immunohistochemically in 1?±?0.5% (n?=?7), 15?±?4.7% (n?=?6), and 24?±?4% (n?=?7) of biotinamide-labeled extrinsic axons in myenteric ganglia. Immunoreactivity for vasoactive intestinal polypeptide, nitric oxide synthase, somatostatin, and vesicular glutamate transporters 1 and 2 accounted for a combined maximum of 14% of biotinamide-labeled axons in myenteric ganglia. Thus, a maximum of 53% of biotinamide-labeled extrinsic axons in myenteric ganglia were labeled by antisera to one of these eight markers. Viscerofugal neurons were also labeled by biotinamide. They had distinct morphologies and spatial distributions that correlated closely with their immunoreactivity for nitric oxide synthase and choline acetyltransferase. As reported for the rectum, nearly half of all extrinsic nerve fibers to the distal colon lack the key immunohistochemical markers commonly used for their identification. Their abundance may therefore have been significantly underestimated in previous immunohistochemical studies. PMID:25380190

  10. Congenital Abnormalities and Multiple Sclerosis

    PubMed Central

    2010-01-01

    Background There is a strong maternal parent-of-origin effect in determining susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal intrauterine milieu leading to impaired fetal development could plausibly also result in increased susceptibility to MS. A possible marker for this intrauterine insult is the presence of a non-fatal congenital anomaly. Methods We investigated whether or not congenital anomalies are associated with MS in a population-based cohort. We identified 7063 MS index cases and 2655 spousal controls with congenital anomaly information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). Results The frequency of congential anomalies were compared between index cases and controls. No significant differences were found. Conclusions Congenital anomalies thus do not appear to be associated with MS. However, we did not have complete data on types and severity of congenital anomalies or on maternal birth history and thus this study should be regarded as preliminary. PMID:21080921

  11. [Phenomenology of abnormal body perceptions].

    PubMed

    Schäfer, M L

    1983-01-01

    The present paper deals with the problematic nature of the phenomenological grasping of the consciousness of the body and its pathological modifications. The reasoning is oriented by the doctrine of Husserl of the so-called sentiments as the fundamentals of the experience of the own body. This basic approach does not only seem to be basically for a psychology of the consciousness of the body, but also to give the theoretical-conceptual structure for a great number of psychopathological modifications. Subsequent to a criticism of the conventional use of the term 'hallucination of the body' we attempt to chart elements of a scheme of the abnormal consciousness of the body. PMID:6647887

  12. Segmentation of Nerve Bundles and Ganglia in Spine MRI Using Particle Filters

    PubMed Central

    Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

    2011-01-01

    Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation. PMID:22003741

  13. Segmentation of nerve bundles and ganglia in spine MRI using particle filters.

    PubMed

    Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

    2011-01-01

    Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation. PMID:22003741

  14. Analysis of Basal Plane Bending and Basal Plane Dislocations in 4H-SiC Single Crystals

    NASA Astrophysics Data System (ADS)

    Ohtani, Noboru; Katsuno, Masakazu; Fujimoto, Tatsuo; Nakabayashi, Masashi; Tsuge, Hiroshi; Yashiro, Hirokatsu; Aigo, Takashi; Hirano, Hosei; Hoshino, Taizo; Ohashi, Wataru

    2009-06-01

    4H-SiC single crystals were grown by the physical vapor transport (PVT) growth method under different thermoelastic stress conditions, and the degree of basal plane bending in the crystals was characterized by the peak shift measurement of X-ray rocking curves. The results indicate that the degree of basal plane bending largely depends on the magnitude of the thermoelastic stresses imposed on the crystals during PVT growth. Quantitative analysis of basal plane bending revealed that the density of basal plane dislocations (BPDs) estimated from basal plane bending is much smaller than that obtained from defect-selective etching. It was also found that the BPD density is correlated with the threading screw dislocation (TSD) density in PVT-grown SiC crystals. These aspects of BPDs were discussed in terms of the BPD multiplication process triggered by the intersection of BPDs with a forest of TSDs extending along the c-axis.

  15. Cytochalasin D inhibits basal body migration and ciliary elongation in quail oviduct epithelium.

    PubMed

    Boisvieux-Ulrich, E; Lainé, M C; Sandoz, D

    1990-03-01

    The effects of cytochalasin D (CD) were studied by scanning (SEM) and transmission (TEM) electron-microscopic examination at different stages of ciliary differentiation in epithelial cells of quail oviduct. Immature quails were prestimulated by estradiol benzoate injections to induce ciliogenesis in the undifferentiated oviduct. After 24 h of CD culture, SEM study revealed inhibition of ciliogenesis and dilation of the apex of non-ciliated cells. TEM study showed that 2 h of CD treatment produced dilation of lateral intercellular spaces, after 6 h of treatment, this resulted in intracellular macrovacuolation. Vacuoles were surrounded by aggregates of dense felt-like material. CD also induced the disappearance of microvilli, and rounding of the apical surface of undifferentiated cells and those blocked in ciliogenesis. Centriologenesis was not inhibited by CD; basal bodies assembled in generative complexes in the supranuclear region after 24 h of treatment. However, the migration of mature basal bodies towards the apical surface was impaired. Instead, they anchored onto the membrane of intracellular vacuoles; growth of cilia was induced in the vacuole lumen. Cilium elongation was disturbed, giving abnormally short cilia with a dilated tip; microtubules failed to organize correctly. PMID:2317839

  16. Abnormal fat distribution in PMM2-CDG.

    PubMed

    Wolthuis, D F G J; van Asbeck, E V; Kozicz, T; Morava, E

    2013-11-01

    We hypothesize that abnormal fat distribution, a common feature of PMM2-CDG, is associated with abnormal perinatal hormone regulation. We assessed 32 cases with PMM2-CDG, for the comorbidity of hypoglycemia/hyperinsulinism and fat pads. Ninety percent of patients with hypoketotic hypoglycemia and/or hyperinsulinism had abnormal fat distribution, while normoglycemic patients showed this feature in 50% of the cases. This statistically significant difference suggests an etiological role of the insulin receptor in developing abnormal fat distribution in PMM2-CDG. PMID:24063868

  17. Notch Signaling May Be Involved in the Abnormal Differentiation of Epidermal Keratinocytes in Psoriasis

    PubMed Central

    Ota, Tami; Takekoshi, Susumu; Takagi, Tatsuya; Kitatani, Kanae; Toriumi, Kentaro; Kojima, Tomoko; Kato, Masayuki; Ikoma, Norihiro; Mabuchi, Tomotaka; Ozawa, Akira

    2014-01-01

    Localization of each keratin isoform differs among epidermal layers. Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells express keratin 10 (K10) in normal skin. Notch signaling is essential for keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2 in the basal cell layer and Notch3 in basal cell and spinous cell layers in normal epidermis. It has been poorly elucidated how localization and expression levels of Notch molecules are related to epidermal molecular markers K10 and K14 in psoriatic skin with abnormal differentiation of epidermal tissue. This study aimed to investigate the relationship between abnormal differentiation of epidermal cells in psoriatic skin and expression of Notch molecules. We investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal layer while it and K10 were co-expressed in some middle suprabasal layer cells. Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared with normal epidermis. These data suggest that decrements in these Notch molecules might cause aberrant expression of K10 and K14 leading to anomalous differentiation of the epidermis in psoriatic lesions. PMID:25392571

  18. Identification of bladder and colon afferents in the nodose ganglia of male rats.

    PubMed

    Herrity, April N; Rau, Kristofer K; Petruska, Jeffrey C; Stirling, David P; Hubscher, Charles H

    2014-11-01

    The sensory neurons innervating the urinary bladder and distal colon project to similar regions of the central nervous system and often are affected simultaneously by various diseases and disorders, including spinal cord injury. Anatomical and physiological commonalities between the two organs involve the participation of shared spinally derived pathways, allowing mechanisms of communication between the bladder and colon. Prior electrophysiological data from our laboratory suggest that the bladder also may receive sensory innervation from a nonspinal source through the vagus nerve, which innervates the distal colon as well. The present study therefore aimed to determine whether anatomical evidence exists for vagal innervation of the male rat urinary bladder and to assess whether those vagal afferents also innervate the colon. Additionally, the relative contribution to bladder and colon sensory innervation of spinal and vagal sources was determined. By using lipophilic tracers, neurons that innervated the bladder and colon in both the nodose ganglia (NG) and L6/S1 and L1/L2 dorsal root ganglia (DRG) were quantified. Some single vagal and spinal neurons provided dual innervation to both organs. The proportions of NG afferents labeled from the bladder did not differ from spinal afferents labeled from the bladder when considering the collective population of total neurons from either group. Our results demonstrate evidence for vagal innervation of the bladder and colon and suggest that dichotomizing vagal afferents may provide a neural mechanism for cross-talk between the organs. PMID:24845615

  19. Latency of Varicella Zoster Virus in Dorsal Root, Cranial, and Enteric Ganglia in Vaccinated Children

    PubMed Central

    Gershon, Anne A.; Chen, Jason; Davis, Larry; Krinsky, Clarissa; Cowles, Robert; Reichard, Ross; Gershon, Michael

    2012-01-01

    Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation. PMID:23303966

  20. The transthyretin gene is expressed in human and rodent dorsal root ganglia.

    PubMed

    Murakami, Tatsufumi; Ohsawa, Yutaka; Sunada, Yoshihide

    2008-05-16

    The transthyretin (TTR) gene is mainly expressed in the liver and choroid plexus of the brain. Most cases of familial amyloidotic polyneuropathy (FAP) are caused by TTR gene mutations, and characterized by amyloid deposition in the peripheral nervous system. We hypothesized that the TTR gene may be expressed in the peripheral nervous system. We analyzed TTR gene expression in several parts of the human, mouse and rat peripheral nervous systems using RT-PCR. To determine the sites of TTR synthesis in the dorsal root ganglia (DRG), mouse DRG were examined by in situ hybridization, laser capture microdissection and RT-PCR, and immunohistochemistry. TTR mRNA was detected in the DRG and cauda equina of humans and rodents by RT-PCR. TTR mRNA was not detected in the sural nerve, lumbar plexus or sympathetic ganglia in humans, or in the sciatic nerve in rodents. In mouse DRG, TTR mRNA was localized in the peripheral glial cells. No TTR-like immunoreactivity was observed in these tissues except for the perineurium. The TTR gene is probably expressed in the peripheral glial cells of the DRG. TTR synthesis in the DRG may be important for the involvement of the peripheral nervous system in FAP. PMID:18406527

  1. Immunohistochemical demonstration of cholinergic structures in central ganglia of the slug (Limax maximus, Limax valentianus).

    PubMed

    D'Este, Loredana; Casini, Arianna; Kimura, Shin; Bellier, Jean-Pierre; Ito, Etsuro; Kimura, Hiroshi; Renda, Tindaro G

    2011-04-01

    Immunohistochemical techniques were used to study the distribution of cholinergic neurons containing choline acetyltransferase of the common type (cChAT), the synthetic enzyme of acetylcholine, in the central nervous system of the slug Limax maximus and Limax valentianus. Because the antiserum applied here was raised against a recombinant protein encoded by exons 7 and 8 of the rat gene for ChAT, three methods were used in order to validate antibody specificity for the Limax counterpart enzyme. Western blot combined with ChAT activity assay following native gel electrophoresis and immunoprecipitation analysis both indicated that immunoreactive Limax brain molecules were capable of synthesizing acetylcholine. Western blot after denatured gel electrophoresis of Limax brain extracts revealed a single band of about 67kDa. All findings obtained with these three methods clearly indicated that the antiserum effectively recognized Limax cChAT. 1400 neuronal cell bodies positive for cChAT, mainly small to medium-sized, were found in various brain regions in the buccal, cerebral, pleural, parietal, visceral and pedal ganglia. cChAT immunoreactive nerve fibers were distributed extensively in the neuropil, connectives and commissures of these central ganglia. The map of cChAT-positive cells provided here are valuable for understanding the cholinergic mechanism in the slug brain, as well as giving an important hint to clarifying the mechanisms of learning and memory in higher vertebrates including humans. PMID:21315127

  2. Cysteinyl leukotrienes mediate the response of submucosal ganglia from rat colon to bradykinin.

    PubMed

    Rehn, Matthias; Diener, Martin

    2012-04-15

    The aim of the present study was to find out the mechanism by which the inflammatory mediator, bradykinin, induces an increase of the cytosolic Ca(2+) concentration ([Ca(2+)](i)) in enteric neurons. For this purpose, ganglia in the isolated submucosa from rat colon were loaded with the Ca(2+)-sensitive dye, fura-2, and were exposed to bradykinin (2·10(-8)mol/l). Under control conditions, the kinin evoked a transient increase in [Ca(2+)](i). Preincubation with quinacrine or arachidonyltrifluoromethylketone (AACOCF(3)), i.e. blockers of cytosolic phospholipase A(2), prevented the raise of [Ca(2+)](i). This inhibition was mimicked by 5,8,11,14-eicosatetrayonic acid (ETYA), an inhibitor of cyclooxygenases as well as lipoxygenases, and by BWA4C, a selective inhibitor of lipoxygenases, whereas indomethacin was ineffective, suggesting the mediation of the kinin response by a lipoxygenase metabolite. Indeed, a leukotriene, leukotriene D(4) (LTD(4)), mimicked the effect of bradykinin. The LTD(4) receptor blocker, MK-571, inhibited the increase in [Ca(2+)](i) evoked by LTD(4) and by bradykinin. Consequently, bradykinin receptors in submucosal ganglia from rat colon are coupled to a stimulation of phospholipase A(2), the release of arachidonic acid and the production of LTD(4), which seems to be finally responsible for the change in the cytosolic Ca(2+) concentration. PMID:22366210

  3. Characterization by immunocytochemistry of ionic channels in Helix aspersa suboesophageal brain ganglia neurons.

    PubMed

    Azanza, M J; Pérez-Castejón, C; Pes, N; Pérez-Bruzón, R N; Aisa, J; Junquera, C; Maestú, C; Lahoz, M; Martínez-Ciriano, C; Vera-Gil, A; Del Moral, A

    2008-04-01

    The aim of this work was to characterize several ionic channels in nervous cells of the suboesophageal visceral, left and right parietal, and left and right pleural brain ganglia complex of the snail Helix aspersa by immunocytochemistry. We have studied the immunostaining reaction for a wide panel of eleven polyclonal antibodies raised against mammal antigens as follows: voltage-gated-Na+ channel; voltage-gated-delayed-rectifier-K+ channel; SK2-small-conductance-Ca2+-dependent-K+ channel apamin sensitive; SK3 potassium channel; charybdotoxin-sensitive voltage-dependent potassium channel; BKCa-maxi-conductance-Ca2+-dependent-K+ channel; hyperpolarization-activated cyclic nucleotide-gated potassium channel 4; G-protein-activated inwardly rectifying potassium channel GIRK2 and voltage-gated-calcium of L, N and P/Q type channels. Our results show positive reaction in neurons, but neither in glia cells nor in processes in the Helix suboesophageal ganglia. Our results suggest the occurrence of molecules in Helix neurons sharing antigenic determinants with mammal ionic channels. The reaction density and distribution of immunoreactive staining within neurons is specific for each one of the antisera tested. The studies of co-localization of immunoreaction, on alternate serial sections of the anterior right parietal ganglion, have shown for several recognized mapped neurons that they can simultaneously be expressed among two and seven different ionic protein channels. These results are considered a key structural support for the interpretation of Helix aspersa neuron electrophysiological activity. PMID:18228196

  4. Real-time control of walking using recordings from dorsal root ganglia

    PubMed Central

    Holinski, B J; Everaert, D G; Mushahwar, V K; Stein, R B

    2013-01-01

    Objective The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the dorsal root ganglia. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modeled from recorded neural firing rates. These models were then used for closed-loop feedback. Main Results Overall, firing-rate based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48±13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development. PMID:23928579

  5. Differential expression of microRNAs in dorsal root ganglia after sciatic nerve injury

    PubMed Central

    Lu, Anjie; Huang, Zufa; Zhang, Chaoyue; Zhang, Xianfang; Zhao, Jiuhong; Zhang, Haiying; Zhang, Quanpeng; Wu, Song; Yi, Xinan

    2014-01-01

    This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identified whose expression was significantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3?-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization verified that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a combination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neurons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that microRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection. PMID:25206756

  6. A comparative study of three cranial sensory ganglia projecting into the oral cavity: in situ hybridization analyses of neurotrophin receptors and thermosensitive cation channels

    Microsoft Academic Search

    Ichiro Matsumoto; Yasufumi Emori; Yuzo Ninomiya; Keiko Abe

    2001-01-01

    Peripheral cranial sensory nerves projecting into the oral cavity receive food intake stimuli and transmit sensory signals to the central nervous system. To describe and compare the features of the cranial sensory ganglia that innervate the oral cavity, i.e., the trigeminal, petrosal, and geniculate ganglia (TG, PG, and GG, respectively), in situ hybridization was conducted using riboprobes for neurotrophin receptors

  7. Substrate Metabolism During Basal and Hyperinsulinemic Conditions in Adolescents and Young-Adults with Barth Syndrome

    PubMed Central

    Cade, W. Todd; Spencer, Carolyn T.; Reeds, Dominic N.; Waggoner, Alan D.; O'Connor, Robert; Maisenbacher, Melissa; Crowley, Jan R.; Byrne, Barry J.; Peterson, Linda R.

    2013-01-01

    Summary Background Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high mortality rates. It is currently unknown if BTHS related mitochondrial dysfunction results in substrate metabolism abnormalities and thereby contributes to cardioskeletal myopathy in patients with BTHS. Methods Adolescents and young adults with BTHS (n=5, 20 ± 4 yrs) and age and activity matched healthy controls (n=5, 18 ± 4 yrs) underwent an hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of body composition and 2-D and strain echocardiography for measurement of left ventricular function. Results Participants with BTHS had lower fat-free mass (FFM) (BTHS: 31.4 ± 6.9 vs. Control: 46.7 ± 5.3 kg, p<0.005), lower systolic function (strain, BTHS: -15.2 ± 2.4 vs. Control: -19.0 ± 2.4 %, p<0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5 ± 16.3 vs. Control: 67.4 ± 17.6 ?mol/kgFFM/min, p<0.05), lower basal (BTHS: 4.6 ± 2.7 vs. Control: 11.9 ± 4.4 ?mol/kgFM/min, p<0.05) and hyperinsulinemic (BTHS: 1.6 ± 0.4 vs. Control: 3.6 ± 1.6 ?mol/kgFM/min, p<0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal leucine rate of appearance per kg FFM (BTHS: 271.4 ± 69.3 vs. Control: 193.1 ± 28.7 ?mol/kgFFM/hr, p=0.07) compared to controls. Higher basal leucine rate of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be associated with lower left ventricular systolic strain (r=-0.57, p=0.09). Conclusion Whole-body fatty acid, glucose and amino acid metabolism kinetics when expressed per unit of body composition are altered and appear to be related to cardioskeletal myopathy in humans with BTHS. Further studies examining myocardial substrate metabolism and whole-body substrate metabolism during increased energy demands (e.g. exercise) and their relationships to skeletal and cardiac function are recommended. PMID:22580961

  8. Clinical and pathologic findings in two draft horses with progressive muscle atrophy, neuromuscular weakness, and abnormal gait characteristic of shivers syndrome.

    PubMed

    Valentine, B A; de Lahunta, A; Divers, T J; Ducharme, N G; Orcutt, R S

    1999-12-01

    Two Belgian geldings, 4 and 14 years old, respectively, with muscle atrophy, weakness, and abnormal gait characteristic of severe advanced shivers were examined clinically and on necropsy. Neurologic examination revealed no evidence of ataxia, and the clinical diagnosis was neuromuscular weakness and shivers. Necropsies of both horses, including examination of pituitary, brain, spinal cord, spinal roots and ganglia, and peripheral nerves, revealed no gross or histologic abnormalities. Examination of multiple skeletal muscle specimens revealed chronic myopathic changes and periodic acid-Schiff positive, amylase-resistant inclusions within muscle fibers, characteristic of equine polysaccharide storage myopathy. It is suggested that underlying metabolic myopathy may be the cause of muscle weakness and cramping in horses with shivers. PMID:14567431

  9. LRGUK-1 Is Required for Basal Body and Manchette Function during Spermatogenesis and Male Fertility

    PubMed Central

    Liu, Yan; DeBoer, Kathleen; de Kretser, David M.; O’Donnell, Liza; O’Connor, Anne E.; Merriner, D. Jo; Okuda, Hidenobu; Whittle, Belinda; Jans, David A.; Efthymiadis, Athina; McLachlan, Robert I.; Ormandy, Christopher J.; Goodnow, Chris C.; Jamsai, Duangporn; O’Bryan, Moira K.

    2015-01-01

    Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line. PMID:25781171

  10. Semen abnormalities with SSRI antidepressants.

    PubMed

    2015-01-01

    Despite decades of widespread use, the adverse effect profile of "selective" serotonin reuptake inhibitor (SSRI) antidepressants has still not been fully elucidated. Studies in male animals have shown delayed sexual development and reduced fertility. Three prospective cohort studies conducted in over one hundred patients exposed to an SSRI for periods ranging from 5 weeks to 24 months found altered semen param-eters after as little as 3 months of exposure: reduced sperm concentration, reduced sperm motility, a higher percentage of abnormal spermatozoa, and increased levels of sperm DNA fragmentation. One clinical trial showed growth retardation in children considered depressed who were exposed to SSRls. SSRls may have endocrine disrupting properties. Dapoxetine is a short-acting serotonin reuptake inhibitor that is chemically related to fluoxetine and marketed in the European Union for men complaining of premature ejaculation. But the corresponding European summary of product characteristics does not mention any effects on fertility. In practice, based on the data available as of mid-2014, the effects of SSRI exposure on male fertility are unclear. However, it is a risk that should be taken into account and pointed out to male patients who would like to father a child or who are experiencing fertility problems. PMID:25729824

  11. Biochemical abnormalities in Pearson syndrome.

    PubMed

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders. PMID:25691415

  12. Interferometric Synthetic Aperture Radar (InSAR) for Fine-resolution Basal Ice Sheet Imaging

    E-print Network

    Blake, William Arthur

    2010-08-31

    by the MCRDS radar around the NEEM drill site. Reflectivity maps were generated leading to the possibility of extracting useful basal composition data. Extraction of basal composition information was examined including estimating the roughness of basal...

  13. Androgen receptor gene sequence and basal cortisol concentrations predict men's

    E-print Network

    Cosmides, Leda

    Androgen receptor gene sequence and basal cortisol concentrations predict men's hormonal responses these differences. Replicating past research, the present study found that men's salivary testosterone and cortisol receptor gene, and lower baseline cortisol concentrations, each predicted larger testosterone responses

  14. Golf club related basal skull fracture: a case study.

    PubMed

    Hance, Katherine

    2011-10-01

    Basal skull fractures, although rare, do occur and a high index of suspicion for high velocity injuries, should be at the forefront of the clinicians mind, particularly those from a golf club. Head injury in children is a common presentation to any Paediatric Emergency Department. With effective examination skills, recognition of signs of basal skull fracture such as haemotympanum, even in the absence of altered neurological findings, ensures safe and effective practice enabling correct and justifiable clinical decisions to be made. This is vital to ensure not only the correct investigative procedure is requested and performed, but also on discussion with the appropriate specialists, the correct treatment is also prescribed. This case study examines the use of computed tomography in the diagnosis of basal skull fractures and highlights further discussion into the appropriate treatment of children diagnosed with basal skull fractures. PMID:21968414

  15. Abnormal Web Usage Control by Proxy Strategies.

    ERIC Educational Resources Information Center

    Yu, Hsiang-Fu; Tseng, Li-Ming

    2002-01-01

    Approaches to designing a proxy server with Web usage control and to making the proxy server effective on local area networks are proposed to prevent abnormal Web access and to prioritize Web usage. A system is implemented to demonstrate the approaches. The implementation reveals that the proposed approaches are effective, such that the abnormal

  16. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  17. Renal abnormalities and their developmental origin

    Microsoft Academic Search

    Andreas Schedl

    2007-01-01

    Congenital abnormalities of the kidney and urinary tract (CAKUT) occur in 1 out of 500 newborns, and constitute approximately 20–30% of all anomalies identified in the prenatal period. CAKUT has a major role in renal failure, and there is increasing evidence that certain abnormalities predispose to the development of hypertension and cardiovascular disease in adult life. Moreover, defects in nephron

  18. Pathophysiology of Cancer: Hormonal and Metabolic Abnormalities

    Microsoft Academic Search

    David Heber; N. S. Tchekmedyian

    1992-01-01

    Despite the development of advanced nutritional support technology, malnutrition remains a significant morbid and mortal complication of cancer. A number of metabolic abnormalities have been demonstrated in malnourished cancer patients, including increased protein breakdown, increased glucose production, increased lipolysis, hypogonadism in male patients, and insulin resistance. Previous studies conducted under metabolic ward conditions have demonstrated that metabolic abnormalities interfere with

  19. Dark Immunofluorescence: Correlation with Serum Immunoglobulin Abnormalities?

    PubMed Central

    List, J.; Buckland, M. S.; Thobhani, B.; Sheed, C. J.; Mann, J. C.; Claxton, M.; Heelan, B.

    2006-01-01

    Occasional serum samples (<0.5%) tested by indirect immunofluorescence showed less fluorescence than did negative-control serum. A retrospective review of these patients' serum immunoglobulins revealed a high percentage of abnormalities (71%, versus 22% of controls). We suggest that this observation should be reported when seen and that the clinician should be alerted to an association with immunoglobulin abnormalities. PMID:16971516

  20. An Abnormal Psychology Community Based Interview Assignment

    ERIC Educational Resources Information Center

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  1. Sonographically detected abnormalities of the umbilical cord

    Microsoft Academic Search

    T. D. Shipp; B. Bromley; B. R. Benacerraf

    1995-01-01

    Objectives: This study was undertaken as a retrospective chart review to evaluate the range of umbilical cord abnormalities detected by prenatal sonography, as well as the outcome and pathologic correlation. Methods: We identified 13 cases of umbilical cord abnormalities detected sonographically over a 46-month period. We evaluated the ultrasound appearance, size, location, and color Doppler characteristic in each case. Results:

  2. Unsupervised Abnormality Detection in Video Surveillance

    Microsoft Academic Search

    Takuya Nanri; Nobuyuki Otsu

    2005-01-01

    The detection of abnormal movements is an important prob- lem in video surveillance applications. We propose an unsupervised method for abnormal movement detection in scenes containing multiple persons. Our method uses cu- bic higher-order local auto-correlation (CHLAC) to extract movement features. We show that the additive property of CHLAC in combination with a linear subspace method is well suited to

  3. Detecting electrocardiogram abnormalities with independent component analysis

    E-print Network

    Noel, Steven

    detection of abnormal conditions in the heart. Unsupervised ICA neural networks can demix the components of measured ECG signals. Such components may correspond to individual heart functions, either normal for diagnosis well in advance of the actual onset of heart attack, in which abnormalities in the original

  4. Retinal Circulatory Abnormalities in Type 1 Diabetes

    Microsoft Academic Search

    Gilbert T. Feke; Sheldon M. Buzney; Hironobu Ogasawara; Naoki Fujio; Douglas G. Goger; Norman P. Spack; Kenneth H. GabbayX

    Purpose. To quantify retinal circulatory abnormalities in patients with type 1 diabetes; to compare blood speed and blood flow in major temporal retinal arteries as well as total retinal arterial cross-section measured in patients to that measured in controls without diabetes; to determine which factors are related to the measured abnormalities within the patient group. Methods. The laser Doppler technique

  5. Multiparametric tissue abnormality characterization using manifold regularization

    NASA Astrophysics Data System (ADS)

    Batmanghelich, Kayhan; Wu, Xiaoying; Zacharaki, Evangelia; Markowitz, Clyde E.; Davatzikos, Christos; Verma, Ragini

    2008-03-01

    Tissue abnormality characterization is a generalized segmentation problem which aims at determining a continuous score that can be assigned to the tissue which characterizes the extent of tissue deterioration, with completely healthy tissue being one end of the spectrum and fully abnormal tissue such as lesions, being on the other end. Our method is based on the assumptions that there is some tissue that is neither fully healthy or nor completely abnormal but lies in between the two in terms of abnormality; and that the voxel-wise score of tissue abnormality lies on a spatially and temporally smooth manifold of abnormality. Unlike in a pure classification problem which associates an independent label with each voxel without considering correlation with neighbors, or an absolute clustering problem which does not consider a priori knowledge of tissue type, we assume that diseased and healthy tissue lie on a manifold that encompasses the healthy tissue and diseased tissue, stretching from one to the other. We propose a semi-supervised method for determining such as abnormality manifold, using multi-parametric features incorporated into a support vector machine framework in combination with manifold regularization. We apply the framework towards the characterization of tissue abnormality to brains of multiple sclerosis patients.

  6. Ovarian dysgenesis in individuals with chromosomal abnormalities

    Microsoft Academic Search

    Christopher Cunniff; Kenneth Lyons Jones; Kurt Benirschke

    1991-01-01

    To understand better the pathogenesis of ovarian dysgenesis in individuals with abnormalities such as 45,X Turner syndrome, trisomy 13, and trisomy 18, we have examined microscopically the ovaries of 36 infants with a number of chromosomal abnormalities confirmed by karyotype analysis. All infants with trisomy 13, trisomy 18, triploidy, and 45,X were found to have severe ovarian dysgenesis characterized by

  7. Modulation of Tyrosine Hydroxylase, Neuropeptide Y, Glutamate, and Substance P in Ganglia and Brain Areas Involved in Cardiovascular Control after Chronic Exposure to Nicotine

    PubMed Central

    Ferrari, Merari F. R.; Coelho, Emerson F.; Farizatto, Karen L. G.; Chadi, Gerson; Fior-Chadi, Debora R.

    2011-01-01

    Considering that nicotine instantly interacts with central and peripheral nervous systems promoting cardiovascular effects after tobacco smoking, we evaluated the modulation of glutamate, tyrosine hydroxylase (TH), neuropeptide Y (NPY), and substance P (SP) in nodose/petrosal and superior cervical ganglia, as well as TH and NPY in nucleus tractus solitarii (NTS) and hypothalamic paraventricular nucleus (PVN) of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after 8 weeks of nicotine exposure. Immunohistochemical and in situ hybridization data demonstrated increased expression of TH in brain and ganglia related to blood pressure control, preferentially in SHR, after nicotine exposure. The alkaloid also increased NPY immunoreactivity in ganglia, NTS, and PVN of SHR, in spite of decreasing its receptor (NPY1R) binding in NTS of both strains. Nicotine increased SP and glutamate in ganglia. In summary, nicotine positively modulated the studied variables in ganglia while its central effects were mainly constrained to SHR. PMID:21822476

  8. Nevoid basal cell carcinoma syndrome. A case report.

    PubMed

    Piattelli, A

    1991-12-01

    Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder and is characterized by a great variety of signs and symptoms. The most important are a characteristic facies, the occurrence of basal cell carcinomas and odontogenic keratocysts. In view of the neoplastic skin change, constant review of the patients is indicated. Any jaw film revealing two or more dentigerous or follicular cysts should alert the clinician to the possibility of this underlying syndrome. PMID:1822063

  9. Multidetector computed tomography of congenital aortic abnormalities.

    PubMed

    Lindsay, Alistair C; Sriharan, Mona; Lazoura, Olga; Padley, Simon P G; Nicol, Edward D; Rubens, Michael B

    2014-04-01

    For many years invasive angiographic techniques have been considered as the gold standard for the assessment of large arterial abnormalities. However, the complexities and complications inherent to invasive imaging have meant that more recently non-invasive techniques such as echocardiography, Magnetic Resonance Imaging (MRI) and multidetector CT (MDCT) have been increasingly used in congenital cardiovascular disorders. In particular, MDCT has emerged as a fundamental tool for the diagnosis and pre-surgical work-up of aortic abnormalities due to its high spatial resolution, large area of coverage, and short scan time, and therefore is now one of the most widely used modalities for the detection of congenital abnormalities of the aorta. The purpose of this pictorial review is to review the spectrum of abnormalities of the aorta than can be reliably detected by MDCT both in infants and in adulthood. Abnormalities of the aortic root, ascending aorta, aortic arch, and descending aorta will be described separately. PMID:24560026

  10. The ABC Model and its Applicability to Basal Angiosperms

    PubMed Central

    Soltis, Douglas E.; Chanderbali, André S.; Kim, Sangtae; Buzgo, Matyas; Soltis, Pamela S.

    2007-01-01

    Background Although the flower is the central feature of the angiosperms, little is known of its origin and subsequent diversification. The ABC model has long been the unifying paradigm for floral developmental genetics, but it is based on phylogenetically derived eudicot models. Synergistic research involving phylogenetics, classical developmental studies, genomics and developmental genetics has afforded valuable new insights into floral evolution in general, and the early flower in particular. Scope and Conclusions Genomic studies indicate that basal angiosperms, and by inference the earliest angiosperms, had a rich tool kit of floral genes. Homologues of the ABCE floral organ identity genes are also present in basal angiosperm lineages; however, C-, E- and particularly B-function genes are more broadly expressed in basal lineages. There is no single model of floral organ identity that applies to all angiosperms; there are multiple models that apply depending on the phylogenetic position and floral structure of the group in question. The classic ABC (or ABCE) model may work well for most eudicots. However, modifications are needed for basal eudicots and, the focus of this paper, basal angiosperms. We offer ‘fading borders’ as a testable hypothesis for the basal-most angiosperms and, by inference, perhaps some of the earliest (now extinct) angiosperms. PMID:17616563

  11. Bilateral basal Xe-133 retention and ventilation/perfusion patterns in mild and subclinical congestive heart failure

    SciTech Connect

    Lee, H.K.; Skarzynski, J.J.; Spadaro, A. (Mount Sinai Services-City Hospital Center, Elmhurst, NY (USA))

    1989-12-01

    The Xe-133 ventilation pattern in congestive heart failure (CHF) was assessed using 24 inpatient ventilation/perfusion studies performed to rule out pulmonary embolism. Patients with histories of CHF, myocardial infarction (MI), and cardiomyopathy were included in the study. Frank pulmonary edema, pulmonary embolism, and other known lung diseases such as chronic obstructive lung disease, tumor, and pneumonia were excluded. Fifteen of the 24 patients had abnormal ventilation scans. Twelve of the 15 showed bilateral basal Xe-133 retention on washout; the remaining 3 showed diffuse, posterior regional retention. On perfusion scans, 14 of the 15 abnormal ventilation patients showed evidence of CHF such as inverted perfusion gradient, enlarged cardiac silhouette, or patchy perfusion, and all of them had a history of CHF or cardiac disease. Nine of the 24 patients had normal ventilation scans, including normal washout patterns. Seven of the nine had normal perfusion (p less than 0.01). Four of the nine normal ventilation patients had a history of cardiac disease or CHF but no recent acute MI. Bilateral basal regional Xe-133 retention, coupled with perfusion scan evidence of CHF such as inverted perfusion gradient, enlarged cardiac silhouette, and patchy perfusion pattern, appears to be a sensitive and characteristic ventilation/perfusion finding in mild or subclinical CHF.

  12. Analysis and diagnosis of basal cell carcinoma (BCC) via infrared imaging

    NASA Astrophysics Data System (ADS)

    Flores-Sahagun, J. H.; Vargas, J. V. C.; Mulinari-Brenner, F. A.

    2011-09-01

    In this work, a structured methodology is proposed and tested through infrared imaging temperature measurements of a healthy control group to establish expected normality ranges and of basal cell carcinoma patients (a type of skin cancer) previously diagnosed through biopsies of the affected regions. A method of conjugated gradients is proposed to compare measured dimensionless temperature difference values (? ?) between two symmetric regions of the patient's body, that takes into account the skin, the surrounding ambient and the individual core temperatures and doing so, the limitation of the results interpretation for different individuals become simple and nonsubjective. The range of normal temperatures in different regions of the body for seven healthy individuals was determined, and admitting that the human skin exhibits a unimodal normal distribution, the normal range for each region was considered to be the mean dimensionless temperature difference plus/minus twice the standard deviation of the measurements (??±2?) in order to represent 95% of the population. Eleven patients with previously diagnosed basal cell carcinoma through biopsies were examined with the method, which was capable of detecting skin abnormalities in all cases. Therefore, the conjugated gradients method was considered effective in the identification of the basal cell carcinoma through infrared imaging even with the use of a low optical resolution camera (160 × 120 pixels) and a thermal resolution of 0.1 °C. The method could also be used to scan a larger area around the lesion in order to detect the presence of other lesions still not perceptible in the clinical exam. However, it is necessary that a temperature differences mesh-like mapping of the healthy human body skin is produced, so that the comparison of the patient ? ? could be made with the exact region of such mapping in order to possibly make a more effective diagnosis. Finally, the infrared image analyzed through the conjugated gradients method could be useful in the definition of a better safety margin in the surgery for the removal of the lesion, both minimizing esthetics damage to the patient and possibly avoiding basal cell carcinoma recurrence.

  13. Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

    SciTech Connect

    Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

    1987-03-01

    Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects.

  14. A case of epiphora and recurrent basal cell carcinoma of the nasal tip and review of acquired nasolacrimal system obstruction

    PubMed Central

    Parker, Wendy Lynne; Lessard, Marie-Lucie

    2004-01-01

    A case of a 67-year-old man with recurrent basal cell carcinoma of the nasal tip and an incidental symptom of epiphora (volunteered by the patient) is presented. Epiphora is an abnormal overflow of tears that fail to drain into the inferior nasal meatus via the nasolacrimal system. Within the differential diagnosis of epiphora and nasolacrimal obstruction is neoplasm – primary, secondary or metastatic. On further investigation, including computed tomography imaging, he was subsequently found to have invasive disease extending along the left embryological cleavage plane superiorly to the medial canthal tendon. An excision attempt using Mohs technique by the dermatological surgeon was unsuccessful in adequately clearing the margins, and revealed a diagnosis of morphea-like basal cell cancer. This failure, taken together with the extent of disease identified by computed tomography scan, resulted in significant alteration of the operative approach. The patient underwent extensive tumour extirpation and nasal reconstruction using a forehead flap. The present case alerts surgeons involved in the management of skin cancers to the importance of the anatomical relationship of the nasolacrimal apparatus to embryological soft tissue cleavage planes when dealing with recurrent and aggressive lesions. In addition, it serves as a reminder to inquire about the signs and symptoms associated with nasolacrimal obstruction. Moreover, when preparing for surgical excision of recurrent aggressive basal cell carcinoma, high-quality imaging is essential to tailor the operative plan. PMID:24115897

  15. Neurotrophin3 administration alters neurotrophin, neurotrophin receptor and nestin mRNA expression in rat dorsal root ganglia following axotomy

    Microsoft Academic Search

    L.-T. Kuo; M. J. Groves; F. Scaravilli; D. Sugden; S. F. An

    2007-01-01

    In the months following transection of adult rat peripheral nerve some sensory neurons undergo apoptosis. Two weeks after sciatic nerve transection some neurons in the L4 and L5 dorsal root ganglia begin to show immunoreactivity for nestin, a filament protein expressed by neuronal precursors and immature neurons, which is stimulated by neurotrophin-3 (NT-3) administration. The aim of this study was

  16. ? 2Adrenergic receptor activation inhibits calcitonin gene-related peptide expression in cultured dorsal root ganglia neurons

    Microsoft Academic Search

    Scott C Supowit; Diane M Hallman; Huawei Zhao; Donald J DiPette

    1998-01-01

    Calcitonin gene-related peptide (CGRP), a potent vasodilator, is produced in dorsal root ganglia (DRG) neurons which extend nerves peripherally to blood vessels and centrally to the spinal cord. We previously reported that neuronal CGRP expression is significantly reduced in the spontaneously hypertensive rat (SHR) which could contribute to the elevated BP. Other studies suggest that the enhanced activity of the

  17. Rare Cytogenetic Abnormalities in Myelodysplastic Syndromes

    PubMed Central

    Bacher, Ulrike; Schanz, Julie; Braulke, Friederike; Haase, Detlef

    2015-01-01

    The karyotype represents one of the main cornerstones for the International Prognostic Scoring System (IPSS) and the revised IPSS-R (IPSS-R) that are most widely used for prognostication in patients with myelodysplastic syndromes (MDS). The most frequent cytogenetic abnormalities in MDS, i.e. del(5q), -7/del(7q), +8, complex karyotypes, or ?Y have been extensively explored for their prognostic impact. The IPSS-R also considers some less frequent abnormalities such as del(11q), isochromosome 17, +19, or 3q abnormalities. However, more than 600 different cytogenetic categories had been identified in a previous MDS study. This review aims to focus interest on selected rare cytogenetic abnormalities in patients with MDS. Examples are numerical gains of the chromosomes 11 (indicating rapid progression), of chromosome 14 or 14q (prognostically intermediate to favorable), -X (in females, with an intermediate prognosis), or numerical abnormalities of chromosome 21. Structural abnormalities are also considered, e.g. del(13q) that is associated with bone marrow failure syndromes and favorable response to immunosuppressive therapy. These and other rare cytogenetic abnormalities should be integrated into existing prognostication systems such as the IPSS-R. However, due to the very low number of cases, this is clearly dependent on international collaboration. Hopefully, this article will help to inaugurate this process. PMID:25960862

  18. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    PubMed

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented. Vismodegib should only be proposed to patients in whom basal cell cancer markedly undermines quality of life, and only in the context of clinical research. PMID:25729822

  19. Studies of herpes virus latency in the sensory spinal ganglia of rabbits.

    PubMed Central

    Tosolini, F. A.; McCarthy, K.; Baker, B. F.

    1982-01-01

    Experimental latent herpes infection of rabbit dorsal root ganglia (DRG) is reported. The simian herpes virus used was derived from fatal natural infection in owl monkeys and has limited neurotropism in the rabbit. Following intradermal injection of the flank it causes a local lesion followed only by dorsal root ganglionitis; segmental paraesthesia and/or sensory loss going on to clinical recovery. Methods were developed for mapping sensory losses. Virus could be immediately re-isolated from skin or DRG homogenates in the acute (first week) stage but from 8-550 days by DRG organ culture only. Spontaneous recurrence does not occur but reactivation can be provoked. The system provides an improved analogue model for the study of the pathogenesis and symptomatic treatment of herpes zoster. Images Plate 1 Plate 2 PMID:7153508

  20. Microcirculation of human fetal posterior root ganglia: a scanning electron microscopic study of corrosion casts.

    PubMed

    Gorczyca, J; Skawina, A; Litwin, J A; Miodo?ski, A J

    1998-02-01

    The vasculature of lumbar posterior root ganglia was investigated in human fetuses aged 17-24 weeks; using the corrosion casting technique and scanning electron microscopy. The arterial supply consisted of one main artery and occasional arterioles entering the ganglion at its pole and running axially, while the venous drainage was located at the periphery of the ganglion, thus indicating a centrifugal pattern of blood flow. The dense capillary network of the ganglion showed the roughly parallel course of the vessels in the central zone and an irregular arrangement in the peripheral zone where capillaries formed "nests", probably surrounding individual perikaryons of ganglionic cells. The capillaries had a sinusoidal character with numerous dilatations about twice the normal capillary size, as well as occasional larger vascular spaces resulting from capillary interconnections and suggesting the intussusceptive type of angiogenesis. PMID:9488902

  1. Online Feedback Control of Functional Electrical Stimulation Using Dorsal Root Ganglia Recordings

    PubMed Central

    Bauman, Matthew J.; Bruns, Tim M.; Wagenaar, Joost B.; Gaunt, Robert A.; Weber, Douglas J.

    2012-01-01

    In neuroprostheses that use functional electrical stimulation (FES) to restore motor function, closed-loop feedback control may compensate for muscle fatigue, perturbations and nonlinearities in the behavior of the effected muscles. Kinematic state information is naturally represented in the firing rates of primary afferent neurons, which may be recorded with multi-electrode arrays at the level of the dorsal root ganglia (DRG). Previous work in cats has shown that it is feasible to estimate the kinematic state of the hind limb with a multivariate linear regression model of the neural activity in the DRG. In this study we extend these results to estimate the limb state in real-time during intramuscular stimulation in an anesthetized cat. Furthermore, we used the limb state estimates as feedback to a finite state FES controller to generate rudimentary walking behavior. This work demonstrates the feasibility of using DRG activity in a closed-loop FES system. PMID:22256011

  2. Numerically abnormal chromosome constitutions in humans

    SciTech Connect

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  3. A fate-map for cranial sensory ganglia in the sea lamprey?

    PubMed Central

    Modrell, Melinda S.; Hockman, Dorit; Uy, Benjamin; Buckley, David; Sauka-Spengler, Tatjana; Bronner, Marianne E.; Baker, Clare V.H.

    2014-01-01

    Cranial neurogenic placodes and the neural crest make essential contributions to key adult characteristics of all vertebrates, including the paired peripheral sense organs and craniofacial skeleton. Neurogenic placode development has been extensively characterized in representative jawed vertebrates (gnathostomes) but not in jawless fishes (agnathans). Here, we use in vivo lineage tracing with DiI, together with neuronal differentiation markers, to establish the first detailed fate-map for placode-derived sensory neurons in a jawless fish, the sea lamprey Petromyzon marinus, and to confirm that neural crest cells in the lamprey contribute to the cranial sensory ganglia. We also show that a pan-Pax3/7 antibody labels ophthalmic trigeminal (opV, profundal) placode-derived but not maxillomandibular trigeminal (mmV) placode-derived neurons, mirroring the expression of gnathostome Pax3 and suggesting that Pax3 (and its single Pax3/7 lamprey ortholog) is a pan-vertebrate marker for opV placode-derived neurons. Unexpectedly, however, our data reveal that mmV neuron precursors are located in two separate domains at neurula stages, with opV neuron precursors sandwiched between them. The different branches of the mmV nerve are not comparable between lampreys and gnatho-stomes, and spatial segregation of mmV neuron precursor territories may be a derived feature of lampreys. Nevertheless, maxillary and mandibular neurons are spatially segregated within gnathostome mmV ganglia, suggesting that a more detailed investigation of gnathostome mmV placode development would be worthwhile. Overall, however, our results highlight the conservation of cranial peripheral sensory nervous system development across vertebrates, yielding insight into ancestral vertebrate traits. PMID:24513489

  4. Optical recording of membrane potential responses from early embryonic chick ganglia using voltage-sensitive dyes.

    PubMed

    Sakai, T; Hirota, A; Komuro, H; Fujii, S; Kamino, K

    1985-01-01

    Changes in absorbance of voltage-sensitive merocyanine-rhodanine dyes were used to monitor electrical responses in the semilunar ganglion of 4-10-day-old developing chick embryos. The electrical responses were simultaneously recorded from many positions in the ganglion. Stimulation of the afferent nerve fibers (the ophthalmic division of cranial nerve V) with a suction electrode led to changes in light absorption of the stained ganglia. With both the depolarizing and hyperpolarizing pulses, the change was largest at 700 nm and was eliminated at a wavelength of 620 nm where the voltage-dependent absorption change of the dyes disappears. In the 4-10-day-old embryonic ganglia, two types of optical membrane potential responses, 'non-conducted' and 'conducted' responses, were identified. The non-conducted response varied with the intensity of the stimulus and had the nature of an electrotonic spread. Furthermore, this non-conducted response exhibited an 'initial upstroke-response' followed by the steady-state plateau evoked by larger depolarizing pulses. The conducted responses were blocked by tetrodotoxin (TTX) or by high external potassium concentration. The incidence of the conducted responses increased as development proceeded from the 5th to the 10th day of age. Thus, the TTX-sensitive action potential activity is probably generated initially in the semilunar ganglion during the 5-10-day-stage of development. These data represent the first demonstration of membrane potential responses in early embryonic intact nervous system. Furthermore, these studies demonstrate the usefulness of voltage-sensitive dyes in the analysis of the organizing process of embryonic neuronal functions during these early stages of development. PMID:3872700

  5. Functional expression of TRPV1 and TRPA1 in rat vestibular ganglia.

    PubMed

    Kamakura, Takefumi; Ishida, Yusuke; Nakamura, Yukiko; Yamada, Takahiro; Kitahara, Tadashi; Takimoto, Yasumitsu; Horii, Arata; Uno, Atsuhiko; Imai, Takao; Okazaki, Suzuyo; Inohara, Hidenori; Shimada, Shoichi

    2013-09-27

    Both TRPV1 and TRPA1 are non-selective cation channels. They are co-expressed, and interact in sensory neurons such as dorsal root ganglia (DRG) and trigeminal ganglia (TG), and are involved in nociception, being activated by nociceptive stimuli. Immunohistological localization of TRPV1 in vestibular ganglion (VG) neurons has been reported. Although TRPA1 is co-expressed with TRPV1 in DRG and TG neurons, it is unclear whether TRPA1 channels are expressed in VG neurons. Moreover, it is unknown whether TRPV1 and TRPA1 channels are functional in VG neurons. We investigated the expression of TRPV1 and TRPA1 in rat VG neurons by RT-PCR, in situ hybridization, immunohistochemistry, and Ca(2+) imaging experiments. Both TRPV1 and TRPA1 RT-PCR products were amplified from the mRNA of rat VG neurons. In situ hybridization experiments showed TRPV1 and TRPA1 mRNA expression in the majority of VG neurons. Immunohistochemistry experiments confirmed TRPV1 protein expression. In Ca(2+) imaging experiments, capsaicin, a TRPV1 agonist, induced a significant increase in intracellular calcium ion concentration ([Ca(2+)]i) in rat primary cultured VG neurons, which was almost completely blocked by capsazepine, a TRPV1-specific antagonist. Cinnamaldehyde, a TRPA1 agonist, also caused an increase in [Ca(2+)]i, which was completely inhibited by HC030031, a TRPA1-specific antagonist. Moreover, in some VG neurons, a [Ca(2+)]i increase was evoked by both capsaicin and cinnamaldehyde in the same neuron. In summary, our histological and physiological studies reveal that TRPV1 and TRPA1 are expressed in VG neurons. It is suggested that TRPV1 and TRPA1 in VG neurons might participate in vestibular function and/or dysfunction such as vertigo. PMID:23916509

  6. Abnormalities of lung function in hay fever.

    PubMed Central

    Morgan, E J; Hall, D R

    1976-01-01

    Twenty subjects with symptoms of hay fever were studied to see whether abnormalities could be detected in the function of small airways. The investigations included dynamic compliance at varying respiratory frequencies, closing capacity, residual volume, transfer factor, and maximal expiratory flow-volume curves. The tests were repeated in the winter when symptoms had resolved. Frequency dependence of compliance was found in eight subjects with symptoms (40%), closing capacities being abnormal in only two instances. Conventional pulmonary function tests, including expiratory flow rates at mid vital capacity, were within the predicted range of all subjects. When tests were repeated in the winter, frequency dependence of compliance was no longer present in subjects whose symptoms had resolved. The study suggests that reversible small airway abnormalities are present in a significant proportion of subjects with symptoms of hay fever and that such abnormalities are best detected by the measurement of dynamic compliance at varying respiratory frequencies. PMID:769243

  7. Four families with immunodeficiency and chromosome abnormalities.

    PubMed Central

    Candy, D C; Hayward, A R; Hughes, D T; Layward, L; Soothill, J F

    1979-01-01

    Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two. Images Fig. 1 Fig. 3 PMID:314782

  8. Abnormal Cervical Cancer Screening Test Results

    MedlinePLUS

    ... freeze abnormal cervical tissue, which then sloughs off. • Laser therapy—A focused beam of light is used ... tissue is removed from the cervix. Cryotherapy: A freezing technique used to destroy diseased tissue; also known ...

  9. Pinna abnormalities and low-set ears

    MedlinePLUS

    ... Common abnormalities include cysts in the pinna or skin tags . Many children are born with ears that stick ... affect hearing. However, sometimes cosmetic surgery is recommended. Skin tags may be tied off, unless there is cartilage ...

  10. T cell immune abnormalities in immune thrombocytopenia.

    PubMed

    Ji, Xuebin; Zhang, Liping; Peng, Jun; Hou, Ming

    2014-01-01

    Immune thrombocytopenia is an autoimmune disease with abnormal T cell immunity. Cytotoxic T cells, abnormal T regulatory cells, helper T cell imbalance, megakaryocyte maturation abnormalities and abnormal T cell anergy are involved in the pathogenesis of this condition. The loss of T cell-mediated immune tolerance to platelet auto-antigens plays a crucial role in immune thrombocytopenia. The induction of T cell tolerance is an important mechanism by which the pathogenesis and treatment of immune thrombocytopenia can be studied. Studies regarding the roles of the new inducible costimulator signal transduction pathway, the ubiquitin proteasome pathway, and the nuclear factor kappa B signal transduction pathway in the induction of T cell tolerance can help improve our understanding of immune theory and may provide a new theoretical basis for studying the pathogenesis and treatment of immune thrombocytopenia. PMID:25274611

  11. ICSN Data - Abnormal Result Technologies and Procedures

    Cancer.gov

    Skip to Main Content Search International Cancer Screening Network Sponsored by the National Cancer Institute Home | About ICSN | Collaborative Projects | Meetings | Cancer Sites | Publications | Contact Us Breast Cancer (Archived Tables): Home Abnormal

  12. Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin

    PubMed Central

    Kwon, Oh-Joon; Zhang, Li; Ittmann, Michael M.; Xin, Li

    2014-01-01

    Chronic inflammation has been shown to promote the initiation and progression of diverse malignancies by inducing genetic and epigenetic alterations. In this study, we investigate an alternative mechanism through which inflammation promotes the initiation of prostate cancer. Adult murine prostate epithelia are composed predominantly of basal and luminal cells. Previous studies revealed that the two lineages are largely self-sustained when residing in their native microenvironment. To interrogate whether tissue inflammation alters the differentiation program of basal cells, we conducted lineage tracing of basal cells using a K14-CreER;mTmG model in concert with a murine model of prostatitis induced by infection from the uropathogenic bacteria CP9. We show that acute prostatitis causes tissue damage and creates a tissue microenvironment that induces the differentiation of basal cells into luminal cells, an alteration that rarely occurs under normal physiological conditions. Previously we showed that a mouse model with prostate basal cell-specific deletion of Phosphatase and tensin homolog (K14-CreER;Ptenfl/fl) develops prostate cancer with a long latency, because disease initiation in this model requires and is limited by the differentiation of transformation-resistant basal cells into transformation-competent luminal cells. Here, we show that CP9-induced prostatitis significantly accelerates the initiation of prostatic intraepithelial neoplasia in this model. Our results demonstrate that inflammation results in a tissue microenvironment that alters the normal prostate epithelial cell differentiation program and that through this cellular process inflammation accelerates the initiation of prostate cancer with a basal cell origin. PMID:24367088

  13. Normal and Abnormal Behavior in Early Childhood

    PubMed Central

    Spinner, Miriam R.

    1981-01-01

    Evaluation of normal and abnormal behavior in the period to three years of age involves many variables. Parental attitudes, determined by many factors such as previous childrearing experience, the bonding process, parental psychological status and parental temperament, often influence the labeling of behavior as normal or abnormal. This article describes the forms of crying, sleep and wakefulness, and affective responses from infancy to three years of age. PMID:21289833

  14. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food...Packages § 864.7415 Abnormal hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the...

  15. Reasoning in a reading context: Deductive inferences in basal reading series

    Microsoft Academic Search

    Bridget A. Franks; Sharon L. Mulhern; Susan M. Schillinger

    1997-01-01

    This study examined three basal reading programs published by Heath (1989), Silver Burdett Ginn (1993) and Houghton Mifflin (1993), to determine how frequently logically necessary relationships are expressed in text used by basal readers, and whether direct instruction in making logically necessary inferences accompanies such expressions in basal reader series. The complete contents of the basal readers, from grades one

  16. Immunohistochemical study of basal cell adenoma in the parotid gland.

    PubMed

    Hamano, H; Abiko, Y; Hashimoto, S; Inoue, T; Shimono, M; Takagi, T; Noma, H

    1990-02-01

    Basal cell adenoma of the parotid gland was studied with immunohistochemical methods. We observed cells in the tumor with positive reaction to polyclonal keratin, prekeratin, monoclonal PKK-1, polyclonal S-100 protein, monoclonal S-100 protein (alpha), secretory component, actin and laminin. However, no cells which stained positively with monoclonal KL-1, amylase, carcinoembryonic antigen, or epithelial membrane antigen were recognized. From these immunohistochemical results and our ultrastructural observations reported previously, we conclude that the cells constituting the basal cell adenoma are ductal, myoepithelial, and squamous cells but not secretory ones. It is also suggested that the origins of basal cell ademona as well as those of pleomorphic and clear cell adenoma are undifferentiated cells of intercalated duct. PMID:2133439

  17. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents, apparatus, instrumentation, and controls necessary to isolate and identify abnormal genetically determined hemoglobin types. (b)...

  18. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents, apparatus, instrumentation, and controls necessary to isolate and identify abnormal genetically determined hemoglobin types. (b)...

  19. Basal cell carcinomas in elderly patients treated by cryotherapy

    PubMed Central

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

  20. Basal cell carcinomas in elderly patients treated by cryotherapy.

    PubMed

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

  1. Fetal Calcifications Are Associated with Chromosomal Abnormalities

    PubMed Central

    Sahlin, Ellika; Sirotkina, Meeli; Marnerides, Andreas

    2015-01-01

    Objective The biological importance of calcifications occasionally noted in fetal tissues (mainly liver) at autopsy or ultrasound is largely unexplored. Previous reports hint at an association to infection, circulatory compromise, malformations or chromosomal abnormalities. To identify factors associated with calcifications, we have performed a case-control study on the largest cohort of fetuses with calcifications described thus far. Methods One-hundred and fifty-one fetuses with calcifications and 302 matched controls were selected from the archives of the Department of Pathology, Karolinska University Hospital. Chromosome analysis by karyotyping or quantitative fluorescence-polymerase chain reaction was performed. Autopsy and placenta reports were scrutinized for presence of malformations and signs of infection. Results Calcifications were mainly located in the liver, but also in heart, bowel, and other tissues. Fetuses with calcifications showed a significantly higher proportion of chromosomal abnormalities than controls; 50% vs. 20% (p<0.001). The most frequent aberrations among cases included trisomy 21 (33%), trisomy 18 (22%), and monosomy X (18%). A similar distribution was seen among controls. When comparing cases and controls with chromosomal abnormalities, the cases had a significantly higher prevalence of malformations (95% vs. 77%, p=0.004). Analyzed the other way around, cases with malformations had a significantly higher proportion of chromosomal abnormalities compared with controls, (66% vs. 31%, p<0.001). Conclusion The presence of fetal calcifications is associated with high risk of chromosomal abnormality in combination with malformations. Identification of a calcification together with a malformation at autopsy more than doubles the probability of detecting a chromosomal abnormality, compared with identification of a malformation only. We propose that identification of a fetal tissue calcification at autopsy, and potentially also at ultrasound examination, should infer special attention towards co-existence of malformations, as this would be a strong indicator for a chromosomal abnormality. PMID:25923652

  2. Abnormal hepatocellular mitochondria in methylmalonic acidemia.

    PubMed

    Wilnai, Yael; Enns, Gregory M; Niemi, Anna-Kaisa; Higgins, John; Vogel, Hannes

    2014-10-01

    Methylmalonic acidemia (MMA) is one of the most frequently encountered forms of branched-chain organic acidemias. Biochemical abnormalities seen in some MMA patients, such as lactic acidemia and increased tricarboxylic acid cycle intermediate excretion, suggest mitochondrial dysfunction. In order to investigate the possibility of mitochondrial involvement in MMA, we examined liver tissue for evidence of mitochondrial ultrastructural abnormalities. Five explanted livers obtained from MMA mut(0) patients undergoing liver transplantation were biopsied. All patients had previous episodes of metabolic acidosis, lactic acidemia, ketonuria, and hyperammonemia. All biopsies revealed a striking mitochondriopathy by electron microscopy. Mitochondria were markedly variable in size, shape, and conformation of cristae. The inner matrix appeared to be greatly expanded and the cristae were diminutive and disconnected. No crystalloid inclusions were noted. This series clearly documents extensive mitochondrial ultrastructure abnormalities in liver samples from MMA patients undergoing transplantation, providing pathological evidence for mitochondrial dysfunction in the pathophysiology of MMA mut(0). Considering the trend to abnormally large mitochondria, the metabolic effects of MMA may restrict mitochondrial fission or promote fusion. The correlation between mitochondrial dysfunction and morphological abnormalities in MMA may provide insights for better understanding and monitoring of optimized or novel therapeutic strategies. PMID:24933007

  3. Electroencephalographic abnormalities in patients with snake bites.

    PubMed

    Ramachandran, S; Ganaikabahu, B; Pushparajan, K; Wijesekera, J

    1995-01-01

    Electroencephalograms (EEGs) were obtained for 26 patients with snake bite to observe the cerebral impact of snake venom. All snakes were identified; 19 (73%) were Russell's vipers, one (4%) was a common cobra, five (19%) were hump-nosed vipers, and one (4%) was a dog-faced fresh water snake. The EEG was abnormal in 25 patients (96%) and these results included all the snake species identified. The EEG abnormalities observed were reduced alpha activity, increased theta/beta activity or sharp waves (grade 1), sharp waves or spikes and slow waves (grade 2), or diffuse delta activity (grade 3). Grade 1 changes occurred in 16 patients (62%), grade 11 in eight patients (31%), and grade 111 in one patient (4%). Thus, grade 2 and 3 changes, which were moderately severe to severe abnormalities, occurred in nine patients (35%). One patient had acute renal failure and two others had mild jaundice and hyponatremia. These three patients had EEG abnormalities that were similar to those observed in the remaining 22 patients. The altered EEG, suggestive of an encephalopathy, appeared within hours of the bite and persisted for several days without clinical neurologic effects. The changes were seen mainly in the temporal lobe. Similar changes occurred in both patients with and without antivenom therapy. It appeared that the EEG abnormalities are a consequence of the effects of venom from the bites of a variety of snakes. PMID:7856822

  4. The electrophysiological effects of neurotensin on neurones of guinea-pig prevertebral sympathetic ganglia.

    PubMed Central

    Stapelfeldt, W H; Szurszewski, J H

    1989-01-01

    1. The membrane effects of neurotensin on neurons of guinea-pig prevertebral ganglia were investigated by means of intracellular recording techniques in vitro. 2. Neurotensin (2-5 microM) applied by superfusion caused depolarizing responses in fifty-seven of seventy-four neurones tested in the inferior mesenteric ganglion and thirty-seven of forty-seven neurones tested in the coeliac plexus. The remaining neurones tested showed no membrane response. 3. Responses to neurotensin could be discriminated into two different types of membrane depolarizations on the basis of their different time courses and pharmacological characteristics: a steady-state type of depolarization and a transient type of depolarization. Seven of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and ten of thirty-seven responsive neurones tested in the coeliac plexus responded to neurotensin with a depolarization which was maintained constant as long as neurotensin was superfused over the preparation (steady-state type). Forty-eight of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and twenty of thirty-seven responsive neurones tested in the coeliac plexus responded with a transient depolarization which was followed by a repolarization in the maintained presence of neurotensin (transient type). A combination of both types of responses was observed in two neurones tested in the inferior mesenteric ganglion and in seven neurones tested in the coeliac plexus. 4. Steady-state type responses were characterized by a slowly developing membrane depolarization which reached a plateau and lasted throughout the presence of neurotensin. Amplitude and time course of this response were not altered in a solution containing hexamethonium (10 microM) and atropine (10 microM) or by a solution low in calcium (1 mM) and high in magnesium (15 mM). 5. Transient type depolarizations evoked by neurotensin were faster in reaching their maximum and were followed by a repolarization during the maintained presence of neurotensin. Responses similar in time course and amplitude were obtained in solutions containing hexamethonium (10-100 microM) and atropine (10 microM). However, transient responses were abolished in a solution low in calcium (1 mM) and high in magnesium (15 mM) and were markedly attenuated in ganglia treated with capsaicin (3 microM). 6. Both types of depolarizations were associated with increases in membrane input resistance. Both responses converted subthreshold depolarizing electrotonic potentials and subthreshold fast EPSPs to action potentials. 7. Both types of depolarizations were observed when the C-terminal hexapeptide fragment neurotensin 8-13 was used.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 8 PMID:2575666

  5. Basal melt rates beneath Whillans Ice Stream, West Antarctica

    E-print Network

    Beem, Lucas H.; Jezek, Ken C.; van der Veen, Cornelis J.

    2010-08-05

    . Downstream of the onset of shear crevasses, strong basal melt (20–50 mm a?1) is concentrated beneath the relatively narrow shear margins. Farther upstream, melt rates are consistently 3–7 mm a?1 across the width of the ice stream. We show that the transition...

  6. Environmental correlates of tree biomass, basal area, wood specific

    E-print Network

    Slik, Ferry

    density gradients in Borneo's tropical forestsgeb_489 50..60 J. W. F. Slik1 *, Shin-Ichiro Aiba2 , Francis their spatial patterns in an Asian tropical forest. Location Borneo, Southeast Asia. Methods We combined stem density, basal area, community wood density and AGB data from 83 locations in Borneo with an environmental

  7. Aggressive basal cell carcinoma: Presentation, pathogenesis, and management

    Microsoft Academic Search

    Hobart W. Walling; Scott W. Fosko; Pedram A. Geraminejad; Duane C. Whitaker; Christopher J. Arpey

    2004-01-01

    Basal cell carcinoma (BCC) is the most common cutaneous skin malignancy. BCC generally has a clinical course characterized by slow growth, minimal soft tissue invasiveness, and a high cure rate. Occasionally, however, BCC behaves aggressively with deep invasion, recurrence, and potential regional and distant metastasis. Several factors, including tumor size, duration, histology, and perineural spread, have been postulated as markers

  8. Distribution of Fibronectin and Laminin in Basal Cell Epitheliomas

    Microsoft Academic Search

    Douglas L. Nelson; Charles D. Little; Gary Ballan

    1983-01-01

    The distribution of fibronectin (FN) and laminin (LM) in basal cell epithelioma was evaluated by indirect immunofluorescence. FN is a glycoprotein which promotes interaction between cells and the extracellular matrix, and is present at the dermal-epidermal junction (DEJ) and throughout the dermis, but absent in the normal epidermis. LM, a noncollagenous basement membrane protein, plays a role in epithelial adhesion

  9. Short term evolution of the basal magma ocean

    Microsoft Academic Search

    M. Ulvrova; S. Labrosse; N. Coltice; P. J. Tackley

    2010-01-01

    It has been proposed that the ultra low velocity zones at the base of the mantle are the remnants of the initially thick magma ocean (the basal magma ocean, BMO) that undergoes slow crystallization. The presence of a molten silicate layer between the solid mantle and the core can dramatically change the thermal coupling between them and affect the ability

  10. Reassessment of the phylogenetic interrelationships of basal turtles (Testudinata)

    Microsoft Academic Search

    Jérémy Anquetin

    2011-01-01

    Recent discoveries from the Late Triassic and Middle Jurassic have significantly improved the fossil record of early turtles. These new forms offer a unique opportunity to test the interrelationships of basal turtles. Nineteen fossil species are added to the taxon sample of the most comprehensive morphological phylogenetic analysis of the turtle clade. Among these additional species are recently discovered forms

  11. Wideband measurements of ice sheet attenuation and basal scattering

    E-print Network

    Allen, Christopher Thomas; Gogineni, Sivaprasad; Paden, J. D.; Jezek, K. C.; Dahl-Jensen, D.; Larsen, L. B.

    2005-04-01

    transfer function. Over this frequency range, we observe an increase in total loss of 8 +/- 2.5 dB using a linear regression to the log-scale data. With the ice sheet transfer function and an ice extinction model, we estimate the return loss from the basal...

  12. CREB expression mediates amyloid ?-induced basal BDNF downregulation.

    PubMed

    Rosa, Elyse; Fahnestock, Margaret

    2015-08-01

    In Alzheimer's disease, accumulation of amyloid-? (A?) is associated with loss of brain-derived neurotrophic factor (BDNF), synapses, and memory. Previous work demonstrated that A? decreases activity-induced BDNF transcription by regulating cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation. However, the specific mechanism by which A? reduces basal BDNF expression remains unclear. Differentiated, unstimulated human neuroblastoma (SH-SY5Y) cells treated with oligomeric A? exhibited significantly reduced CREB messenger RNA compared with controls. Phosphorylated and total CREB proteins were decreased in both the cytoplasm and nucleus of A?-treated cells. However, neither pCREB129 nor pCREB133 levels were altered relative to total CREB levels. The protein kinase A activator forskolin increased pCREB133 levels and prevented A?-induced basal BDNF loss when administered before A? but did not rescue BDNF expression when administered later. These data demonstrate a new mechanism for A?-induced BDNF downregulation: in the absence of cell stimulation, A? downregulates basal BDNF levels via A?-induced CREB transcriptional downregulation, not changes in CREB phosphorylation. Thus, A? reduces basal and activity-induced BDNF expression by different mechanisms. PMID:26025137

  13. THE DEPICTION OF OLD AGE IN SIX BASAL READERS

    Microsoft Academic Search

    A. J. Kingston; Molly W. Drotter

    1981-01-01

    Six commonly used basal readers were examined to determine how the aged were depicted. The results indicated that although the aged were shown in a positive manner, rarely were they the main characters of the stories and rarely were their personalities fully portrayed. An adjective checklist revealed that the aged typically were shown as active, kind, wise, and hardworking. They

  14. Terahertz Pulse Imaging of ex vivo Basal Cell Carcinoma

    Microsoft Academic Search

    Ruth M Woodward; Vincent P Wallace; Richard J Pye; Bryan E Cole; Donald D Arnone; Edmund H Linfield; Michael Pepper

    2003-01-01

    Terahertz pulse imaging has been used for the first time to study basal cell carcinoma ex vivo, the most common form of skin cancer. This noninvasive technique uses part of the electromagnetic spectrum in the frequency range 0.1–2.7 THz. A total of 21 samples were imaged; the study was performed blind and results were compared to histology. Each image consisted

  15. Easy Reader Books: A Viable Supplement to Today's Basals?

    ERIC Educational Resources Information Center

    Kegley, Peggy Ann

    A study investigated whether trade books labeled "easy reader" consistently conform to specific sight word lists and to what degree the vocabulary in those books matches that in K-2 basals. Ten "easy reader" books were chosen at random from each of three publishers. Three popular sight word lists were matched separately to every one of the words…

  16. Diet, phylogeny, and basal metabolic rate in phyllostomid bats

    Microsoft Academic Search

    Ariovaldo P. Cruz-Neto; Theodore Garland; Augusto Shinya Abe

    2006-01-01

    Summary Aside from the pervasive effects of body mass, much controversy exists as to what factors account for interspecific variation i n basal metabolic rates (BMR) of mammals; however, both diet and phylogeny have been strongly implicated. We examined variation in BMR within the New World bat family Phyllostomidae, which shows the largest diversity of food habits among mammalian families,

  17. The BASAL: What Does It Demand of the Beginning Reader?

    ERIC Educational Resources Information Center

    Osburn, Bess; Bobruk, Toni

    To determine the general characteristics of beginning reading materials, to establish categories in regard to concepts and the instruction of concepts, and to search for a common framework among concepts, a study surveyed six popular, widely promoted basal series which had been copyrighted within the past 5 years. For each lesson, the stated…

  18. Shear Jamming in Granular Experiments without Basal Friction

    E-print Network

    Hu Zheng; Joshua A. Dijksman; Robert P. Behringer

    2014-08-08

    Jammed states of frictional granular systems can be induced by shear strain at densities below the isostatic jamming density ($\\phi_c$). It remains unclear, however, how much friction affects this so-called shear-jamming. Friction appears in two ways in this type of experiment: friction between particles, and friction between particles and the base on which they rest. Here, we study how particle-bottom friction, or basal friction, affects shear jamming in quasi-two dimensional experiments. In order to study this issue experimentally, we apply simple shear to a disordered packing of photoelastic disks. We can tune the basal friction of the particles by immersing the particles in a density matched liquid, thus removing the normal force, hence the friction, between the particles and base. We record the overall shear stress, and particle motion, and the photoelastic response of the particles. We compare the shear response of dry and immersed samples, which enables us to determine how basal friction affects shear jamming. Our findings indicate that changing the basal friction shifts the point of shear jamming, but it does not change the basic phenomenon of shear jamming.

  19. Surgical vs Nonsurgical Treatment of Basal Cell Carcinoma

    Microsoft Academic Search

    I. R. Aguayo-Leiva; L. Ríos-Buceta; P. Jaén-Olasolo

    2010-01-01

    Numerous therapeutic options are now available for the treatment of basal cell carcinoma. However, few randomized controlled trials with 5-year follow-up have compared the effectiveness of the different treatments. Such a comparison is difficult, probably because efficacy depends on several factors: those related to the tumor, the patient, the technique, and the dermatologist's experience. We first describe the available therapeutic

  20. Curcumin Ameliorates Functional and Structural Abnormalities in Cisplatin-induced Neuropathy

    PubMed Central

    Kaewsema, Athitaya; Charoensub, Thuntawat

    2015-01-01

    Peripheral neuropathy is one of the major side effects of cisplatin; however, effective treatments are lacking. Curcumin is a polyphenol found in the root of Curcuma longa and has been shown neuroprotective against several neurological diseases. Nevertheless, its effects on cisplatin neuropathy remain unclear. This study aimed to clarify this issue by inducing neuropathy in the rats with intraperitoneal injection of cisplatin 2 mg/kg twice a week for 5 consecutive weeks. Curcumin 200 mg/kg/day was given by gavage to a group of cisplatin-treated rats during these five weeks. The results showed that cisplatin induced thermal hypoalgesia in the 5th week which could be prevented by curcumin. In the 5th and 8th weeks, sciatic motor nerve conduction velocity was reduced in the cisplatin compared with the control groups. Curcumin significantly attenuated this deficit. Morphometric analysis of L4 dorsal root ganglia from the cisplatin group revealed nuclear and nucleolar atrophy including loss of neurons in the 8th week. These alterations were significantly blocked by curcumin. Moreover, curcumin also ameliorated the reduced myelin thickness in the sciatic nerve of cisplatin-treated rats. Taken together, our findings suggest the favorable effects of curcumin on both functional and structural abnormalities in cisplatin neuropathy. Future studies are needed to clarify the exact underlying mechanisms.