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1

Anti-basal ganglia antibody abnormalities in Sydenham chorea  

Microsoft Academic Search

Anti-basal ganglia antibodies (ABGA) were measured in nine children with Sydenham chorea (SC) and compared to nine controls. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) methods were used to detect ABGA against supernatant (S1), pellet, and synaptosomal preparations from adult and pediatric postmortem caudate, putamen, and globus pallidus. ELISA optical density (OD) values were higher in SC patients than

Harvey S Singer; Christopher R Loiselle; Olivia Lee; Marjorie A Garvey; Franz H Grus

2003-01-01

2

Anti-basal ganglia antibody abnormalities in Sydenham chorea.  

PubMed

Anti-basal ganglia antibodies (ABGA) were measured in nine children with Sydenham chorea (SC) and compared to nine controls. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) methods were used to detect ABGA against supernatant (S1), pellet, and synaptosomal preparations from adult and pediatric postmortem caudate, putamen, and globus pallidus. ELISA optical density (OD) values were higher in SC patients than controls across all preparations, but did not reach a level of significance. Although WB identified multiple bands in all subjects, discriminant analysis showed that the mean binding patterns of SC patients were significantly different from control, most notably in the caudate S1 fraction (Wilks' lambda=0.011, p<0.0001). Numerous antigens contributed to differences between groups; the two most defining molecular masses were at 126 and 113 kDa. In contrast to WB with discriminant analysis, ELISA measurements did not significantly differentiate between the SC group and controls. PMID:12620655

Singer, Harvey S; Loiselle, Christopher R; Lee, Olivia; Garvey, Marjorie A; Grus, Franz H

2003-03-01

3

Autoimmune basal ganglia disorders.  

PubMed

The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

Dale, Russell C; Brilot, Fabienne

2012-11-01

4

Basal Ganglia and Learning  

NSDL National Science Digital Library

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

2009-04-14

5

Stereotactic MRI in Dyt1 Dystonia: Focal Signal Abnormalities in the Basal Ganglia Do Not Contraindicate Deep Brain Stimulation  

Microsoft Academic Search

Aims: To study stereotactic magnetic resonance imaging (MRI) features of the basal ganglia in DYT1 primary dystonia. Methods: Twenty-five genetically confirmed DYT1 dystonia patients (age range, 8–66 years; mean age, 22 years) underwent brain MRI under general anesthesia at the time of globus pallidus internus (GPi) deep brain stimulation (DBS) surgery. MR images were retrospectively reviewed for signal intensity alterations.

S. Gavarini; N. Vayssière; P. Delort; L. Cif; B. Biolsi; C. Tancu; X. Vasques; S. Plagnol; A. Bonafe; P. Coubes

2008-01-01

6

Behavior and the basal ganglia.  

PubMed

When viewed as a whole, these basal ganglia-thalamo-cortical circuits appear to play a modulating role in a wide range of behaviors. At the cortical level, given convergence upon specified regions within the frontal lobes, the behaviors in question would be those dependent upon SMA, premotor, frontal eye fields, dorsolateral, and orbitofrontal outflow targets. Broadly speaking, processes such as the generation, maintenance, switching, and blending of motor, mental, or emotional sets would be involved. Accordingly, in basal ganglia disease, the planning and the execution of the above behavioral domains can be affected. Given the diversity and complexity of activity within the basal ganglia, the consequences of disruption depend largely upon lesion site and the associated interplay of neurochemical factors. For example, in the motor domain, damage to various striatal circuitry levels can result in either hypo- or hyperkinetic disorders of movement. Following this analogy, it might also be said that diverse lesions, depending on site, can result in problems with the development and maintenance of behavioral sets ("hypophrenic") versus problems in relinquishing preferential sets ("hyperphrenic"). These contrasting patterns are best represented in PD and OCD, respectively. In the latter case, however, the "hyperphrenic" pattern would only apply to those behaviors which are part of the obsessional rituals. This suggests that procedural system "overdrive" remains domain-specific as is the case for most operations within the procedural system. To return to the broad principle of habituation, a process first described in the context of the visual system and its connections with the tail of the caudate nucleus, it would be tempting to view PD and OCD as disorders of "under" and "over" habituation to behavioral routines. Unfortunately, the situation has proven to be more complex in view of recent neuropsychological findings (Nicholson et al., in preparation). Using a variety of problem-solving and other cognitive tasks, both PD and OCD patients were found to require more practice and/or the provision of external guidelines to facilitate habit formation. Thus, in both cases, as in other disorders of the basal ganglia, the establishment of useful heuristics by which to direct adaptive behavior suffers. OCD patients therefore appear to have at least two compartmentalized types of basal ganglia dysfunction: the ritualistic compulsions and obsessions as well as the heuristic inefficiency (i.e., poor procedural mobilization). PD patients would also suffer a similar fate as it is known that the degrees of motor versus nonmotor (i.e., procedural) deficit are poorly correlated (42).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7872134

Saint-Cyr, J A; Taylor, A E; Nicholson, K

1995-01-01

7

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

ERIC Educational Resources Information Center

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…

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

2010-01-01

8

Basal ganglia lesions in children and adults.  

PubMed

The term "basal ganglia" refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) - to a lesser degree - allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or - more frequently - bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic-ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive. PMID:23313708

Bekiesinska-Figatowska, Monika; Mierzewska, Hanna; Jurkiewicz, El?bieta

2013-05-01

9

Functional neuroanatomy of the basal ganglia.  

PubMed

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

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

2012-12-01

10

Striatal plasticity and basal ganglia circuit function  

PubMed Central

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

Kreitzer, Anatol C.; Malenka, Robert C.

2009-01-01

11

Basal Ganglia Volumes in Patients With Gilles de la Tourette Syndrome  

Microsoft Academic Search

Background: Despite strong circumstantial evidence that the pathophysiology of Gilles de la Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia, inconsistent findings from relatively small in vivo TS imaging studies have supported contradictory conclu- sions concerning the role of abnormal anatomical charac- teristics of the basal ganglia in the pathophysiology of TS. Methods: Basal ganglia volumes

Bradley S. Peterson; Prakash Thomas; Michael J. Kane; Lawrence Scahill; Heping Zhang; Richard Bronen; Robert A. King; James F. Leckman; Lawrence Staib

2003-01-01

12

Action, time and the basal ganglia.  

PubMed

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

Yin, Henry H

2014-03-01

13

Psychopharmacologic intervention after hemorrhagic basal ganglia damage.  

PubMed

Traumatic brain injury (TBI) can result in cognitive and behavioral impairments such as poor attention, learning, memory and planning ability and uncontrolled crying that can be more persistent problems than the physical disabilities. Cognitive enhancers have been shown to improve cognitive and behavioral impairments in patients with hemorrhagic basal ganglia lesions as well as other forms of TBI. There is little research about the use of cognitive enhancers after hemorrhagic basal ganglia damage. We present a case of a 38 year old male who made significant recovery with the use of cognitive enhancers. PMID:22795553

Al Owesie, Rafat Mohammed; Morton, Catherine Saino

2012-11-15

14

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

PubMed

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

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

2013-10-01

15

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

Microsoft Academic Search

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

André Parent; Lili-Naz Hazrati

1995-01-01

16

Basal ganglia and dopamine contributions to probabilistic category learning  

Microsoft Academic Search

Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward

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

2008-01-01

17

Network-level neuroplasticity in cortico-basal ganglia pathways  

Microsoft Academic Search

The striatum, the largest input nucleus of the basal ganglia, receives massive inputs from the neocortex and thalamus, and gives rise to the direct, indirect and striosomal pathways of the basal ganglia. Here, the view is developed that the striatum is a major site for adaptive plasticity in cortico-basal ganglia circuits, affecting in the normal state a broad range of

Ann M. Graybiel

2004-01-01

18

Transient bilateral Basal Ganglia lesions in rotavirus encephalopathy. A case report.  

PubMed

Rotavirus gastroenteritis may be associated with the onset of an acute reversible encephalitis. We describe a case of transient bilateral basal ganglia lesions after a prodromal gastroenteritis which completely resolved four months later. Diffusion weighted images were determinant to depict the basal ganglia abnormalities and were helpful to evaluate the prognosis. A review of the literature indicates that many diseases may be accompanied by signal abnormalities within the basal ganglia and that differential diagnosis is possible only through the simultaneous evaluation of imaging, clinical and laboratory findings. PMID:24148332

Messina, M; Meli, G A; Viglianesi, A; Scavone, G; Belfiore, G; Di Bella, D

2010-03-01

19

Dopaminergic innervation of human basal ganglia.  

PubMed

This paper summarises the results of some of our recent tyrosine hydroxylase (TH) immunohistochemical studies of the dopaminergic innervation of the human basal ganglia. It also reports new findings on the presence of TH-immunoreactive (ir) neurons in the striatum. Our data show the existence of nigrostriatal TH-ir axons that provide collaterals arborizing in the globus pallidus and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson's pencils. We postulate that this extrastriatal innervation, which allows nigral dopaminergic neurons to directly affect the pallidum and subthalamic nucleus, plays a critical role in the functional organisation of human basal ganglia. The TH-ir fibres that reach the striatum arborize according to a highly heterogeneous pattern. At rostral striatal levels, numerous small TH-poor zones embedded in a TH-rich matrix correspond to calbindin-poor striosomes and calbindin-rich extrastriosomal matrix, respectively. At caudal striatal levels, in contrast, striosomes display a TH immunostaining that is more intense than that of the matrix. A significant number of small, oval, aspiny TH-ir neurons scattered throughout the rostrocaudal extent of the caudate nucleus and putamen, together with a few larger, multipolar, spiny TH-ir neurons lying principally within the ventral portion of the putamen, were disclosed in human. This potential source of intrinsic striatal dopamine might play an important role in the functional organisation of the human striatum, particularly in case of Parkinson's disease. PMID:11207419

Prensa, L; Cossette, M; Parent, A

2000-12-01

20

The Basal Ganglia and Adaptive Motor Control  

NASA Astrophysics Data System (ADS)

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.

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

1994-09-01

21

Polymicrogyria with dysmorphic basal ganglia? Think tubulin!  

PubMed

Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function. PMID:23495813

Amrom, D; Tanyalçin, I; Verhelst, H; Deconinck, N; Brouhard, Gj; Décarie, J-C; Vanderhasselt, T; Das, S; Hamdan, Ff; Lissens, W; Michaud, Jl; Jansen, Ac

2013-03-15

22

Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease).  

PubMed

Familial idiopathic basal ganglia calcification (IBGC, Fahr disease) is an inherited neurologic condition characterized by basal ganglia and extra-basal ganglia brain calcifications, parkinsonism, and neuropsychiatric symptoms. The authors examined six families for linkage to the previously identified genetic locus (IBGC1) located on chromosome 14q. The authors found evidence against linkage to IBGC1 in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC. PMID:15596772

Oliveira, J R M; Spiteri, E; Sobrido, M J; Hopfer, S; Klepper, J; Voit, T; Gilbert, J; Wszolek, Z K; Calne, D B; Stoessl, A J; Hutton, M; Manyam, B V; Boller, F; Baquero, M; Geschwind, D H

2004-12-14

23

Basal Ganglia Mechanisms Underlying Precision Grip Force Control  

PubMed Central

The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force.

Prodoehl, Janey; Corcos, Daniel M.; Vaillancourt, David E.

2009-01-01

24

Basal ganglia mechanisms underlying precision grip force control.  

PubMed

The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review, we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force. PMID:19428499

Prodoehl, Janey; Corcos, Daniel M; Vaillancourt, David E

2009-06-01

25

Structural and functional evolution of the basal ganglia in vertebrates.  

PubMed

While a basal ganglia with striatal and pallidal subdivisions is 1 clearly present in many extant anamniote species, this basal ganglia is cell sparse and receives only a relatively modest tegmental dopaminergic input and little if any cortical input. The major basal ganglia influence on motor functions in anamniotes appears to be exerted via output circuits to the tectum. In contrast, in modern mammals, birds, and reptiles (i.e., modern amniotes), the striatal and pallidal parts of the basal ganglia are very neuron-rich, both consist of the same basic populations of neurons in all amniotes, and the striatum receives abundant tegmental dopaminergic and cortical input. The functional circuitry of the basal ganglia also seems very similar in all amniotes, since the major basal ganglia influences on motor functions appear to be exerted via output circuits to both cerebral cortex and tectum in sauropsids (i.e., birds and reptiles) and mammals. The basal ganglia, output circuits to the cortex, however, appear to be considerably more developed in mammals than in birds and reptiles. The basal ganglia, thus, appears to have undergone a major elaboration during the evolutionary transition from amphibians to reptiles. This elaboration may have enabled amniotes to learn and/or execute a more sophisticated repertoire of behaviors and movements, and this ability may have been an important element of the successful adaptation of amniotes to a fully terrestrial habitat. The mammalian lineage appears, however, to have diverged somewhat from the sauropsid lineage with respect to the emergence of the cerebral cortex as the major target of the basal ganglia circuitry devoted to executing the basal ganglia-mediated control of movement. PMID:9858740

Reiner, A; Medina, L; Veenman, C L

1998-12-01

26

Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder.  

PubMed

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

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

2014-08-30

27

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

PubMed Central

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.

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

28

[Primary hypoparathyroidism with basal ganglia calcification: report of a case].  

PubMed

A 3 years old boy was admitted due to recurrent attacks of tetany and carpopedal spasm since one and a half years of age. The tetany lasting for 1-2 minutes in each episode was often preceded by an upper respiratory tract infection and occurred 2-3 times a month. Both birth and family history were unremarkable. Physical findings showed mild psychomotor retardation with positive Chvostek sign. Laboratory examination revealed hypocalcemia, hyperphosphatemia, and low serum parathyroid hormone level. EEG showed abnormal tracing with increased slow waves. Head CT Scan demonstrated symmetrical calcification in the basal ganglia region. The clinical features and laboratory findings were consistent with hypoparathyroidism. The mechanism of calcium deposit in the basal ganglia still remains unclear. Tetany, muscle cramping and seizures secondary to hypocalcemia are the most common neurologic signs which respond quickly to calcium replacement. Subsequent supplemental therapy resolved movement disorders and mental retardation. If early treatment prior to the tetanic episodes is instituted in a patient with hypoparathyroidism, it may prevent the development of complications such as intracranial calcifications, cataract and permanent retardation. PMID:2637591

Chow, K S; Lu, D N

1989-01-01

29

Primary yolk sac tumor of bilateral basal ganglia.  

PubMed

A primary intracranial yolk sac tumor (YST) is a type of germ cell tumor (GCT) and usually involves the pineal or suprasellar regions, as do other GCTs. Primary YST in the basal ganglia is not common, and bilateral basal ganglia involvement is even rarer. Early diagnosis is often difficult because of minimal or subtle findings without space-occupying lesions shown on neuroimaging during the early course of the disease. We report a case of primary intracranial YST encountered in the basal ganglia bilaterally and describe the clinical presentation, diagnostic problem, imaging characteristics, histopathologic features, and prognosis of the tumor. To the best of our knowledge, this is only the third reported case of primary YST confined to the basal ganglia in the literature. PMID:20728859

Wang, Chung-Hao; Hsu, Ting-Rong; Yang, Tzu-Ying; Wong, Tai-Tong; Chang, Feng-Chi; Ho, Donald Ming-Tak; Chiang, Kuo-Liang; Chang, Kai-Ping

2010-08-01

30

Simultaneous Multiple Basal Ganglia and Cerebellar Hemorrhage: Case Report  

PubMed Central

A 35-year-old man presented with simultaneous multiple intracranial hematomas in the right cerebellar dentate nucleus and left basal ganglia. The hematomas were visible by computed tomography performed within two hours of the patient's arrival. The initial computed tomography showed acute hemorrhage in the left basal ganglia and dentate nucleus in cerebellum. The patient then experienced a change of consciousness due to newly developed hydrocephalus, and emergent extra-ventricular drainage was performed. By discharge, fortunately, the patient was fully recovered.

Yi, Ho Jun; Hwang, Hyung Sik

2013-01-01

31

Basal ganglia activity patterns in parkinsonism and computational modeling of their downstream effects  

PubMed Central

The availability of suitable animal models and of the opportunity to record electrophysiologic data in movement disorder patients undergoing neurosurgical procedures has allowed researchers to investigate parkinsonism-related changes in neuronal firing patterns in the basal ganglia and associated areas of thalamus and cortex. These studies have shown that parkinsonism is associated with increased activity in the basal ganglia output nuclei, along with an increase in burst discharges, oscillatory firing, and synchronous firing patterns throughout the basal ganglia. Computational approaches have the potential to play an important role in the interpretation of these data. Such efforts can provide a formalized view of neuronal interactions in the network of connections between basal ganglia, thalamus and cortex, allow for the exploration of possible contributions of particular network components to parkinsonism, and potentially result in new conceptual frameworks and hypotheses that can be subjected to biological testing. It has proven very difficult, however, to integrate the wealth of the experimental findings into coherent models of the disease. In this review, we provide an overview of the abnormalities in neuronal activity that have been associated with parkinsonism. Subsequently, we discuss some particular efforts to model the pathophysiologic mechanisms that may link abnormal basal ganglia activity to the cardinal parkinsonian motor signs and may help explain the mechanisms underlying the therapeutic efficacy of deep brain stimulation for Parkinson’s disease. We emphasize the logical structure of these computational studies, making clear the assumptions from which they proceed and the consequences and predictions that follow from these assumptions.

Rubin, Jonathan E.; McIntyre, Cameron C.; Turner, Robert S.; Wichmann, Thomas

2012-01-01

32

Loss of Specificity in Basal Ganglia Related Movement Disorders  

PubMed Central

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

Bronfeld, Maya; Bar-Gad, Izhar

2011-01-01

33

Structural Analysis of the Basal Ganglia in Schizophrenia  

PubMed Central

Increases in the total volume of basal ganglia structures have been reported in schizophrenia. However, patterns of basal ganglia shape change, which can reveal localized changes in substructure volumes, have not been investigated. In this study, the total volume and shape of several basal ganglia structures were compared in subjects with and without schizophrenia. T1-weighted magnetic resonance scans were collected in 54 schizophrenia and 70 comparison subjects. High-dimensional (large-deformation) brain mapping was used to assess the shape and volume of several basal ganglia structures. The relationships of shape and volume measures with psychopathology, cognition and motor function were also assessed. Left and right volumes of the caudate and putamen, as well as the right globus pallidus volume, were significantly increased in subjects with schizophrenia as compared to comparison subjects after total brain volume was included as a covariate. Significant differences in shape accompanied these volume changes in the caudate, putamen and globus pallidus, after their total volumes were included as covariates. There were few significant correlations between volume or shape measures and either cognitive function or clinical symptoms, other than a positive correlation between an attention/vigilance cognitive dimension and the volume of the caudate and putamen, and a negative correlation between nucleus accumbens volume and delusions. In conclusion, basal ganglia volumes relative to total brain volume were larger in schizophrenia subjects than healthy comparison subjects. Specific patterns of shape change accompanied these volume differences.

Mamah, Daniel; Wang, Lei; de Erausquin, Deanna Barch Gabriel A.; Gado, Mokhtar; Csernansky, John G.

2007-01-01

34

Oscillations and the basal ganglia: motor control and beyond.  

PubMed

Oscillations form a ubiquitous feature of the central nervous system. Evidence is accruing from cortical and sub-cortical recordings that these rhythms may be functionally important, although the precise details of their roles remain unclear. The basal ganglia share this predilection for rhythmic activity which, as we see in Parkinson's disease, becomes further enhanced in the dopamine depleted state. While certain cortical rhythms appear to penetrate the basal ganglia, others are transformed or blocked. Here, we discuss the functional association of oscillations in the basal ganglia and their relationship with cortical activity. We further explore the neural underpinnings of such oscillatory activity, including the important balance to be struck between facilitating information transmission and limiting information coding capacity. Finally, we introduce the notion that synchronised oscillatory activity can be broadly categorised as immutability promoting rhythms that reinforce incumbent processes, and mutability promoting rhythms that favour novel processing. PMID:23711535

Brittain, John-Stuart; Brown, Peter

2014-01-15

35

BASAL GANGLIA PATHOLOGY IN SCHIZOPHRENIA: DOPAMINE CONNECTIONS and ANOMALIES  

PubMed Central

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

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

2010-01-01

36

Time representation in reinforcement learning models of the basal ganglia.  

PubMed

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

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

2014-01-01

37

Deep-Brain Stimulation for Basal Ganglia Disorders  

PubMed Central

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

Wichmann, Thomas; DeLong, Mahlon R.

2011-01-01

38

Task-related "cortical" bursting depends critically on basal ganglia input and is linked to vocal plasticity.  

PubMed

Basal ganglia-thalamocortical circuits are critical for motor control and motor learning. Classically, basal ganglia nuclei are thought to regulate motor behavior by increasing or decreasing cortical firing rates, and basal ganglia diseases are assumed to reflect abnormal overall activity levels. More recent studies suggest instead that motor disorders derive from abnormal firing patterns, and have led to the hypothesis that surgical treatments, such as pallidotomy, act primarily by eliminating pathological firing patterns. Surprisingly little is known, however, about how the basal ganglia normally influence task-related cortical activity to regulate motor behavior, and how lesions of the basal ganglia influence cortical firing properties. Here, we investigated these questions in a songbird circuit that has striking homologies to mammalian basal ganglia-thalamocortical circuits but is specialized for singing. The "cortical" outflow nucleus of this circuit is required for song plasticity and normally exhibits increased firing during singing and song-locked burst firing. We found that lesions of the striato-pallidal nucleus in this circuit prevented hearing-dependent song changes. These basal ganglia lesions also stripped the cortical outflow neurons of their patterned burst firing during singing, without changing their spontaneous or singing-related firing rates. Taken together, these results suggest that the basal ganglia are essential not for normal cortical firing rates but for driving task-specific cortical firing patterns, including bursts. Moreover, such patterned bursting appears critical for motor plasticity. Our findings thus provide support for therapies that aim to treat basal ganglia movement disorders by normalizing firing patterns. PMID:23449880

Kojima, Satoshi; Kao, Mimi H; Doupe, Allison J

2013-03-19

39

Prefrontal cortex and basal ganglia control access to working memory  

Microsoft Academic Search

Our capacity to store information in working memory might be determined by the degree to which only relevant information is remembered. The question remains as to how this selection of relevant items to be remembered is accomplished. Here we show that activity in the prefrontal cortex and basal ganglia preceded the filtering of irrelevant information and that activity, particularly in

Fiona McNab; Torkel Klingberg

2007-01-01

40

Adenosine A2A receptors and basal ganglia physiology  

PubMed Central

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

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

2007-01-01

41

Role of Individual Basal Ganglia Nuclei in Force Amplitude Generation  

PubMed Central

The basal ganglia-thalamo-cortical loop is an important neural circuit that regulates motor control. A key parameter that the nervous system regulates is the level of force to exert against an object during tasks such as grasping. Previous studies indicate that the basal ganglia do not exhibit increased activity with increasing amplitude of force, although these conclusions are based mainly on the putamen. The present study used functional magnetic resonance imaging to investigate which regions in the basal ganglia, thalamus, and motor cortex display increased activity when producing pinch-grip contractions of increasing force amplitude. We found that the internal portion of the globus pallidus (GPi) and subthalamic nucleus (STN) had a positive increase in percent signal change with increasing force, whereas the external portion of the globus pallidus, anterior putamen, posterior putamen, and caudate did not. In the thalamus we found that the ventral thalamic regions increase in percent signal change and activation volume with increasing force amplitude. The contralateral and ipsilateral primary motor/somatosensory (M1/S1) cortices had a positive increase in percent signal change and activation volume with increasing force amplitude, and the contralateral M1/S1 had a greater increase in percent signal change and activation volume than the ipsilateral side. We also found that deactivation did not change across force in the motor cortex and basal ganglia, but that the ipsilateral M1/S1 had greater deactivation than the contralateral M1/S1. Our findings provide direct evidence that GPi and STN regulate the amplitude of force output. These findings emphasize the heterogeneous role of individual nuclei of the basal ganglia in regulating specific parameters of motor output.

Spraker, Matthew B.; Yu, Hong; Corcos, Daniel M.; Vaillancourt, David E.

2008-01-01

42

Nonlinear analysis of discharge patterns in monkey basal ganglia.  

PubMed

Spontaneous discharge of basal ganglia neurons is often analyzed with time- or frequency-domain methods. However, it has been shown that sequences of inter-spike interval series are not fully described by such linear procedures. We therefore carried out a characterization of the nonlinear features of spontaneous discharge of neurons in the primate basal ganglia. We studied the spontaneous activity of neurons in the subthalamic nucleus (22 cells), as well as neurons in the external and internal pallidal segments (53 and 39 cells, respectively), recorded with standard extracellular recording methods in two awake Rhesus monkeys. As a measure of the statistical irregularity of neuronal discharge, we compared the approximate entropy of inter-spike interval sequences with that of shuffled representations of the same data. In all three basal ganglia structures, approximately 95% of the original data showed lower approximate entropy values than the shuffled data, suggesting a temporal organization in the original sequence. Fano factor analysis confirmed the presence of a temporal organization of inter-spike interval sequences, and indicated the presence of self-similarity in the great majority of them. In addition, Hurst exponent analysis showed that the inter-spike interval series are persistent. Hurst exponents often differ between short and long scaling ranges. Subsequent principal component analyses allowed us to identify three distinct patterns of the temporal evolution of inter-spike interval sequences in the phase space. These types were found in varying distributions in all three nuclei. Our analyses demonstrate that the discharge of most neurons in the basal ganglia of awake monkeys has nonlinear features that may be important for information coding in the basal ganglia. PMID:16989784

Darbin, Olivier; Soares, Jesus; Wichmann, Thomas

2006-11-01

43

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

Microsoft Academic Search

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

André Parent; Lili-Naz Hazrati

1995-01-01

44

Cerebellar networks with the cerebral cortex and basal ganglia  

PubMed Central

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.

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

2013-01-01

45

Canceling actions involves a race between basal ganglia pathways  

PubMed Central

Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return.

Schmidt, Robert; Leventhal, Daniel K.; Mallet, Nicolas; Chen, Fujun; Berke, Joshua D.

2013-01-01

46

A role for Sv2c in basal ganglia functions.  

PubMed

SV2C is an isoform of the synaptic vesicle 2 protein family that exhibits a particular pattern of brain expression with enriched expression in several basal ganglia nuclei. In the present study, we have investigated SV2C implication in both normal and pathological basal ganglia functioning with a peculiar attention to dopamine neuron containing regions. In SV2C-/- mice, the expression of tyrosine hydroxylase mRNA in midbrain dopaminergic neurons was largely and significantly increased and enkephalin mRNA expression was significantly decreased in the caudate-putamen and accumbens nucleus. The expression of SV2C was studied in two models of dopaminergic denervation (6-OHDA- and MPTP-induced lesions). In dopamine-depleted animals, SV2C mRNA expression was significant increased in the striatum. In order to further understand the role of SV2C, we performed behavioral experiments on SV2C-/- mice and on knock-down mice receiving an injection of adeno-associated virus expressing SV2C miRNA specifically in the ventral midbrain. These modifications of SV2C expression had little or no impact on behavior in open field and elevated plus maze. However, even if complete loss of SV2C had no impact on conditioned place preference induced by cocaine, the specific knock-down of SV2C expression in the dopaminergic neurons completely abolished the development of a CPP while the reaction to an acute drug injection remains similar in these mice compared to control mice. These results showed that SV2C, a poorly functionally characterized protein is strongly involved in normal operation of the basal ganglia network and could be also involved in system adaptation in basal ganglia pathological conditions. PMID:23458503

Dardou, D; Monlezun, S; Foerch, P; Courade, J P; Cuvelier, L; De Ryck, M; Schiffmann, S N

2013-04-24

47

Endovascular embolization for deep Basal Ganglia arteriovenous malformations.  

PubMed

We report our experience with basal ganglia AVM embolization and clinical outcomes after embolization. We retrospectively evaluated consecutive 15 patients with AVMs in the basal ganglia with respect to the endovascular treatment of these lesions. Treatment consisted of embolization and radiosurgery in combination. The angiographic follow-up after the last management was 24-36 months (mean 27 months). Clinical follow-up monitoring (range, 24-120 months, mean 76 months) was measured by the Modified Rankin Scale (mRS). The 15 patients studied had a mean age of 25.1 years at diagnosis, and 33.3% were male. Intracranial hemorrhage (ICH) was the event leading to clinical detection in eight patients (53.3%), and 85.5% of these patients were left with hemiparesis. At presentation, eight (53.3%) patients bled a total of 11 times. Twenty-four embolization procedures (16 pedicles embolized) were performed in 15 patients with embolization as the adjunct to radiosurgery. There were three clinically significant complications. Excellent or good outcomes (mRS?2) were observed in 13 (86.7%) patients. Unfavorable outcomes (mRS?2) were 13.3% at follow-up, without mortality. Seven (46.7%) patients had complete AVM obliteration at follow-up. The risk of incurring a neurological deficit with basal ganglia AVM is high. Treatment of these patients is endovascular embolization with a combination of radiosurgery to prevent neurological injury from a spontaneous ICH. PMID:24148599

Sun, Y; Lv, X; Li, Y; Jiang, C; Wu, Z; Li, A M

2010-06-01

48

Modulation of the basal ganglia dopaminergic system in a transgenic mouse exhibiting dystonia-like features  

PubMed Central

Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected) transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates A decrease in the density of striatal D2 binding sites, measured by [3H]raclopride binding, and D2 mRNA expression in substantia nigra pars compacta (SNpc) was revealed in affected an unaffected transgenic mice when compared with non-transgenic. No difference in D1 receptor binding and DAT binding, measured by [3H]SCH23390 and [3H]WIN35428 binding, respectively, was found in striatum of transgenic animals. In SNpc, increased levels of DAT binding sites were observed in affected and unaffected animals compared to non-transgenic, whereas no change in DAT mRNA expression was found. Our results show selective neurochemical changes in the basal ganglia dopaminergic system, suggesting a possible involvement in the pathophysiology of dystonialike motor hyperactivity.

Giannakopoulou, D.; Armata, I. A.; Mitsacos, A.; Shashidharan, P.; Giompres, P.

2011-01-01

49

Asymptomatic moyamoya syndrome, atlantoaxial subluxation and basal ganglia calcification in a child with Down syndrome  

PubMed Central

Down syndrome, the most common chromosomal abnormality, may be associated with various neurologic complications such as moyamoya syndrome, cervical spinal cord compression due to atlantoaxial subluxation, and basal ganglia damage, as well as epileptic seizures and stroke. Many cases of Down syndrome accompanied by isolated neurologic manifestations have been reported in children; however, Down syndrome with multiple neurologic conditions is rare. Here, we have reported a case of Down syndrome in a 10-year-old girl who presented with asymptomatic moyamoya syndrome, atlantoaxial subluxation with spinal cord compression, and basal ganglia calcification. To the best of our knowledge, this is the first report of Down syndrome, in a child, which was accompanied by these 3 neurologic complications simultaneously. As seen in this case, patients with Down syndrome may have neurologic conditions without any obvious neurologic symptoms; hence, patients with Down syndrome should be carefully examined for the presence of neurologic conditions.

Lee, Kun-Soo; Weon, Young Cheol

2013-01-01

50

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

PubMed

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

Mufaddel, Amir A; Al-Hassani, Ghanem A

2014-07-01

51

? oscillations in the cortico-basal ganglia loop during parkinsonism.  

PubMed

In the normal brain beta band oscillatory activity has been associated with retaining of ongoing motor activities. In Parkinson's disease, enhanced beta band oscillatory activity is displayed across the cortico-basal ganglia pathway and is one of the prominent neurophysiological phenomena associated with the disorder. Intraoperative and postoperative recordings of neural activity in patients undergoing stereotactic neurosurgery combined with studies in animal models of parkinsonism have led to the accumulation of complementary data regarding these oscillations. In this review we address some of the key issues facing researchers in the field. These issues encompass existing agreements as well as open debates in modern studies of beta band oscillations, including their defining characteristics, links to clinical symptoms and the functional properties of their formation and effects on behavior. We address these questions by comparing and contrasting the results of neurophysiological observations in human patients, MPTP primate model and 6-OHDA rat model with conceptual and computational models of the normal and parkinsonian basal ganglia. Defining a unifying scheme of beta band oscillations and their relation to neurophysiological, functional and clinical phenomena will enable future targeting of these oscillations for both diagnosis and treatment of Parkinson's disease. PMID:22921537

Stein, Edward; Bar-Gad, Izhar

2013-07-01

52

Saccade learning with concurrent cortical and subcortical basal ganglia loops  

PubMed Central

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

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

2014-01-01

53

Basal ganglia-cortical interactions in Parkinsonian patients  

PubMed Central

Parkinson's disease is a common and debilitating condition, caused by aberrant activity in a complex basal ganglia–thalamocortical circuit. Therapeutic advances rely on characterising interactions in this circuit. However, recording electrophysiological responses over the entire circuit is impractical. Dynamic causal modelling offers large-scale models of predictive value based on a limited or partial sampling of complex networks. Using dynamic causal modelling, we determined the network changes underlying the pathological excess of beta oscillations that characterise the Parkinsonian state. We modelled data from five patients undergoing surgery for deep brain stimulation of more than one target. We found that connections to and from the subthalamic nucleus were strengthened and promoted beta synchrony, in the untreated compared to the treated Parkinsonian state. Dynamic causal modelling was able to replicate the effects of lesioning this nucleus and may provide a new means of directing the search for therapeutic targets.

Marreiros, Andre C.; Cagnan, Hayriye; Moran, Rosalyn J.; Friston, Karl J.; Brown, Peter

2013-01-01

54

Queuing of concurrent movement plans by basal ganglia.  

PubMed

How the brain converts parallel representations of movement goals into sequential movements is not known. We tested the role of basal ganglia (BG) in the temporal control of movement sequences by a convergent approach involving inactivation of the BG by muscimol injections into the caudate nucleus of monkeys and assessing behavior of Parkinson's disease patients, performing a modified double-step saccade task. We tested a critical prediction of a class of competitive queuing models that explains serial behavior as the outcome of a selection of concurrently activated goals. In congruence with these models, we found that inactivation or impairment of the BG unmasked the parallel nature of goal representations such that a significantly greater extent of averaged saccades, curved saccades, and saccade sequence errors were observed. These results suggest that the BG perform a form of competitive queuing, holding the second movement plan in abeyance while the first movement is being executed, allowing the proper temporal control of movement sequences. PMID:23761894

Bhutani, Neha; Sureshbabu, Ramakrishnan; Farooqui, Ausaf A; Behari, Madhuri; Goyal, Vinay; Murthy, Aditya

2013-06-12

55

The temporal lobe is a target of output from the basal ganglia.  

PubMed Central

The basal ganglia are known to receive inputs from widespread regions of the cerebral cortex, such as the frontal, parietal, and temporal lobes. Of these cortical areas, only the frontal lobe is thought to be the target of basal ganglia output. One of the cortical regions that is a source of input to the basal ganglia is area TE, in inferotemporal cortex. This cortical area is thought to be critically involved in the recognition and discrimination of visual objects. Using retrograde transneuronal transport of herpes simplex virus type 1, we have found that one of the output nuclei of the basal ganglia, the substantia nigra pars reticulata, projects via the thalamus to TE. Thus, TE is not only a source of input to the basal ganglia, but also is a target of basal ganglia output. This result implies that the output of the basal ganglia influences higher order aspects of visual processing. In addition, we propose that dysfunction of the basal ganglia loop with TE leads to alterations in visual perception, including visual hallucinations. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5

Middleton, F A; Strick, P L

1996-01-01

56

The role of the basal ganglia in learning and memory: Neuropsychological studies  

Microsoft Academic Search

In recent years, a common approach to understanding how the basal ganglia contribute to learning and memory in humans has been to study the deficits that occur in patients with basal ganglia pathology, such as Parkinson's disease and Huntington's disease. Pharmacological manipulations in patients and in healthy volunteers have also been conducted to investigate the role of dopamine, a neurotransmitter

Jessica A. Grahn; John A. Parkinson; Adrian M. Owen

2009-01-01

57

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

Microsoft Academic Search

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

Daphna Joel; Yael Niv; Eytan Ruppin

58

Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin  

PubMed Central

Summary The lateral habenula (LHb) has recently been identified as a key regulator of the reward system by driving inhibition onto dopaminergic neurons. However, the nature and potential modulation of the major input to the LHb originating from the basal ganglia are poorly understood. Although the output of the basal ganglia is thought to be primarily inhibitory, here we show that transmission from the basal ganglia to the LHb is excitatory, glutamatergic and suppressed by serotonin. Behaviorally, activation of this pathway is aversive, consistent with its role as an ‘anti-reward’ signal. Our demonstration of an excitatory projection from the basal ganglia to the LHb explains how LHb-projecting basal ganglia neurons can have similar encoding properties as LHb neurons themselves. Our results also provide a link between ‘anti-reward’ excitatory synapses and serotonin, a neuromodulator implicated in depression.

Shabel, Steven J.; Proulx, Christophe D.; Trias, Anthony; Murphy, Ryan T.; Malinow, Roberto

2012-01-01

59

Basal ganglia network mediates the control of movement amplitude.  

PubMed

In the present study we address the hypothesis that the basal ganglia are specifically involved in the planning of movement amplitude (or related covariates). This prediction has often been put forward based on the observation that Parkinson's disease (PD) patients exhibit hypokinesia. A close examination of the literature shows, however, that this commonly reported clinical symptom is not consistently echoed by experimental observations. When required to point to visual targets in the absence of vision of the moving limb, PD subjects exhibit various patterns of inaccuracy, including hypometria, hypermetria, systematic direction bias, or direction-dependent errors. They have even been shown to be as accurate as healthy, age-matched subjects. The main aim of the current study is to address the origin of these inconsistencies. To this end, we required nine patients presenting with advanced PD and 15 age-matched control subjects to perform planar reaching movements to visual targets. Eight targets were presented in equally spaced directions around a circle centered on the hand's starting location. Based on a previously validated parsing procedure, end-point errors were segmented into localization and planning errors. Localization errors refer to the existence of systematic biases in the estimation of the initial hand location. These biases can potentially transform a simple pattern of pure amplitude errors into a complex pattern involving both amplitude and direction errors. Results indicated that localization errors were different in the PD patients and the control subjects. This is not surprising knowing both that proprioception is altered in PD patients and that the ability to locate the hand at rest relies mainly on the proprioceptive sense, even when vision is available. Unlike normal subjects, localization errors in PD were idiosyncratic, lacking a consistent pattern across subjects. When the confounding effect of initial hand localization errors was canceled, we found that end-point errors were only due to the implementation of an underscaled movement gain (15%), without direction bias. Interestingly, the level of undershoot was found to increase with the severity of the disease (inferred from the Unified Parkinson's Disease Rating Scale, UPDRS, motor score). We also observed that movement variability was amplified (32%), but only along the main movement axis (extent variability). Direction variability was not significantly different in the patient population and the control group. When considered together, these results support the idea that the basal ganglia are specifically involved in the control of movement amplitude (or of some covariates). We propose that this structure participates in extent planning by modulating cortical activity and/or the tuning of the spinal interneuronal circuits. PMID:13680045

Desmurget, M; Grafton, S T; Vindras, P; Gréa, H; Turner, R S

2003-11-01

60

Predicting grip force amplitude involves circuits in the anterior basal ganglia.  

PubMed

The ability to grip objects allows us to perform many activities of daily living such as eating and drinking. Lesions to and disorders of the basal ganglia can cause deficits in grip force control. Although the prediction of grip force amplitude is an important component of performing a grip force task, the extant literature suggests that this process may not include the basal ganglia. This study used functional magnetic resonance imaging (fMRI) to explore the functional brain mechanisms underlying the prediction of grip force amplitude. The mean force and duration of force did not vary across prediction levels. As anticipated, the reaction time decreased with the level of grip force predictions. In confirmation of previous studies, the parieto-frontal and cerebellar circuits increased their fMRI signal as grip force predictability increased. In addition, the novel finding was that anterior nuclei in the basal ganglia such as caudate and anterior putamen also had an fMRI signal that increased with the level of grip force prediction. In contrast, the fMRI signal in posterior nuclei of the basal ganglia did not change with the level of prediction. These findings provide new evidence indicating that anterior basal ganglia nuclei are involved in the predictive scaling of precision grip force control. Further, the results provide additional support for the planning and parameterization model of the basal ganglia by demonstrating that specific anterior nuclei of the basal ganglia are involved in planning grip force. PMID:19944767

Wasson, Pooja; Prodoehl, Janey; Coombes, Stephen A; Corcos, Daniel M; Vaillancourt, David E

2010-02-15

61

Severe bruxism following basal ganglia infarcts: insights into pathophysiology.  

PubMed

Bruxism characterized by clenching and grinding of teeth can lead to toothwear, headaches and depression. While bruxism has been associated with a number of neurological diseases, it has not been highlighted following cerebral infarction. An elderly man presented with an acute onset of tooth grinding and jaw clenching associated with dysarthria. His bruxism was worse during the day and resolved during sleep. He had frequent jaw aches, headaches and swallowing difficulty. Examination demonstrated the presence of dysarthria with jaw clenching and tooth grinding, producing persistent high pitch and loud squeaky sounds. A magnetic resonance imaging and angiography examination revealed a recent infarct in the right thalamus. In addition, chronic lacunar infarcts were present in the bilateral caudate nuclei with severe basilar artery stenosis. He was successfully treated with botulinum toxin. We discuss the pathophysiologic mechanisms of bruxism associated with basal ganglia infarcts. Dysfunction of the efferent and/or afferent thalamic or striatopallidal tracts may play a role in bruxism. Early recognition of bruxism following stroke could reduce unnecessary suffering since the condition can be effectively treated. PMID:14706229

Tan, Eng-King; Chan, Ling-Ling; Chang, Hui-Meng

2004-02-15

62

Observation of sonified movements engages a basal ganglia frontocortical network  

PubMed Central

Background Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements. Results Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli. Conclusions We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation.

2013-01-01

63

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

PubMed Central

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.

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

2010-01-01

64

The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines  

PubMed Central

Amphetamines are psychostimulant drugs with high abuse potential. Acute and chronic doses of amphetamines affect dopamine (DA) neurotransmission in the basal ganglia. The basal ganglia are a group of subcortical nuclei that are anatomically positioned to integrate cognitive, motor and sensorimotor inputs from the cortex. Amphetamines can differentially alter the functioning of specific BG circuits to produce neurochemical changes that affect cognition, movement, and drug seeking behavior through their effects on DA neurotransmission. This review focuses on how alterations in dopaminergic neurotransmission within distinct basal ganglia pathways can modify their functional output to predict and explain the acute and long term behavioral consequences of amphetamine exposure.

Natarajan, Reka; Yamamoto, Bryan K.

2011-01-01

65

Involvement of dopamine loss in extrastriatal basal ganglia nuclei in the pathophysiology of Parkinson's disease  

PubMed Central

Parkinson’s disease (PD) is a neurological disorder characterized by the manifestation of motor symptoms, such as akinesia, muscle rigidity and tremor at rest. These symptoms are classically attributed to the degeneration of dopamine neurons in the pars compacta of substantia nigra (SNc), which results in a marked dopamine depletion in the striatum. It is well established that dopamine neurons in the SNc innervate not only the striatum, which is the main target, but also other basal ganglia nuclei including the two segments of globus pallidus and the subthalamic nucleus (STN). The role of dopamine and its depletion in the striatum is well known, however, the role of dopamine depletion in the pallidal complex and the STN in the genesis of their abnormal neuronal activity and in parkinsonian motor deficits is still not clearly determined. Based on recent experimental data from animal models of Parkinson’s disease in rodents and non-human primates and also from parkinsonian patients, this review summarizes current knowledge on the role of dopamine in the modulation of basal ganglia neuronal activity and also the role of dopamine depletion in these nuclei in the pathophysiology of Parkinson’s disease.

Benazzouz, Abdelhamid; Mamad, Omar; Abedi, Pamphyle; Bouali-Benazzouz, Rabia; Chetrit, Jonathan

2014-01-01

66

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

PubMed Central

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.

Felger, Jennifer C.; Miller, Andrew H.

2012-01-01

67

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

PubMed Central

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

Gale, Samuel D.; Perkel, David J.

2009-01-01

68

Emergence of context-dependent variability across a basal ganglia network.  

PubMed

Context dependence is a key feature of cortical-basal ganglia circuit activity, and in songbirds the cortical outflow of a basal ganglia circuit specialized for song, LMAN, shows striking increases in trial-by-trial variability and bursting when birds sing alone rather than to females. To reveal where this variability and its social regulation emerge, we recorded stepwise from corticostriatal (HVC) neurons and their target spiny and pallidal neurons in Area X. We find that corticostriatal and spiny neurons both show precise singing-related firing across both social settings. Pallidal neurons, in contrast, exhibit markedly increased trial-by-trial variation when birds sing alone, created by highly variable pauses in firing. This variability persists even when recurrent inputs from LMAN are ablated. These data indicate that variability and its context sensitivity emerge within the basal ganglia network, suggest a network mechanism for this emergence, and highlight variability generation and regulation as basal ganglia functions. PMID:24698276

Woolley, Sarah C; Rajan, Raghav; Joshua, Mati; Doupe, Allison J

2014-04-01

69

Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences.  

PubMed

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

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

2014-03-01

70

The evolutionary origin of the vertebrate basal ganglia and its role in action selection.  

PubMed

The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters. We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding. A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended. Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the 'indirect loop' in mammals as well as lamprey. We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour. PMID:23318875

Grillner, Sten; Robertson, Brita; Stephenson-Jones, Marcus

2013-11-15

71

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

PubMed Central

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

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

2011-01-01

72

Mouse models of neurodevelopmental disease of the Basal Ganglia and associated circuits.  

PubMed

This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role-Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. PMID:24947237

Pappas, Samuel S; Leventhal, Daniel K; Albin, Roger L; Dauer, William T

2014-01-01

73

[A case of neonatal herpes simplex virus encephalitis with calcifications of thalamus and basal ganglia].  

PubMed

A male infant developed left-sided myoclonus associated with low grade fever at 21 days of age. The course of pregnancy and delivery had been uneventful. Birth weight was 2,240g at 38 weeks of gestation. Physical examination at 26 days of age revealed hyperirritability and incomplete Moro reflex. EEG showed periodic discharges originating in the right central region. Initial brain CT at 26 days of age showed no apparent abnormality. In lumbar CSF protein was 173 mg/dl, and nucleated cells 328/mm3 (polynuclear cells 6 and mononuclear cells 322). Cultures of CSF for bacteria and viruses were negative. Although, the serum titers of CF antibody to herpes simplex virus (HSV) were 1:4 to 1:8 during hospitalization and those in CSF were not increased significantly, ELISA titers for IgG and IgM in serum and CSF rose significantly. The diagnosis of HSV encephalitis was made at 41 days of age. His myoclonus was well controlled with phenobarbital and clonazepam. He was treated with acyclovir and CSF findings returned to normal. On 2nd brain CT (39 days of age), calcification at thalamus, basal ganglia and right frontal lobe, which is extremely rare CT findings for HSV encephalitis, was noticed. His DQ at discharge was about 90. It is emphasized that the early diagnosis of HSV encephalitis can be made by ELISA and serial brain CT examinations, and that HSV encephalitis should be considered when calcification of thalamus and basal ganglia are detected on brain CT. PMID:2331400

Takahashi, H; Sato, Y; Urata, S; Kaneko, K

1990-03-01

74

Role of the Basal Ganglia and Frontal Cortex in Selecting and Producing Internally Guided Force Pulses  

PubMed Central

The basal ganglia comprise a crucial circuit involved in force production and force selection, but the specific role of each nucleus to the production of force pulses and the selection of pulses of different force amplitudes remains unknown. We conducted an fMRI study in which participants produced force using a precision grip while a) holding a steady-state force, b) performing a series of force pulses with similar amplitude, and c) selecting force pulses of different amplitude. Region of interest analyses were conducted in the basal ganglia and frontal cortex to compare percent signal change during force pulse versus steady-state force production, and compare force amplitude selection to force production when selection of force amplitude was not present. There were three novel findings in the basal ganglia. First, the caudate nucleus increased activation during the selection of different force amplitudes when compared to producing a series of similar force pulses. Second, GPi, STN, and posterior putamen increased activation during the production of similar force amplitudes when compared to holding a steady-state force, and maintained similar activation during the production of different force amplitudes in which force selection was required. Third, GPe and anterior putamen had increased activation during the production of similar force pulses and further increased activation during the selection of different force pulses. These findings suggest that anterior basal ganglia nuclei are involved in selecting the amplitude of force contractions and posterior basal ganglia nuclei regulate basic aspects of dynamic force pulse production.

Vaillancourt, David E.; Yu, Hong; Mayka, Mary A.; Corcos, Daniel M.

2007-01-01

75

A neural model of basal ganglia-thalamocortical relations in normal and parkinsonian movement.  

PubMed

Anatomical, neurophysiological, and neurochemical evidence supports the notion of parallel basal ganglia-thalamocortical motor systems. We developed a neural network model for the functioning of these systems during normal and parkinsonian movement. Parkinson's disease (PD), which results predominantly from nigrostriatal pathway damage, is used as a window to examine basal ganglia function. Simulations of dopamine depletion produce motor impairments consistent with motor deficits observed in PD that suggest the basal ganglia play a role in motor initiation and execution, and sequencing of motor programs. Stereotaxic lesions in the model's globus pallidus and subthalamic nucleus suggest that these lesions, although reducing some PD symptoms, may constrain the repertoire of available movements. It is proposed that paradoxical observations of basal ganglia responses reported in the literature may result from regional functional neuronal specialization, and the non-uniform distributions of neurochemicals in the basal ganglia. It is hypothesized that dopamine depletion produces smaller-than-normal pallidothalamic gating signals that prevent rescalability of these signals to control variable movement speed, and that in PD can produce smaller-than-normal movement amplitudes. PMID:7578481

Contreras-Vidal, J L; Stelmach, G E

1995-10-01

76

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

PubMed

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

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

2014-01-01

77

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

PubMed Central

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

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

2014-01-01

78

[Satellite systems of the Basal Ganglia - anatomic position, clinical relevance].  

PubMed

The interaction of basal ganglia and other brain regions is more complex regarding anatomic and functional perspectives than previously assumed. Hence, the classical basal ganglia model has to be extended to at least four satellite systems modulating motor-executive, associative and limbic-motivational brain regions: (i) an indirect projection system, (ii) a striato-nigro-striatal loop, (iii) a "hyperdirect" projection system as well as additional projections to the subthalamic nucleus and (iv) multisynaptic connections from the cerebellum exerting influence on the indirect projection system. The investigation of these satellite systems would be invaluable to foster our understanding of basal ganglia circuitries and may yield a better appreciation of largely opaque symptoms like resting tremor in Parkinson's disease; analysis of these anatomic pathways and functional implications may facilitate explanatory model approaches to side effects due to dopaminergic therapy and deep brain stimulation in humans and thereby offer the possibility for new therapeutic approaches in movement disorders. PMID:24901315

Pelzer, E A; Hintzen, A; Timmermann, L; Tittgemeyer, M

2014-06-01

79

MR-DTI and PET multimodal imaging of dopamine release within subdivisions of basal ganglia  

NASA Astrophysics Data System (ADS)

The basal ganglia is a group of anatomical nuclei, functionally organised into limbic, associative and sensorimotor regions, which plays a central role in dopamine related neurological and psychiatric disorders. In this study, we combine two imaging modalities to enable the measurement of dopamine release in functionally related subdivisions of the basal ganglia. [11C]-(+)-PHNO Positron Emission Tomography (PET) measurements in the living human brain pre- and post-administration of amphetamine allow for the estimation of regional dopamine release. Combined Magnetic Resonance Diffusion Tensor Imaging (MR-DTI) data allows for the definition of functional territories of the basal ganglia from connectivity information. The results suggest that there is a difference in dopamine release among the connectivity derived functional subdivisions. Dopamine release is highest in the limbic area followed by the sensorimotor and then the associative area with this pattern reflected in both striatum and pallidum.

Tziortzi, A.; Searle, G.; Tsoumpas, C.; Long, C.; Shotbolt, P.; Rabiner, E.; Jenkinson, M.; Gunn, R. N.

2011-09-01

80

Neural responses in multiple basal ganglia regions during spontaneous and treadmill locomotion tasks in rats.  

PubMed

To investigate the role of basal ganglia in locomotion, a multiple-channel, single-unit recording technique was used to record neural activity simultaneously in the dorsal lateral striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) during spontaneous and treadmill locomotion tasks in freely moving rats. Active and quiescent phases appeared alternately in a spontaneous movement session that lasted 60 min. Principal component analysis of the ensemble neural activity from each region revealed a close correlation with spontaneous motor activity. Most of the neurons in these four basal ganglia areas increased their firing rates during the active phase. In the treadmill locomotion task, the firing rates of neurons in all recording areas, especially in the STN, increased significantly during locomotion. In addition, neural responses related to tone cue, initiation and termination of treadmill were observed in a subset of neurons in each basal ganglia region. Detailed video analysis revealed a limb movement related neural firing, predominantly in the STR and the GP, during treadmill walking. However, the proportion of neurons exhibiting limb movement related firing was significantly greater only in the STR. A few neurons in the STR (4.8%) and the GP (3.4%) discharged in an oscillatory pattern during treadmill walking, and the oscillatory frequency was similar to the frequency of the step cycle. This study demonstrates a variety of neural responses in the major basal ganglia regions during spontaneous and forced locomotion. General activation of all major basal ganglia regions during locomotion is more likely to provide a dynamic background for cortical signal processing rather than to directly control precise movements. Implications of these findings in the model of basal ganglia organization are discussed. PMID:15067433

Shi, L H; Luo, F; Woodward, D J; Chang, J Y

2004-08-01

81

Sydenham Chorea: magnetic resonance imaging reveals permanent basal ganglia injury.  

PubMed

MRI of the brain of a 3-year-old boy performed 3 days after the onset of hemichorea (Sydenham Chorea) revealed abnormal signal and enlargement of the contralateral caudate and putamen. Follow-up imaging 40 months later showed a persistent cystic appearance of the caudate and putamen. This case is the first report of permanent MRI abnormalities after Sydenham Chorea. PMID:9040753

Emery, E S; Vieco, P T

1997-02-01

82

Hyperechoic lesions in the basal ganglia: An incidental sonographic finding in neonates and infants  

Microsoft Academic Search

Cerebral ultrasound (US) imaging was performed as a screening procedure in approximately 3,600 neonates and infants over a period of 18 months. Hyperechoic lesions in the basal ganglia and thalamic region were detected incidentally in 15 of these patients. Clinical diagnoses included cytomegalovirus infection, asphyxia, rotavirus infection, prematurity, amniotic infection, dysmorphic stigmata, hyperbilirubinemia, congenital heart disease, and diabetic fetopathia. Lesions

K. Weber; Th. Riebel; R. Nasir

1992-01-01

83

The Role of Inhibition in Generating and Controlling Parkinson's Disease Oscillations in the Basal Ganglia  

PubMed Central

Movement disorders in Parkinson’s disease (PD) are commonly associated with slow oscillations and increased synchrony of neuronal activity in the basal ganglia. The neural mechanisms underlying this dynamic network dysfunction, however, are only poorly understood. Here, we show that the strength of inhibitory inputs from striatum to globus pallidus external (GPe) is a key parameter controlling oscillations in the basal ganglia. Specifically, the increase in striatal activity observed in PD is sufficient to unleash the oscillations in the basal ganglia. This finding allows us to propose a unified explanation for different phenomena: absence of oscillation in the healthy state of the basal ganglia, oscillations in dopamine-depleted state and quenching of oscillations under deep-brain-stimulation (DBS). These novel insights help us to better understand and optimize the function of DBS protocols. Furthermore, studying the model behavior under transient increase of activity of the striatal neurons projecting to the indirect pathway, we are able to account for both motor impairment in PD patients and for reduced response inhibition in DBS implanted patients.

Kumar, Arvind; Cardanobile, Stefano; Rotter, Stefan; Aertsen, Ad

2011-01-01

84

Effects of Focal Basal Ganglia Lesions on Timing and Force Control  

ERIC Educational Resources Information Center

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

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

2005-01-01

85

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

PubMed Central

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

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

2014-01-01

86

Control of Basal Ganglia Output by Direct and Indirect Pathway Projection Neurons  

PubMed Central

The direct and indirect efferent pathways from striatum ultimately reconverge to influence basal ganglia output nuclei, which in turn regulate behavior via thalamocortical and brainstem motor circuits. However, the distinct contributions of these two efferent pathways in shaping basal ganglia output are not well understood. We investigated these processes using selective optogenetic control of the direct and indirect pathways, in combination with single-unit recording in the basal ganglia output nucleus substantia nigra pars reticulata (SNr) in mice. Optogenetic activation of striatal direct and indirect pathway projection neurons produced diverse cellular responses in SNr neurons, with stimulation of each pathway eliciting both excitations and inhibitions. Despite this response heterogeneity, the effectiveness of direct pathway stimulation in producing movement initiation correlated selectively with the subpopulation of inhibited SNr neurons. In contrast, effective indirect pathway-mediated motor suppression was most strongly influenced by excited SNr neurons. Our results support the theory that key basal ganglia output neurons serve as an inhibitory gate over motor output that can be opened or closed by striatal direct and indirect pathways, respectively.

Freeze, Benjamin S.; Kravitz, Alexxai V.; Hammack, Nora; Berke, Joshua D.

2013-01-01

87

Control of basal ganglia output by direct and indirect pathway projection neurons.  

PubMed

The direct and indirect efferent pathways from striatum ultimately reconverge to influence basal ganglia output nuclei, which in turn regulate behavior via thalamocortical and brainstem motor circuits. However, the distinct contributions of these two efferent pathways in shaping basal ganglia output are not well understood. We investigated these processes using selective optogenetic control of the direct and indirect pathways, in combination with single-unit recording in the basal ganglia output nucleus substantia nigra pars reticulata (SNr) in mice. Optogenetic activation of striatal direct and indirect pathway projection neurons produced diverse cellular responses in SNr neurons, with stimulation of each pathway eliciting both excitations and inhibitions. Despite this response heterogeneity, the effectiveness of direct pathway stimulation in producing movement initiation correlated selectively with the subpopulation of inhibited SNr neurons. In contrast, effective indirect pathway-mediated motor suppression was most strongly influenced by excited SNr neurons. Our results support the theory that key basal ganglia output neurons serve as an inhibitory gate over motor output that can be opened or closed by striatal direct and indirect pathways, respectively. PMID:24259575

Freeze, Benjamin S; Kravitz, Alexxai V; Hammack, Nora; Berke, Joshua D; Kreitzer, Anatol C

2013-11-20

88

A resting state network in the motor control circuit of the basal ganglia  

Microsoft Academic Search

BACKGROUND: In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large

Simon Robinson; Gianpaolo Basso; Nicola Soldati; Uta Sailer; Jorge Jovicich; Lorenzo Bruzzone; Ilse Kryspin-Exner; Herbert Bauer; Ewald Moser

2009-01-01

89

Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication.  

PubMed

We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness. PMID:24210948

Hutcheson, Nathan L; Clark, David G; Bolding, Mark S; White, David M; Lahti, Adrienne C

2014-01-30

90

Basal ganglia hypoactivity during grip force in drug naïve Parkinson's disease.  

PubMed

The basal ganglia (BG) are impaired in Parkinson's disease (PD), but it remains unclear which nuclei are impaired during the performance of motor tasks in early-stage PD. Therefore, this study was conducted to determine which nuclei function abnormally, and whether cortical structures are also affected by early-stage PD. The study also determined if cerebellar hyperactivity is found early in the course of PD. Blood oxygenation level dependent activation was compared between 14 early-stage drug-naïve PD patients and 14 controls performing two precision grip force tasks using functional magnetic resonance imaging at 3 T. The grip tasks used in this study were chosen because both tasks are known to provide robust activation in BG nuclei, and the two tasks were similar except that the 2-s task required more switching between contraction and relaxation than the 4-s task. The 4-s task revealed that PD patients were hypoactive relative to controls only in putamen and external globus pallidus, and thalamus. In the 2-s task, PD patients were hypoactive throughout all BG nuclei, thalamus, M1, and supplementary motor area. There were no differences in cerebellar activation between groups during either task. Regions of interest analysis revealed that the hypoactivity observed in PD patients during the 2-s task became more pronounced over time as patients performed the task. This suggests that a motor task that requires switching can accentuate abnormal activity throughout all BG nuclei of early-stage, drug-naive PD, and that the abnormal activity becomes more pronounced with repeated task performance in these patients. PMID:20225221

Spraker, Matthew B; Prodoehl, Janey; Corcos, Daniel M; Comella, Cynthia L; Vaillancourt, David E

2010-12-01

91

A resting state network in the motor control circuit of the basal ganglia  

PubMed Central

Background In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond. Results An RSN is identified in the basal ganglia and thalamus, comprising the pallidum, putamen, subthalamic nucleus and substantia nigra, with a projection also to the supplementary motor area. Participating nuclei and thalamo-cortical connection probabilities allow this network to be identified as the motor control circuit of the basal ganglia. The network was reproducibly identified across subjects, behavioural conditions (fixation, eyes closed), field strength and echo-planar imaging parameters. It shows a frequency peak at 0.025 ± 0.007 Hz and is most similar in spectral composition to the Default Mode (DM), a network of regions that is more active at rest than during task processing. Frequency features allow the network to be classified as an RSN rather than a physiological artefact. Fluctuations in this RSN are correlated with those in the task-positive fronto-parietal network and anticorrelated with those in the DM, whose hemodynamic response it anticipates. Conclusion Although the basal ganglia RSN has not been reported in most ICA-based studies using a similar methodology, we demonstrate that it is reproducible across subjects, common resting state conditions and imaging parameters, and show that it corresponds with the motor control circuit. This characterisation of the basal ganglia network opens a potential means to investigate the motor-related neuropathologies in which the basal ganglia are involved.

2009-01-01

92

Neuroanatomical Correlates of Intelligence in Healthy Young Adults: The Role of Basal Ganglia Volume  

PubMed Central

Background In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions. Methodology/Principal Findings We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur-Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor; in females, the pallidum volumes were correlated with crystallised figural intelligence (r?=?0.372, p?=?0.01), whereas in males, the caudate volumes were correlated with fluid figural intelligence (r?=?0.507, p?=?0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r?=?0.306, p?=?0.04 and r?=?0.459, p?=?0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses. Conclusions/Significance The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia nuclei in a sex-specific manner. Subcortical brain structures thus may contribute substantially to cognitive performance.

Rhein, Cosima; Muhle, Christiane; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Doerfler, Arnd; Kornhuber, Johannes

2014-01-01

93

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

PubMed Central

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.

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

2014-01-01

94

Decreased Basal Ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue.  

PubMed

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

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

2014-01-01

95

Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X.  

PubMed

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

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

2007-12-01

96

Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys.  

PubMed

Parkinsonism is associated with changes in oscillatory activity patterns and increased synchronization of neurons in the basal ganglia and cortex in patients and animal models of Parkinson's disease, but the relationship between these changes and the severity of parkinsonian signs remains unclear. We examined this relationship by studying changes in local field potentials (LFPs) in the internal pallidal segment (GPi) and the subthalamic nucleus (STN), and in encephalographic signals (EEG) from the primary motor cortex (M1) in Rhesus monkeys which were rendered progressively parkinsonian by repeated systemic injections of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Observations during wakefulness and sleep (defined by EEG and video records) were analyzed separately. The severity of parkinsonism correlated with increases in spectral power at frequencies below 15.5Hz in M1 and GPi and reductions in spectral power at frequencies above 15.6Hz with little change in STN. The severity of parkinsonism also correlated with increases in the coherence between M1 EEG and basal ganglia LFPs in the low frequency band. Levodopa treatment reduced low-frequency activity and increased high-frequency activity in all three areas, but did not affect coherence. The state of arousal also affected LFP and EEG signals in all three structures, particularly in the STN. These results suggest that parkinsonism-associated changes in alpha and low-beta band oscillatory activity can be detected early in the parkinsonian state in M1 and GPi. Interestingly, oscillations detectable in STN LFP signals (including oscillations in the beta-band) do not appear to correlate strongly with the severity of mild-to-moderate parkinsonism in these animals. Levodopa-induced changes in oscillatory M1 EEG and basal ganglia LFP patterns do not necessarily represent a normalization of abnormalities caused by dopamine depletion. PMID:24768805

Devergnas, Annaelle; Pittard, Damien; Bliwise, Donald; Wichmann, Thomas

2014-08-01

97

Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat  

PubMed Central

Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and ‘global activation’. During SWA, there was coherence at ?1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at ?1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15–60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change.

Sharott, Andrew; Magill, Peter J; Bolam, J Paul; Brown, Peter

2005-01-01

98

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

PubMed Central

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

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

2014-01-01

99

Balanced activity in basal ganglia projection pathways is critical for contraversive movements  

PubMed Central

The basal ganglia, and the striatum in particular, have been implicated in the generation of contraversive movements. The striatum projects to downstream basal ganglia nuclei through two main circuits, originating in striatonigral and striatopallidal neurons, and different models postulate that the two pathways can work in opposition or synergistically. Here we show striatonigral and striatopallidal neurons are concurrently active during spontaneous contraversive movements. Furthermore, we show that unilateral optogenetic inhibition of either or both projection pathways disrupts contraversive movements. Consistently, simultaneous activation of both neuron types produces contraversive movements. Still, we also show that imbalanced activity between the pathways can result in opposing movements being driven by each projection pathway. These data show that balanced activity in both striatal projection pathways is critical for the generation of contraversive movements and highlights that imbalanced activity between the two projection pathways can result in opposing motor output.

Tecuapetla, Fatuel; Matias, Sara; Dugue, Guillaume P.; Mainen, Zachary F.; Costa, Rui M.

2014-01-01

100

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

PubMed Central

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.

Hikosaka, Okihide; Isoda, Masaki

2010-01-01

101

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

PubMed

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

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

2014-04-22

102

Balanced activity in basal ganglia projection pathways is critical for contraversive movements.  

PubMed

The basal ganglia, and the striatum in particular, have been implicated in the generation of contraversive movements. The striatum projects to downstream basal ganglia nuclei through two main circuits, originating in striatonigral and striatopallidal neurons, and different models postulate that the two pathways can work in opposition or synergistically. Here we show striatonigral and striatopallidal neurons are concurrently active during spontaneous contraversive movements. Furthermore, we show that unilateral optogenetic inhibition of either or both projection pathways disrupts contraversive movements. Consistently, simultaneous activation of both neuron types produces contraversive movements. Still, we also show that imbalanced activity between the pathways can result in opposing movements being driven by each projection pathway. These data show that balanced activity in both striatal projection pathways is critical for the generation of contraversive movements and highlights that imbalanced activity between the two projection pathways can result in opposing motor output. PMID:25002180

Tecuapetla, Fatuel; Matias, Sara; Dugue, Guillaume P; Mainen, Zachary F; Costa, Rui M

2014-01-01

103

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

PubMed Central

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

Schroll, Henning; Hamker, Fred H.

2013-01-01

104

Monitoring and switching of cortico-basal ganglia loop functions by the thalamo-striatal system  

Microsoft Academic Search

Recent physiological and tract tracing studies revealed tight coupling of the centre médian and parafascicular nuclei (the CM–Pf complex), which are posterior intralaminar nuclei (ILN) of the thalamus, with basal ganglia circuits. These nuclei have previously been classified as part of the ascending reticulo-thalamo-cortical activating system, with studies of single neuron activity and of interruption of neuronal activity suggested that

Minoru Kimura; Takafumi Minamimoto; Naoyuki Matsumoto; Yukiko Hori

2004-01-01

105

Shape of the basal ganglia in preadolescent children is associated with cognitive performance.  

PubMed

Current studies support the belief that high levels of performance and intellectual abilities are associated with increased brain size or volume. With few exceptions, this conclusion is restricted to studies of post-adolescent subjects and to cerebral cortex. There is evidence that "bigger is better" may not pertain to children and further, that there are areas of the brain in which larger structures are associated with cognitive deficits. In 50 preadolescent children (21 girls) a structural survey of the brain (VBM) was conducted to determine and locate areas in which gray matter volume was associated with poor cognitive performance. Only increased gray matter volume in particular areas of the basal ganglia and specifically the putamen was significantly associated with poor performance on tests of memory, response speed and a general marker and subtests of intelligence. Based on the VBM findings, volumetric analysis of basal ganglia structures was performed using FSL/FIRST. However, no significant changes in total volume of putamen or other basal ganglia structures were detected with this analysis. The disagreement between measures of localized gray matter differences and volumetric analysis suggested that there might be local regional deformity rather than widespread volumetric changes of the putamen. Surface analysis with FSL/FIRST demonstrated that bilateral outward deformation of the putamen, but especially the left, was associated with poor performance on several cognitive tests. Expansion of the globus pallidus and caudate nucleus also was associated with poor performance. Moreover a significant association was detected between a reliable test of language-free intelligence and topographically distinct outward and inward deformation of the putamen. Expansion and contraction of the putamen as a predictor of intelligence may explain why this association was not observed with measures of total volume. These results suggest that deformity is a sensitive measure of function, and that distortion of the basal ganglia may be a neurophenotype for risk of developmental impairment. PMID:24844741

Sandman, Curt A; Head, Kevin; Muftuler, L Tugan; Su, Lydia; Buss, Claudia; Davis, Elysia Poggi

2014-10-01

106

[Role of the basal ganglia in the occurrence of paradoxical sleep dreams (hypothetical mechanism)].  

PubMed

A hypothetical mechanism of the basal ganglia involvement in the occurrence of paradoxical sleep dreams and rapid eye movements is proposed. According to this mechanism, paradoxical sleep is provided by facilitation of activation of cholinergic neurons in the pedunculopontine nucleus as a result of suppression of their inhibition from the output basal ganglia nuclei. This disinhibition is promoted by activation of dopaminergic cells by pedunculopontine neurons, subsequent rise in dopamine concentration in the input basal ganglia structure. striatum, and modulation of the efficacy of cortico-striatal inputs. In the absence of signals from retina, a disinhibition of neurons in the pedunculopontine nucleus and superior colliculus allows them to excite neurons in the lateral geniculate body and other thalamic nuclei projecting to the primary and higher visual cortical areas, prefrontal cortex and back into the striatum. Dreams as visual images and "motor hallucinations" are the result of an increase in activity of definitely selected groups of thalamic and neocortical neurons. This selection is caused by modifiable action of dopamine on long-term changes in the efficacy of synaptic transmission during circulation of signals in closed interconnected loops, each of which includes one of the visual cortical areas (motor cortex), one of the thalamic nuclei, limbic and one of the visual areas (motor area) of the basal ganglia. pedunculopontine nucleus, and superior colliculus. Simultaneous modification and modulation of synapses in diverse units of neuronal loops is provided by PGO waves. Disinhibition of superioir colliculus neurons and their excitation by pedunculopontine nucleus lead to an appearance of rapid eye movements during paradoxical sleep. PMID:16583673

Sil'kis, I G

2006-01-01

107

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

PubMed

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

Alegre, Manuel; Valencia, Miguel

2013-10-01

108

Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia  

Microsoft Academic Search

The functions of glutamate and GABA in the CNS are mediated by ionotropic and metabotropic, G protein-coupled, receptors. Both receptor families are widely expressed in basal ganglia structures in primates and nonprimates. The recent development of highly specific antibodies and\\/or cDNA probes allowed the better characterization of the cellular localization of various GABA and glutamate receptor subtypes in the primate

Yoland Smith; Ali Charara; Maryse Paquet; Jeremy Z Kieval; Jean-François Paré; Jesse E Hanson; George W Hubert; Masaaki Kuwajima; Allan I Levey

2001-01-01

109

Role of primate basal ganglia and frontal cortex in the internal generation of movements  

Microsoft Academic Search

The purpose of these studies was to investigate neuronal activity in the basal ganglia and frontal cortex in relation to the internal generation of goal-directed movements. Monkeys performed goal-directed arm movements at a self-chosen moment in the absence of phasic stimuli providing external temporal reference. They were rewarded with a small morsel of food for each movement, although automatic or

Wolfram Schultz; Ranulfo Romo

1992-01-01

110

Basal ganglia modulation of thalamocortical relay in Parkinson's disease and dystonia  

PubMed Central

Basal ganglia dysfunction has being implied in both Parkinson's disease and dystonia. While these disorders probably involve different cellular and circuit pathologies within and beyond basal ganglia, there may be some shared neurophysiological pathways. For example, pallidotomy and pallidal Deep Brain Stimulation (DBS) are used in symptomatic treatment of both disorders. Both conditions are marked by alterations of rhythmicity of neural activity throughout basal ganglia-thalamocortical circuits. Increased synchronized oscillatory activity in beta band is characteristic of Parkinson's disease, while different frequency bands, theta and alpha, are involved in dystonia. We compare the effect of the activity of GPi, the output nuclei of the basal ganglia, on information processing in the downstream neural circuits of thalamus in Parkinson's disease and dystonia. We use a data-driven computational approach, a computational model of the thalamocortical (TC) cell modulated by experimentally recorded data, to study the differences and similarities of thalamic dynamics in dystonia and Parkinson's disease. Our analysis shows no substantial differences in TC relay between the two conditions. Our results suggest that, similar to Parkinson's disease, a disruption of thalamic processing could also be involved in dystonia. Moreover, the degree to which TC relay fidelity is impaired is approximately the same in both conditions. While Parkinson's disease and dystonia may have different pathologies and differ in the oscillatory content of neural discharge, our results suggest that the effect of patterning of pallidal discharge is similar in both conditions. Furthermore, these results suggest that the mechanisms of GPi DBS in dystonia may involve improvement of TC relay fidelity.

Guo, Yixin; Park, Choongseok; Worth, Robert M.; Rubchinsky, Leonid L.

2013-01-01

111

Alpha 2-adrenoceptors in the basal ganglia have a role in memory consolidation and reinforcement.  

PubMed

This study demonstrates a role for alpha(2)-adrenoceptors in the basal ganglia in the consolidation of memory using weakly and strongly reinforced models of discriminated avoidance learning in the chick. The memory enhancing action of noradrenaline injected into the basal ganglia (lobus parolfactorius-LPO) was reduced in the presence of the alpha(2)-adrenoceptor antagonist yohimbine, but when noradrenaline was injected into the multi-modal association area (intermediate medial hyperstriatum ventrale-IMHV), yohimbine failed to prevent memory enhancement. Yohimbine injected into the LPO prevented, whereas the alpha(2)-adrenoceptor agonists oxymetazoline and clonidine enhanced, consolidation of memory. The timing of the inhibitory effect of yohimbine in the LPO suggested that alpha(2)-adrenoceptor involvement occurs 10-15 min after training, and that stimulation of alpha(2)-ARs in LPO is necessary for subsequent consolidation of memory. Oxymetazoline, being hydrophilic, was ineffective injected into IMHV, whereas the action of the lipophilic alpha(2)-adrenoceptor agonist clonidine in the IMHV was interpreted as an action at a site more distal in the brain, probably the LPO. The results suggest that noradrenaline release in the basal ganglia in the chick stimulates alpha(2)-adrenoceptors, which modulate and consolidate memory formation mediated by beta(2)- or beta(3)-ARs in the association area. The LPO may be responsible for the reinforcement of memory in the IMHV. PMID:12871653

Gibbs, Marie E; Summers, Roger J

2003-09-01

112

Effect of Methamphetamine Self-Administration on Neurotensin Systems of the Basal Ganglia  

PubMed Central

Methamphetamine (METH) dependence causes alarming personal and social damage. Even though many of the problems associated with abuse of METH are related to its profound actions on dopamine (DA) basal ganglia systems, there currently are no approved medications to treat METH addiction. For this reason, we and others have examined the METH-induced responses of neurotensin (NT) systems in the basal ganglia. This neuropeptide is associated with inhibitory feedback pathways to nigrostriatal DA projections, and NT tissue levels are elevated in response to high doses of noncontingent METH because of its increased synthesis in the striatonigral pathway. The present study reports the contingent responses of NT in the basal ganglia to self-administration of METH (SAM). Intravenous infusions of METH linked to appropriate lever-pressing behavior by rats significantly elevated NT content in both dorsal striatum (210%) and substantia nigra (202%). In these same structures, NT levels were also elevated in yoked METH animals (160 and 146%, respectively) but not as much as in the SAM rats. These effects were blocked by a D1, but not D2, antagonist. A NT agonist administered before the day 5 of operant behavior blocked lever-pressing behavior in responding rats, but a NT antagonist had no significant effect on this behavior. These are the first reports that NT systems associated with striatonigral pathway are significantly altered during METH self-administration, and our findings suggest that activation of NT receptors during maintenance of operant responding reduces the associated lever-pressing behavior.

Frankel, Paul S.; Hoonakker, Amanda J.; Alburges, Mario E.; McDougall, Jacob W.; McFadden, Lisa M.; Fleckenstein, Annette E.

2011-01-01

113

Type 1 GM1 gangliosidosis with basal ganglia calcification: a case report.  

PubMed

This report concerns a 10-month-old boy, admitted to the Veterans General Hospital-Kaohsiung with generalized tonic convulsion and aspiration pneumonia. He was found to have had developmental regression, progressive hypotonia and hepatosplenomegaly since four months of age. Physical examination revealed a large head circumference (97th percentile), frontal bossing, depressed nasal bridge, hepatosplenomegaly, broad hands and short fingers. Neurologic examination showed poor control of eye movement, profound hypotonia, muscle weakness, brisk deep tendon reflexes and Babinski's sign. Hypoplasia of the vertebral bodies with anterior beaking, wedge-shaped metacarpals, spatulated ribs and a J-shaped sella turcica were displayed on bone radiographs. Cranial computerized tomography scans showed diffuse brain atrophy, dilated ventricles and calcification of the bilateral basal ganglia. Vacuolated lymphocytes were noted in a peripheral blood smear. Type 1 GM1 gangliosidosis was diagnosed based on a deficiency of beta-galactosidase activity. To our knowledge, basal ganglia calcification in type 1 GM1 gangliosidosis has never been reported in the literature. We suggest that type 1 GM1 gangliosidosis be considered in the differential diagnosis of patients with an early onset of neurologic decline, organomegaly and basal ganglia calcification. PMID:10063711

Chen, C C; Chiu, P C; Shieh, K S

1999-01-01

114

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

PubMed

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

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

2013-09-17

115

Simulation of cortico-basal ganglia oscillations and their suppression by closed loop deep brain stimulation.  

PubMed

A new model of deep brain stimulation (DBS) is presented that integrates volume conduction effects with a neural model of pathological beta-band oscillations in the cortico-basal ganglia network. The model is used to test the clinical hypothesis that closed-loop control of the amplitude of DBS may be possible, based on the average rectified value of beta-band oscillations in the local field potential. Simulation of closed-loop high-frequency DBS was shown to yield energy savings, with the magnitude of the energy saved dependent on the strength of coupling between the subthalamic nucleus and the remainder of the cortico-basal ganglia network. When closed-loop DBS was applied to a strongly coupled cortico-basal ganglia network, the stimulation energy delivered over a 480 s period was reduced by up to 42%. Greater energy reductions were observed for weakly coupled networks, as the stimulation amplitude reduced to zero once the initial desynchronization had occurred. The results provide support for the application of closed-loop high-frequency DBS based on electrophysiological biomarkers. PMID:22695362

Grant, Peadar F; Lowery, Madeleine M

2013-07-01

116

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

PubMed Central

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

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

2013-01-01

117

Altered Basal Ganglia echogenicity early in sporadic creutzfeldt-jakob disease.  

PubMed

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by conformational alteration of the ubiquitous prion protein. Sporadic CJD appears to progress faster if the basal ganglia are shown to be affected on magnetic resonance imaging. Transcranial B-mode sonography (TCS) enables visualization of differences in tissue echogenicity, which can be associated with changes in the cerebral metabolism of various metals. These metabolic changes are considered 1 of the potential mechanisms of the brain damage in CJD; TCS hyperechogenicity may reflect changes in metal homeostasis in CJD. We report a 63-year-old woman who presented with typical sporadic CJD. One month after she fell ill, a magnetic resonance imaging scan of her brain showed diffuse cortical but no obvious basal ganglia involvement. However, TCS revealed moderate hyperechogenicity of both lentiform nuclei. The patient's disease progressed quickly and she died 2 months later. TCS may show basal ganglia alteration early in the disease course of patients with quickly progressing CJD, thus aiding in premortem diagnosis. PMID:24674965

Veselinovic, Nikola; Pavlovic, Aleksandra M; Petrovic, Boris; Ristic, Aleksandar; Novakovic, Ivana; Svabic Medjedovic, Tamara; Pavlovic, Dragan; Sternic, Nada

2014-03-01

118

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

PubMed

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

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

119

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

PubMed Central

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

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

2010-01-01

120

Prediction of the Location of the Pyramidal Tract in Patients with Thalamic or Basal Ganglia Tumors  

PubMed Central

Background Locating the pyramidal tract (PT) is difficult in patients with thalamic or basal ganglia tumors, especially when the surrounding anatomical structures cannot be identified using computed tomography or magnetic resonance images. Hence, we objected to find a way to predict the location of the PT in patients with thalamic and basal ganglia tumors Methodology/Principal Findings In 59 patents with thalamic or basal ganglia tumors, the PTs were constructed by with diffusion tensor imaging (DTI)-based fiber tracking (FT). In axial slices crossing the foramen of Monro, the tumor position was classified according to three lines. Line 1 was vertical and crossed the vertex point of the anterior limbs of the internal capsule. Lines 2 and line 3 were horizontal and crossed the foramen of Monro and joint of the middle and lateral thirds of the posterior limbs, respectively. Six (10.17%) patients were diagnosed with type 1 tumor, six (10.17%) with type 2, seven (11.86%) with type 3a, five (8.47%) with type 3b, 17 (28.81%) with type 4a, six (10.17%) with type 4b, three (5.08%) with type 5, and nine (15.25%) with type 6. In type 1 tumors, the PTs were located at the 12 o'clock position of the tumor, type 2 at six o'clock, type 3a between nine and 12 o'clock, type 3 between six and nine o'clock, type 4a between 12 and three o'clock, type 4b at three o'clock, type 5 between six and nine o'clock, and type 6 between three and six o'clock. Conclusions/Significance The position of the PT relative to the tumor could be determined according to the tumor location. These results could prove helpful in determining the location of the PT preoperatively.

Xu, BaiNan

2012-01-01

121

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

PubMed Central

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.

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

2014-01-01

122

Pigeon basal ganglia: insights into the neuroanatomy underlying telencephalic sensorimotor processes in birds.  

PubMed

This paper reviews the organization of the avian and mammalian striatum. The striatum receives input from virtually the entire rostrocaudal and mediolateral expanse of the cerebral cortex. The corticostriatal projections appear to be glutamatergic, forming excitatory synapses in the striatum. Another major projection to the avian striatum that also appears to be glutamatergic stems from a set of nuclei in the dorsal zone of the avian thalamus that are comparable to the mammalian intralaminar, mediodorsal, and midline nuclei. Furthermore, the striatum receives a massive projection from dopaminergic neurons of the ventral tegmental area and substantia nigra in the midbrain tegmentum. In return, the midbrain tegmentum receives a direct GABAergic/substance P-ergic/ dynorphinergic projection from the striatum, as well as an indirect one formed by GABAergic/substance P-ergic/ dynorphinergic and GABA-ergic/enkephalinergic striatal neurons projecting to the pallidum in the first step, and pallidal GABAergic/LANT6/parvalbumin neurons projecting to the midbrain tegmentum in the second step. In addition to its projection neurons, the striatum possesses GABAergic and cholinergic interneurons. One motor output pathway of the striatum runs via the pallidum and dorsal thalamic ventral tier nulei to the motor cortex. In addition to this pathway, birds possess a major descending pathway from the basal ganglia to the tectum via the GABAergic nucleus spiriformis lateralis in the pretectum. On hodological and topological grounds, similar nuclei, although not GABAergic, can be found in mammals. Finally, an other striatal motor output is formed by a sequential GABAergic pathway from the basal ganglia via the substantia nigra to the tectum. In conclusion, it appears that the organization of the avian and mammalian basal ganglia is similar rather than different. PMID:9290931

Veenman, C L

1997-10-01

123

Rhythmic cortical neurons increase their oscillations and sculpt basal ganglia signaling during motor learning.  

PubMed

The function and modulation of neural circuits underlying motor skill may involve rhythmic oscillations (Feller, 1999; Marder and Goaillard, 2006; Churchland et al., 2012). In the proposed pattern generator for birdsong, the cortical nucleus HVC, the frequency and power of oscillatory bursting during singing increases with development (Crandall et al., 2007; Day et al., 2009). We examined the maturation of cellular activity patterns that underlie these changes. Single unit ensemble recording combined with antidromic identification (Day et al., 2011) was used to study network development in anesthetized zebra finches. Autocovariance quantified oscillations within single units. A subset of neurons oscillated in the theta/alpha/mu/beta range (8-20 Hz), with greater power in adults compared to juveniles. Across the network, the normalized oscillatory power in the 8-20 Hz range was greater in adults than juveniles. In addition, the correlated activity between rhythmic neuron pairs increased with development. We next examined the functional impact of the oscillators on the output neurons of HVC. We found that the firing of oscillatory neurons negatively correlated with the activity of cortico-basal ganglia neurons (HVC(X)s), which project to Area X (the song basal ganglia). If groups of oscillators work together to tonically inhibit and precisely control the spike timing of adult HVC(X)s with coordinated release from inhibition, then the activity of HVC(X)s in juveniles should be decreased relative to adults due to uncorrelated, tonic inhibition. Consistent with this hypothesis, HVC(X)s had lower activity in juveniles. These data reveal network changes that shape cortical-to-basal ganglia signaling during motor learning. PMID:23776169

Day, Nancy F; Nick, Teresa A

2013-10-01

124

Models of basal ganglia and cerebellum for sensorimotor integration and predictive control  

NASA Astrophysics Data System (ADS)

This paper presents a sensorimotor architecture integrating computational models of a cerebellum and a basal ganglia and operating on a microrobot. The computational models enable a microrobot to learn to track a moving object and anticipate future positions using a CCD camera. The architecture features pre-processing modules for coordinate transformation and instantaneous orientation extraction. Learning of motor control is implemented using predictive Hebbian reinforcement-learning algorithm in the basal ganglia model. Learning of sensory predictions makes use of a combination of long-term depression (LTD) and long-term potentiation (LTP) adaptation rules within the cerebellum model. The basal ganglia model uses the visual inputs to develop sensorimotor mapping for motor control, while the cerebellum module uses robot orientation and world- coordinate transformed inputs to predict the location of the moving object in a robot centered coordinate system. We propose several hypotheses about the functional role of cell populations in the cerebellum and argue that mossy fiber projections to the deep cerebellar nucleus (DCN) could play a coordinate transformation role and act as gain fields. We propose that such transformation could be learnt early in the brain development stages and could be guided by the activity of the climbing fibers. Proprioceptor mossy fibers projecting to the DCN and providing robot orientation with respect to a reference system could be involved in this case. Other mossy fibers carrying visual sensory input provide visual patterns to the granule cells. The combined activities of the granule and the Purkinje cells store spatial representations of the target patterns. The combinations of mossy and Purkinje projections to the DCN provide a prediction of the location of the moving target taking into consideration the robot orientation. Results of lesion simulations based on our model show degradations similar to those reported in cerebellar lesion studies on monkeys.

Jabri, Marwan A.; Huang, Jerry; Coenen, Olivier J. D.; Sejnowski, Terrence J.

2000-10-01

125

Small-vessel disease in the basal ganglia: lacune or microbleed?  

PubMed

Brain microbleeds (BMBs) can be detected on the gradient-echo T2*-weighted magnetic resonance imaging and are considered a risk factor for cognitive impairment and intracerebral hemorrhage. Detailed radiologic findings on the etiology of BMBs and their changes remain scarce. We present a case of subacute change in a BMB in the basal ganglia that mimicked a subacute lacunar infarct. Our findings underscore the need for physicians to be careful to not erroneously diagnose BMBs as lacunar infarctions and prescribe unnecessary antiplatelet medication. PMID:21757373

Nezu, Tomohisa; Arihiro, Shoji; Toyoda, Kazunori; Minematsu, Kazuo

2012-11-01

126

Multiple controls exerted by 5-HT2C receptors upon basal ganglia function: from physiology to pathophysiology.  

PubMed

Serotonin2C (5-HT2C) receptors are expressed in the basal ganglia, a group of subcortical structures involved in the control of motor behaviour, mood and cognition. These receptors are mediating the effects of 5-HT throughout different brain areas via projections originating from midbrain raphe nuclei. A growing interest has been focusing on the function of 5-HT2C receptors in the basal ganglia because they may be involved in various diseases of basal ganglia function notably those associated with chronic impairment of dopaminergic transmission. 5-HT2C receptors act on numerous types of neurons in the basal ganglia, including dopaminergic, GABAergic, glutamatergic or cholinergic cells. Perhaps inherent to their peculiar molecular properties, the modality of controls exerted by 5-HT2C receptors over these cell populations can be phasic, tonic (dependent on the 5-HT tone) or constitutive (a spontaneous activity without the presence of the ligand). These controls are functionally organized in the basal ganglia: they are mainly localized in the input structures and preferentially distributed in the limbic/associative territories of the basal ganglia. The nature of these controls is modified in neuropsychiatric conditions such as Parkinson's disease, tardive dyskinesia or addiction. Most of the available data indicate that the function of 5-HT2C receptor is enhanced in cases of chronic alterations of dopamine neurotransmission. The review illustrates that 5-HT2C receptors play a role in maintaining continuous controls over the basal ganglia via multiple diverse actions. We will discuss their interest for treatments aimed at ameliorating current pharmacotherapies in schizophrenia, Parkinson's disease or drugs abuse. PMID:23615975

De Deurwaerdère, P; Lagière, M; Bosc, M; Navailles, S

2013-10-01

127

Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation.  

PubMed

Atypical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). "Neurally impaired" versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable's motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H

2013-09-01

128

An interactive channel model of the Basal Ganglia: bifurcation analysis under healthy and parkinsonian conditions.  

PubMed

Oscillations in the basal ganglia are an active area of research and have been shown to relate to the hypokinetic motor symptoms of Parkinson's disease. We study oscillations in a multi-channel mean field model, where each channel consists of an interconnected pair of subthalamic nucleus and globus pallidus sub-populations.To study how the channels interact, we perform two-dimensional bifurcation analysis of a model of an individual channel, which reveals the critical boundaries in parameter space that separate different dynamical modes; these modes include steady-state, oscillatory, and bi-stable behaviour. Without self-excitation in the subthalamic nucleus a single channel cannot generate oscillations, yet there is little experimental evidence for such self-excitation. Our results show that the interactive channel model with coupling via pallidal sub-populations demonstrates robust oscillatory behaviour without subthalamic self-excitation, provided the coupling is sufficiently strong. We study the model under healthy and Parkinsonian conditions and demonstrate that it exhibits oscillations for a much wider range of parameters in the Parkinsonian case. In the discussion, we show how our results compare with experimental findings and discuss their possible physiological interpretation. For example, experiments have found that increased lateral coupling in the rat basal ganglia is correlated with oscillations under Parkinsonian conditions. PMID:23945348

Merrison-Hort, Robert; Yousif, Nada; Njap, Felix; Hofmann, Ulrich G; Burylko, Oleksandr; Borisyuk, Roman

2013-01-01

129

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification  

PubMed Central

Familial idiopathic basal ganglia calcification (IBGC) or Fahr’s disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient’s disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.

Hsu, Sandy Chan; Sears, Renee L.; Lemos, Roberta R.; Quintans, Beatriz; Huang, Alden; Spiteri, Elizabeth; Nevarez, Lisette; Mamah, Catherine; Zatz, Mayana; Pierce, Kerrie D.; Fullerton, Janice M.; Adair, John C.; Berner, Jon E.; Bower, Matthew; Brodaty, Henry; Carmona, Olga; Dobricic, Valerija; Fogel, Brent L.; Garcia-Estevez, Daniel; Goldman, Jill; Goudreau, John L.; Hopfer, Suellen; Jankovic, Milena; Jauma, Serge; Jen, Joanna C.; Kirdlarp, Suppachok; Klepper, Joerg; Kostic, Vladimir; Lang, Anthony E.; Linglart, Agnes; Maisenbacher, Melissa K.; Manyam, Bala V.; Mazzoni, Pietro; Miedzybrodzka, Zofia; Mitarnun, Witoon; Mitchell, Philip B.; Mueller, Jennifer; Novakovic, Ivana; Paucar, Martin; Paulson, Henry; Simpson, Sheila A.; Svenningsson, Per; Tuite, Paul; Vitek, Jerrold; Wetchaphanphesat, Suppachok; Williams, Charles; Yang, Michele; Schofield, Peter R.; de Oliveira, Joao R. M.; Sobrido, Maria-Jesus

2014-01-01

130

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.  

PubMed

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41% of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation. PMID:23334463

Hsu, Sandy Chan; Sears, Renee L; Lemos, Roberta R; Quintáns, Beatriz; Huang, Alden; Spiteri, Elizabeth; Nevarez, Lisette; Mamah, Catherine; Zatz, Mayana; Pierce, Kerrie D; Fullerton, Janice M; Adair, John C; Berner, Jon E; Bower, Matthew; Brodaty, Henry; Carmona, Olga; Dobrici?, Valerija; Fogel, Brent L; García-Estevez, Daniel; Goldman, Jill; Goudreau, John L; Hopfer, Suellen; Jankovi?, Milena; Jaumà, Serge; Jen, Joanna C; Kirdlarp, Suppachok; Klepper, Joerg; Kosti?, Vladimir; Lang, Anthony E; Linglart, Agnès; Maisenbacher, Melissa K; Manyam, Bala V; Mazzoni, Pietro; Miedzybrodzka, Zofia; Mitarnun, Witoon; Mitchell, Philip B; Mueller, Jennifer; Novakovi?, Ivana; Paucar, Martin; Paulson, Henry; Simpson, Sheila A; Svenningsson, Per; Tuite, Paul; Vitek, Jerrold; Wetchaphanphesat, Suppachok; Williams, Charles; Yang, Michele; Schofield, Peter R; de Oliveira, João R M; Sobrido, María-Jesús; Geschwind, Daniel H; Coppola, Giovanni

2013-02-01

131

A left basal ganglia case of dynamic aphasia or impairment of extra-language cognitive processes?  

PubMed

We report the case of OTM who presented with dynamic aphasia following a stroke that occurred in the left basal ganglia. He showed drastically reduced spontaneous speech in the context of well preserved naming, repetition and comprehension skills. OTM was particularly impaired in generating words, sentences and phrases when cued by a stimulus allowing many response options. By contrast, when a single response was strongly suggested by a stimulus, he could generate verbal responses adequately. OTM's non-verbal response generation abilities varied across tasks. He performed in the normal range in a motor movement generation test and he produced as many figures as controls when tested on a figural fluency task. He showed, however, many perseverations on this test. Moreover in a random number generation task he produced more responses that were part of ascending and descending series of numbers. The patient's impairments are interpreted as a consequence of two deficits. The first of these consists of an inability to generate verbal responses particularly in situations of high competition and involves the function of left frontal regions. The second deficit is one of impaired novel thought generation as evidenced by perseverations. This second deficit has been proposed to be a function of basal ganglia damage. PMID:18569743

Crescentini, Cristiano; Lunardelli, Alberta; Mussoni, Alessandro; Zadini, Antonietta; Shallice, Tim

2008-01-01

132

Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.  

PubMed

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

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

2013-01-01

133

DARPP-32 to quantify intracerebral hemorrhage-induced neuronal death in basal ganglia  

PubMed Central

Quantification of acute brain injury in basal ganglia is essential for mechanistic and therapeutic studies in experimental intracerebral hemorrhage (ICH). Using conventional counting of degenerating cells based on morphological or immunohistochemical criteria, it is hard to define the boundary of the whole lesion area. Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) is a cytosolic protein highly enriched in medium-sized spiny neurons of the striatum. We developed new methods for quantifying lesion area by detecting the difference of the DARPP-32 negative area and the hematoma clot, and by measuring DARPP-32 protein level for semi-qualification in rat model of ICH. We found that DARPP-32 negative area around hematoma was present at day-1, peaked at day-3, and decreased at day-14 after ICH, a time course paralleled by DARPP-32 Western blots. The DARPP-32 negative area matched well with the necrotic area determined using propidium iodide. Treatment with an iron chelator, deferoxamine, attenuated the ICH-induced reduction in DARPP-32 protein levels. These results suggest that DARPP-32 is a simple and quantifiable indicator of ICH-induced neuronal death in basal ganglia.

Jin, Hang; Xi, Guohua; Keep, Richard F.; Wu, Jiang; Hua, Ya

2012-01-01

134

Distinct basal ganglia territories are engaged in early and advanced motor sequence learning  

PubMed Central

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Lehericy, Stephane; Benali, Habib; Van de Moortele, Pierre-Francois; Pelegrini-Issac, Melanie; Waechter, Tobias; Ugurbil, Kamil; Doyon, Julien

2005-01-01

135

Basal Ganglia Neuronal Activity during Scanning Eye Movements in Parkinson's Disease  

PubMed Central

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

Sieger, Tomas; Bonnet, Cecilia; Serranova, Tereza; Wild, Jiri; Novak, Daniel; Ruzicka, Filip; Urgosik, Dusan; Ruzicka, Evzen; Gaymard, Bertrand; Jech, Robert

2013-01-01

136

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

PubMed Central

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.

Seger, Carol A.

2008-01-01

137

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

PubMed Central

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

Galvan, Adriana; Kuwajima, Masaaki; Smith, Yoland

2006-01-01

138

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

PubMed Central

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.

Thibeault, Corey M.; Srinivasa, Narayan

2013-01-01

139

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

PubMed

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

Thibeault, Corey M; Srinivasa, Narayan

2013-01-01

140

Evolutionary and developmental contributions for understanding the organization of the basal ganglia.  

PubMed

Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons containing LANT6). Based on the presence of neurons containing enkephalin or SP, it is possible that the pallidum of these animals also includes the Islet1 lineage cell subpopulation, and both neuron subtypes were likely present in the pallidum of the first jawed vertebrates. In contrast, lampreys (jawless fishes) appear to lack the pallidal embryonic domain and the Nkx2.1 lineage cell population that mainly characterize the pallidum in jawed vertebrates. In the absence of data in other jawless fishes, the ancestral condition in vertebrates remains to be elucidated. Perhaps, a major event in telencephalic evolution was the novel expression of Nkx2.1 in the subpallium, which has been related to Hedgehog expression and changes in the regulatory region of Nkx2.1. PMID:24776992

Medina, Loreta; Abellán, Antonio; Vicario, Alba; Desfilis, Ester

2014-01-01

141

Robust Representation of Stable Object Values in the Oculomotor Basal Ganglia  

PubMed Central

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

Yasuda, Masaharu; Yamamoto, Shinya; Hikosaka, Okihide

2012-01-01

142

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

PubMed

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

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

2014-06-01

143

Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry.  

PubMed

Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bidirectionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia, decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers. PMID:24411738

Cazorla, Maxime; de Carvalho, Fernanda Delmondes; Chohan, Muhammad O; Shegda, Mariya; Chuhma, Nao; Rayport, Stephen; Ahmari, Susanne E; Moore, Holly; Kellendonk, Christoph

2014-01-01

144

Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys  

PubMed Central

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

Rommelfanger, Karen S.; Masilamoni, Gunasingh J.; Smith, Yoland; Wichmann, Thomas

2012-01-01

145

Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.  

PubMed

Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. PMID:23276479

Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

2013-02-01

146

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

PubMed Central

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

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

2012-01-01

147

Response of neurotensin basal ganglia systems during extinction of methamphetamine self-administration in rat.  

PubMed

Because of persistent social problems caused by methamphetamine (METH), new therapeutic strategies need to be developed. Thus, we investigated the response of central nervous system neurotensin (NT) systems to METH self-administration (SA) and their interaction with basal ganglia dopamine (DA) pathways. Neurotensin is a peptide associated with inhibitory feedback pathways to nigrostriatal DA projections. We observed that NT levels decreased in rats during extinction of METH SA when lever pressing resulted in intravenous infusions of saline rather than METH. Thus, 6 h after the first session of extinction, NT levels were 53, 42, and 49% of corresponding controls in the anterior dorsal striatum, posterior dorsal striatum, and globus pallidus, respectively. NT levels were also significantly reduced in corresponding yoked rats in the anterior dorsal striatum (64% of control), but not the other structures examined. The reductions in NT levels in the anterior dorsal striatum particularly correlated with the lever pressing during the first session of extinction (r =s; 0.745). These, and previously reported findings, suggest that the extinction-related reductions in NT levels were mediated by activation of D2 receptors. Finally, administration of the neurotensin receptor 1 (NTR1) agonist [PD149163 [Lys(CH2NH)Lys-Pro,Trp-tert-Leu-Leu-Oet]; 0.25 or 0.5 mg/kg] diminished lever pressing during the first extinction session, whereas the NTR1 antagonist [SR48692 [2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-imethoxyphenyl)pyrazol-3-yl)carbonylamino]tricyclo(3.3.1.1.(3.7))decan-2-carboxylic acid]; 0.3 mg/kg per administration] attenuated the reduction of lever pressing during the second to fourth days of extinction. In summary, these findings support the hypothesis that some of the endogenous basal ganglia NT systems contribute to the elimination of contingent behavior during the early stages of the METH SA extinction process. PMID:23685547

Hanson, Glen R; Hoonakker, Amanda J; Robson, Christina M; McFadden, Lisa M; Frankel, Paul S; Alburges, Mario E

2013-08-01

148

Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus.  

PubMed

The basal ganglia and thalamus are involved in processing all physiological behaviors and affected by many diseases. Accurate localization is a crucial issue in neuroimaging, particularly when working with groups of normalized images in a standard stereotaxic space. Here, manual delineation of the central structures (thalamus; nucleus caudatus and accumbens; putamen, pallidum, substantia nigra) was performed on 30 high resolution MRIs of healthy young adults (15 female, median age 31 years) in native space. Protocol inter-rater reliabilities were quantified as structure overlap (similarity indices, SIs). Structural volumes were calculated in native space, and after spatial normalization to stereotaxic space (MNI/ICBM152) and in relation to hemispheric volumes. Spatial extents relative to the anterior commissure (AC) were extracted. The 30 resulting atlases were then used to create probabilistic maps in stereotaxic space. Inter-rater SIs were high at 0.85-0.92 except for the nucleus accumbens. In native space, caudate, nucleus accumbens and putamen were significantly larger on the left, and the globus pallidus larger in males. After normalizing for brain volume, the nucleus accumbens, putamen and thalamus were larger on the left, with the gender difference in the globus pallidus still detectable. Some of these volume differences translated into significantly different distances from the AC. The probabilistic maps showed that overall the central structures' boundaries are relatively unchanged after spatial normalization. We present a comprehensive assessment of thalamic and basal ganglia volumetric and geometric data in both native and stereotaxic spaces. Probabilistic maps in MNI/ICBM152 space will allow accurate localization in group analyses. PMID:17851093

Ahsan, R Laila; Allom, Richard; Gousias, Ioannis S; Habib, Helai; Turkheimer, Federico E; Free, Samantha; Lemieux, Louis; Myers, Ralph; Duncan, John S; Brooks, David J; Koepp, Matthias J; Hammers, Alexander

2007-11-01

149

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

PubMed Central

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.

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

2012-01-01

150

Basal ganglia and internal capsule stroke in childhood--risk factors, neuroimaging, and outcome in a series of 28 patients: a tertiary hospital experience.  

PubMed

We present 28 patients with basal ganglia ischemic stroke and describe the main neurological manifestations, neuroimaging findings, risk factors, and outcome. In 23 cases, at least 1 risk factor was identified. A total of 7 cases (25%) had antecedent of varicella infection and 7 cases (25%) had preceding mild head trauma. Similar antecedents were present only in 2.6% and 5.3% of patients with nonbasal ganglia stroke, respectively (odds ratio: 12.2, 95% confidence interval: 2.04-124.65 and odds ratio: 5.92, 95% confidence interval: 1.32-29.7). The arterial abnormalities identified in 10 patients were narrowing (6) or occlusion (4) of the M1 segment. After a median follow-up of 24 months, 19 patients had a good outcome. Magnetic resonance angiography and catheter cerebral angiography played an important role in the identification of arterial disease. We propose that basal ganglia infarction is a different group of ischemic stroke with prevalent risk factors (varicella infection and mild head trauma) and good outcome. PMID:19264737

Buompadre, María Celeste; Arroyo, Hugo Antonio

2009-06-01

151

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

ERIC Educational Resources Information Center

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…

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

152

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

Microsoft Academic Search

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

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

153

Mechanism of parkinsonian neuronal oscillations in the primate basal ganglia: some considerations based on our recent work  

PubMed Central

Accumulating evidence suggests that abnormal neuronal oscillations in the basal ganglia (BG) contribute to the manifestation of parkinsonian symptoms. In this article, we would like to summarize our recent work on the mechanism underlying abnormal oscillations in the parkinsonian state and discuss its significance in pathophysiology of Parkinson’s disease. We recorded neuronal activity in the BG of parkinsonian monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Systemic administration of L-DOPA alleviated parkinsonian motor signs and decreased abnormal neuronal oscillations (8–15 Hz) in the internal (GPi) and external (GPe) segments of the globus pallidus and the subthalamic nucleus (STN). Inactivation of the STN by muscimol (GABAA receptor agonist) injection also ameliorated parkinsonian signs and suppressed GPi oscillations. The blockade of glutamatergic inputs to the STN by local microinjection of a mixture of 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (glutamatergic NMDA receptor antagonist) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (glutamatergic AMPA/kainate receptor antagonist) suppressed neuronal oscillations in the STN. STN oscillations were also attenuated by the blockade of GABAergic neurotransmission from the GPe to the STN by muscimol inactivation of the GPe. These results suggest that cortical glutamatergic inputs to the STN and reciprocal GPe-STN interconnections are both important for the generation and amplification of the oscillatory activity of GPe and STN neurons in the parkinsonian state. The oscillatory activity in the STN is subsequently transmitted to the GPi and may contribute to manifestation of parkinsonian symptoms.

Nambu, Atsushi; Tachibana, Yoshihisa

2014-01-01

154

Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders  

PubMed Central

Introduction Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. Methods The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD?10, G20–26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n?=?49?488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n?=?489?572). Results The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR)?=?0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR?=?0.95; 95% CI 0.70 to 1.28). Conclusion This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders.

Fored, C M; Fryzek, J P; Brandt, L; Nise, G; Sjogren, B; McLaughlin, J K; Blot, W J; Ekbom, A

2006-01-01

155

Plastic effects of L-DOPA treatment in the basal ganglia and their relevance to the development of dyskinesia.  

PubMed

The development of L-DOPA-induced dyskinesia (LID) is attributed to plastic responses triggered by dopamine (DA) receptor stimulation in the parkinsonian brain. This article reviews studies that have uncovered different levels of maladaptive plasticity in animal models of LID. Rats developing dyskinesia on chronic L-DOPA treatment show abnormal patterns of signaling pathway activation and synaptic plasticity in striatal neurons. In addition, these animals show a gene expression profile indicative of structural cellular plasticity, including pronounced upregulation of genes involved in extracellular matrix remodeling, neurite extension, synaptic vesicle trafficking, and endothelial and cellular proliferation. Structural changes of neurons and microvessels within the basal ganglia are currently being unraveled by detailed morphological analyses. The structural and functional adaptations induced by L-DOPA in the brain can be viewed as an attempt to meet increased metabolic demands and to boost cellular defense mechanisms. These homeostatic responses, however, also predispose to the appearance of dyskinesia and other complications during the course of the treatment. PMID:20083009

Cenci, M Angela; Ohlin, K Elisabet; Rylander, Daniella

2009-12-01

156

In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.  

PubMed

The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7832434

Chiueh, C C; Wu, R M; Mohanakumar, K P; Sternberger, L M; Krishna, G; Obata, T; Murphy, D L

1994-11-17

157

Evolution of the basal ganglia: new perspectives through a comparative approach  

PubMed Central

The basal ganglia (BG) have received much attention during the last 3 decades mainly because of their clinical relevance. Our understanding of their structure, organisation and function in terms of chemoarchitecture, compartmentalisation, connections and receptor localisation has increased equally. Most of the research has been focused on the mammalian BG, but a considerable number of studies have been carried out in nonmammalian vertebrates, in particular reptiles and birds. The BG of the latter 2 classes of vertebrates, which together with mammals constitute the amniotic vertebrates, have been thoroughly studied by means of tract-tracing and immunohistochemical techniques. The terminology used for amniotic BG structures has frequently been adopted to indicate putative corresponding structures in the brain of anamniotes, i.e. amphibians and fishes, but data for such a comparison were, until recently, almost totally lacking. It has been proposed several times that the occurrence of well developed BG structures probably constitutes a landmark in the anamniote-amniote transition. However, our recent studies of connections, chemoarchitecture and development of the basal forebrain of amphibians have revealed that tetrapod vertebrates share a common pattern of BG organisation. This pattern includes the existence of dorsal and ventral striatopallidal systems, reciprocal connections between the striatopallidal complex and the diencephalic and mesencephalic basal plate (striatonigral and nigrostriatal projections), and descending pathways from the striatopallidal system to the midbrain tectum and reticular formation. The connectional similarities are paralleled by similarities in the distribution of chemical markers of striatal and pallidal structures such as dopamine, substance P and enkephalin, as well as by similarities in development and expression of homeobox genes. On the other hand, a major evolutionary trend is the progressive involvement of the cortex in the processing of the thalamic sensory information relayed to the BG of tetrapods. By using the comparative approach, new insights have been gained with respect to certain features of the BG of vertebrates in general, such as the segmental organisation of the midbrain dopaminergic cell groups, the occurrence of large numbers of dopaminergic cell bodies within the telencephalon itself and the variability in, among others, connectivity and chemoarchitecture. However, the intriguing question whether the basal forebrain organisation of nontetrapods differs essentially from that observed in tetrapods still needs to be answered.

SMEETS, WILHELMUS J. A. J.; MARIN, OSCAR; GONZALEZ, AGUSTIN

2000-01-01

158

Effects of visual and auditory feedback on sensorimotor circuits in the basal ganglia.  

PubMed

Previous work using visual feedback has identified two distinct sensorimotor circuits in the basal ganglia (BG): one that scaled with the duration of force and one that scaled with the rate of change of force. The present study compared functional MRI signal changes in the BG during a grip force task using either visual or auditory feedback to determine whether the BG nuclei process auditory and visual feedback similarly. We confirmed the same two sensorimotor circuits in the BG. Activation in the striatum and external globus pallidus (GPe) scaled linearly with the duration of force under visual and auditory feedback conditions, with similar slopes and intercepts across feedback type. The pattern of signal change for the internal globus pallidus (GPi) and subthalamic nucleus (STN) was nonlinear and parameters of the exponential function were altered by feedback type. Specifically, GPi and STN activation decreased exponentially with the rate of change of force. The rate constant and asymptote of the exponential functions for GPi and STN were greater during auditory than visual feedback. In a comparison of the BOLD signal between BG regions, GPe had the highest percentage of variance accounted for and this effect was preserved for both feedback types. These new findings suggest that neuronal activity of specific BG nuclei is affected by whether the feedback is derived from visual or auditory inputs. Also, the data are consistent with the hypothesis that the GPe has a high level of information convergence from other BG nuclei, which is preserved across different sensory feedback modalities. PMID:18287549

Prodoehl, Janey; Yu, Hong; Wasson, Pooja; Corcos, Daniel M; Vaillancourt, David E

2008-06-01

159

Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease).  

PubMed Central

Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative syndrome that is associated with a variety of movement disorders and neurobehavioral and cognitive manifestations. Despite numerous clinical, pathological, and biochemical investigations, its etiology remains unknown. We have identified a multigenerational family with dominantly inherited IBGC and, in 24 members of this family, performed a whole-genome scan using polymorphic microsatellite markers to identify the first chromosomal locus for this disorder (IBGC1). A maximum two-point LOD score of 3.37 was obtained at marker D14S1014, and a maximum multipoint LOD score of 4.95 was obtained between D14S75 and D14S306. The minimal haplotype shared by affected patients extended over a 17.1-cM region bounded by D14S70 and D14S66, which is potentially further narrowed to a 13.3-cM region by a recombination observed in a patient with probable affected status. The age at onset appeared to be decreasing by an average of >20 years with each transmission, which is consistent with genetic anticipation.

Geschwind, D H; Loginov, M; Stern, J M

1999-01-01

160

Multiplicity of control in the basal ganglia: Computational roles of striatal subregions  

PubMed Central

The Basal Ganglia, in particular the striatum, are central to theories of behavioral control, and often identified as a seat of action selection. Reinforcement Learning (RL) models - which have driven much recent experimental work on this region - cast striatum as a dynamic controller, integrating sensory and motivational information to construct efficient and enriching behavioral policies. Befitting this informationally central role, the BG sit at the nexus of multiple anatomical “loops” of synaptic projections, connecting a wide range of cortical and sub-cortical structures. Numerous pioneering anatomical studies conducted over the past several decades have meticulously catalogued these loops, and labeled them according to the inferred functions of the connected regions. The specific cotermina of the projections are highly localized to several different subregions of the striatum, leading to the suggestion that these subregions perform complementary but distinct functions. However, until recently, the dominant computational framework outlined only a bipartite, dorsal/ventral, division of striatum. We review recent computational and experimental advances that argue for a more finely fractionated delineation. In particular, experimental data provides extensive insight on unique functions subserved by the dorsomedial striatum (DMS). These functions appear to correspond well to theories of a “model-based” RL subunit, and may also shed light on the suborganization of ventral striatum. Finally, we discuss the limitations of these ideas and how they point the way toward future refinements of neurocomputational theories of striatal function, bringing them into contact with other areas of computational theory and other regions of the brain.

Bornstein, Aaron M; Daw, Nathaniel D

2011-01-01

161

Anterograde Axonal Transport of AAV2-GDNF in Rat Basal Ganglia  

PubMed Central

We elucidated the effects of parkinsonian degeneration on trafficking of AAV2-GDNF in the nigro-striatum (nigro-ST) of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. Vector infused into striatum (ST) was transported to substantia nigra (SN), both pars compacta (SNc), and pars reticulata (SNr). In the lesioned hemisphere, glial cell line–derived neurotrophic factor (GDNF) immunoreactivity was only found in SNr consistent with elimination of SNc dopaminergic (DA) neurons by 6-OHDA. Further analysis showed that striatal delivery of AAV2-GDNF resulted in GDNF expression in globus pallidus (GP), entopeduncular nucleus (EPN), and subthalamic nucleus (STN) in both lesioned and unlesioned hemispheres. Injection of vector into SN, covering both SNc and SNr, resulted in striatal expression of GDNF in the unlesioned hemisphere but not in the lesioned hemisphere. No expression was seen in GP or EPN. We conclude that adeno-associated virus serotype 2 (AAV2) is transported throughout the nigro-ST exclusively by anterograde transport. This transport phenomenon directs GDNF expression throughout the basal ganglia in regions that are adversely affected in Parkinson's disease (PD) in addition to SNc. Delivery of vector to SN, however, does not direct expression of GDNF in ST, EPN, or GP. On this basis, we believe that striatal delivery of AAV2-GDNF is the preferred course of action for trophic rescue of DA function.

Ciesielska, Agnieszka; Mittermeyer, Gabriele; Hadaczek, Piotr; Kells, Adrian P; Forsayeth, John; Bankiewicz, Krystof S

2011-01-01

162

Anterograde axonal transport of AAV2-GDNF in rat basal ganglia.  

PubMed

We elucidated the effects of parkinsonian degeneration on trafficking of AAV2-GDNF in the nigro-striatum (nigro-ST) of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. Vector infused into striatum (ST) was transported to substantia nigra (SN), both pars compacta (SNc), and pars reticulata (SNr). In the lesioned hemisphere, glial cell line-derived neurotrophic factor (GDNF) immunoreactivity was only found in SNr consistent with elimination of SNc dopaminergic (DA) neurons by 6-OHDA. Further analysis showed that striatal delivery of AAV2-GDNF resulted in GDNF expression in globus pallidus (GP), entopeduncular nucleus (EPN), and subthalamic nucleus (STN) in both lesioned and unlesioned hemispheres. Injection of vector into SN, covering both SNc and SNr, resulted in striatal expression of GDNF in the unlesioned hemisphere but not in the lesioned hemisphere. No expression was seen in GP or EPN. We conclude that adeno-associated virus serotype 2 (AAV2) is transported throughout the nigro-ST exclusively by anterograde transport. This transport phenomenon directs GDNF expression throughout the basal ganglia in regions that are adversely affected in Parkinson's disease (PD) in addition to SNc. Delivery of vector to SN, however, does not direct expression of GDNF in ST, EPN, or GP. On this basis, we believe that striatal delivery of AAV2-GDNF is the preferred course of action for trophic rescue of DA function. PMID:21102559

Ciesielska, Agnieszka; Mittermeyer, Gabriele; Hadaczek, Piotr; Kells, Adrian P; Forsayeth, John; Bankiewicz, Krystof S

2011-05-01

163

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

PubMed Central

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

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

2011-01-01

164

Point process models show temporal dependencies of basal ganglia nuclei under deep brain stimulation.  

PubMed

Deep Brain Stimulation (DBS) is an effective treatment for patients with Parkinsons disease, but its impact on basal ganglia nuclei is not fully understood. DBS applied to the subthalamic nucleus (STN) affects neurons in the Globus Pallidus pars interna (GPi) through direct projections, as well as indirectly through the Globus Pallidus pars externa (GPe). Since traditional statistical analyses of electrophysiological data provide too coarse a view of circuit dynamics, and mesoscopic biophysical dynamic models contain an intractable number of state variables for small populations of neurons, we apply a modular approach and treat each region in the STN-GPe-GPi circuit as a multi-input multi-output point process system. We use microelectrode recordings of a normal primate with DBS applied to STN at 100 and 130 Hz to estimate point process models (PPMs) for recorded regions in GPi. Our PPMs uncovered distinct dependencies between regions of GPe and GPi neurons, separated by the position of the GPi neurons, and showed normal refractory periods, inhibition from projecting neurons in the GPe, and DBS-induced oscillatory effects. The PPMs also showed the relative impact of the above factors, which traditional statistics fail to capture. Our PPM framework suggests a useful approach for understanding dynamics of complex neural circuits. PMID:21096637

Saxena, Shreya; Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

2010-01-01

165

PDGF, Pericytes and the Pathogenesis of Idiopathic Basal Ganglia Calcification (IBGC).  

PubMed

Platelet-derived growth factors (PDGFs) are important mitogens for various types of mesenchymal cells, and as such, they exert critical functions during organogenesis in mammalian embryonic and early postnatal development. Increased or ectopic PDGF activity may also cause or contribute to diseases such as cancer and tissue fibrosis. Until recently, no loss-of-function (LOF) mutations in PDGF or PDGF receptor genes were reported as causally linked to a human disease. This changed in 2013 when reports appeared on presumed LOF mutations in the genes encoding PDGF-B and its receptor PDGF receptor-beta (PDGF-R?) in familial idiopathic basal ganglia calcification (IBGC), a brain disease characterized by anatomically localized calcifications in or near the blood microvessels. Here, we review PDGF-B and PDGF-R? biology with special reference to their functions in brain-blood vessel development, pericyte recruitment and the regulation of the blood-brain barrier. We also discuss various scenarios for IBGC pathogenesis suggested by observations in patients and genetically engineered animal models of the disease. PMID:24946076

Betsholtz, Christer; Keller, Annika

2014-07-01

166

Disconnection of a basal ganglia circuit in juvenile songbirds attenuates the spectral differentiation of song syllables.  

PubMed

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 premotor pathways: a posterior pathway that encodes the adult song syllables and an anterior pathway that includes a basal ganglia (BG)-thalamo-cortical circuit. Similar to mammalian motor-learning systems, the songbird BG circuit is thought to be necessary for shaping juvenile vocal behaviour (undifferentiated protosyllables) toward 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 lateral magnocellular nucleus of the anterior nidopallium (LMAN) was used to disconnect BG circuitry at ages before 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 behaviour toward 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

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

2014-06-01

167

Impaired frontal-Basal Ganglia connectivity in adolescents with internet addiction.  

PubMed

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

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

2014-01-01

168

Manganese Exposure is Cytotoxic and Alters Dopaminergic and GABAergic Neurons within the Basal Ganglia  

PubMed Central

Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson’s disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alterations induced by manganese exposure. Primary mesencephalic cultures were treated with 10–00µM manganese chloride (MnCl2) which resulted in dramatic changes in the neuronal cytoskeleton even at subtoxic concentrations. Using cultures from mice with red fluorescent protein (RFP) driven by the tyrosine hydroxylase (TH) promoter, we found that dopaminergic neurons were more susceptible to manganese toxicity. To understand the vulnerability of dopaminergic cells to chronic manganese exposure, mice were given IP injections of MnCl2 for 30 days. We observed a 20% reduction in TH-positive neurons in the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as evidenced by the loss of GAD67 in the striatum. These studies suggest that acute manganese exposure induces cytoskeletal dysfunction prior to degeneration and that chronic manganese exposure results in neurochemical dysfunction with overlapping features to PD.

Stanwood, Gregg D.; Leitch, Duncan B.; Savchenko, Valentina; Wu, Jane; Fitsanakis, Vanessa A.; Anderson, Douglas J.; Stankowski, Jeannette N.; Aschner, Michael; McLaughlin, BethAnn

2009-01-01

169

A hypothesis for basal ganglia-dependent reinforcement learning in the songbird  

PubMed Central

Most of our motor skills are not innately programmed, but are learned by a combination of motor exploration and performance evaluation, suggesting that they proceed through a reinforcement learning (RL) mechanism. Songbirds have emerged as a model system to study how a complex behavioral sequence can be learned through an RL-like strategy. Interestingly, like motor sequence learning in mammals, song learning in birds requires a basal ganglia (BG)-thalamocortical loop, suggesting common neural mechanisms. Here we outline a specific working hypothesis for how BG-forebrain circuits could utilize an internally computed reinforcement signal to direct song learning. Our model includes a number of general concepts borrowed from the mammalian BG literature, including a dopaminergic reward prediction error and dopamine mediated plasticity at corticostriatal synapses. We also invoke a number of conceptual advances arising from recent observations in the songbird. Specifically, there is evidence for a specialized cortical circuit that adds trial-to-trial variability to stereotyped cortical motor programs, and a role for the BG in ‘biasing’ this variability to improve behavioral performance. This BG-dependent ‘premotor bias’ may in turn guide plasticity in downstream cortical synapses to consolidate recently-learned song changes. Given the similarity between mammalian and songbird BG-thalamocortical circuits, our model for the role of the BG in this process may have broader relevance to mammalian BG function.

Fee, Michale S.; Goldberg, Jesse H.

2011-01-01

170

Indirection and symbol-like processing in the prefrontal cortex and basal ganglia  

PubMed Central

The ability to flexibly, rapidly, and accurately perform novel tasks is a hallmark of human behavior. In our everyday lives we are often faced with arbitrary instructions that we must understand and follow, and we are able to do so with remarkable ease. It has frequently been argued that this ability relies on symbol processing, which depends critically on the ability to represent variables and bind them to arbitrary values. Whereas symbol processing is a fundamental feature of all computer systems, it remains a mystery whether and how this ability is carried out by the brain. Here, we provide an example of how the structure and functioning of the prefrontal cortex/basal ganglia working memory system can support variable binding, through a form of indirection (akin to a pointer in computer science). We show how indirection enables the system to flexibly generalize its behavior substantially beyond its direct experience (i.e., systematicity). We argue that this provides a biologically plausible mechanism that approximates a key component of symbol processing, exhibiting both the flexibility, but also some of the limitations, that are associated with this ability in humans.

Kriete, Trenton; Noelle, David C.; Cohen, Jonathan D.; O'Reilly, Randall C.

2013-01-01

171

Indirection and symbol-like processing in the prefrontal cortex and basal ganglia.  

PubMed

The ability to flexibly, rapidly, and accurately perform novel tasks is a hallmark of human behavior. In our everyday lives we are often faced with arbitrary instructions that we must understand and follow, and we are able to do so with remarkable ease. It has frequently been argued that this ability relies on symbol processing, which depends critically on the ability to represent variables and bind them to arbitrary values. Whereas symbol processing is a fundamental feature of all computer systems, it remains a mystery whether and how this ability is carried out by the brain. Here, we provide an example of how the structure and functioning of the prefrontal cortex/basal ganglia working memory system can support variable binding, through a form of indirection (akin to a pointer in computer science). We show how indirection enables the system to flexibly generalize its behavior substantially beyond its direct experience (i.e., systematicity). We argue that this provides a biologically plausible mechanism that approximates a key component of symbol processing, exhibiting both the flexibility, but also some of the limitations, that are associated with this ability in humans. PMID:24062434

Kriete, Trenton; Noelle, David C; Cohen, Jonathan D; O'Reilly, Randall C

2013-10-01

172

A model of the basal ganglia in voluntary movement and postural reactions.  

PubMed

A basal ganglia central pattern generator (CPG) is developed and its role in voluntary movements on the ground and postural reactions on a disturbed platform are studied and analysed by simulation. Biped dynamics and platform kinematics are utilised. The effects of agonist-antagonist muscular co-activation and joint stiffness are formulated. The implementation of the necessary counter-manoeuvres for maintaining balance and postural stability is studied. A control strategy, applicable to large systems, is formulated. The biped manoeuvres and transitions terminate in pre-specified intervals of time. Gravity is included and compensated for. Certain voluntary and postural adjustment strategies are the same but are initiated differently. Further experimental/computational research may identify the central nervous system and sensory paths that lead to the CPG. All actuator forces linearly evolve in time from their original values to their terminal values. There are no central continuous feedback loops present. Monitoring and sensing, however, are ongoing. The counter-manoeuvres are based on learned human-like voluntary movements that are triggered by the disturbance. The required central inputs to the musculoskeletal system are designed in the CPG. A functional structure for the CPG is proposed. The effect of certain disorders and malfunctions of the CPG are studied by simulation. PMID:23282072

Hemami, Hooshang; Moussavi, Zahra

2014-10-01

173

Impaired Frontal-Basal Ganglia Connectivity in Adolescents with Internet Addiction  

PubMed Central

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

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

2014-01-01

174

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

PubMed Central

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

Cohen, Michael X; Frank, Michael J.

2009-01-01

175

Predictive and reactive control of grasping forces: on the role of the basal ganglia and sensory feedback  

Microsoft Academic Search

We comparatively investigated predictive and reactive grip force behaviour in 12 subjects with basal ganglia dysfunction (six subjects with Parkinson’s disease, six subjects with writer’s cramp), two subjects chronically lacking all tactile and proprioceptive sensory feedback and 16 sex- and age-matched control subjects. Subjects held an instrumented receptacle between the index finger and thumb. A weight was dropped into the

Dennis A. Nowak; Joachim Hermsdörfer

2006-01-01

176

[Idiopathic Bilateral Basal Ganglia Calcification (Fahr's Disease) Presenting with Psychotic Depression and Criminal Violence: A Case Report With Forensic Aspect].  

PubMed

Fahr's disease is a rare neuropsychiatric disease characterized by bilateral intracranial calcification, primarily in the basal ganglia. The more general term, Fahr's syndrome, is used for primary and secondary basal ganglia calcification, regardless of the etiology, but the term Fahr's disease is used to describe primary, idiopathic cases. Fahr's disease may present with neurological symptoms, such as parkinsonism and extrapyramidal symptoms, dysarthria, paresis, convulsion, and syncope. Psychiatric disorders, including behavioral disorders, psychosis, and mood disorders, as well as cognitive disorders can occur. CT is useful for the diagnosis of Fahr's disease. Herein we present a patient diagnosed as Fahr's disease that presented with symptoms of depression, delusions, and auditory hallucinations. The 47-year-old male patient was hospitalized in a forensic psychiatry inpatient clinic due to aggressive behavior and was subsequently diagnosed with major depressive disorder with psychotic features. While hospitalized he was treated with antidepressant and antipsychotic drugs, as well as electroconvulsive therapy, resulting in significant improvement in his symptoms. As bilateral basal ganglia calcification was observed via CT, the patient was diagnosed as Fahr's disease. This case report emphasizes the importance of cranial imaging and detailed laboratory examination when evaluating patients with psychosis and affective symptoms. Pathologies such as Fahr's disease must be included in the differential diagnosis, especially in cases with neurological symptoms and cranial imaging findings. PMID:24936761

Ozer, Urün; Görgülü, Yasemin; Can Güngör, Ferda; Gençtürk, Mert

2014-01-01

177

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

PubMed Central

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

Black, Kevin J.

2013-01-01

178

Song Selectivity in the Pallial-Basal Ganglia Song Circuit of Zebra Finches Raised Without Tutor Song Exposure  

PubMed Central

Acoustic experience critically influences auditory cortical development as well as emergence of highly selective auditory neurons in the songbird sensorimotor circuit. In adult zebra finches, these “song-selective” neurons respond better to the bird's own song (BOS) than to songs of other conspecifics. Birds learn their songs by memorizing a tutor's song and then matching auditory feedback of their voice to the tutor song memory. Song-selective neurons in the pallial-basal ganglia circuit called the anterior forebrain pathway (AFP) reflect the development of BOS. However, during learning, they also respond strongly to tutor song and are compromised in their adult selectivity when birds are prevented from matching BOS to tutor, suggesting that selectivity depends on tutor song learning as well as sensorimotor matching of BOS feedback to the tutor song memory. We examined the contribution of sensory learning of tutor song to song selectivity by recording from AFP neurons in birds reared without exposure to adult conspecifics. We found that AFP neurons in these “isolate” birds had highly tuned responses to isolate BOS. The selectivity was as high, and in the striato-pallidal nucleus Area X, even higher than that in normal birds, due to abnormally weak responsiveness to conspecific song. These results demonstrate that sensory learning of tutor song is not necessary for BOS tuning of AFP neurons. Because isolate birds develop their song via sensorimotor learning, our data further illustrate the importance of individual sensorimotor learning for song selectivity and provide insight into possible functions of song-selective neurons.

Kojima, Satoshi; Doupe, Allison J.

2008-01-01

179

Automated segmentation of basal ganglia and deep brain structures in MRI of Parkinson's disease  

PubMed Central

Purpose Template-based segmentation techniques have been developed to facilitate the accurate targeting of deep brain structures in patients with movement disorders. Three template-based brain MRI segmentation techniques were compared to determine the best strategy for segmenting the deep brain structures of patients with Parkinson’s disease. Methods T1-weighted and T2-weighted magnetic resonance (MR) image templates were created by averaging MR images of 57 patients with Parkinson’s disease. Twenty-four deep brain structures were manually segmented on the templates. To validate the template-based segmentation, 14 of the 24 deep brain structures from the templates were manually segmented on 10 MR scans of Parkinson’s patients as a gold standard. We compared the manual segmentations with three methods of automated segmentation: two registration-based approaches, Automatic Nonlinear Image Matching and Anatomical Labelling -(ANIMAL) and Symmetric Image Normalization - (SyN), and one patch-label fusion technique. The automated labels were then compared with the manual labels using a Dice-kappa metric and center of gravity. A Friedman test was used to compare the Dice-kappa values and paired t-tests for the center of gravity. Results The Friedman test showed a significant difference between the three methods for both thalami (p < 0.05) and not for the subthalamic nuclei. Registration with ANIMAL was better than with SyN for the left thalamus, and was better than the patch-based method for the right thalamus. Conclusion Although template-based approaches are the most used techniques to segment basal ganglia by warping onto MR images, we found that the patch-based method provided similar results and was less-time consuming. Patch-based method may be preferable for the subthalamic nucleus segmentation in patients with Parkinson’s disease.

Haegelen, Claire; Coupe, Pierrick; Fonov, Vladimir; Guizard, Nicolas; Jannin, Pierre; Morandi, Xavier; Collins, D Louis

2013-01-01

180

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

PubMed

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

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

2014-04-23

181

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

PubMed Central

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.

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

2014-01-01

182

Millisecond timescale disinhibition mediates fast information transmission through an avian basal ganglia loop.  

PubMed

Avian song learning shares striking similarities with human speech acquisition and requires a basal ganglia (BG)-thalamo-cortical circuit. Information processing and transmission speed in the BG is thought to be limited by synaptic architecture of two serial inhibitory connections. Propagation speed may be critical in the avian BG circuit given the temporally precise control of musculature during vocalization. We used electrical stimulation of the cortical inputs to the BG to study, with fine time resolution, the functional connectivity within this network. We found that neurons in thalamic and cortical nuclei that are not directly connected with the stimulated area can respond to the stimulation with extremely short latencies. Through pharmacological manipulations, we trace this property back to the BG and show that the cortical stimulation triggers fast disinhibition of the thalamic neurons. Surprisingly, feedforward inhibition mediated by striatal inhibitory neurons onto BG output neurons sometimes precedes the monosynaptic excitatory drive from cortical afferents. The fast feedforward inhibition lengthens a single interspike interval in BG output neurons by just a few milliseconds. This short delay is sufficient to drive a strong, brief increase in firing probability in the target thalamic neurons, evoking short-latency responses. By blocking glutamate receptors in vivo, we show that thalamic responses do not appear to rely on excitatory drive, and we show in a theoretical model that they could be mediated by postinhibitory rebound properties. Such fast signaling through disinhibition and rebound may be a crucial specialization for learning of rapid and temporally precise motor acts such as vocal communication. PMID:20007467

Leblois, Arthur; Bodor, Agnes L; Person, Abigail L; Perkel, David J

2009-12-01

183

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

PubMed

Parkinson's disease is the most frequent movement disorder caused by loss of dopaminergic neurons in the midbrain. Intentions to avoid side effects of the conventional therapy should aim to identify additional targets for potential pharmacological intervention. In principle, every step of a signal transduction cascade such as presynaptic transmitter release, type and occupation of postsynaptic receptors, G protein-mediated effector mechanisms, and the alterations of pre- or postsynaptic potentials as determined by the local ion channel composition, have to be considered. Due to their diversity and their widespread but distinct localizations, potassium channels represent interesting candidates for new therapeutic strategies. As a first step, the present report aimed to study in the striatum the cellular and subcellular distribution of the individual members of the Kir2 family, a group of proteins forming inwardly rectifying potassium channels. For this purpose polyclonal monospecific affinity-purified antibodies against the less conserved carboxyterminal sequences from the Kir2.1, Kir2.2, Kir2.3, and Kir2.4 proteins were prepared. All subunits of the Kir2 family were detected on somata and dendrites of most striatal neurons. However, the distribution of two of them was not homogeneous. Striatal patch areas were largely devoid of the Kir2.3 protein, and the Kir2.4 subunit was most prominently expressed on the tonically active, giant cholinergic interneurons of the striatum. These two structures are among the key players in regulating dopaminergic and cholinergic neurotransmission within the striatum, and therefore are of major importance for the output of the basal ganglia. The heterogeneous localization of the Kir2.3 and the Kir2.4 subunits with respect to these strategic structures pinpoints to these channel proteins as promising targets for future pharmacological efforts. PMID:12591157

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

2003-02-20

184

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

PubMed Central

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

Ebdrup, B.H; N?rbak, H; Borgwardt, S; Glenth?j, B

2013-01-01

185

Millisecond timescale disinhibition mediates fast information transmission through an avian basal ganglia loop  

PubMed Central

Avian song learning shares striking similarities with human speech acquisition and requires a basal ganglia (BG)-thalamo-cortical circuit. Information processing and transmission speed in the BG is thought to be limited by synaptic architecture of two serial inhibitory connections. Propagation speed may be critical in the avian BG circuit given the temporally precise control of musculature during vocalization. We used electrical stimulation of the cortical inputs to the BG to study, with fine time resolution, the functional connectivity within this network. We found that neurons in thalamic and cortical nuclei that are not directly connected with the stimulated area can respond to the stimulation with extremely short latencies. Through pharmacological manipulations, we trace this property back to the BG, and show that the cortical stimulation triggers fast disinhibition of the thalamic neurons. Surprisingly, feedforward inhibition mediated by striatal inhibitory neurons onto BG output neurons sometimes precedes the monosynaptic excitatory drive from cortical afferents. The fast feedforward inhibition lengthens a single inter-spike interval in BG output neurons by just a few milliseconds. This short delay is sufficient to drive a strong, brief increase in firing probability in the target thalamic neurons, evoking short latency responses. By blocking glutamate receptors in vivo, we show that thalamic responses do not appear to rely on excitatory drive, and we show in a theoretical model that they could be mediated by post-inhibitory rebound properties. Such fast signalling through disinhibition and rebound may be a crucial specialization for learning of rapid and temporally precise motor acts such as vocal communication.

Leblois, Arthur; Bodor, Agnes L; Person, Abigail L; Perkel, David J

2010-01-01

186

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

PubMed Central

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

Crittenden, Jill R.; Graybiel, Ann M.

2011-01-01

187

Glutamate decarboxylase-67 messenger RNA expression in normal human basal ganglia and in Parkinson's disease.  

PubMed

Expression of glutamate decarboxylase-67 messenger RNA was examined in the basal ganglia of normal controls and of cases of Parkinson's disease using in situ hybridization histochemistry in human post mortem material. In controls glutamate decarboxylase-67 messenger RNA expression was detected in all large neurons in both segments of the globus pallidus and in three neuronal subpopulations in the striatum as well as in substantia nigra reticulata neurons and in a small sub-population of subthalamic neurons. In Parkinson's disease, there was a statistically significant decrease of 50.7% in glutamate decarboxylase-67 messenger RNA expression per neuron in the lateral segment of the globus pallidus (controls: mean 72.8 microns2 +/- S.E.M. 8.7 of silver grain/neuron, n = 12; Parkinson's disease: mean 35.9 microns2 +/- S.E.M. 9.7 of silver grain/neuron, n = 9, P = 0.01, Student's t-test). In the medial segment of the globus pallidus, there was a small, but non-significant decrease of glutamate decarboxylase-67 messenger RNA expression in Parkinson's disease (controls: mean 100.6 microns2 +/- S.E.M. 7.2 of silver grain/neuron, n = 11; Parkinson's disease: mean 84.8 microns2 +/- S.E.M. 13.0 of silver grain/neuron, n = 7, P = 0.1, Student's t-test). No significant differences in glutamate decarboxylase-67 messenger RNA were detected in striatal neuronal sub-populations between Parkinson's disease cases and controls. These results are the first direct evidence in humans that there is increased inhibitory drive to the lateral segment of the globus pallidus in Parkinson's disease, as suggested by data from animal models. We therefore provide theoretical support for current experimental neurosurgical approaches to Parkinson's disease. PMID:8931005

Nisbet, A P; Eve, D J; Kingsbury, A E; Daniel, S E; Marsden, C D; Lees, A J; Foster, O J

1996-11-01

188

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

PubMed Central

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.

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

2014-01-01

189

Population and Computational Analysis of the MGEA6 P521A Variation as a Risk Factor for Familial Idiopathic Basal Ganglia Calcification (Fahr’s Disease)  

Microsoft Academic Search

Familial idiopathic basal ganglia calcification, also known as “Fahr’s disease” (FD), is a neuropsychiatric disorder with\\u000a autosomal dominant pattern of inheritance and characterized by symmetric basal ganglia calcifications and, occasionally, other\\u000a brain regions. Currently, there are three loci linked to this devastating disease. The first one (IBGC1) is located in 14q11.2-21.3\\u000a and the other two have been identified in 2q37

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

2011-01-01

190

In vivo basal ganglia volumetry through application of NURBS models to MR images.  

PubMed

Volumetry of basal ganglia (BG) based on magnetic resonance imaging (MRI) provides a sensitive marker in differential diagnosis of BG disorders. The non-uniform rational B-spline (NURBS) surfaces are mathematical representations of three-dimensional structures which have recently been applied in volumetric studies. In this study, a volumetric evaluation of BG based on NURBS was performed in 35 right-handed volunteers. We aimed to compare and validate this technique with respect to manual MRI volumetry and evaluate possible side differences between these structures. Intra- and interobserver biases less than 1.5% demonstrated the method's stability. The mean percentage differences between NURBS and manual methods were less than 1% for all the structures considered; however, the internal segments of the globus pallidus showed a mean percentage difference of about 1.7%. Rightward asymmetry was found for the caudate nucleus (mean+/-SD 3.20+/-0.20 cm(3) vs. 3.10+/-0.19 cm(3), P<0.001) for both its head (1.44+/-0.10 cm(3) vs. 1.41+/-0.09 cm(3), P<0.01) and its body/tail (1.73+/-0.11 cm(3) and 1.68+/-0.12 cm(3), P<0.01), and for the globus pallidus (1.23+/-0.08 cm(3) and 1.18+/-0.09 cm(3), P<0.001) for both the internal (0.33+/-0.05 cm(3) vs. 0.31+/-0.05 cm(3), P<0.01) and external (0.90+/-0.05 cm(3) vs. 0.86+/-0.05 cm(3), P<0.001) segments. No volumetric side differences were found for the putamen (3.43+/-0.14 cm(3) vs. 3.39+/-0.17 cm(3), P>0.05). The rightward asymmetry of the BG may be ascribed to the predominant use of the right hand. In conclusion, NURBS is an accurate and reliable method for quantitative volumetry of nervous structures. It offers the advantage of giving a three-dimensional representation of the structures examined. PMID:16568299

Anastasi, Giuseppe; Cutroneo, Giuseppina; Tomasello, Francesco; Lucerna, Sebastiano; Vitetta, AntonGiulio; Bramanti, Placido; Di Bella, Paolo; Parenti, Anna; Porzionato, Andrea; Macchi, Veronica; De Caro, Raffaele

2006-05-01

191

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

PubMed

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

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

2010-11-01

192

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

PubMed Central

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive–compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1–8?Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative–limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative–limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

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

2011-01-01

193

Delta-mediated cross-frequency coupling organizes oscillatory activity across the rat cortico-basal ganglia network  

PubMed Central

The brain's ability to integrate different behavioral and cognitive processes relies on its capacity to generate neural oscillations in a cooperative and coordinated manner. Cross-frequency coupling (CFC) has recently been proposed as one of the mechanisms involved in organizing brain activity. Here we investigated the phase-to-amplitude CFC (PA-CFC) patterns of the oscillatory activity in the cortico-basal ganglia network of healthy, freely moving rats. Within-structure analysis detected consistent PA-CFC patterns in the four regions analyzed, with the phase of delta waves modulating the amplitude of activity in the gamma (low-gamma ~50 Hz; high-gamma ~80 Hz) and high frequency ranges (high frequency oscillations HFO, ~150 Hz). Between-structure analysis revealed that the phase of delta waves parses the occurrence of transient episodes of coherence in the gamma and high frequency bands across the entire network, providing temporal windows of coherence between different structures. Significantly, this specific spatio-temporal organization was affected by the action of dopaminergic drugs. Taken together, our findings suggest that delta-mediated PA-CFC plays a key role in the organization of local and distant activities in the rat cortico-basal ganglia network by fine-tuning the timing of synchronization events across different structures.

Lopez-Azcarate, Jon; Nicolas, Maria Jesus; Cordon, Ivan; Alegre, Manuel; Valencia, Miguel; Artieda, Julio

2013-01-01

194

Synchronous high-voltage spindles in the cortex-basal ganglia network of awake and unrestrained rats.  

PubMed

Synchronous oscillations in various frequency ranges have been recorded in several nuclei of the basal ganglia (BG) and are thought to be an information processing mechanism. High-voltage spindles (HVSs) are 5-13 Hz spike-and-wave oscillations, which are commonly recorded in rats and which have been reported in some recent studies where their occurrence in the BG has been investigated. We recorded single neurons and local field potentials (LFPs) simultaneously in the motor cortex, striatum and substantia nigra pars reticulata (SNr) of the freely moving rat. We took advantage of the high level of synchronization observed during HVSs to study signal transmission in the cortex-BG network in the awake animals. The results show that LFPs are synchronized in the motor cortex, striatum and SNr during HVS episodes and that the latter propagate from the cortex to the SNr via the striatum. Moreover, > 50% of single neurons in each of these structures are triggered by the HVS. Following the discharge of cortical cells, SNr neurons are first inhibited after approximately 19 ms and then activated after approximately 45 ms. This response is probably driven by the direct and indirect pathways, respectively, without any involvement of the hyperdirect pathway. Here, it is shown that cortex-BG connectivity can be studied using physiological signals in the freely moving animal as opposed to artificial stimulation under anaesthetized conditions. This opens the door to further studies under various experimental conditions, such as animal models of basal ganglia disorders. PMID:17313572

Dejean, Cyril; Gross, Christian E; Bioulac, Bernard; Boraud, Thomas

2007-02-01

195

Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia.  

PubMed

ARPP-21 is a cyclic AMP-regulated phosphoprotein of M(r) 21 kDa that is enriched in the cell bodies and terminals of medium-sized spiny neurons in the basal ganglia. Using a new phosphorylation state-specific antibody selective for the detection of ARPP-21 phosphorylated on Ser(55), we have demonstrated that activation of dopamine D1 receptors increased the level of ARPP-21 phosphorylation in mouse striatal slices. Conversely, activation of D2 receptors caused a large decrease in ARPP-21 phosphorylation. Treatment of mice with either methamphetamine or cocaine resulted in increased ARPP-21 phosphorylation in vivo. Studies using specific inhibitors of protein phosphatases and experiments in mice bearing a targeted deletion of the gene for DARPP-32, a dopamine-activated inhibitor of protein phosphatase-1, indicated that protein phosphatase-2A is primarily responsible for dephosphorylation of ARPP-21 in mouse striatum. These results demonstrate that phosphorylation and dephosphorylation of ARPP-21 are tightly regulated in the striatum. We speculate that ARPP-21 might mediate some of the physiologic effects of dopamine and certain drugs of abuse in the basal ganglia. PMID:10854908

Caporaso, G L; Bibb, J A; Snyder, G L; Valle, C; Rakhilin, S; Fienberg, A A; Hemmings, H C; Nairn, A C; Greengard, P

2000-07-10

196

Delta-mediated cross-frequency coupling organizes oscillatory activity across the rat cortico-basal ganglia network.  

PubMed

The brain's ability to integrate different behavioral and cognitive processes relies on its capacity to generate neural oscillations in a cooperative and coordinated manner. Cross-frequency coupling (CFC) has recently been proposed as one of the mechanisms involved in organizing brain activity. Here we investigated the phase-to-amplitude CFC (PA-CFC) patterns of the oscillatory activity in the cortico-basal ganglia network of healthy, freely moving rats. Within-structure analysis detected consistent PA-CFC patterns in the four regions analyzed, with the phase of delta waves modulating the amplitude of activity in the gamma (low-gamma ~50 Hz; high-gamma ~80 Hz) and high frequency ranges (high frequency oscillations HFO, ~150 Hz). Between-structure analysis revealed that the phase of delta waves parses the occurrence of transient episodes of coherence in the gamma and high frequency bands across the entire network, providing temporal windows of coherence between different structures. Significantly, this specific spatio-temporal organization was affected by the action of dopaminergic drugs. Taken together, our findings suggest that delta-mediated PA-CFC plays a key role in the organization of local and distant activities in the rat cortico-basal ganglia network by fine-tuning the timing of synchronization events across different structures. PMID:24106462

López-Azcárate, Jon; Nicolás, María Jesús; Cordon, Ivan; Alegre, Manuel; Valencia, Miguel; Artieda, Julio

2013-01-01

197

Stress-induced upregulation of SLC19A3 is impaired in biotin-thiamine-responsive basal ganglia disease.  

PubMed

Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a potentially treatable disorder caused by mutations in the SLC19A3 gene, encoding the human thiamine transporter 2. Manifestation of BTBGD as acute encephalopathy triggered by a febrile infection has been frequently reported, but the underlying mechanisms are not clear. We investigated a family with two brothers being compound heterozygous for the SLC19A3 mutations p.W94R and p.Q393*fs. Post-mortem analysis of the brain of one brother showed a mixture of acute, subacute and chronic changes with cystic and necrotic lesions and hemorrhage in the putamen, and hemorrhagic lesions in the caudate nucleus and cortical layers. SLC19A3 expression was substantially reduced in the cortex, basal ganglia and cerebellum compared with an age-matched control. Importantly, exposure of fibroblasts to stress factors such as acidosis or hypoxia markedly upregulated SLC19A3 in control cells, but failed to elevate SLC19A3 expression in the patient's fibroblasts. These results demonstrate ubiquitously reduced thiamine transporter function in the cerebral gray matter, and neuropathological alterations similar to Wernicke's disease in BTBGD. They also suggest that episodes of encephalopathy are caused by a substantially reduced capacity of mutant neuronal cells to increase SLC19A3 expression, necessary to adapt to stress conditions. PMID:24372704

Schänzer, Anne; Döring, Barbara; Ondrouschek, Michelle; Goos, Sarah; Garvalov, Boyan K; Geyer, Joachim; Acker, Till; Neubauer, Bernd; Hahn, Andreas

2014-04-01

198

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

PubMed

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

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

1991-09-01

199

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

PubMed

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

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

2014-05-16

200

Sensory stimulus-sensitive drop attacks and basal ganglia calcification: new findings in a patient with FOLR1 deficiency.  

PubMed

Loss-of-function mutations in the FOLR1 gene (MIM *136430), encoding the folate receptor alpha, impair cerebral folate transport and lead to a progressive neurometabolic disorder. We report on a 5-year-old boy with progressive ataxia, from the age of 2 years and 6 months, with myoclonic jerks, regression, and impressive myoclonic tonic spasms with drop attacks, which were partially provoked by touching his face or washing his hands. Delayed myelination and cerebellar atrophy on cranial MRI were important clues to the diagnosis of cerebral folate transport deficiency, which was confirmed by homozygosity for the known nonsense mutation p.R204X in the FOLR1 gene. Computed tomography taken after head injury revealed bilateral calcifications in the basal ganglia as a novel finding in a patient with FOLR1 mutation. PMID:24556562

Toelle, Sandra P; Wille, David; Schmitt, Bernhard; Scheer, Ianina; Thöny, Beat; Plecko, Barbara

2014-03-01

201

Effective deep brain stimulation suppresses low frequency network oscillations in the basal ganglia by regularizing neural firing patterns  

PubMed Central

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson’s disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90Hz) improve motor symptoms, while low frequencies (<50Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high frequency DBS reversed motor symptoms and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high frequency DBS, but not low frequency DBS, reduced pathological low frequency oscillations (~9Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low frequency band to the stimulation frequency during high frequency DBS, but not during low frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high frequency DBS is more effective than low frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low frequency network oscillations with a regularized pattern of neuronal firing.

McConnell, George C.; So, Rosa Q.; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M.

2012-01-01

202

The efferent projections of the dorsal and ventral pallidal parts of the pigeon basal ganglia, studied with biotinylated dextran amine.  

PubMed

In the present study we have investigated the efferent projections of both the dorsal and the ventral pallidum of the pigeon basal ganglia, using the sensitive anterograde tracer biotinylated dextran amine [Veenman C. L. et al. (1992) J. Neurosci. Meth. 41, 239-254]. Injections of biotinylated dextran amine in the pigeon dorsal pallidum produced numerous fibers and terminals in specific nuclei of the thalamus, hypothalamus, pretectum and midbrain tegmentum. In the thalamus, labeled fibers and terminals were observed in the avian thalamic reticular nucleus, the proposed motor part of the avian ventral tier (ventrointermediate area), the avian parafascicular nucleus (nucleus dorsointermedius posterior), as well as in the avian nucleus subrotundus (which may be comparable to the posterior intralaminar nuclei of mammals). Labeled fibers and terminals were also observed in the avian subthalamic nucleus (anterior nucleus of the ansa lenticularis), in the pretectum (nucleus spiriformis lateralis) and in the avian substantia nigra pars reticulata. Injections of biotinylated dextran amine in the pigeon ventral pallidum produced fibers and terminals in specific centers of the telencephalon, hypothalamus, thalamus, epithalamus, and midbrain and isthmic tegmentum. Labeled fibers and terminals were also observed in the avian subthalamic nucleus and the inmediately adjacent lateral hypothalamus, the avian thalamic reticular nucleus, the avian medidorsal nucleusaand posterior intralaminar nuclei, and the lateral habenula. Finally, labeled fibers and terminals were found in the ventral tegmental area, the avian substantia nigra pars compacta and the midbrain/isthmic tegmentum, which includes the pedunculopontine tegmental nucleus. Our results indicate that both the dorsal and ventral pallida of birds have unique and specific projection patterns, which are very similar to those of their counterparts in mammals. Our study suggests that these avian basal ganglia regions may be related mainly to somatomotor and limbic functions, respectively. PMID:9316028

Medina, L; Reiner, A

1997-12-01

203

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

PubMed

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

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

2010-03-01

204

Distribution of glutamic acid decarboxylase (M r 67 000) in the basal ganglia of the rat: an immunohistochemical study with a selective cDNA-generated polyclonal antibody  

Microsoft Academic Search

Summary Distinct isoforms of glutamic acid decarboxylase, the synthetic enzyme for GABA, exist in brain. Their distribution at the cellular level is not known, because previous studies have been confounded by the lack of monospecificity of available antibodies. We have examined the distribution of glutamic acid decarboxylase (Mr 67 000; GAD67) in the basal ganglia of the rat with a

C. Gonzales; D. L. Kaufman; A. J. Tobin; M.-F. Chesselet

1991-01-01

205

Regional differences in the distribution of endogenous receptors for carbohydrate constituents of cellular glycoconjugates, especially lectins, in cortex, hippocampus, basal ganglia and thalamus of adult human brain  

Microsoft Academic Search

Ten different types of labelled neoglycoproteins, exposing glycohistochemically pivotal carbohydrate moieties that mostly are constituents of naturally occurring glycoconjugates with an aromatic spacer, were synthesized. The panel was applied to fixed, paraffin-embedded sections of different cortical regions and white matter, of hippocampal gyrus, basal ganglia, thalamus nuclei and adjacent areas of adult human brain to comprehensively map the presence of

H.-J. Gabius; A. Bardosi

1990-01-01

206

Multiple Sclerosis and the Accumulation of Iron in the Basal Ganglia: Quantitative Assessment of Brain Iron Using MRI T2 Relaxometry  

Microsoft Academic Search

The aim of this work was to quantify the accumulation of iron in the basal ganglia in multiple sclerosis (MS) patients and in a control group, and to investigate the relationship between iron accumulation and other parameters assessed in MS, i.e. lesion load (LL) and brain parenchymal fraction (BPF). Magnetic resonance imaging T2 relaxometry was used for the measurement. 970

A. Burgetova; Z. Seidl; J. Krasensky; D. Horakova; M. Vaneckova

2010-01-01

207

Dose and behavioral context dependent inhibition of movement and basal ganglia neural activity by ??9-tetrahydrocannabinol during spontaneous and treadmill locomotion tasks in rats  

Microsoft Academic Search

9-THC ABSTRACT The effects of 9-tetrahydrocannabinole (9-THC) on locomotor ac- tivities and related basal ganglia neural responses were investigated in rats. A multiple- channel, single unit recording method was used to record neuronal activity in the dorsal lateral striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra pars reticulata simultaneously during spontaneous movement and treadmill locomotion. 9-THC treatment

L. H. Shi; F. Luo; D. J. Woodward; J. Y. Chang

2005-01-01

208

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

PubMed Central

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.

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

2014-01-01

209

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

PubMed Central

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.

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

2013-01-01

210

Basal hypersecretion of cortisol in relation to abnormal dexamethasone suppression test response in depression.  

PubMed

The activity of the hypothalamus-hypophysis-adrenal axis was evaluated in a group of patients with primary affective disorder by correlation of basal cortisol hypersecretion and abnormal response to dexamethasone suppression test (DST). The increase in basal cortisol was not found to be responsible for suppression failure. Moreover, this biochemical abnormality was common in the groups of psychiatric patients studied, although the physiopathologic mechanisms involved are different. Further research is necessary to clarify the results. PMID:3809524

Cabranes-Diaz, J A; Almoguera, I; Ayuso, J L; Garcia-Camba, E; Prensa, A

1986-01-01

211

High-signal basal ganglia on T1-weighted images in a patient with Sydenham's chorea  

Microsoft Academic Search

We report a 16-year-old girl with Sydenham's chorea. Choreiform movements involved both sides of her body. MRI 2 months after\\u000a the onset revealed abnormal increased signal on T2-weighted images and enlargement of the caudate and putamen bilaterally.\\u000a MRI 5 months later showed resolution of the swelling, but with increased signal on T1-weighted images in the putamen, globus\\u000a pallidus and the

N. Ikuta; M. Hirata; F. Sasabe; K. Negoro; M. Morimatsu

1998-01-01

212

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

NASA Astrophysics Data System (ADS)

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.

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

2011-08-01

213

"Habit" gambling behaviour caused by ischemic lesions affecting the cognitive territories of the basal ganglia.  

PubMed

We report the case of a patient suffering from sudden apathy and pathological gambling-like behaviour after bilateral ischemic lesions involving the dorsal portion of the head of the caudate nuclei and adjacent anterior limb of the internal capsules. This is the first report of the association of an apathy and abnormal gambling behaviour following a stroke affecting sub-cortical structures. Although the location of the lesions, affecting the dorsal striatum, may explain the emergence of an apathetic state, it is, however, at first sight, not easy to explain the gambling behaviour because the patient was normal in tests evaluating sensitivity to reward, and no radiological abnormality was found in the cortical-sub-cortical system of reward. It is proposed that, for this patient, the mechanism of maladaptive gambling behaviour was the development of a routine behaviour related to the patient's cognitive inertia, a mechanism different from the changes in reward sensitivity observed after damage to the orbital ventral prefrontal-ventral striatum system or in dopamine dysregulation syndrome in Parkinson's disease. PMID:20443019

Cognat, Emmanuel; Lagarde, Julien; Decaix, Caroline; Hainque, Elodie; Azizi, Louisa; Gaura-Schmidt, Veronique; Mesnage, Valerie; Levy, Richard

2010-10-01

214

Rare Case of Reversible Acute Symmetrical Lesions of the Bilateral Basal Ganglia Associated with Diabetic Nephropathy and Chronic Renal Failure  

PubMed Central

Reversible acute symmetrical basal ganglial lesion on magnetic resonance imaging and/or computed tomography in cases of diabetic nephropathy and chronic renal failure exhibiting acute onset of movement abnormalities like chorea is a very rare entity. It has characteristic clinical and imaging features. Only 29 cases are described in the literature, including the current one. These cases are predominantly Asian patients from the Far East and only one Asian Indian patient has been described. We report the second Asian Indian case of this condition and describe its various clinical and imaging features. Our aim is to educate the clinicians and radiologists about this condition, so that more such cases can be detected.

Mahajan, Parag Suresh; El Esnawi, Mohamed Amin; Hussein, Sheik Akbar; Al Maslamani, Nasser Jassim

2014-01-01

215

Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease  

PubMed Central

The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4–7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Miguelez, Cristina; Morera-Herreras, Teresa; Torrecilla, Maria; Ruiz-Ortega, Jose A.; Ugedo, Luisa

2014-01-01

216

Blood oxygenation level-dependent activation in basal ganglia nuclei relates to specific symptoms in de novo Parkinson's disease.  

PubMed

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

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

2010-10-15

217

Restoring the Basal Ganglia in Parkinson's disease to Normal via Multi-Input Phase-Shifted Deep Brain Stimulation  

PubMed Central

Deep brain stimulation (DBS) injects a high frequency current that effectively disables the diseased basal ganglia (BG) circuit in Parkinson’s disease (PD) patients, leading to a reversal of motor symptoms. Though therapeutic, high frequency stimulation consumes significant power forcing frequent surgical battery replacements and causing widespread influence into other brain areas which may lead to adverse side effects. In this paper, we conducted a rigorous study to assess whether low frequency signals can restore behavior in PD patients by restoring neural activity in the BG to the normal state. We used a biophysical-based model of BG nuclei and motor thalamus whose parameters can be set to simulate the normal state and the PD state with and without DBS. We administered pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies ranging from 1–150Hz. For each DBS frequency, we computed statistics on the simulated neural activity to assess whether it is restored to the normal state. In particular, we searched for DBS waveforms that suppress pathological bursting, oscillations, correlations and synchronization prevalent in the PD state and that enable thalamic cells to relay cortical inputs reliably. We found that none of the tested waveforms restores neural activity to the normal state. However, our simulations led us to construct a novel DBS strategy involving low frequency multi-input phaseshifted DBS to be administered into the STN. This strategy successfully suppressed all pathological symptoms in the BG in addition to enabling thalamic cells to relay cortical inputs reliably.

Agarwal, Rahul; Sarma, Sridevi V.

2014-01-01

218

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

PubMed Central

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.

Montgomery, Erwin B.

2011-01-01

219

Infarct of the right basal ganglia in a male spinal cord injury patient: adverse effect of autonomic dysreflexia.  

PubMed

Autonomic dysreflexia is a clinical emergency that occurs in individuals with spinal cord injury at level T-6 and above. We present a 58-year-old male patient with paraplegia who developed a severe, recurrent, throbbing headache during the night, which was relieved by emptying the urinary bladder by intermittent catheterisation. As this person continued to get episodes of severe headache for more than 6 months, computed tomography (CT) of the brain was performed. CT revealed an infarct measuring 1.2 cm in the right basal ganglia. In order to control involuntary detrusor contractions, the patient was prescribed propiverine hydrochloride 15 mg four times a day. The alpha-adrenoceptor blocking drug doxazosin was used to reduce the severity of autonomic dysreflexia. Following 4 weeks of treatment with propiverine and doxazosin, the headache subsided completely. We learned from this case that bladder spasms in individuals with spinal cord injury can lead to severe, recurrent episodes of autonomic dysreflexia that, in turn, can predispose to vascular complications in the brain. Therefore, it is important to take appropriate steps to control bladder spasms and thereby prevent recurrent episodes of autonomic dysreflexia. Intermittent catheterisations along with an alpha-adrenoceptor blocking drug (doxazosin) and an antimuscarinic drug (propiverine hydrochloride) helped this individual to control autonomic dysreflexia, triggered by bladder spasms during the night. PMID:21442144

Vaidyanathan, Subramanian; Soni, Bakul M; Singh, Gurpreet; Hughes, Peter L; Pulya, Kamesh; Oo, Tun

2011-01-01

220

The substantia nigra conveys target-dependent excitatory and inhibitory outputs from the Basal Ganglia to the thalamus.  

PubMed

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

Antal, Miklos; Beneduce, Brandon M; Regehr, Wade G

2014-06-01

221

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

PubMed Central

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.

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

2014-01-01

222

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

PubMed Central

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

Franz, E. A.

2012-01-01

223

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

PubMed Central

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

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

2011-01-01

224

Mutation Analysis of SLC20A2 and SPP2 as Candidate Genes for Familial Idiopathic Basal Ganglia Calcification  

PubMed Central

Background Familial Idiopathic Basal Ganglia Calcification (IBGC) is a rare neurodegenerative disorder which is usually transmitted as an autosomal dominant trait. IBGC is genetically heterogeneous and SLC20A2, on chromosome 8p21.1–8q11.23, is the first gene found in IBGC-affected patients with varied ancestry. On the other hand, several candidate genes for IBGC on chromosome 2q37, including the SPP2 gene, may play a role in inhibiting calcification. Methods Totally, 22 members of a three generational Iranian family affected by IBGC, with an autosomal dominant pattern of inheritance were included in this study. DNA was extracted from the whole blood using standard salting out method. To find a mutation responsible for IBGC, we sequenced the coding region of SLC20A2 as well as promoter and coding region of SPP2 in the index subject of IBGC-affected family. Results Pathogenic mutation was found neither in SLC20A2 nor in SPP2. Conclusion Our results strengthen genetic heterogeneity of this condition. Additional mutation studies are necessary to find a gene or genes responsible for IBGC in this affected family.

Ashtari, Fereshteh; Saliminejad, Kioomars; Ahani, Ali; Kamali, Koorosh; Pahlevanzadeh, Zhamak; Khorshid, Hamid Reza Khorram

2013-01-01

225

The role of extracellular adenosine in chemical neurotransmission in the hippocampus and Basal Ganglia: pharmacological and clinical aspects.  

PubMed

Now there is general agreement that the purine nucleoside adenosine is an important neuromodulator in the central nervous system, playing a crucial role in neuronal excitability and synaptic/non-synaptic transmission in the hippocampus and basal ganglia. Adenosine is derived from the breakdown of extra- or intracellular ATP and is released upon a variety of physiological and pathological stimuli from neuronal and non-neuronal sources, i.e. from glial cells and exerts effects diffusing far away from release sites. The resultant elevation of adenosine levels in the extracellular space reaches micromolar level, and leads to the activation A(1), A(2A), A(2B) and A(3) receptors, localized to pre- and postsynaptic as well as extrasynaptic sites. Activation of presynaptic A(1) receptors inhibits the release of the majority of transmitters including glutamate, acetylcholine, noradrenaline, 5-HT and dopamine, whilst the stimulation of A(2A) receptors facilitates the release of glutamate and acetylcholine and inhibits the release of GABA. These actions underlie modulation of neuronal excitability, synaptic plasticity and coordination of neural networks and provide intriguing target sites for pharmacological intervention in ischemia and Parkinson's disease. However, despite that adenosine is also released during ischemia, A(1) adenosine receptors do not participate in the modulation of excitotoxic glutamate release, which is nonsynaptic and is due to the reverse operation of transporters. Instead, extrasynaptic A(1) receptors might be responsible for the neuroprotection afforded by A(1) receptor activation. PMID:21401497

Sperlágh, Beáta; Vizi, E Sylvester

2011-01-01

226

Basal Ganglia Enlarged Perivascular Spaces are Linked to Cognitive Function in Patients with Cerebral Small Vessel Disease.  

PubMed

Enlarged perivascular spaces (EPVS) are a feature of cerebral small vessel disease (cSVD) and have been related to cSVD severity. A higher number of EPVS were related to decreased cognition in healthy elderly, but this has never been investigated in patients at high risk of cSVD. We included 189 patients with a high risk of cSVD (hypertensive patients and lacunar stroke patients). Patients underwent brain MRI and extensive neuropsychological assessment. EPVS were rated in the basal ganglia (BG) and centrum semiovale (CSO). Correlation analyses between EPVS and cognitive domains were adjusted for white matter lesions (WMLs), age, sex and symptomatic stroke. Negative correlations were found between EPVS in the BG and all cognitive domains, independent of WMLs. After correction for age, results remained significant for information processing speed (IPS) only. No independent correlation was found between EPVS in the CSO and cognition. We demonstrated that more BG EPVS were associated with a decrease in IPS, independent of age and WMLs. This emphasizes that specifically EPVS in the BG are associated with cSVD, and with cSVD-related decreases in cognition. PMID:24606607

Huijts, Marjolein; Duits, Annelien; Staals, Julie; Kroon, Abraham A; de Leeuw, Peter W; van Oostenbrugge, Robert J

2014-05-01

227

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

PubMed Central

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

Fee, Michale S.

2012-01-01

228

Evaluation of the effect of treatment on movement disorders in astrocytomas of the basal ganglia and the thalamus.  

PubMed Central

Twenty patients with movement disorders associated with astrocytomas (grade I-IV according to the WHO tumour classification) of the basal ganglia and the thalamus were evaluated for the effects of treatment. Five patients had more than one movement disorder when the histological diagnosis was verified by stereotactic biopsy. Twelve had tremors, eight hemidystonia, three hemichorea, and one hemichorea/ballismus, and myoclonus respectively. Ten patients died during the follow up period, and for the surviving patients follow up periods ranged from 6-21 years. The movement disorders changed over long periods of time related to therapeutic interventions. CSF shunt operations and percutaneous radiotherapy had no definite effect on the movement disorders. There was a moderate response to medical treatment in a few patients. Stereotactic aspiration of tumour cysts had a marked influence on the movement disorder in two patients, and functional stereotactic surgery abolished tumour induced tremor in one. Interstitial radiotherapy was performed in fifteen patients for treatment of the underlying neoplasm and resulted in different and variable alterations of the movement disorders. These differences may be explained by complex interactions involving structures affected primarily by the tumour, as well as by secondary functional lesions of adjacent structures. Images

Krauss, J K; Braus, D F; Mohadjer, M; Nobbe, F; Mundinger, F

1993-01-01

229

Exploring the cognitive and motor functions of the basal ganglia: an integrative review of computational cognitive neuroscience models  

PubMed Central

Many computational models of the basal ganglia (BG) have been proposed over the past twenty-five years. While computational neuroscience models have focused on closely matching the neurobiology of the BG, computational cognitive neuroscience (CCN) models have focused on how the BG can be used to implement cognitive and motor functions. This review article focuses on CCN models of the BG and how they use the neuroanatomy of the BG to account for cognitive and motor functions such as categorization, instrumental conditioning, probabilistic learning, working memory, sequence learning, automaticity, reaching, handwriting, and eye saccades. A total of 19 BG models accounting for one or more of these functions are reviewed and compared. The review concludes with a discussion of the limitations of existing CCN models of the BG and prescriptions for future modeling, including the need for computational models of the BG that can simultaneously account for cognitive and motor functions, and the need for a more complete specification of the role of the BG in behavioral functions.

Helie, Sebastien; Chakravarthy, Srinivasa; Moustafa, Ahmed A.

2013-01-01

230

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

Microsoft Academic Search

Summary In this study we examined the effects of striatal dopamine depletion on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Regional cerebral blood flow was measured in six patients with moderate Parkinson's disease and in six age-matched control subjects while they performed easy and difficult versions of a modified Tower of London planning

Adrian M. Owen; Julien Doyon; Alain Dagher; A. Sadikot; Alan C. Evans

1998-01-01

231

Basal ganglia and thalamic input from neurons located within the ventral tier cell cluster region of the substantia nigra pars compacta in the rat.  

PubMed

The most caudally located dopaminergic (DA) ventral tier neurons of the substantia nigra pars compacta (SNc) form typical cell clusters that are deeply embedded in the substantia nigra pars reticulata (SNr). Here we examine the efferent projections of 35 neurons located in the SNr region where these SNc cell clusters reside. The neuronal cell body was injected with biotinylated dextran amine so as to trace each complete axon in the sagittal or the coronal plane. Electrophysiological guidance guaranteed that the tracer was ejected among neurons displaying a typical SNc discharge pattern. Furthermore, double immunofluorescence and immunohistochemical labeling ensured that the tracer deposits were placed within the DA cell clusters. Three types of projection neurons occurred in the SNc ventral tier cell cluster region: type I neurons, projecting to basal ganglia; type II neurons, targeting both the basal ganglia and thalamus; and type III neurons, projecting only to the thalamus. The striatum was targeted by most of the type I and II neurons and the innervation reached both the striosome/subcallosal streak and matrix compartments. Many nigrostriatal fibers provided collaterals to the globus pallidus and, less frequently, to the subthalamic nucleus. At a thalamic level, type II and III neurons preferentially targeted the reticular, ventral posterolateral, and ventral medial nuclei. Our results reveal that the SNr region where DA ventral tier cell clusters reside harbors neurons projecting to the basal ganglia and/or the thalamus, thus suggesting that neurodegeneration of nigral neurons in Parkinson's disease might affect various extrastriatal basal ganglia structures and multiple thalamic nuclei. PMID:20151360

Cebrián, Carolina; Prensa, Lucía

2010-04-15

232

Neuronal activity in the substantia nigra in the anaesthetized rat has fractal characteristics. Evidence for firing-code patterns in the basal ganglia  

Microsoft Academic Search

Current models of the basal ganglia assume a firing-rate code for information processing. We have applied five complementary\\u000a computing methods to assess firing patterns in 188 cells of the substantia nigra in the anaesthetized rat. Fractal firing\\u000a activity was found in 100% of nigral cells projecting to the superior colliculus, in 51% of cells projecting to the thalamus\\u000a and in

M. Rodríguez; E. Pereda; J. González; P. Abdala; J. A. Obeso

2003-01-01

233

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

Microsoft Academic Search

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

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

2006-01-01

234

An age and gender dependency of metabolite concentrations in basal ganglia in children with spastic diplegia: proton magnetic resonance spectroscopy study.  

PubMed

We determined metabolite profile in spastic diplegic children compared to controls in left basal ganglia of brain in using proton magnetic resonance spectroscopy in correlation with age and gender. Twenty-four patients with spastic diplegia and twenty-six healthy children were examined. The relative concentrations of N-acetylaspartate, choline, and myoinositol were measured in relation to creatine and different combinations of metabolites within 8-cm(3) brain voxel. Children with spastic diplegia showed reduced ratios of N-acetylaspartate/creatine, N-acetylaspartate/ choline, and N-acetylaspartate/myoinositol in the basal ganglia compared to the control group. Patients and controls subjects demonstrated a significant age-dependent increase in N-acetylaspartate/creatine, N-acetylaspartate/choline in the basal ganglia. No gender-dependent difference was shown in children with cerebral palsy for all tested metabolite ratios. Gender-related differences because of increased ratio N-acetylaspartate/choline in girls in controls were detected. These results indicate that maturation of brain exists in cerebral palsy and healthy children to a higher degree in healthy children. PMID:18936194

Kulak, Wojciech; Sobaniec, Wojciech; Smigielska-Kuzia, Joanna; Kubas, Bozena; Zawada, Bozena; Otapowicz, Dorota

2009-01-01

235

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

PubMed Central

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

Morita, Kenji; Kato, Ayaka

2014-01-01

236

Action selection performance of a reconfigurable basal ganglia inspired model with Hebbian-Bayesian Go-NoGo connectivity  

PubMed Central

Several studies have shown a strong involvement of the basal ganglia (BG) in action selection and dopamine dependent learning. The dopaminergic signal to striatum, the input stage of the BG, has been commonly described as coding a reward prediction error (RPE), i.e., the difference between the predicted and actual reward. The RPE has been hypothesized to be critical in the modulation of the synaptic plasticity in cortico-striatal synapses in the direct and indirect pathway. We developed an abstract computational model of the BG, with a dual pathway structure functionally corresponding to the direct and indirect pathways, and compared its behavior to biological data as well as other reinforcement learning models. The computations in our model are inspired by Bayesian inference, and the synaptic plasticity changes depend on a three factor Hebbian–Bayesian learning rule based on co-activation of pre- and post-synaptic units and on the value of the RPE. The model builds on a modified Actor-Critic architecture and implements the direct (Go) and the indirect (NoGo) pathway, as well as the reward prediction (RP) system, acting in a complementary fashion. We investigated the performance of the model system when different configurations of the Go, NoGo, and RP system were utilized, e.g., using only the Go, NoGo, or RP system, or combinations of those. Learning performance was investigated in several types of learning paradigms, such as learning-relearning, successive learning, stochastic learning, reversal learning and a two-choice task. The RPE and the activity of the model during learning were similar to monkey electrophysiological and behavioral data. Our results, however, show that there is not a unique best way to configure this BG model to handle well all the learning paradigms tested. We thus suggest that an agent might dynamically configure its action selection mode, possibly depending on task characteristics and also on how much time is available.

Berthet, Pierre; Hellgren-Kotaleski, Jeanette; Lansner, Anders

2012-01-01

237

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

PubMed Central

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.

Hoshi, Eiji

2013-01-01

238

Model-Based Analysis and Control of a Network of Basal Ganglia Spiking Neurons in the Normal and Parkinsonian States  

PubMed Central

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 PD and pave the way towards a model-based, network level analysis and closed-loop control and optimization of DBS parameters, among many other applications.

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

2011-01-01

239

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

PubMed

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

Morita, Kenji; Kato, Ayaka

2014-01-01

240

Thalamic haemorrhage vs internal capsule-basal ganglia haemorrhage: clinical profile and predictors of in-hospital mortality  

PubMed Central

Background There is a paucity of clinical studies focused specifically on intracerebral haemorrhages of subcortical topography, a subject matter of interest to clinicians involved in stroke management. This single centre, retrospective study was conducted with the following objectives: a) to describe the aetiological, clinical and prognostic characteristics of patients with thalamic haemorrhage as compared with that of patients with internal capsule-basal ganglia haemorrhage, and b) to identify predictors of in-hospital mortality in patients with thalamic haemorrhage. Methods Forty-seven patients with thalamic haemorrhage were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 17 years. Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The region of the intracranial haemorrhage was identified on computerized tomographic (CT) scans and/or magnetic resonance imaging (MRI) of the brain. Results Thalamic haemorrhage accounted for 1.4% of all cases of stroke (n = 3420) and 13% of intracerebral haemorrhage (n = 364). Hypertension (53.2%), vascular malformations (6.4%), haematological conditions (4.3%) and anticoagulation (2.1%) were the main causes of thalamic haemorrhage. In-hospital mortality was 19% (n = 9). Sensory deficit, speech disturbances and lacunar syndrome were significantly associated with thalamic haemorrhage, whereas altered consciousness (odds ratio [OR] = 39.56), intraventricular involvement (OR = 24.74) and age (OR = 1.23), were independent predictors of in-hospital mortality. Conclusion One in 8 patients with acute intracerebral haemorrhage had a thalamic hematoma. Altered consciousness, intraventricular extension of the hematoma and advanced age were determinants of a poor early outcome.

Arboix, Adria; Rodriguez-Aguilar, Raquel; Oliveres, Montserrat; Comes, Emili; Garcia-Eroles, Luis; Massons, Joan

2007-01-01

241

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

PubMed

Activation of type 1 cannabinoid receptors (CB(1)R) 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 CB(1)R expression in song control nuclei peaks around the closure of the sensori-motor integration phase of song development. Also, systemic administration of a CB(1)R agonist during vocal development impairs song learning. Here we test whether activation of CB(1)R alters excitatory synaptic input on spiny neurons in area X of adult male zebra finches. Application of the CB(1)R agonist WIN55212-2 decreased excitatory postsynaptic current (EPSC) amplitude; that decrease was blocked by the CB(1)R antagonist AM251. Guided by eCB experiments in mammalian striatum, we tested and verified that at least two mechanisms indirectly activate CB(1)Rs through eCBs in area X. First, activation of group I metabotropic glutamate receptors with the agonist 3,5-dihydroxyphenylglycine (DHPG) induced a CB(1)R-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 CB(1)R 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

Thompson, John A; Perkel, David J

2011-03-01

242

MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation  

PubMed Central

Background Propionic acidaemia (PA) results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS) to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes. Methods Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging. Results MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group. Conclusions The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to replenish a compromised Krebs cycle and that this is a marker of compromised aerobic respiration within brain tissue. Thus there is a need for improved brain protective strategies during acute metabolic decompensations. MRS provides a non-invasive tool for which could be employed to evaluate novel treatments aimed at restoring basal ganglia homeostasis. The results from the liver transplantation sub-group supports the hypothesis that liver transplantation provides systemic metabolic stability by providing a hepatic pool of functional propionyl CoA carboxylase, thus preventing further acute decompensations which are associated with the risk of brain infarction.

2011-01-01

243

Basal ganglia dysfunction  

MedlinePLUS

... Pa: Saunders Elsevier; 2011:chap 416. Jankovic J. Movement disorders. In: Daroff RB, Fenichel GM, Jankovic J, Mazziotta ... Saunders Elsevier; 2012:chap 71. Lang AE. Other movement disorders. In: Goldman L, SchaferAI, eds. Cecil Medicine . 24th ...

244

The distribution of GABA-containing perikarya, fibers, and terminals in the forebrain and midbrain of pigeons, with particular reference to the basal ganglia and its projection targets.  

PubMed

Immunohistochemical techniques were used to study the distributions of glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in pigeon forebrain and midbrain to determine the organization of GABAergic systems in these brain areas in birds. In the basal ganglia, numerous medium-sized neurons throughout the striatum were labeled for GABA, while pallidal neurons, as well as a small population of large, aspiny striatal neurons, labeled for GAD and GABA. GAD+ and GABA+ fibers and terminals were abundant throughout the basal ganglia, and GABAergic fibers were found in all extratelencephalic targets of the basal ganglia. Most of these targets also contained numerous GABAergic neurons. In pallial regions, approximately 10-12% of the neurons were GABAergic. The outer rind of the pallium was more intensely labeled for GABAergic fibers than the core. The olfactory tubercle region, the ventral pallidum, and the hypothalamus were extremely densely labeled for GABAergic fibers, while GABAergic neurons were unevenly distributed in the hypothalamus. GABAergic neurons and fibers were abundant in the dorsalmost part of thalamus and the dorsal geniculate region, while GABAergic neurons and fibers were sparse (or lightly labeled) in the thalamic nuclei rotundus, triangularis, and ovoidalis. Further, GABAergic neurons were abundant in the superficial tectal layers, the magnocellular isthmic nucleus, the inferior colliculus, the intercollicular region, the central gray, and the reticular formation. GABAergic fibers were particularly abundant in the superficial tectal layers, the parvocellular isthmic nucleus, the inferior colliculus, the intercollicular region, the central gray, and the interpeduncular nucleus. These results suggest that GABA plays a role as a neurotransmitter in nearly all fore- and midbrain regions of birds, and in many instances the observed distributions of GABAergic neurons and fibers closely resemble the patterns seen in mammals, as well as in other vertebrates. PMID:8300906

Veenman, C L; Reiner, A

1994-01-01

245

Auditory experience refines cortico-basal ganglia inputs to motor cortex via remapping of single axons during vocal learning in zebra finches  

PubMed Central

Experience-dependent changes in neural connectivity underlie developmental learning and result in life-long changes in behavior. In songbirds axons from the cortical region LMANcore (core region of lateral magnocellular nucleus of anterior nidopallium) convey the output of a basal ganglia circuit necessary for song learning to vocal motor cortex [robust nucleus of the arcopallium (RA)]. This axonal projection undergoes remodeling during the sensitive period for learning to achieve topographic organization. To examine how auditory experience instructs the development of connectivity in this pathway, we compared the morphology of individual LMANcore?RA axon arbors in normal juvenile songbirds to those raised in white noise. The spatial extent of axon arbors decreased during the first week of vocal learning, even in the absence of normal auditory experience. During the second week of vocal learning axon arbors of normal birds showed a loss of branches and varicosities; in contrast, experience-deprived birds showed no reduction in branches or varicosities and maintained some arbors in the wrong topographic location. Thus both experience-independent and experience-dependent processes are necessary to establish topographic organization in juvenile birds, which may allow birds to modify their vocal output in a directed manner and match their vocalizations to a tutor song. Many LMANcore axons of juvenile birds, but not adults, extended branches into dorsal arcopallium (Ad), a region adjacent to RA that is part of a parallel basal ganglia pathway also necessary for vocal learning. This transient projection provides a point of integration between the two basal ganglia pathways, suggesting that these branches convey corollary discharge signals as birds are actively engaged in learning.

Miller-Sims, Vanessa C.

2012-01-01

246

Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials  

NASA Astrophysics Data System (ADS)

We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity.

Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe

2004-09-01

247

Auditory-dependent vocal recovery in adult male zebra finches is facilitated by lesion of a forebrain pathway that includes the basal ganglia.  

PubMed

The integration of two neural pathways generates learned song in zebra finches. The vocal motor pathway (VMP) is a direct connection between HVC (proper name) and the robust nucleus of the arcopallium (RA), whereas the anterior forebrain pathway (AFP) comprises an indirect circuit from HVC to RA that traverses the basal ganglia. Partial ablation (microlesion) of HVC in adult birds alters the integration of VMP and AFP synaptic input within RA and destabilizes singing. However, the vocal pattern shows surprising resilience because birds subsequently recover their song in approximately 1 week. Here, we show that deafening prevents vocal recovery after HVC microlesions, indicating that birds require auditory feedback to restore/relearn their vocal patterns. We then tested the role of the AFP (basal ganglia circuit) in this feedback-based recovery by ablating the output nucleus of the AFP [lateral magnocellular nucleus of the anterior nidopallium (LMAN)]. We found that LMAN ablation after HVC microlesions induced a sudden recovery of the vocal pattern. Thus, the AFP cannot be the neural locus of an instructive/learning mechanism that uses auditory feedback to guide vocal recovery, at least in this form of adult vocal plasticity. Instead, the AFP appears to be the source of the variable motor patterns responsible for vocal destabilization. In part, auditory feedback may restore song by strengthening the VMP component of synaptic input to RA relative to the AFP component. PMID:17989295

Thompson, John A; Wu, Wei; Bertram, Richard; Johnson, Frank

2007-11-01

248

Abnormal basal-body number, location, and orientation in a striated fiber-defective mutant of Chlamydomonas reinhardtii  

PubMed Central

We describe a mutant of Chlamydomonas reinhardtii in which basal body associated striated fibers are absent or incomplete. Basal body spacing, angle, and relative rotational orientation are abnormal and extremely variable. Abnormal partitioning of cellular contents at cytokinesis is also evident. Mating, maintenance of flagellar length equality, and backward swimming response are normal. Genetic analysis indicates mutation of a new Mendelian gene--vfl-3--linked to the centromere of Chromosome VI.

1983-01-01

249

Modulatory Effect of Acupuncture at Waiguan (TE5) on the Functional Connectivity of the Central Nervous System of Patients with Ischemic Stroke in the Left Basal Ganglia  

PubMed Central

Objective To study the influence of acupuncture at Waiguan (TE5) on the functional connectivity of the central nervous system of patients with ischemic stroke. Methods Twenty-four patients with ischemic stroke in the left basal ganglia were randomized based on gender to receive TE5 acupuncture (n?=?12) or nonacupoint acupuncture (n?=?12). Each group underwent sham acupuncture and then verum acupuncture while being scanned with functional magnetic resonance imaging. Six regions of interest (ROI) were defined, including bilateral motor, somatosensory, and bilateral basal ganglia areas. The functional connectivity between these ROIs and all voxels of the brain was analyzed in Analysis of Functional NeuroImages(AFNI) to explore the differences between verum acupuncture and sham acupuncture at TE5 and between TE5 acupuncture and nonacupoint acupuncture. The participants were blinded to the allocation. Result The effect of acupuncture on six seed-associated networks was explored. The result demonstrated that acupuncture at Waiguan (TE5) can regulate the sensorimotor network of the ipsilesional hemisphere, stimulate the contralesional sensorimotor network, increase cooperation of bilateral sensorimotor networks, and change the synchronization between the cerebellum and cerebrum. Furthermore, a lot of differences of effect existed between verum acupuncture and sham acupuncture at TE5, but there was little difference between TE5 acupuncture and nonacupoint acupuncture. Conclusion The modulation of synchronizations between different regions within different brain networks might be the mechanism of acupuncture at Waiguan (TE5). Stimulation of the contralesional sensorimotor network and increase of cooperation of bilateral hemispheres imply a compensatory effect of the intact hemisphere, whereas changes in synchronization might influence the sensorimotor function of the affected side of the body. Trial Registration Chinese Clinical Trial Registry ChiCTR-ONRC-08000255

Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Wu, Junxian; Zeng, Tongjun; Qu, Shanshan

2014-01-01

250

Downregulation of cannabinoid receptor 1 from neuropeptide Y interneurons in the basal ganglia of patients with Huntington's disease and mouse models  

PubMed Central

Cannabinoid receptor 1 (CB1 receptor) controls several neuronal functions, including neurotransmitter release, synaptic plasticity, gene expression and neuronal viability. Downregulation of CB1 expression in the basal ganglia of patients with Huntington’s disease (HD) and animal models represents one of the earliest molecular events induced by mutant huntingtin (mHtt). This early disruption of neuronal CB1 signaling is thought to contribute to HD symptoms and neurodegeneration. Here we determined whether CB1 downregulation measured in patients with HD and mouse models was ubiquitous or restricted to specific striatal neuronal subpopulations. Using unbiased semi-quantitative immunohistochemistry, we confirmed previous studies showing that CB1 expression is downregulated in medium spiny neurons of the indirect pathway, and found that CB1 is also downregulated in neuropeptide Y (NPY)/neuronal nitric oxide synthase (nNOS)-expressing interneurons while remaining unchanged in parvalbumin- and calretinin-expressing interneurons. CB1 downregulation in striatal NPY/nNOS-expressing interneurons occurs in R6/2 mice, HdhQ150/Q150 mice and the caudate nucleus of patients with HD. In R6/2 mice, CB1 downregulation in NPY/nNOS-expressing interneurons correlates with diffuse expression of mHtt in the soma. This downregulation also occludes the ability of cannabinoid agonists to activate the pro-survival signaling molecule cAMP response element-binding protein in NPY/nNOS-expressing interneurons. Loss of CB1 signaling in NPY/nNOS-expressing interneurons could contribute to the impairment of basal ganglia functions linked to HD.

Horne, Eric A.; Coy, Jonathan; Swinney, Katie; Fung, Susan; Cherry, Allison E. T.; Marrs, William R.; Naydenov, Alipi V.; Lin, Yi Hsing; Sun, Xiaocui; Keene, C. Dirk; Grouzmann, Eric; Muchowski, Paul; Bates, Gillian P.; Mackie, Ken; Stella, Nephi

2013-01-01

251

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

PubMed

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

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

2013-01-01

252

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

PubMed Central

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

Hamaguchi, Kosuke; Mooney, Richard

2012-01-01

253

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

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.

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

2014-01-01

254

Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia activity and changes in tissue levels of monoamines in the rat.  

PubMed

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

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

2014-01-01

255

Dysfunction of the cortico-basal ganglia-cortical loop in a rat model of early parkinsonism is reversed by metabotropic glutamate receptor 5 antagonism.  

PubMed

This study examined the cellular correlates of the akinetic deficits produced in Wistar rats by discrete bilateral 6-hydroxydopamine (6-OHDA) striatal infusions in the dorsolateral striatum, mimicking the preferential denervation of the motor striatal territory in early symptomatic stage of Parkinson's disease (PD). Intraneuronal gene expression of cytochrome oxidase subunit I (COI), a metabolic index of neuronal activity, was increased in the subthalamic nucleus, substantia nigra pars reticulata and decreased in frontal cortical areas, but paradoxically unchanged in the striatum, globus pallidus, entopeduncular nucleus and ventrolateral thalamic nucleus. Neither preproenkephalin A nor preprotachykinin mRNA expression, markers of striatal projection neurons, were modified in the denervated striatal area despite 90% loss of dopamine (DA) terminals. Preproenkephalin A mRNA expression was however, decreased in the nondepleted striatal region, suggesting compensatory increase of dopamine tone from those spared areas. A chronic treatment with the metabotropic glutamate receptor 5 (mGluR5) antagonist 2-methyl-6-(phenylethylnyl)-pyridine (MPEP), which alleviated the akinetic disorders produced by the lesion, reversed the lesion-induced variations of COI gene expression, moderately increased this marker in the structures unaffected by the lesion and did not modify the striatal neuropeptides gene expression. These data suggest that the expression of akinetic deficits in early parkinsonism is associated with focused metabolic changes in the cortico-basal ganglia-cortical loop downstream of the striatum and pallidal complex. PMID:16324110

Oueslati, Abid; Breysse, Nathalie; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Salin, Pascal

2005-12-01

256

Basal ganglia stroke due to mild head trauma in pediatric age - clinical and therapeutic management: a case report and 10 year literature review.  

PubMed

Ischemia of the basal ganglia as an immediate consequence of minor head injury in children is rare (< 2% of all ischemic stroke in childhood) and is due to vasospasm of the lenticulostriate arteries. The clinical history of these lesions is particularly favourable because they are usually small, and also because the facial-brachial-crural hemiparesis typical of this pathology usually regresses after a period ranging from several weeks to several months, despite the persistence of an ischemic area on MRI. This is due to the well known neuronal plasticity of the CNS, in particular, of the primary motor cortex. The most effective therapeutic approach appears to be the conservative one, although the best treatment regimen is still not well defined.Young patients should be closely monitored and treated conservatively with osmotic diuretics to reduce perilesional edema. At the same time, however, it is very important to exclude, by means of instrumental and laboratory studies, conditions that could favour the onset of ischemia, including emboligen heart disease, thrombophilia and acute traumatic arterial dissections. Generally speaking, the prognosis in these cases is good. The authors describe their experience treating a 10-month old baby girl, with a left lenticular nucleus ischemia and report a literature review. PMID:21210991

Landi, Alessandro; Marotta, Nicola; Mancarella, Cristina; Marruzzo, Daniele; Salvati, Maurizio; Delfini, Roberto

2011-01-01

257

The basal ganglia and thalamus of the long-tailed macaque in stereotaxic coordinates. A template atlas based on coronal, sagittal and horizontal brain sections.  

PubMed

A stereotaxic brain atlas of the basal ganglia and thalamus of Macaca fascicularis presented here is designed with a surgical perspective. In this regard, all coordinates have been referenced to a line linking the anterior and posterior commissures (ac-pc line) and considering the center of the ac at the midline as the origin of the bicommissural space. The atlas comprises of 43 different plates (19 coronal levels, 10 sagittal levels and 14 horizontal levels). In addition to 'classical' cyto- and chemoarchitectural techniques such as the Nissl method and the acetylcholinesterase stain, several immunohistochemical stains have been performed in adjacent sections, including the detection of tyrosine hydroxylase, enkephalin, neurofilaments, parvalbumin and calbindin. In comparison to other existing stereotaxic atlases for M. fasicularis, this atlas has two main advantages: firstly, brain cartography is based on a wide variety of cyto- and chemoarchitectural stains carried out on adjacent sections, therefore enabling accurate segmentation. Secondly and most importantly, sagittal and horizontal planes are included. Sagittal planes are very useful for calculating oblique trajectories, whereas, clinical researchers engaged in neuroimaging studies will be more familiar with horizontal sections, as they use horizontal (also called "axial") brain images in their daily routine of their clinical practices. PMID:22179107

Lanciego, José L; Vázquez, Alfonso

2012-04-01

258

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

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

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

2014-01-01

259

A De Novo Mutation in the ?-Tubulin Gene TUBB4A Results in the Leukoencephalopathy Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum  

PubMed Central

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare hereditary leukoencephalopathy that was originally identified by MRI pattern analysis, and it has thus far defied all attempts at identifying the causal mutation. Only 22 cases are published in the literature to date. We performed exome sequencing on five family trios, two family quartets, and three single probands, which revealed that all eleven H-ABC-diagnosed individuals carry the same de novo single-nucleotide TUBB4A mutation resulting in nonsynonymous change p.Asp249Asn. Detailed investigation of one of the family quartets with the singular finding of an H-ABC-affected sibling pair revealed maternal mosaicism for the mutation, suggesting that rare de novo mutations that are initially phenotypically neutral in a mosaic individual can be disease causing in the subsequent generation. Modeling of TUBB4A shows that the mutation creates a nonsynonymous change at a highly conserved asparagine that sits at the intradimer interface of ?-tubulin and ?-tubulin, and this change might affect tubulin dimerization, microtubule polymerization, or microtubule stability. Consistent with H-ABC’s clinical presentation, TUBB4A is highly expressed in neurons, and a recent report has shown that an N-terminal alteration is associated with a heritable dystonia. Together, these data demonstrate that a single de novo mutation in TUBB4A results in H-ABC.

Simons, Cas; Wolf, Nicole I.; McNeil, Nathan; Caldovic, Ljubica; Devaney, Joseph M.; Takanohashi, Asako; Crawford, Joanna; Ru, Kelin; Grimmond, Sean M.; Miller, David; Tonduti, Davide; Schmidt, Johanna L.; Chudnow, Robert S.; van Coster, Rudy; Lagae, Lieven; Kisler, Jill; Sperner, Jurgen; van der Knaap, Marjo S.; Schiffmann, Raphael; Taft, Ryan J.; Vanderver, Adeline

2013-01-01

260

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

PubMed Central

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.

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

2014-01-01

261

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

PubMed

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

Thompson, Christopher K; Brenowitz, Eliot A

2005-01-17

262

Distribution of dopamine transporters in basal ganglia of cerebellar ataxic mice by [125I]RTI-121 quantitative autoradiography.  

PubMed

Dopamine (DA) uptake sites, or transporters, were examined with [125I]RTI-121 in mutant mice that exhibit motor control deficits, namely weaver, lurcher and dystonia musculorum. In lurcher mice, the distribution of [125I]RTI-121 binding was similar to controls, except for a decrease in the subthalamic nucleus. For dystonia musculorum mice, the labelling presented no differences between controls and mutants, except for decreases in the dorsal half of caudal neostriatum and in the ventral tegmental area. Moreover, in this mutant the left rostral neostriatum DA transporters were reduced, when compared to the right counterpart. In weaver heterozygote (wv/+) mice, the distribution and density gradients of [125I]RTI-121 labelling were similar as in their controls, except in caudal neostriatum, where binding was slightly higher. In contrast, the weaver homozygote (wv/wv) showed important decreases in labelling of the dorsal quadrant of rostral neostriatum as well as of the dorsal half of caudal neostriatum, where the reductions of binding densities were of 65% to 70%, respectively. There were also slight decreases in [125I]RTI-121 binding in olfactory tubercles as well as in subthalamic nucleus, but only in wv/wv mice. In substantia nigra pars compacta and ventral tegmental area of wv/wv mice the labelling was lower; however, while the 60% decrease in labelling in substantia nigra was highly significant, the 30% reduction in ventral tegmental area did not attain statistical significance. In summary, in the ataxic neurological mutant mice studied, important reductions of DA transporters were documented only for the weaver mice, the cerebellar mutant presenting, besides its cerebellar pathology, a known degeneration of mesencephalic dopaminergic neurons. The results rule out major alterations of the central DA systems in lurcher and dystonia musculorum, and are compatible with the hypothesis that the dopaminergic abnormalities of weaver mutants are not secondary to cerebellar atrophy, but may be a direct consequence of the abnormal weaver gene expressed by DA neurons leading to their apoptotic death. PMID:9460703

Strazielle, C; Lalonde, R; Amdiss, F; Botez, M I; Hébert, C; Reader, T A

1998-01-01

263

Distribution of SV2C mRNA and protein expression in the mouse brain with a particular emphasis on the basal ganglia system.  

PubMed

Synaptic vesicle 2 proteins (SV2), SV2A, SV2B and SV2C, are integral proteins localized on the surface of synaptic vesicles in all neurons. SV2 proteins appear to play an important, but not yet fully understood role in synaptic vesicle exocytosis and neurotransmitter release. Moreover, SV2 seems to be the receptor of the botulinum neurotoxin A. In the present study, using single and double-labeling fluorescent immunohistochemistry and in situ hybridization we have identified the brain pattern of SV2C mRNA and protein expression in mice. Our results indicated that SV2C protein was expressed in a small subset of brain regions including the olfactory bulb, olfactory tubercle, nucleus accumbens, caudate-putamen, ventral pallidum, globus pallidus, substantia nigra and the ventral tegmental area. These results were confirmed by means of in situ hybridization, except for the globus pallidus and the substantia nigra pars reticulata, in which no labeling was found, suggesting that SV2C-positive fibers in these areas are terminals of striatal projecting neurons. In the striatum, we found that, in addition to its presence in the projection neurons, SV2C was densely expressed in a fraction (around 45%) of cholinergic interneurons. In addition, our data also showed that SV2C was densely expressed in most dopaminergic neurons in the substantia nigra pars compacta and the ventral tegmental area (more than 70% of the dopaminergic neurons analyzed were SV2C-positive). Altogether, our results suggest that SV2C may contribute to the regulation of neurotransmitter release and synaptic transmission in the basal ganglia including cholinergic striatal interneurons and nigro-striatal/mesolimbic dopamine neurons. PMID:20869353

Dardou, D; Dassesse, D; Cuvelier, L; Deprez, T; De Ryck, M; Schiffmann, S N

2011-01-01

264

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

PubMed

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

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

265

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

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.

Segovia, Kristen N.; Vontell, Regina; Lopez-Cruz, Laura; Salamone, John D.; Correa, Merce

2013-01-01

266

Abnormal movements are associated with poor psychosocial functioning in adolescents at high risk for psychosis  

Microsoft Academic Search

The period immediately preceding the onset of overt psychosis is characterized by a range of symptoms and behaviors including emerging attenuated psychosis, spontaneous movement abnormalities, and a broad decline in role and social functioning. Recent evidence suggests that basal ganglia dysfunction, which is implicated in the development of psychotic symptomatology, may manifest in the form of both movement abnormalities and

Vijay A. Mittal; Maria Jalbrzikowski; Melita Daley; Cristina Roman; Carrie E. Bearden; Tyrone D. Cannon

2011-01-01

267

Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia  

ERIC Educational Resources Information Center

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…

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

268

Opposing actions of adenosine A2a and dopamine D2 receptor activation on GABA release in the basal ganglia: evidence for an A2a/D2 receptor interaction in globus pallidus.  

PubMed

There is increasing evidence that adenosine (ADO) and dopamine (DA) interact directly in the basal ganglia via actions at ADO A2a and DA D2 receptors, respectively. The purpose of this study was to determine 1) the extent to which these receptors modulate endogenous GABA release in discrete regions of the rat basal ganglia and 2) whether GABA release is modulated by a direct and opposing interaction between ADO A2a and DA D2 receptors. Tissue slices of striatum (STR) containing globus pallidus (GP; STR/GP) and micropunches of STR, GP, and substantia nigra pars reticulata (SNr) were studied. Radioligand binding demonstrated that ADO A1, ADO A2a, and DA D2 receptors were present in each of the tissue preparations with the exception of SNr, in which ADO A2a receptors were not detected. Stimulation of ADO A2a receptors with CGS 21680 (1-10 nM) increased electrically stimulated GABA release in STR/GP slices and GP micropunches. Consistent with the lack of A2a receptors in SNr, CGS 21680 had no effect on GABA release from this region. In contrast, stimulation of DA D2 receptors with N-0437 (1-100 nM) inhibited evoked GABA release from STR/GP slices and both GP and SNr micropunches. The D2-mediated inhibition of GABA release in GP was abolished in the presence of CGS 21680 (10 nM). These experiments demonstrate that stimulation of ADO A2a and DA D2 receptors has opposing effects on endogenous GABA release in STR and GP. These opposing actions may explain the antagonistic interactions between ADO and DA that have been observed in behavioral studies and support the hypothesis that the striatopallidal efferent system is an important anatomical substrate for the A2a/D2 receptor interaction. PMID:8787129

Dayne Mayfield, R; Larson, G; Orona, R A; Zahniser, N R

1996-02-01

269

Microdialysis in Parkinsonian patient basal ganglia: acute apomorphine-induced clinical and electrophysiological effects not paralleled by changes in the release of neuroactive amino acids.  

PubMed

During stereotaxic neurosurgery for deep brain stimulation in Parkinson's disease (PD), we performed a microdialysis study of the extracellular amino acid (aspartate, glutamate, glycine, and GABA) concentrations. Their levels were measured in the GPe/GPi of five and in the STN of four different PD patients, after prolonged therapy washout. The results show stable values of basal release of the examined amino acids within 1 h. The basal levels of GABA in "OFF" state were significantly higher in the GPi than in the GPe. Acute apomorphine administration, while inducing clinical amelioration and electrophysiological changes in the examined nuclei, did not change amino acid concentrations. This result could be related to a limited microdialysis ability to detect subtle changes in amino acid spontaneous release. Alternatively, it could suggest that dopaminergic receptors located in the output nuclei, possibly present also in humans, might mediate the acute apomorphine clinical effects, not involving amino acid changes along the direct and/or indirect pathway. PMID:11161624

Fedele, E; Mazzone, P; Stefani, A; Bassi, A; Ansaldo, M A; Raiteri, M; Altibrandi, M G; Pierantozzi, M; Giacomini, P; Bernardi, G; Stanzione, P

2001-02-01

270

Abnormal resonance behavior of the postural control loop in Parkinson’s disease  

Microsoft Academic Search

Human postural control of upright stance sporadically can show an oscillatory behavior. Based on previous work, we assessed whether an abnormal tendency for such oscillations might contribute to the motor impairments in patients with basal ganglia dysfunction such as Parkinson’s disease (PD). We investigated postural control during unperturbed stance in normal control subjects and in PD patients off and under

C. Maurer; T. Mergner; R. J. Peterka

2004-01-01

271

Abnormalities of basal cell keratin in epidermolysis bullosa simplex do not affect the expression patterns of suprabasal keratins and cornified cell envelope proteins.  

PubMed

Basal keratins, suprabasal keratins, filaggrin, and cornified cell envelope (CCE) precursor proteins are expressed during the differentiation of epidermal keratinocytes. These molecules are coordinately expressed during epidermal differentiation. The present study investigated the expression patterns of keratins and CCE precursor proteins in 15 patients with epidermolysis bullosa simplex (EBS), which is caused by mutations in the genes that encode for the basal keratins, keratins 5 and 14. The patterns of expression of keratins 5, 14, 1 and 10, filaggrin, and of the three major CCE precursor proteins, involucrin, loricrin and small proline-rich proteins 1 and 2 (SPRs), were studied immunohistochemically and by electron microscopy. In 14 of the 15 patients with EBS, the distribution pattern of keratins was not altered. In one neonate with EBS, basal cell keratins were expressed in the suprabasal layers. Ultrastructurally, numerous clumped tonofilaments were observed in the basal and suprabasal cells. In all cases, findings were positive for filaggrin in the granular cells, with positivity for involucrin in the upper spinous and granular cells. The upper spinous cells and granular cells were positive for SPRs 1 and 2, and loricrin was expressed in granular cells. Ultrastructurally, no marked abnormality was observed in the suprabasal layers such as a decrease in, or agglutination of, keratin filaments, except in one neonate. A CCE about 15 nm thick was formed normally in the cell membrane of cornified cells. The patterns of distributions of basal cell keratins, suprabasal keratins, filaggrin, and CCE precursor proteins, as well as the ultrastructural findings, resembled those of normal skin. Thus, the abnormality in basal cell keratins in patients with EBS did not appear to alter the patterns of expression of the keratins and CCE precursor proteins. PMID:9860278

Sasaki, Y; Shimizu, H; Akiyama, M; Yoneda, K; Ishida-Yamamoto, A; Watanabe, S; Hata, J; Nishikawa, T

1998-11-01

272

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

Microsoft Academic Search

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

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

273

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

PubMed

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

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

2014-04-01

274

Eye movement abnormalities.  

PubMed

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

Moncayo, Jorge; Bogousslavsky, Julien

2012-01-01

275

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

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

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

2014-05-01

276

Multiple abnormalities in the ultraviolet light response of cultured fibroblasts derived from patients with the basal cell nevus syndrome.  

PubMed

Basal Cell Nevus Syndrome (BCNS) is a rare autosomal-dominant inherited disorder associated with a marked hypersusceptibility to spontaneous and radiation-induced skin cancer. We examined the changes in cell survival, unscheduled DNA synthesis (UDS) and the frequency of sister chromatid exchanges (SCE) induced by ultraviolet light (UVL) in confluent normal and BCNS fibroblasts. BCNS cells appeared slightly hypersensitive to the cytotoxic effects of UVL. The rate of UDS induced by UVL exposure in normal cell strains increased linearly following doses up to 30 J/m2, whereas in BCNS cells UDS became saturated at doses of 10 J/m2 showing no further increase with doses up to 30 J/m2. UDS activity persisted for longer periods after UVL exposure in BCNS as compared with normal cells. The dose-response relationship for UVL-induced SCE was similar in normal and BCNS fibroblasts. However, the frequencies of UVL-induced SCE declined to near background levels in normal cells following 12-24 hr of confluent holding prior to subculture whereas they remained elevated in BCNS cells with holding times up to 24 hr after UVL exposure. Overall, these results suggest that BCNS fibroblasts may have a diminished capacity for the repair of some type of DNA damage as compared with normal fibroblasts. PMID:2897722

Nagasawa, H; Burke, M J; Little, F F; McCone, E F; Chan, G L; Little, J B

1988-01-01

277

Basal Bioenergetic Abnormalities in Skeletal Muscle from Ryanodine Receptor Malignant Hyperthermia-susceptible R163C Knock-in Mice*  

PubMed Central

Malignant hyperthermia (MH) and central core disease in humans have been associated with mutations in the skeletal ryanodine receptor (RyR1). Heterozygous mice expressing the human MH/central core disease RyR1 R163C mutation exhibit MH when exposed to halothane or heat stress. Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca2+ concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions. R163C skeletal muscle exhibited a significant increase in matrix Ca2+, increased reactive oxygen species production, lower expression of mitochondrial proteins, and higher mtDNA copy number. These changes, in conjunction with lower myoglobin and glycogen contents, Myh4 and GAPDH transcript levels, GAPDH activity, and lower glucose utilization suggested a switch to a compromised bioenergetic state characterized by both low oxidative phosphorylation and glycolysis. The shift in bioenergetic state was accompanied by a dysregulation of Ca2+-responsive signaling pathways regulated by calcineurin and ERK1/2. Chronically elevated resting Ca2+ in R163C skeletal muscle elicited the maintenance of a fast-twitch fiber program and the development of insulin resistance-like phenotype as part of a metabolic adaptation to the R163C RyR1 mutation.

Giulivi, Cecilia; Ross-Inta, Catherine; Omanska-Klusek, Alicja; Napoli, Eleonora; Sakaguchi, Danielle; Barrientos, Genaro; Allen, Paul D.; Pessah, Isaac N.

2011-01-01

278

Bilateral lunate intraosseous ganglia.  

PubMed

An intraosseous ganglion is a relatively uncommon, benign cystic lesion that occurs in young and middle-aged adults. Bilateral and symmetrical lesions of the wrist are rare. Intraosseous ganglia of the carpal bones are uncommon causes of chronic wrist pain. Isolated cases of intraosseous ganglion have been reported most commonly in the lunate and scaphoid. The lunate was most frequently affected, followed by the capitate, scaphoid, and triquetrum bones. Radiolucent lesions in the carpal bones are not uncommon and are often seen incidentally in asymptomatic patients. The differential diagnosis of a lytic lesion in a carpal bone includes unicameral bone cyst, degenerative cyst, fibrous developmental defect, osteomyelitis, and intraosseous ganglion cyst. This article describes a case of bilateral lunate intraosseous ganglia. A review of the literature revealed that bilateral and symmetrical intraosseous ganglia of the wrist are rare, with only 3 other reported cases of bilateral lunate lesions. PMID:20608626

Kural, Cemal; Sungur, Ibrahim; Cetinus, Ercan

2010-07-01

279

Mobilization of oil ganglia  

Microsoft Academic Search

Following secondary recovery processes in conventional light oil reservoirs, more than half the original oil in place may remain trapped as a discontinuous phase. During the previous recovery processes these oil ganglia have been pinched off by capillary forces and remain immobile while the continuous phase which surrounds them is able to flow freely. Furthermore if a portion of this

V. De La Cruz; T. J. T. Spanos

1983-01-01

280

Automatic Quantitative MRI Texture Analysis in Small-for-Gestational-Age Fetuses Discriminates Abnormal Neonatal Neurobehavior  

PubMed Central

Background We tested the hypothesis whether texture analysis (TA) from MR images could identify patterns associated with an abnormal neurobehavior in small for gestational age (SGA) neonates. Methods Ultrasound and MRI were performed on 91 SGA fetuses at 37 weeks of GA. Frontal lobe, basal ganglia, mesencephalon and cerebellum were delineated from fetal MRIs. SGA neonates underwent NBAS test and were classified as abnormal if ?1 area was <5th centile and as normal if all areas were >5th centile. Textural features associated with neurodevelopment were selected and machine learning was used to model a predictive algorithm. Results Of the 91 SGA neonates, 49 were classified as normal and 42 as abnormal. The accuracies to predict an abnormal neurobehavior based on TA were 95.12% for frontal lobe, 95.56% for basal ganglia, 93.18% for mesencephalon and 83.33% for cerebellum. Conclusions Fetal brain MRI textural patterns were associated with neonatal neurodevelopment. Brain MRI TA could be a useful tool to predict abnormal neurodevelopment in SGA.

Sanz-Cortes, Magdalena; Ratta, Giuseppe A.; Figueras, Francesc; Bonet-Carne, Elisenda; Padilla, Nelly; Arranz, Angela; Bargallo, Nuria; Gratacos, Eduard

2013-01-01

281

Motor Control Abnormalities in Parkinson's Disease  

PubMed Central

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

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

2012-01-01

282

Stereotactic microdialysis of the basal ganglia in Parkinson's disease.  

PubMed

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious treatment in patients with advanced Parkinson's disease, yet the mechanisms of STN DBS are poorly understood. The aims of this study were to develop a useful method for studying neurotransmitter alterations during DBS and for the pharmacokinetics of L-dopa in brain tissue. Ten patients with Parkinson's disease participated, whereof two had no previous L-dopa medication. The electrodes and catheters were placed using MRI-guided stereotaxic targeting. Two microdialysis probes were placed, one in the right internal globus pallidus, and one in a brachial vein. The quadripolar deep brain electrodes were placed in the right STN. Microdialysates from brain tissue and blood were collected in 15-min fractions at baseline and during DBS. After stimulation new baseline fractions were taken and finally three fractions during continuous intravenous infusion of L-dopa. Clinical evaluation showed that both DBS and L-dopa infusion gave good relief of rigidity and tremor in all ten patients. During DBS the L-dopa levels in the brain increased in some of the patients but did not persist during the whole stimulation period. The concentration in brain increased substantially during intravenous L-dopa infusion. A number of catecholamines and their metabolites were analysed with high pressure liquid chromatography (HPLC). With our study we could show that this model is suitable for the monitoring of neurotransmitters and for pharmacokinetic studies in human brain, although we found that the sampling time was too short to follow the possible alterations in brain activity caused by DBS. PMID:22450238

Zsigmond, Peter; Dernroth, Nezirevi?; Kullman, Anita; Augustinsson, Lars-Erik; Dizdar, Nil

2012-05-30

283

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

MedlinePLUS

... moves thiamine into cells. Thiamine, also known as vitamin B1, is obtained from the diet and is necessary ... prevalence ; protein ; psychomotor ; quadriparesis ; recessive ; seizure ; syndrome ; thiamine ; vitamin B1 ; vitamins You may find definitions for these and ...

284

Basal ganglia involvement in a child with herpes simplex encephalitis  

Microsoft Academic Search

Herpes simplex encephalitis (HSE) is a leading cause of sporadic, nonepidemic viral encephalitis in children and adults. We\\u000a report a very rare case of HSE with involvement of bilateral thalamus, putamen, upper pons and midbrain, with development\\u000a of extrapyramidal symptoms which responded to corticosteroid therapy. A 15-mth-old female baby admitted with complaint of\\u000a fever for 5 days and generalised tonic

Gobinda Mondal; Roopesh Kumar; Jayant Kumar Ghosh; Kaberi Basu; Sukanta Chatterjee

2009-01-01

285

Electrophysiological Effects of Cannabinoids in the Basal Ganglia  

Microsoft Academic Search

\\u000a The hemp plant contains more than 416 chemicals of which more than 60 are cannabinoids (Turner. 1984). These compounds have\\u000a been known for their therapeutic and psychoactive properties for at least 4000 years. The principal rleuroactive constituent\\u000a is ?9-tetrahydrocannabinol (?9-TAC), often used as the prototype of the entire cannabinoid family due to its presence in derivatives ofcannabis sativa(marijuana and hashish)

Anna Lisa Muntoni; Miriam Melis; Marco Diana

286

Genetics Home Reference: Familial idiopathic basal ganglia calcification  

MedlinePLUS

... changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). An estimated ... imaging ; inheritance ; involuntary ; pattern of inheritance ; phosphate ; protein ; psychosis ; sodium ; syndrome You may find definitions for these ...

287

Basal Ganglia involvement in Wernicke encephalopathy: report of 2 cases.  

PubMed

We present the neuroimaging and clinical findings in 2 nonalcoholic adult patients with WE as assessed by MR imaging. The first patient presented with gait ataxia and changes in consciousness. MR imaging disclosed bilateral lesions in the dorsal striatum and cerebellum. None of the regions typically affected in WE were involved. The second patient showed symmetric lesions in the posterior putamen associated with the alterations frequently and infrequently found WE. PMID:20634304

Zuccoli, G; Cravo, I; Bailey, A; Venturi, A; Nardone, R

2011-08-01

288

HyperBrain: Pathway Quiz 14 - Basal Ganglia  

NSDL National Science Digital Library

One of eighteen quizzes on neuroanatomy accompanying the HyperBrain tutorial. The quizzes require the free Macromedia Flash player plugin. Illustrations modified from "Neuroanatomy - An Atlas of Structures, Sections, and Systems," Fourth Edition, Duane E. Haines, Ph.D., Professor and Chairman, Department of Anatomy, The University of Mississippi Medical Center, Jackson, Mississippi, Copyright 1995. With permission from Lippincott Williams & Wilkins Baltimore, Maryland, USA.Orientation: coronalAnnotated: false

Haines, Duane E.; Stensaas, Suzanne S.

2010-09-17

289

Default Mode Network Abnormalities in Bipolar Disorder and Schizophrenia  

PubMed Central

The default-mode network (DMN) consists of a set of brain areas preferentially activated during internally focused tasks. We used functional MRI to study the DMN in bipolar mania and acute schizophrenia. 17 bipolar disorder (BD), 14 schizophrenia (SZ) and 15 normal control (NC) subjects underwent 10-minute resting scans. The DMN was extracted using independent component analysis and template-matching; spatial extent and timecourse were examined. Both patient groups showed reduced DMN connectivity in the medial prefrontal cortex (mPFC) (BD:x=-2,y=54,z=-12; SZ:x=-2,y=22,z=18). BD subjects showed abnormal recruitment of parietal cortex (correlated with mania severity) while SZ subjects showed greater recruitment of the frontopolar cortex/basal ganglia. Both groups had significantly higher frequency fluctuations than controls (frequency × diagnosis:F(43,2)=3.183,p=0.05). We found ventral mPFC abnormalities in BD and dorsal mPFC abnormalities in SZ. The higher frequency of BOLD signal oscillations observed in patients suggests abnormal functional organization of circuits in both disorders. Further studies are needed to determine how these abnormalities are related to specific symptoms of each condition.

Ongur, Dost; Lundy, Miriam; Greenhouse, Ian; Shinn, Ann K.; Menon, Vinod; Cohen, Bruce M.; Renshaw, Perry F.

2010-01-01

290

Basal Cell Carcinoma  

MedlinePLUS

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

291

Studies on deficiency of Schwann cell basal lamina and deformation of collagen fibres induced by beta-aminopropionitrile in cultures of developing rat peripheral neurons.  

PubMed Central

The morphological analysis in culture of superior cervical ganglia and dorsal root ganglia showed the following: (1) collagen fibres external to the neurite bundles were larger than those inside the neurite bundles in both control and BAPN-treated cultures; (2) there was much more irregularity of shape in external than in internal fibres in dorsal root ganglia with BAPN; (3) there was reduced basal lamina formation by Schwann cells in both types of ganglia (Okada & Bunge, 1981); (4) basal lamina formation in the superior cervical ganglion was reduced as the days of treatment with BAPN increased (from 94.7% with one day of treatment to 66.7% with 8 days of treatment; (5) in the dorsal root ganglion preparation, the myelin internode was shorter in BAPN (105.1 micron +/- 34.5 micron) than in control media (127.8 micron +/- 32.8 micron: P less than 0.001); (6) there was no significant difference in thickness of myelin between controls (2.9 micron +/- 0.9 micron) and those treated with BAPN (2.7 micron +/- 0.7 micron: 0.05 less than P less than 0.1); (7) the node of Ranvier was more elongated in BAPN (5.1 micron +/- 4.1 micron) than in control media (2.5 micron +/- 0.8 micron; P less than 0.01). The relationship between connective tissue abnormalities caused by BAPN and of the basal lamina formation of myelin-forming cells affected by BAPN is discussed. Images Fig. 4 Fig. 5

Ninomiya, T; Kobayashi, E O

1985-01-01

292

Abnormal iron homeostasis and neurodegeneration  

PubMed Central

Abnormal iron metabolism is observed in many neurodegenerative diseases, however, only two have shown dysregulation of brain iron homeostasis as the primary cause of neurodegeneration. Herein, we review one of these - hereditary ferritinopathy (HF) or neuroferritinopathy, which is an autosomal dominant, adult onset degenerative disease caused by mutations in the ferritin light chain (FTL) gene. HF has a clinical phenotype characterized by a progressive movement disorder, behavioral disturbances, and cognitive impairment. The main pathologic findings are cystic cavitation of the basal ganglia, the presence of ferritin inclusion bodies (IBs), and substantial iron deposition. Mutant FTL subunits have altered sequence and length but assemble into soluble 24-mers that are ultrastructurally indistinguishable from those of the wild type. Crystallography shows substantial localized disruption of the normally tiny 4-fold pores between the ferritin subunits because of unraveling of the C-termini into multiple polypeptide conformations. This structural alteration causes attenuated net iron incorporation leading to cellular iron mishandling, ferritin aggregation, and oxidative damage at physiological concentrations of iron and ascorbate. A transgenic murine model parallels several features of HF, including a progressive neurological phenotype, ferritin IB formation, and misregulation of iron metabolism. These studies provide a working hypothesis for the pathogenesis of HF by implicating (1) a loss of normal ferritin function that triggers iron accumulation and overproduction of ferritin polypeptides, and (2) a gain of toxic function through radical production, ferritin aggregation, and oxidative stress. Importantly, the finding that ferritin aggregation can be reversed by iron chelators and oxidative damage can be inhibited by radical trapping may be used for clinical investigation. This work provides new insights into the role of abnormal iron metabolism in neurodegeneration.

Muhoberac, Barry B.; Vidal, Ruben

2013-01-01

293

Stress cardiomyopathy: transient basal ballooning.  

PubMed

Stress cardiomyopathy is a reversible left ventricular dysfunction triggered by emotional stress. We describe a variant of transient left ventricular ballooning in a patient in which basal and midventricular segments are affected. This confirms that there is not just one ventricular dysfunction pattern in Takotsubo cardiomyopathy. The involvement of only the basal and midventricle segments is an intriguing observation with no clear explanation; furthermore, there are no predictive factors for the differently sited wall motion abnormalities. PMID:20093944

Cacciotti, Luca; Camastra, Giovanni S; Musarò, Salvatore; Proietti, Igino; Semeraro, Raffaella; Martina, Cristina; Lupparelli, Fabrizio; Ansalone, Gerardo

2010-10-01

294

Motor symptoms of the Rett syndrome: abnormal muscle tone, posture, locomotion and stereotyped movement.  

PubMed

Amongst the motor, mental, cognitive and emotional symptoms of the Rett syndrome (RS) the motor symptoms stand out as the hallmark in analyzing the essential pathophysiology. Summarizing the motor symptoms and searching into the knowledge of relevant basic sciences, this report aims at stressing the pathophysiological basis of RS which we have reported in previous studies. The core motor symptoms of RS consist of two aspects; firstly the unique developmental abnormalities of the discrepancy of crawling and walking and secondly the pathognomonic symptoms which include the abnormal muscle tone, posture, locomotion and stereotyped movement. The deranged crawling reflects the abnormal locomotive function. The primary responsible neuronal structures of the abnormal muscle tone, posture and locomotion are probably in the brainstem. Aberrantly formed neuronal structures responsible for voluntary movements and modulatory factors from the basal ganglia are the pathophysiological basis of the stereotyped movement of RS. Thus the neuronal structures that underlie the clinical characteristics of RS extend broadly from the motor neurons to the higher cortex, but involve the specific neuronal systems. The most important and primary of these specific neuronal systems are thought to be the monoaminergic systems, originating from the brainstem and midbrain. Abnormally deficient noradrenergic, serotonergic and dopaminergic systems result in the abnormal modulation of ontogeny and function of the higher and lower nervous systems. As we have already stressed, this unique putative pathophysiological basis could explain the very striking set of clinical symptoms of RS and their age dependent appearance despite the lack of major specific findings in neuropathology. PMID:1626630

Nomura, Y; Segawa, M

1992-05-01

295

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

PubMed Central

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

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

2012-01-01

296

Nevoid basal cell carcinoma syndrome.  

PubMed

Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations. PMID:16900896

Karthiga, Kannan S; Sivapatha Sundharam, B; Manikandan, R

2006-01-01

297

Basal Cell Carcinoma (BCC)  

MedlinePLUS

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

298

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging  

PubMed Central

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse.

Roussotte, Florence; Soderberg, Lindsay

2010-01-01

299

Abnormal Striatal Dopaminergic Neurotransmission during Rest and Task Production in Spasmodic Dysphonia  

PubMed Central

Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia–thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [11C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ?BP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ?BP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ?BP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ?BP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

Berman, Brian D.; Herscovitch, Peter; Hallett, Mark

2013-01-01

300

Impaired neural transmission and synaptic plasticity in superior cervical ganglia from ?-amyloid rat model of Alzheimer's disease.  

PubMed

Basal synaptic transmission and activity-dependent synaptic plasticity were evaluated in superior cervical sympathetic ganglia (SCG) of amyloid-? rat model of Alzheimer's disease (A? rat) using electrophysiological and molecular techniques. Rats were administered A? peptides (a mixture of 1:1 A?1-40 and A?1-42) by chronic intracerebroventricular infusion via 14-day mini-osmotic pumps (300 pmol/day). Control rats received A?40-1 (inactive reverse peptide: 300 pmol/day). Ganglionic compound action potentials were recorded before (basal) and after repetitive stimulation. In isolated SCG, ganglionic long-term potentiation (gLTP) was generated by a brief train of stimuli (20Hz for 20s) and ganglionic long-term depression (gLTD) was produced with trains of paired pulses. The input/output (I/O) curves of ganglia from A? rats showed a marked downward shift along all stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission. In addition, repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals, but, the same protocols failed to induce gLTP or gLTD in ganglia from A? rats indicating impairment of activity-dependent synaptic plasticity in these animals. Western blotting of SCG homogenate from A? rats revealed reduction in the ratio of phosphorylated-/total-CaMKII and in calcineurin protein levels. Although other mechanisms could be involved, these changes in signaling molecules could represent an important molecular mechanism linked to the failure to express synaptic plasticity in A? rat ganglia. Results of the current study could explain some of the peripheral nervous system manifestations of Alzheimer's disease. PMID:21453246

Alzoubi, K H; Alhaider, I A; Tran, T T; Mosely, A; Alkadhi, K K

2011-06-01

301

Structural brain abnormalities in cervical dystonia  

PubMed Central

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.

2013-01-01

302

Walking abnormalities  

MedlinePLUS

Gait abnormalities ... of how a person walks is called the gait. Different types of walking problems occur without a ... Some walking abnormalities have been given names: Propulsive gait -- a stooped, stiff posture with the head and ...

303

Abuse of amphetamines and structural abnormalities in the brain.  

PubMed

We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure. PMID:18991959

Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

2008-10-01

304

Nevoid Basal Cell Carcinoma Syndrome: A Case Report and Review  

Microsoft Academic Search

Nevoid basal cell carcinoma syndrome, a rare autosomal dominant disorder, comprises of a number of abnormalities such as multiple\\u000a nevoid basal cell carcinomas, skeletal abnormalities and multiple keratocystic odontogenic tumors. Diagnosis may be difficult\\u000a because of the variability of expressivity and different ages of onset for different traits of this disorder. The dental clinician\\u000a may be the first to encounter

S. Bala Subramanyam; D. Naga Sujata; K. Sridhar; M. Pushpanjali

305

EARLY DIAGNOSIS OF NEVOID BASAL CELL CARCINOMA SYNDROME  

Microsoft Academic Search

Background. Nevoid basal cell carcinoma syndrome, or NBCCS, is a hereditary condition characterized by basal cell car- cinomas, or BCCs; odontogenic keratocysts, or OKCs; and skele- tal abnormalities. The authors conducted this study to determine the early signs of NBCCS. Methods. The authors reviewed files from two Italian den- tal schools from January 1980 to January 1995 to determine the

LORENZO LO MUZIO; PIERFRANCESCO NOCINI; PAOLO BUCCI; GIUSEPPE PANNONE; UGO CONSOLO; MAURIZIO PROCACCINI

306

Radiographic association of schwannomas with sensory ganglia  

PubMed Central

Objective Clinical experience suggests that the majority of schwannomas arise within sensory ganglia, suggesting that intraganglionic glial cells represent a potential cell of origin for schwannomas. To support this clinical impression, we reviewed magnetic resonance imaging (MRI) studies performed over a 5 year period at our institution to determine the relationship of cranial and spinal nerve schwannomas with the ganglia of the associated nerves. Study design Retrospective cohort study Setting Tertiary referral center Patients Patients undergoing imaging study at our institution over a 5 year period. Intervention(s) Radiographical images at our institution were reviewed as well as published studies to determine the anatomic location of schwannomas. Main outcome measure(s) Anatomical location of schwannomas Results A total of 372 patients were found over the 5-year study period, 31 of those were diagnosed with neurofibromatosis type 2 (NF2). Vestibular schwannomas comprised the greatest number of schwannomas, followed by spinal schwannomas. In NF2 patients, spinal schwannomas were the most common tumor, followed by vestibular schwannomas. In NF2 patients and those with sporadic schwannomas, the overwhelming majority of tumors arose in nerves with a sensory component and were associated with sensory ganglia of the nerves (562/607, 92.6%). Very few tumors arose from pure motor nerves. This is supported by review of published articles on anatomic location of schwannomas. Conclusions Schwannomas are strongly associated anatomically with ganglia of sensory nerves. These findings raise the possibility that intraganglionic glial cells give rise to the majority of schwannomas.

Tryggvason, Geir; Barnett, Andrew; Kim, John; Soken, Hakan; Maley, Joan; Hansen, Marlan R.

2012-01-01

307

[Walking abnormalities in children].  

PubMed

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

Segawa, Masaya

2010-11-01

308

X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, "interneuronopathy".  

PubMed

X-linked lissencephaly with abnormal genitalia is the first human disorder in which deficient tangential migration in the brain has been demonstrated. Male patients with X-linked lissencephaly with abnormal genitalia show intractable seizures, especially clonic convulsions or myoclonus from the first day of life, but neither infantile spasms nor hypsarrhythmia on electroencephalograms so far. Brain magnetic resonance imaging shows anterior pachygyria and posterior agyria with a mildly thick cortex, agenesis of the corpus callosum, and dysplastic basal ganglia. ARX, a paired-class homeobox gene with four polyalanine sequences, is a responsible gene for X-linked lissencephaly with abnormal genitalia. The brain of Arx knockout mice shows aberrant tangential migration and differentiation of gamma-aminobutyric acid (GABA)ergic interneurons. In human X-linked lissencephaly with abnormal genitalia, a neuropathologic study has suggested a loss of interneurons. Meanwhile, polyalanine expansion of ARX causes symptomatic or nonsymptomatic West's syndrome and nonsyndromic mental retardation. The striking epileptogenicity of X-linked lissencephaly with abnormal genitalia and West's syndrome associated with ARX mutations i s considered to be caused by a disorder of interneurons involving a tangentialmigration disorder. We propose "interneuronopathy" as a term for this. PMID:15921244

Kato, Mitsuhiro; Dobyns, William B

2005-04-01

309

The clinical usefulness of electrocardiogram-gated Tc-99m methoxy-isobutyl-isonitrile images in the detection of basal wall motion abnormalities and reversibility of stress induced perfusion defects.  

PubMed

Technetium-99m methoxy-isobutyl-isonitrile (SESTAMIBI) has been recently introduced to trace regional myocardial perfusion. Beyond blood flow distribution, a quantitative index of regional myocardial wall motion from SESTAMIBI electrocardiogram (ECG)-gated images was obtained, according to the assumption that changes in the detected radioactivity reflect changes in myocardial wall thickness during the cardiac cycle. As a preliminary study, 20 patients with coronary artery disease and regional wall motion abnormalities and 15 normal subjects were studied by SESTAMIBI scintigraphy and contrast ventriculography. Regional wall motion was analyzed by a radial method applied to both techniques. Absolute systolic changes in radioactivity and its ratio to reference normal values (wall thickening index, WTI) were determined in 9 anatomical cardiac regions according to the formula (endsystolic counting profile-enddiastolic counting profile/enddiastolic counting profile) x 100. The overall agreement between radioisotopic and ventriculographic techniques was 88% (158 of 180 segments). Normal, hypokinetic and akinetic ventriculographic segments showed WTI values of 1.1 +/- 0.2, 0.8 +/- 0.2 and 0.4 +/- 0.3 respectively (P less than 0.001). A second clinical study was performed in 25 patients studied by stress/rest ECG-gated SESTAMIBI scintigraphy. The assumption of this part of the study was to investigate if a preserved wall thickening in segments with stress defects might predict those areas with normal resting perfusion. Partial or total normalization of regional perfusion was observed in 90% of segments with a WTI greater than or equal to 0.8. These studies indicate the ECG-gated SESTAMIBI may represent a suitable technique for the simultaneous analysis of flow distribution and function. Analysis of post-exercise ECG-gated SESTAMIBI can predict the reversibility of transient perfusion defects. PMID:1629639

Marzullo, P; Marcassa, C; Sambuceti, G; Parodi, O; L'Abbate, A

1992-01-01

310

Accumulation of components of basal laminae: association with the failure of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice.  

PubMed

Aganglionosis occurs in the terminal colon of the ls/ls mouse because an intrinsic defect of the presumptive aganglionic tissue prevents the entry and colonization of this portion of the bowel by migrating neural crest cells. The current study was undertaken to determine if abnormalities of the extracellular matrix could be identified in this segment that might account for migratory failure. Since basal laminae of the muscularis mucosa are overproduced in the aganglionic segment of adult ls/ls mice, we examined components of basal laminae in fetal gut from Day E 11 to Day E 16 of gestation. This period spans the time of enteric ganglion formation. Laminin and collagen type IV were studied by immunocytochemistry and proteoglycans by staining glycosaminoglycans with Alcian blue. Abnormalities of each of these components occur during development of the presumptive aganglionic bowel in the ls/ls mouse and could be detected as early as Day E 11. These defects consist mainly of an overabundance of these materials, both in defined basal laminae and throughout the extracellular space of the mesenchyme. Electron microscopic observations in the presumptive aganglionic ls/ls colon revealed a thickening of basal laminae and exceptionally wide intercellular spaces between smooth muscle myoblasts that contained an irregular fibrillar material, consisting of 4.5- to 6.0-nm filaments associated with 14- to 20-nm granules. Fibrillar and flocculant material was continuous with formed basal laminae, and was concentrated in the same areas found to have an overabundance of laminin immunoreactivity. These observations indicate that there is an accumulation of extracellular matrix material, including components of basal laminae, that (i) precedes the formation of enteric ganglia, (ii) is in the path through which enteric neural precursors from the crest would have to migrate, and (iii) is limited to the aganglionic and hypoganglionic ls/ls bowel. These data are consistent with the hypothesis that components of basal laminae contribute to the inability of crest cells to colonize the terminal bowel of ls/ls mice. PMID:3338619

Payette, R F; Tennyson, V M; Pomeranz, H D; Pham, T D; Rothman, T P; Gershon, M D

1988-02-01

311

Basal linear deposit in the human macula  

Microsoft Academic Search

We used electron microscopy and immunohistochemistry to study the macular regions of nine enucleated elderly human eyes and to document the various abnormalities present in the so-called basal linear deposit. These changes include bush-like strands of electron-dense material, which project from the basement membrane of the retinal pigment epithelium, deposition of wide-banded collagen, vesiculoid elements, membrane-bound structures and occasional melanin

K. U. Loffler; W. R. Lee

1986-01-01

312

Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice  

PubMed Central

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

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

2011-01-01

313

Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice.  

PubMed

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

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

2011-04-19

314

Abnormal resonance behavior of the postural control loop in Parkinson's disease.  

PubMed

Human postural control of upright stance sporadically can show an oscillatory behavior. Based on previous work, we assessed whether an abnormal tendency for such oscillations might contribute to the motor impairments in patients with basal ganglia dysfunction such as Parkinson's disease (PD). We investigated postural control during unperturbed stance in normal control subjects and in PD patients off and under treatment, focusing on stabilogram diffusion analysis (SDA) of the foot center of pressure (COP) excursions and conventional measures of the sway amplitude and velocity. We found abnormal 1 Hz body sway oscillation in the SDA curves of PD patients that differed significantly from the body sway typically observed in control subjects during quiet stance. The 1 Hz body sway oscillation was associated with abnormally large and fast sway in the patients off treatment. Under treatment with levodopa, with 'deep brain stimulation' (subthalamic nucleus) and even more so with combined treatment, the oscillations in the SDA curves vanished and the sway became slower. The loss of oscillation and reduction of sway velocity were highly correlated with the improvements of patients' clinical motor assessment score. However, sway amplitude was not correlated with the patients' motor assessment score and patients reported clinical improvement under therapy even though sway amplitude increased on average. A simple feedback model of the postural control system with abnormally large internal noise could predict experimental measures both on and off treatment. The off treatment condition was consistent with a high motor gain in the feedback loop, and the on treatment condition with a reduced motor gain. PMID:15007581

Maurer, C; Mergner, T; Peterka, R J

2004-08-01

315

Plasticity of basal ganglia neurocircuitries following perinatal asphyxia: effect of nicotinamide  

Microsoft Academic Search

The potential neuroprotection of nicotinamide on the consequences of perinatal asphyxia was investigated with triple organotypic\\u000a cultures. Perinatal asphyxia was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver\\u000a rats into a water bath for 20 min. Sibling caesarean-delivered pups were used as controls. Three days later tissue from substantia\\u000a nigra, neostriatum and neocortex was dissected and placed on

Verena Klawitter; Paola Morales; Diego Bustamante; Sonia Gomez-Urquijo; Tomas Hökfelt; Mario Herrera-Marschitz

2007-01-01

316

Typical development of basal ganglia, hippocampus, amygdala and cerebellum from age 7 to 24.  

PubMed

Developmental imaging studies show that cortical grey matter decreases in volume during childhood and adolescence. However, considerably less research has addressed the development of subcortical regions (caudate, putamen, pallidum, accumbens, thalamus, amygdala, hippocampus and the cerebellar cortex), in particular not in longitudinal designs. We used the automatic labeling procedure in FreeSurfer to estimate the developmental trajectories of the volume of these subcortical structures in 147 participants (age 7.0-24.3years old, 94 males; 53 females) of whom 53 participants were scanned twice or more. A total of 223 magnetic resonance imaging (MRI) scans (acquired at 1.5-T) were analyzed. Substantial diversity in the developmental trajectories was observed between the different subcortical gray matter structures: the volume of caudate, putamen and nucleus accumbens decreased with age, whereas the volume of hippocampus, amygdala, pallidum and cerebellum showed an inverted U-shaped developmental trajectory. The thalamus showed an initial small increase in volume followed by a slight decrease. All structures had a larger volume in males than females over the whole age range, except for the cerebellum that had a sexually dimorphic developmental trajectory. Thus, subcortical structures appear to not yet be fully developed in childhood, similar to the cerebral cortex, and continue to show maturational changes into adolescence. In addition, there is substantial heterogeneity between the developmental trajectories of these structures. PMID:24705201

Wierenga, Lara; Langen, Marieke; Ambrosino, Sara; van Dijk, Sarai; Oranje, Bob; Durston, Sarah

2014-08-01

317

Interacting cortical and basal ganglia networks underlying finding and tapping to the musical beat.  

PubMed

Humans are able to find and tap to the beat of musical rhythms varying in complexity from children's songs to modern jazz. Musical beat has no one-to-one relationship with auditory features-it is an abstract perceptual representation that emerges from the interaction between sensory cues and higher-level cognitive organization. Previous investigations have examined the neural basis of beat processing but have not tested the core phenomenon of finding and tapping to the musical beat. To test this, we used fMRI and had musicians find and tap to the beat of rhythms that varied from metrically simple to metrically complex-thus from a strong to a weak beat. Unlike most previous studies, we measured beat tapping performance during scanning and controlled for possible effects of scanner noise on beat perception. Results showed that beat finding and tapping recruited largely overlapping brain regions, including the superior temporal gyrus (STG), premotor cortex, and ventrolateral PFC (VLPFC). Beat tapping activity in STG and VLPFC was correlated with both perception and performance, suggesting that they are important for retrieving, selecting, and maintaining the musical beat. In contrast BG activity was similar in all conditions and was not correlated with either perception or production, suggesting that it may be involved in detecting auditory temporal regularity or in associating auditory stimuli with a motor response. Importantly, functional connectivity analyses showed that these systems interact, indicating that more basic sensorimotor mechanisms instantiated in the BG work in tandem with higher-order cognitive mechanisms in PFC. PMID:23163420

Kung, Shu-Jen; Chen, Joyce L; Zatorre, Robert J; Penhune, Virginia B

2013-03-01

318

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

ERIC Educational Resources Information Center

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

Wiecki, Thomas V.; Frank, Michael J.

2013-01-01

319

Subacute hemicorporal parkinsonism in 5 patients with infarcts of the basal ganglia.  

PubMed

In 1929, Critchley introduced the term "vascular parkinsonism" (VP), which has been the subject of considerable controversy in neurology. Parkinsonism does not appear to be a frequent consequence of striatal infarcts, although unilateral parkinsonism has been reported as an acute or subacute onset syndrome following strategic infarcts in the striatum. Previous 123-I ioflupane SPECT (DaTSCAN) studies involving radioisotope labeling of the dopamine transporter protein at presynaptic level in patients with IPD (idiopathic Parkinson's disease) have found this technique to be highly sensitive in exploring the nigrostriatal pathway. Previous studies of VP with DatSCAN have been inconclusive. The present study correlates clinical data (unilateral parkinsonism following contralateral lenticular infarction), and radiological (CT/MRI) and functional neuroimaging findings (DatSCAN) in 5 patients with CT/MRI criteria for striatal infarcts. Finally, in 2 of these patients a diagnosis of IPD was made because of the follow-up of clinical signs and pathological DaTSCAN findings not concordant with the size and location of the vascular lesion. PMID:17705041

Vaamonde, J; Flores, J M; Gallardo, M J; Ibáñez, R

2007-01-01

320

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

ERIC Educational Resources Information Center

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,…

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

2008-01-01

321

fMRI of Cocaine Self-Administration in Macaques Reveals Functional Inhibition of Basal Ganglia  

Microsoft Academic Search

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

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

2011-01-01

322

Basal Ganglia Volumes in Children With Attention-Deficit Hyperactivity Disorder  

Microsoft Academic Search

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

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

1996-01-01

323

Structural Correlates of Efficient GABAergic Transmission in the Basal Ganglia-Thalamus Pathway  

PubMed Central

Giant inhibitory terminals with multiple synapses, the counterparts of excitatory “detonator” or “driver” terminals, have not been described in the forebrain. Using three-dimensional reconstructions of electron microscopic images, we quantitatively characterize a GABAergic pathway that establishes synaptic contacts exclusively via multiple synapses. Axon terminals of the nigrothalamic pathway formed, on average, 8.5 synapses on large-diameter dendrites and somata of relay cells in the ventromedial nucleus of the rat thalamus. All synapses of a given terminal converged on a single postsynaptic element. The vast majority of the synapses established by a single terminal were not separated by astrocytic processes. Nigrothalamic terminals in the macaque monkey showed the same ultrastructural features both in qualitative and quantitative terms (the median number of synapse per target was also 8.5). The individual synapses were closely spaced in both species. The nearest-neighbor synaptic distances were 169 nm in the rat and 178 nm in the monkey. The average number of synapses within 0.75 ?m from any given synapse was 3.8 in the rat and 3.5 in the monkey. The arrangement of synapses described in this study creates favorable conditions for intersynaptic spillover of GABA among the multiple synapses of a single bouton, which can result in larger charge transfer. This could explain faithful and efficient GABAergic signal transmission in the nigrothalamic pathway in the healthy condition and during Parkinson’s disease. In addition, our structural data suggest that the rodent nigrothalamic pathway can be a valid model of the primate condition, when the mechanism of GABAergic transmission is studied.

Bodor, Agnes L.; Giber, Kristof; Rovo, Zita; Ulbert, Istvan; Acsady, Laszlo

2009-01-01

324

Reversible contrast-enhanced lesions of basal ganglia and brain stem on computed tomography.  

PubMed

Two cases of reversible CT contrast-enhanced lesions simulating brain neoplasms are described. Following steroid therapy and shunting procedure normalization of the clinical signs and of the CT scans occurred. The role of a vasculomyelinopathy as a possible pathogenetic factor of these lesions is stressed. PMID:7246281

Pau, A; Pirisi, A; Sehrbundt Viale, E; Turtas, S

1981-01-01

325

Basal ganglia and gait control: apomorphine administration and internal pallidum stimulation in Parkinson’s disease  

Microsoft Academic Search

Gait coordination was analyzed (four-camera 100 Hz ELITE system) in two groups of idiopathic Parkinson disease (PD) patients.\\u000a Five patients underwent continuous infusion of apomorphine and were recorded in two different sessions (APO OFF and APO ON)\\u000a in the same day. Three patients with a previous chronic electrode implantation in both internal globi pallidi (GPi) were recorded\\u000a in the same

R. Grasso; A. Peppe; F. Stratta; D. Angelini; M. Zago; P. Stanzione; F. Lacquaniti

1999-01-01

326

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

Microsoft Academic Search

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

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

327

Basal Ganglia and Behaviour: Behavioural Effects of Deep Brain Stimulation in Experimental Neurological and Psychiatric Disorders  

Microsoft Academic Search

\\u000a The use of deep brain stimulation (DBS) to control severely disabling neurological and psychiatric conditions is an exciting\\u000a and fast emerging area of neuroscience. Deep brain stimulation has generally the same clinical effects as a lesion with respect\\u000a to the improvement of clinical disability, but has more advantages such as its adjustability and reversibility. To this day,\\u000a fundamental knowledge regarding

Thibault Sesia; Sonny Tan; Rinske Vlamings; Lee Wei Lim; Veerle Visser-Vandewalle; Yasin Temel

328

Ventriculo-peritoneal shunt: A rare cause of basal ganglia and thalamic abscess  

PubMed Central

We report an 18-month-old female child with ventriculo-peritoneal shunt related thalamic abscess treated with stereotactic aspiration. Deep seated abscesses are complex due to difficult access and are associated with an increased risk of intra-ventricular rupture as well as antibiotic resistance, a fact which justifies a more aggressive and immediate neurosurgical management.

Sangwan, Parvesh; Saikia, Bhaskar; Sharma, Pradeep Kumar; Sharma, Rachna; Khilnani, Praveen

2013-01-01

329

Structural correlates of efficient GABAergic transmission in the basal ganglia-thalamus pathway.  

PubMed

Giant inhibitory terminals with multiple synapses, the counterparts of excitatory "detonator" or "driver" terminals, have not been described in the forebrain. Using three-dimensional reconstructions of electron microscopic images, we quantitatively characterize a GABAergic pathway that establishes synaptic contacts exclusively via multiple synapses. Axon terminals of the nigrothalamic pathway formed, on average, 8.5 synapses on large-diameter dendrites and somata of relay cells in the ventromedial nucleus of the rat thalamus. All synapses of a given terminal converged on a single postsynaptic element. The vast majority of the synapses established by a single terminal were not separated by astrocytic processes. Nigrothalamic terminals in the macaque monkey showed the same ultrastructural features both in qualitative and quantitative terms (the median number of synapse per target was also 8.5). The individual synapses were closely spaced in both species. The nearest-neighbor synaptic distances were 169 nm in the rat and 178 nm in the monkey. The average number of synapses within 0.75 microm from any given synapse was 3.8 in the rat and 3.5 in the monkey. The arrangement of synapses described in this study creates favorable conditions for intersynaptic spillover of GABA among the multiple synapses of a single bouton, which can result in larger charge transfer. This could explain faithful and efficient GABAergic signal transmission in the nigrothalamic pathway in the healthy condition and during Parkinson's disease. In addition, our structural data suggest that the rodent nigrothalamic pathway can be a valid model of the primate condition, when the mechanism of GABAergic transmission is studied. PMID:18354012

Bodor, Agnes L; Giber, Kristóf; Rovó, Zita; Ulbert, István; Acsády, László

2008-03-19

330

Abnormal Burst Patterns of Single Neurons Recorded in the Substantia Nigra Reticulata of Behaving 140 CAG Huntington's Disease Mice  

PubMed Central

Huntington’s disease (HD) is an inherited neurodegenerative disorder that causes neurological pathology in the basal ganglia and related circuitry. A key site of HD pathology is striatum, the principal basal ganglia input structure; striatal pathology likely changes basal ganglia output but no existing studies address this issue. In this report, we characterize single-neuron activity in the substantia nigra reticulata (SNr) of awake, freely-behaving 140 CAG knock-in (KI) mice at 16 to 40 weeks. KI mice are a well characterized model of adult HD and are mildly symptomatic in this age range. As the primary basal ganglia output nucleus in rodents, the SNr receives direct innervation from striatum, as well as indirect influence via polysynaptic inputs. We analyzed 32 single neurons recorded from KI animals and 44 from wild-type (WT) controls. We found increased burst rates, without a concordant change in spike discharge rate, in KI animals relative to WTs. Furthermore, although metrics of burst structure, such as the inter-spike interval in bursts, do not differ between groups, burst rate increases with age in KI, but not WT, animals. Our findings suggest that altered basal ganglia output is a physiological feature of early HD pathology.

Murphy-Nakhnikian, Alexander; Dorner, Jenelle L.; Fischer, Benjamin I.; Bower-Bir, Nathan D.; Rebec, George V.

2012-01-01

331

Basal cell carcinoma.  

PubMed Central

Basal cell carcinoma is the commonest malignancy in Caucasians with incidence rates of 300 per 100,000 reported in the USA. Rates are increasing at over 10% per year leading to a lifetime risk of 30%. Although mortality is low, the disease is responsible for considerable morbidity and places a substantial burden on health service provision in the UK. Furthermore, lesions may recur and patients often develop multiple tumours giving major implications for treatment and follow-up. Four main types of basal cell carcinoma are seen: nodulo-ulcerative; pigmented; morpheaform and superficial. Diagnosis is by histological evaluation although many tumours have a characteristic clinical appearance. The differential diagnosis is large. Identified risk factors include male gender, skin type 1, red/blonde hair and increasing age. Patients with basal cell carcinoma are more likely to develop malignant melanoma and squamous cell carcinoma but it is still unclear whether there is a link with internal malignancy. The main treatment modalities are surgery and radiotherapy. Each has advantages and disadvantages. The choice of treatment depends on many factors. Principles of treatment include identification of high-risk patients to enable early detection, complete removal of the lesion, and careful follow-up to detect recurrence or new lesions. Approximately 10% of tumours recur, depending on site, size and treatment modality. Metastatic basal cell carcinoma and the association of ultraviolet radiation to basal cell carcinoma risk are reviewed. Images Figure 1 Figure 2 Figure 3 Figure 4

Lear, J. T.; Smith, A. G.

1997-01-01

332

Immunohistochemical characterisation of pelvic autonomic ganglia in male mice  

Microsoft Academic Search

Pelvic ganglia are mixed sympathetic-parasympathetic ganglia and provide the majority of the autonomic innervation to the urogenital organs. Here we describe the structural and histochemical features of the major pelvic ganglion in the male mouse and compare two different mouse strains. The basic structural features of the ganglion are similar to those in the male rat. Almost all pelvic ganglion

Yewlan Wanigasekara; Mark E. Kepper; Janet R. Keast

2003-01-01

333

Quantitative analysis of herpes simplex virus in cranial nerve ganglia.  

PubMed

A susceptible individual exposed to herpes simplex virus (HSV) will develop latent infection in multiple cranial nerve ganglia. There are a few quantitative studies of the viral load within the trigeminal ganglion, but none that investigate other cranial nerve ganglia. In this study, human trigeminal, geniculate, vestibular (Scarpa's) and cochlear (spiral) ganglia were obtained from willed body donors. Real time quantitative polymerase chain reaction (PCR) analysis of the HSV DNA polymerase gene was performed on ipsilateral ganglion sets from the same individual. Viral load, expressed as HSV genomes per 105 cells, was significantly greater in the vestibular ganglion (mean +/- SD, 176705 +/- 255916) than in the geniculate (9948 +/- 22066), cochlear (3527 +/- 9360), or trigeminal (2017 +/- 5578) ganglia. There was not a significant correlation among ganglia from the same individual. The results support the hypothesis that neuronal subpopulations have variable susceptibility to HSV infection. PMID:15371151

Vrabec, Jeffrey T; Alford, Raye L

2004-08-01

334

Basal cell carcinoma  

Microsoft Academic Search

Basal cell carcinoma is the commonest malignancy in Caucasians with incidence rates of 300 per 100,000 reported in the USA. Rates are increasing at over 10% per year leading to a lifetime risk of 30%. Although mortality is low, the disease is responsible for considerable morbidity and places a substantial burden on health service provision in the UK. Furthermore, lesions

J. T. Lear; A. G. Smith

1997-01-01

335

Life beyond the Basal.  

ERIC Educational Resources Information Center

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…

Grey, Jeanne; Carbone, Carole

1987-01-01

336

MRI abnormalities in neurofibromatosis type 1 (NF1): a study of men and mice  

Microsoft Academic Search

Hyperintense lesions on T2-weighted MR images of the brain, predominantly located in the basal ganglia, the brainstem and cerebellum, are a frequent finding in patients with neurofibromatosis type 1. Nature and significance of these lesions are still unknown so that the term ‘unidentified bright objects’ (UBOs) has been introduced to allow an unbiased description. We analyzed brain MRI scans of

Thorsten Rosenbaum; Volkher Engelbrecht; Wilfried Krölls; Ferdinand A. van Dorsten; Mathias Hoehn-Berlage; Hans-Gerd Lenard

1999-01-01

337

Abnormal amplitude of low-frequency fluctuations of intrinsic brain activity in Alzheimer's disease.  

PubMed

We used resting-state functional magnetic resonance imaging to measure the amplitude of low-frequency fluctuations (ALFF) of intrinsic brain activity in 23 patients with moderate Alzheimer's disease (AD) and 27 age- and gender-matched healthy controls. Two different frequency bands were analyzed (slow-5:0.01-0.027 Hz; slow-4:0.027-0.073 Hz). In many brain regions, widespread ALFF differences between the two frequency bands were observed, including predominantly the posterior cingulate cortex/precuneus (PCC/PCu), hippocampus/parahippocampal gyrus (Hip/PHG), insula, thalamus, and basal ganglia. Compared to controls, AD patients showed decreased ALFF values in the bilateral PCC/PCu, inferior parietal lobe, and several temporal regions, and increased ALFF values mainly in the bilateral Hip/PHG, and middle and inferior temporal gyri. Intriguingly, the ALFF abnormalities in the left PCu, left supramarginal gyrus, and several temporal regions were greater in the slow-5 band compared to the slow-4 band. Moreover, correcting for gray matter volume loss significantly affected the functional analytical results, suggesting that gray matter loss can partially account for the functional imaging analytical results obtained in AD. Finally, we showed that regions with changes in ALFF demonstrated a significant correlation with patient cognitive performance as measured using Mini-Mental State Examination scores. The results also demonstrated a significant correlation between hippocampal volume and the ALFF in slow-5 band in the AD group. This study demonstrated widespread ALFF abnormalities of intrinsic brain activity in AD and revealed that the ALFF abnormalities in severe specific regions were frequency-dependent. Taken together, our findings provided novel insights into the pathophysiological mechanism of AD and may be helpful in the development of imaging biomarkers for disease diagnosis. PMID:24473186

Liu, Xuena; Wang, Siqi; Zhang, Xinqing; Wang, Zhiqun; Tian, Xiaojie; He, Yong

2014-01-01

338

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

PubMed Central

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.

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

2011-01-01

339

Future of newer basal insulin  

PubMed Central

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

Madhu, S. V.; Velmurugan, M.

2013-01-01

340

Future of newer basal insulin.  

PubMed

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

Madhu, S V; Velmurugan, M

2013-03-01

341

Abnormalities of the contingent negative variation in Huntington's disease: correlations with clinical features.  

PubMed

The contingent negative variation (CNV) is a neurophysiological pattern related to planning of external - paced, voluntary movements. The aim of the study, was to examine the CNV in a cohort of mild demented and non-medicated HD patients, evaluating the CNV amplitude modifications in the light of clinical features and performing Low Resolution Brain Electromagnetic Tomography (LORETA) analysis in order to show the CNV multiple generators. Fourteen HD patients and 25 sex and age-matched controls were studied. All subjects were evaluated by the motor section of UHDRS, MMSE and WAIS. The CNV was recorded by 19 scalp electrodes, with a red light flash as visual warning stimulus (S1), followed by a blue light flash (S2) after a fixed interval of 3 s. The amplitude of early CNV was significantly reduced in HD, compared to controls: the amplitude reduction was significantly correlated with the bradikinesia score. LORETA analysis of early CNV significantly discriminated patients from controls, for a prevalent activation of the posterior part of anterior cingulate cortex in HD. An abnormal activation of the associative cortex devoted to the processing of attention preceding voluntary movement may be supposed in HD, probably mediated by the altered basal ganglia modulation. PMID:17300807

de Tommaso, Marina; Difruscolo, Olimpia; Sciruicchio, Vittorio; Specchio, Nicola; Livrea, Paolo

2007-03-15

342

Neuromagnetic Evidence of Abnormal Movement-Related Beta Desynchronization in Parkinson's Disease.  

PubMed

Parkinson's disease (PD) is a neurodegenerative disorder associated with debilitating motor, posture, and gait abnormalities. Human studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchronization throughout the cortical-basal ganglia motor network in PD. Suppression of such pathological beta synchronization has been associated with improved motor function, which may explain the effectiveness of deep-brain stimulation. We used magnetoencephalography (MEG) to investigate neural population-level beta responses, and other oscillatory activity, during a motor task in unmedicated patients with PD and a matched group of healthy adults. MEG is a noninvasive neurophysiological technique that permits the recording of oscillatory activity during movement planning, execution, and termination phases. Each of these phases was independently examined using beamforming to distinguish the brain areas and movement phases, where pathological oscillations exist during motor control. Patients with PD exhibited significantly diminished beta desynchronization compared with controls prior to and during movement, which paralleled reduced alpha desynchronization. This study is the first to systematically investigate neural oscillatory responses in PD during distinct stages of motor control (e.g. planning, execution, and termination) and indicates that these patients have significant difficulty suppressing cortical beta synchronization during movement planning, which may contribute to their diminished movement capacities. PMID:23645717

Heinrichs-Graham, Elizabeth; Wilson, Tony W; Santamaria, Pamela M; Heithoff, Sheila K; Torres-Russotto, Diego; Hutter-Saunders, Jessica A L; Estes, Katherine A; Meza, Jane L; Mosley, R L; Gendelman, Howard E

2013-05-01

343

A novel syndrome of abnormal striatum and congenital cataract: evidence for linkage to chromosomes 11.  

PubMed

We report a consanguineous family of three girls and one boy affected with a novel syndrome involving the lens and the basal ganglia. The phenotype is strikingly similar between affected siblings with cognitive impairment, attention deficit hyperactivity disorder (ADHD), microcephaly, growth retardation, congenital cataract, and dystonia. The magnetic resonance imaging showed unusual pattern of swelling of the caudate heads and thinning of the putamina with severe degree of hypometabolism on the [18F] deoxyglucose positron emission tomography. Furthermore, the clinical assessment provides the evidence that the neurological phenotype is very slowly progressive. We utilized the 10K single-nucleotide polymorphism (SNP) microarray genotyping for linkage analysis. Genome-wide scan indicated a 45.9-Mb region with a 4.2353 logarithm of the odds score on chromosome 11. Affymetrix genome-wide human SNP array 6.0 assay did not show any gross chromosomal abnormality. Targeted sequencing of two candidate genes within the linkage interval (PAX6 and B3GALTL) as well as mtDNA genome sequencing did not reveal any putative mutations. PMID:23181898

Al-Owain, M; Al-Zahrani, J; Al-Bakheet, A; Abudheim, N; Al-Younes, B; Aldhalaan, H; Al-Zaidan, H; Colak, D; Almohaileb, F; Abouzied, M E; Al-Fadhli, F; Meyer, B; Kaya, N

2013-09-01

344

Nerve growth factor promotes neurite outgrowth in guinea pig myenteric plexus ganglia.  

PubMed

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

Mulholland, M W; Romanchuk, G; Lally, K; Simeone, D M

1994-10-01

345

Cortical basal ganglionic degeneration.  

PubMed

In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms. PMID:14602941

Scarmeas, N; Chin, S S; Marder, K

2001-10-01

346

Cortical Basal Ganglionic Degeneration  

PubMed Central

In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms.

Scarmeas, Nikolaos; Chin, Steven S.; Marder, Karen

2011-01-01

347

Varicella-zoster virus DNA in human sensory ganglia  

Microsoft Academic Search

Varicella-zoster virus (VZV) causes chickenpox and shingles1. Clinical and epidemiological evidence indicates that following an episode of childhood chickenpox (varicella), VZV becomes latent, presumably in dorsal root ganglia, and is reactivated many years later to produce shingles (zoster) in adults2. VZV has been demonstrated in ganglia by electron microscopy and by indirect immunofluorescence3-5, and infectious viral particles have been isolated

Donald H. Gilden; Abbas Vafai; Yehuda Shtram; Yechiel Becker; Mary Devlin; Mary Wellish

1983-01-01

348

Autonomic Ganglia: Target and Novel Therapeutic Tool  

PubMed Central

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The muscle AChR mediates transmission at the neuromuscular junction; antibodies against the muscle AChR are the cause of myasthenia gravis. The ganglionic (?3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Pharmacological enhancement of ganglionic synaptic transmission may be a novel way to improve autonomic function. Ganglionic AChR antibodies are found in patients with autoimmune autonomic ganglionopathy (AAG). Patients with AAG typically present with rapid onset of severe autonomic failure. Major clinical features include orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia, AAG is an antibody-mediated neurological disorder. The disease can be reproduced in experimental animals by active immunization or passive antibody transfer. Patient may improve with plasma exchange treatment or other immunomodulatory treatment. Antibodies from patients with AAG inhibit ganglionic AChR currents. Other phenotypes of AAG are now recognized based on the results of antibody testing. These other presentations are generally associated with lower levels of ganglionic AChR antibodies. A chronic progressive form of AAG may resemble pure autonomic failure. Milder forms of dysautonomia, such as postural tachycardia syndrome, are associated with ganglionic AChR in 10–15% of cases. Since ganglionic synaptic transmission is a common pathway for all autonomic traffic, enhancement of autonomic function through inhibition of acetylcholinesterase is a potential specific therapeutic strategy for autonomic disorders. Increasing the strength of ganglionic transmission can ameliorate neurogenic orthostatic hypotension without aggravating supine hypertension. Recent evidence also suggests a potential role for acetylcholinesterase inhibitors in the treatment of postural tachycardia syndrome.

Vernino, Steven; Sandroni, Paola; Singer, Wolfgang; Low, Phillip A.

2009-01-01

349

Degludec: A Novel Basal Insulin.  

PubMed

Limitations of conventional human basal insulins like NPH have led to the development of more stable and peak less analogs. However, the first generation of basal analogs like glargine and detemir has certain shortcomings which do not allow them to be termed ideal basal insulin. Degludec, a novel basal insulin analog has the potential to overcome these limitations. This paper reviews the potential advantages of degludec over existing basal insulins and analogs. It discusses the basic and clinical studies performed on degludec so far, and highlights the possible role this molecule can play in the management of diabetes mellitus. In this paper, the recent patents on basal insulin have been reviewed so as to provide an insight into the advances in this field. In this article, we present a review of Degludec, as well as related patents. PMID:22280218

Kalra, Sanjay; Baruah, Manash P; Niazi, Asfandyar K

2012-01-25

350

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease  

PubMed Central

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

Lammers, Nicolette M.; Sondermeijer, Brigitte M.; Twickler, Th. B. (Marcel); de Bie, Rob M.; Ackermans, Mariette T.; Fliers, Eric; Schuurman, P. Richard; La Fleur, Susanne E.; Serlie, Mireille J.

2014-01-01

351

Basal Twinning of Hematite  

NASA Astrophysics Data System (ADS)

When two crystals share a plane, there is a twinning composition plane. The result is an intergrowth of two separate crystals in a symmetrical manner. Crystallographers classify twinned crystals by a number of twin laws. These twin laws are specific to the crystal system. The type of twinning can be a diagnostic tool in mineral identification and characterization. Many twin laws cannot be recognized in ordinary optical analysis. So, the advent of diffraction techniques to describe punctual crystallographic orientation facilitated the identification of many twinned crystals in rocks. Samples containing hematite of the Quadrilátero Ferrífero, Minas Gerais, Brazil, were analyzed by EBSD technique. Crystallographic orientation data were obtained from automatically indexed EBSD patterns collected on a JEOL JSM-5510. EBSD analysis was carried out on thin sections cut perpendicular to the foliation (XZ plane) and parallel to the stretching lineation (X-direction). Thin sections were polished before EBSD analysis. EBSD patterns were indexed using CHANNEL 5 software from HKL Technology, Oxford Instruments. The resulting data are presented in form of pole figures (upper hemisphere, equal angle, stereographic projection) and of colour-coded maps using Coincidence Site Lattice (? 3) and Twin Boundaries Components. Through electron backscatter diffraction analysis of hematite grains was possible to detect twin boundaries similar to Dauphiné twinning in quartz that is not described for hematite. Dauphiné twinning in trigonal ?-quartz consists of a 60° rotation around the c-axis resulting in a reversal of the crystallographic positive and negative forms (Frondel 1962). As both minerals show similar symmetry, the same mechanism can be described for hematite in this analysis. The basal twinning of hematite developed pervasively during the incipient stage of deformation. This paper investigates the relationships between this kind of twinning, deformation conditions and microstructural modifications in hematite grains. The results show that the presence of twins exerts an important role in the distribution of the intracrystalline plastic deformation in hematite, as well as in the activation of different sets of slip systems. We estimate that basal twin bands can be preferred sites for dynamic recrystallization.

Gonçalves, Fábio; Lagoeiro, Leonardo; Barbosa, Paola

2013-04-01

352

Odontogenic keratocysts in Nevoid basal cell carcinoma syndrome: a case report  

PubMed Central

Nevoid basal cell carcinoma syndrome, a rare autosomal dominant disorder, comprises a number of abnormalities such as multiple nevoid basal cell carcinomas, skeletal abnormalities and multiple odontogenic keratocysts. Considering the rarity of this syndrome, we present a 12-year-old boy affected by this syndrome. He had multiple okcs, calcification of falx cerebri, bifid ribs, frontal bossing and hypertelorism. Characteristic cutaneous manifestation (nevoid basal cell carcinoma) was not present in this patient. The jaw cysts were treated with marsupialization then enucleation. The dental clinician may be the first to encounter and identify this syndrome, when the multiple cystlike radiolucencies are discovered on panoramic view.

2009-01-01

353

Ameloblastoma associated with the nevoid basal cell carcinoma (Gorlin) syndrome.  

PubMed

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a wide range of clinical signs and symptoms. The major criteria for the diagnosis are multiple cutaneous basal cell carcinomas, multiple odontogenic keratocysts of the jaw, palmar and plantar pits, and skeletal abnormalities. Here, we report an unusual case of NBCCS in a 68-year-old woman with late onset of clinical signs and symptoms and with an associated ameloblastoma. Only 4 other cases of this unusual association have been reported. PMID:18417377

Eslami, Behnam; Lorente, Carol; Kieff, David; Caruso, Paul A; Faquin, William C

2008-06-01

354

Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors.  

PubMed

Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest cells coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b) together with markers of Schwann cell precursors. Some give rise to Schwann cells after down-regulation of PHOX2b. Others form parasympathetic ganglia after being guided to the site of ganglion formation by the nerves that carry preganglionic fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development. PMID:24925912

Espinosa-Medina, I; Outin, E; Picard, C A; Chettouh, Z; Dymecki, S; Consalez, G G; Coppola, E; Brunet, J-F

2014-07-01

355

Abnormal Uterine Bleeding  

MedlinePLUS

MENU Return to Web version Abnormal Uterine Bleeding Overview What is abnormal uterine bleeding? Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ...

356

The development of cholinergic ganglia in the chick embryo heart.  

PubMed

Cholinesterase activity was investigated in the heart of the developing chick from the 6th to 20th day of incubation. The earliest cholinesterase-positive nerve cells and fibers could be demonstrated between the 7th and 9th day. On the 13th day the nervous structure attained full development comparable with that seen in the hatched chicken. The number of ganglia increases up to the 15th day, and remains constant thereafter. The right ventricle is associated with the largest number of ganglia. PMID:453544

Rickenbacher, J; Müller, E

1979-04-01

357

Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders.  

PubMed

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

2012-08-01

358

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders  

PubMed Central

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders.

Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

2012-01-01

359

Evidence for Glutamate as a Neuroglial Transmitter within Sensory Ganglia  

PubMed Central

This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (<30 µm) DRG neurons from intact DRGs (ex-vivo whole ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold.

Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T.; Jasmin, Luc

2013-01-01

360

Evidence for glutamate as a neuroglial transmitter within sensory ganglia.  

PubMed

This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (<30 µm) DRG neurons from intact DRGs (ex-vivo whole ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold. PMID:23844184

Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T; Jasmin, Luc

2013-01-01

361

Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy  

PubMed Central

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (?3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Ganglionic AChR antibodies are found in many patients with autoimmune autonomic ganglionopathy (AAG). These antibodies recognize the ?3 subunit of the ganglionic AChR, and thus do not bind non-specifically to other nicotinic AChR. Patients with high levels of ganglionic AChR antibodies typically present with rapid onset of severe autonomic failure, with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia gravis, AAG is an antibody-mediated neurological disorder. Antibodies from patients with AAG inhibit ganglionic AChR currents and impair transmission in autonomic ganglia. An animal model of AAG in the rabbit recapitulates the important clinical features of the human disease and provides additional evidence that AAG is an antibody-mediated disorder caused by impairment of synaptic transmission in autonomic ganglia.

Vernino, Steven; Hopkins, Steve; Wang, Zhengbei

2009-01-01

362

Selective extracellular stimulation of individual neurons in ganglia  

NASA Astrophysics Data System (ADS)

Selective control of individual neurons could clarify neural functions and aid disease treatments. To target specific neurons, it may be useful to focus on ganglionic neuron clusters, which are found in the peripheral nervous system in vertebrates. Because neuron cell bodies are found primarily near the surface of invertebrate ganglia, and often found near the surface of vertebrate ganglia, we developed a technique for controlling individual neurons extracellularly using the buccal ganglia of the marine mollusc Aplysia californica as a model system. We experimentally demonstrated that anodic currents can selectively activate an individual neuron and cathodic currents can selectively inhibit an individual neuron using this technique. To define spatial specificity, we studied the minimum currents required for stimulation, and to define temporal specificity, we controlled firing frequencies up to 45 Hz. To understand the mechanisms of spatial and temporal specificity, we created models using the NEURON software package. To broadly predict the spatial specificity of arbitrary neurons in any ganglion sharing similar geometry, we created a steady-state analytical model. A NEURON model based on cat spinal motor neurons showed responses to extracellular stimulation qualitatively similar to those of the Aplysia NEURON model, suggesting that this technique could be widely applicable to vertebrate and human peripheral ganglia having similar geometry.

Lu, Hui; Chestek, Cynthia A.; Shaw, Kendrick M.; Chiel, Hillel J.

2008-09-01

363

Selective extracellular stimulation of individual neurons in ganglia  

PubMed Central

Selective control of individual neurons could clarify neural functions and aid disease treatments. To target specific neurons, it may be useful to focus on ganglionic neuron clusters, which are found in the peripheral nervous system in vertebrates. Because neuron cell bodies are found primarily near the surface of invertebrate ganglia, and often found near the surface of vertebrate ganglia, we developed a technique for controlling individual neurons extracellularly using the buccal ganglia of the marine mollusc Aplysia californica as a model system. We experimentally demonstrated that anodic currents can selectively activate an individual neuron and cathodic currents can selectively inhibit an individual neuron using this technique. To define spatial specificity, we studied the minimum currents required for stimulation, and to define temporal specificity, we controlled firing frequencies up to 45 Hz. To understand the mechanisms of spatial and temporal specificity, we created models using the NEURON software package. To broadly predict the spatial specificity of arbitrary neurons in any ganglion sharing similar geometry, we created a steady-state analytical model. A NEURON model based on cat spinal motorneurons showed responses to extracellular stimulation qualitatively similar to those of the Aplysia NEURON model, suggesting that this technique could be widely applicable to vertebrate and human peripheral ganglia having similar geometry.

Lu, Hui; Chestek, Cynthia A; Shaw, Kendrick M; Chiel, Hillel J

2008-01-01

364

Secondary herpes simplex virus latent infection in transplanted ganglia.  

PubMed Central

Sensory ganglia latently infected with herpes simplex virus (HSV) were transplanted beneath the renal capsule of syngeneic recipients, and the latent infection remaining was investigated. HSV latency-associated transcript (LAT) expression and reactivation of HSV after explant of transplanted dorsal root ganglia were monitored as markers of latency. Two to four weeks after transplantation, both indicated evidence of HSV latency in transplants. At those times, infectious virus was not detected in direct ganglion homogenates. In addition, viral antigen and infected cell polypeptide 4 RNA were not detected. Taken together, the results suggested that HSV latent infection rather than persistent infection was present in transplants. From these results, two explanations seemed possible: latency was maintained in transplanted neurons, or alternatively, latency developed after transplantation, in neurons not previously latently infected. The latter was considered putative secondary latency and was investigated in three ways. First, evidence of reactivation which might serve as a source for secondary latency was evaluated. Reactivation of HSV in transplants was evident from HSV antigen expression (52% of transplants) and the presence of cell-free virus (38% of transplants) 3 to 5 days after transplantation. Second, putative secondary latency was investigated in recipients immunized with HSV prior to receiving latently infected ganglia. Reactivation was not detected 3 to 5 days after transplantation in immunized recipients, and LAT expression was rare in these recipients after 3 to 4 weeks. Lastly, the possibility of secondary latency was investigated by comparing results obtained with standard HSV and with reactivation-defective thymidine kinase-negative (TK-) HSV. Defective reactivation of TK- HSV was demonstrated by immunohistochemistry and by the inability to isolate infectious virus. Donor dorsal root ganglia latently infected with TK+ HSV showed many LAT-positive neurons 2 or more weeks after transplantation (average, 26 per transplant). However, LAT expression was undetectable or minimal > 2 weeks after transplantation in donor ganglia latently infected with TK- HSV (average, 0.2 per transplant). Impaired reactivation of TK- HSV-infected donor ganglia after transplantation, therefore, was correlated with subsequent limited LAT expression. From these results, the occurrence of secondary latency was concluded for ganglia latently infected with TK+ HSV and transplanted beneath the kidney capsule. In vivo reactivation in this transplant model may provide a more useful means to investigate HSV reactivation than in usual in vitro explant models and may complement other in vivo reactivation models. The occurrence of secondary latency was unique. The inhibition of secondary latency by the immune system may provide an avenue to evaluate immunological control of HSV latency. Images

Tenser, R B; Edris, W A; Gaydos, A; Hay, K A

1994-01-01

365

Maintenance of neuronal positions in organized ganglia by SAX-7, a Caenorhabditis elegans homologue of L1.  

PubMed

The L1 family of cell adhesion molecules is predominantly expressed in the nervous system. Mutations in human L1 cause neuronal diseases such as HSAS, MASA, and SPG1. Here we show that sax-7 gene encodes an L1 homologue in Caenorhabditis elegans. In sax-7 mutants, the organization of ganglia and positioning of neurons are abnormal in the adult stage, but these abnormalities are not observed in early larval stage. Misplacement of neurons in sax-7 mutants is triggered by mechanical force linked to body movement. Short and long forms of SAX-7 exhibited strong and weak homophilic adhesion activities in in vitro aggregation assay, respectively, which correlated with their different activities in vivo. SAX-7 was localized on plasma membranes of neurons in vivo. Expression of SAX-7 only in a single neuron in sax-7 mutants cell-autonomously restored its normal neuronal position. Expression of SAX-7 in two different head neurons in sax-7 mutants led to the forced attachment of these neurons. We propose that both homophilic and heterophilic interactions of SAX-7 are essential for maintenance of neuronal positions in organized ganglia. PMID:15775964

Sasakura, Hiroyuki; Inada, Hitoshi; Kuhara, Atsushi; Fusaoka, Eri; Takemoto, Daisuke; Takeuchi, Kosei; Mori, Ikue

2005-04-01

366

Nevoid Basal Cell Carcinoma Syndrome  

MedlinePLUS

... of the hands or soles of the feet, calcium deposits in the brain, and skeletal (bone) changes. The ... Major Features: Multiple basal cell skin cancers Increased calcium deposits in the head (seen on an x-ray) ...

367

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)  

PubMed Central

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic therapy and topical chemotherapy. Radiotherapy should be avoided. Vitamin A analogs may play a preventive role against development of new BCCs. Life expectancy in NBCCS is not significantly altered but morbidity from complications can be substantial. Regular follow-up by a multi-specialist team (dermatologist, neurologist and odontologist) should be offered. Patients with NBCCS should strictly avoid an excessive sun exposure.

Lo Muzio, Lorenzo

2008-01-01

368

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

PubMed Central

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.

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

2009-01-01

369

SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury.  

PubMed

The purpose of this atlas is to present a review of the literature showing the advantages of SPECT brain perfusion imaging (BPI) in mild or moderate traumatic brain injury (TBI) over other morphologic imaging modalities such as x-ray CT or MRI. The authors also present the technical recommendations for SPECT brain perfusion currently practiced at their center. For the radiopharmaceutical of choice, a comparison between early and delayed images using Tc-99m HMPAO and Tc-99m ECD showed that Tc-99m HMPAO is more stable in the brain with no washout over time. Therefore, the authors feel that Tc-99m HMPAO is preferable to Tc-99m ECD. Recommendations regarding standardizing intravenous injection, the acquisition, processing parameters, and interpretation of scans using a ten grade color scale, and use of the cerebellum as the reference organ are presented. SPECT images of 228 patients (age range, 11 to 88; mean, 40.8 years) with mild or moderate TBI and no significant medical history that interfered with the results of the SPECT BP were reviewed. The etiology of the trauma was in the following order of frequency: motor vehicle accidents (45%) followed by blow to the head (36%) and a fall (19%). Frequency of the symptoms was headache (60.9%), memory problems (27.6