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1

Basal ganglia abnormalities in tardive dyskinesia  

Microsoft Academic Search

The purpose of the present study was to investigate CT abnormalities in tardive dyskinesia (TD) and to search for possible relationships with clinical data. A group of 30 psychotic patients (15 schizophrenic and 15 affective disorder) with TD was compared to a matched group of 30 psychiatric patients without TD and a matched group of 30 healthy controls. CT data

Paulo Dalgalarrondo; Wagner F. Gattaz

1994-01-01

2

Basal Ganglia  

Microsoft Academic Search

\\u000a The basal ganglia are a group of closely connected cell masses, forming a continuum, extending from the telencephalon to the\\u000a midbrain tegmentum (Sect. 11.2). This complex comprises the striatum (the nucleus caudatus and the putamen, largely separated\\u000a by the internal capsule), the globus pallidus, the subthalamic nucleus and the substantia nigra. The output of the basal ganglia\\u000a is aimed at

Hans J. Donkelaar; Bart Warrenburg; Michèl Willemsen; Benno Küsters; Yoshio Hashizume; Akira Hori

3

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia  

PubMed Central

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson’s disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anaesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful, long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment (GPi). Intra-Str injections of a behaviorally effective dose of DA precursor L-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Kita, Hitoshi; Kita, Takako

2011-01-01

4

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

PubMed Central

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

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

2013-01-01

5

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

6

Neuropsychiatry of the basal ganglia  

PubMed Central

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

Ring, H; Serra-Mestres, J

2002-01-01

7

[Anti-basal ganglia antibody].  

PubMed

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

Hayashi, Masaharu

2013-04-01

8

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

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

NMDA receptors in the basal ganglia  

PubMed Central

The basal ganglia consist of several interconnected nuclei located in the telecephalon, diencephalon and mesencephalon that are involved in a variety of motor and non-motor behavioural functions. Glutamate receptors play a major role in neurotransmission within the basal ganglia and are present in all nuclei of the basal ganglia. This review focuses on the contribution of the NMDA class of glutamatergic receptors to various movement disorders whose primary pathology lies within the basal ganglia and discusses how pharmacological manipulation of such receptors may be therapeutically useful.

RAVENSCROFT, PAULA; BROTCHIE, JONATHAN

2000-01-01

11

Multiple Output Channels in the Basal Ganglia  

Microsoft Academic Search

The neural circuits that link the basal ganglia with the cerebral cortex are critically involved in the generation and control of voluntary movement. Retrograde transneuronal transport or herpes simplex virus type 1 was used to examine the organization of connections in the cebus monkey between an output nucleus of the basal ganglia, the internal segment of the globus pallidus (GPi),

John E. Hoover; Peter L. Strick

1993-01-01

12

? oscillations in the human basal ganglia.  

PubMed

Interest in beta activity in the basal ganglia has mushroomed since it was first identified in the subthalamic nucleus of patients with Parkinson's disease in Jonathan Dostrovsky's landmark paper (Levy et al., 2000). Here we consider a less explored phenomenon; namely gamma frequency synchronisation of neurons in the basal ganglia. Gamma oscillations have been reported in a distributed network involving the basal ganglia, thalamus and motor cortex, and have been described in a wide range of diseases as well as during increased arousal and voluntary movement. In Parkinson's disease, gamma activity is promoted by dopaminergic therapy. These features suggest that its elevation may be involved in the production of movement and this hypothesis is supported by the correlation between the amplitude of gamma activity and limb kinematics. Here we review these data, discuss the functional anatomy of gamma activity in basal ganglia and question how closely it relates to the coding of movement parameters. PMID:22841500

Jenkinson, Ned; Kühn, Andrea A; Brown, Peter

2012-07-24

13

Basal Ganglia Beta Oscillations Accompany Cue Utilization  

PubMed Central

SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state.

Leventhal, Daniel K.; Gage, Gregory J.; Schmidt, Robert; Pettibone, Jeffrey R.; Case, Alaina C.; Berke, Joshua D.

2012-01-01

14

Structural and functional evolution of the basal ganglia in vertebrates  

Microsoft Academic Search

While a basal ganglia with striatal and pallidal subdivisions is1Although by its structure the word basal ganglia is plural, the basal ganglia is typically regarded as a single entity. Thus, in the same sense that the structurally plural `United States' is treated as a singular noun, we here treat basal ganglia as a singular noun.1 clearly present in many extant

Anton Reiner; Loreta Medina; C. Leo Veenman

1998-01-01

15

Birdbrains could teach basal ganglia research a new song  

Microsoft Academic Search

Recent advances in anatomical, physiological and histochemical characterization of avian basal ganglia neurons and circuitry have revealed remarkable simi- larities to mammalian basal ganglia. A modern revision of the avian anatomical nomenclature has now provided a common language for studying the function of the cortical-basal-ganglia-cortical loop, enabling neuros- cientists to take advantage of the specialization of basal ganglia areas in

Allison J. Doupe; David J. Perkel; Anton Reiner; Edward A. Stern

2005-01-01

16

Linear Branching Echogenicities in the Basal Ganglia and Thalami  

Microsoft Academic Search

Echogenic vasculature in the basal ganglia and thalami of neonatal brain have been associated with congeni- tal infections such as cytomegalovirus (CMV), rubella, and syphilis, trisomy 13 syndrome, Down syndrome, maternal drug use, neonatal asphyxia, nonimmune hydrops, and fetal alcohol syndrome. This abnormality is believed to result from necrotizing vasculitis with subsequent mineralization. In our study, we encountered 8 small

Han-Hsi Wang; Chih-Hao Chien; Min-Hou Liao; Yu-Nian Wu; Yu-Hsien Su

1998-01-01

17

Psychosis revealing familial idiopathic basal ganglia calcification.  

PubMed

We describe the case of a 39-year-old woman presenting with auditory hallucinations and delusions responsive to antipsychotic drugs. Computerized tomography scans revealed basal ganglia calcifications in the proband and in her two asymptomatic parents. Extensive etiological clinicobiological assessment allowed us to exclude known causes of brain calcifications and diagnose familial idiopathic basal ganglia calcification (IBGC). Neurological symptoms associated with psychiatric symptoms are common in IBGC. Nevertheless, purely psychiatric presentations, as demonstrated by the present case, are possible. However, a fortuitous association between asymptomatic IBGC and schizophrenia cannot be ruled out. Only brain imaging, followed by an extensive etiological assessment, allows for diagnosis of this rare disorder. PMID:23122487

Nicolas, Gaël; Guillin, Olivier; Borden, Alaina; Bioux, Sandrine; Lefaucheur, Romain; Hannequin, Didier

2012-10-31

18

Actions, Policies, Values, and the Basal Ganglia  

Microsoft Academic Search

The basal ganglia are widely believed to be involved in the learned selection of actions. Building on this idea, reinforcement learning (RL) theories of optimal control have had some success in explaining the responses of their key dopaminergic afferents. While these model-free RL theories offer a compelling account of a range of neurophysiological and behavioural data, they offer only an

Nathaniel D. Daw; Yael Niv; Peter Dayan

19

Extrastriatal dopaminergic innervation of human basal ganglia  

Microsoft Academic Search

A tyrosine-hydroxylase immunohistochemical analysis of the brains of normal human individuals has revealed nigrostriatal axons providing collaterals that arborize in the pallidum and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course backward along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson’s pencils. Many of

Martine Cossette; Martin Lévesque; André Parent

1999-01-01

20

Dopamine release in the basal ganglia  

Microsoft Academic Search

Dopamine (DA) is a key transmitter in the basal ganglia, yet DA transmission does not conform to several aspects of the classic synaptic doctrine. Axonal DA release occurs through vesicular exocytosis and is action potential- and Ca2+ -dependent. However, in addition to axonal release, DA neurons in midbrain exhibit somatodendritic release by an incompletely understood, but apparently exocytotic, mechanism. Even

M. E. Rice; J. C. Patel; S. J. Cragg

21

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

2013-09-06

22

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

23

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

PubMed

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

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

2012-07-01

24

Neurochemical oscillations in the basal ganglia.  

PubMed

This work represents an attempt to elucidate the neurochemical processes in the basal ganglia by mathematical modelling. The correlation between neurochemistry and electrophysiology has been used to construct a dynamical system based on the basal ganglia's network structure. Mathematical models were constructed for different physical scales to reformulate the neurochemical and electrophysiological behaviour from synapses up to multi-compartment systems. Transformation functions have been developed to transit between the different scales. We show through numerical simulations that this network produces oscillations in the electrical potentials as well as in neurotransmitter concentrations. In agreement with pharmacological experiments, a parameter sensitivity analysis reveals temporary changes in the neurochemical and electrophysiological systems after single exposure to antipsychotic drugs. This behaviour states the structural stability of the system. The correlation between the neurochemical dynamics and drug-induced behaviour provides the perspective for novel neurobiological hypotheses. PMID:19588207

Noori, Hamid Reza; Jäger, Willi

2009-07-09

25

Dopamine release in the basal ganglia.  

PubMed

Dopamine (DA) is a key transmitter in the basal ganglia, yet DA transmission does not conform to several aspects of the classic synaptic doctrine. Axonal DA release occurs through vesicular exocytosis and is action potential- and Ca²?-dependent. However, in addition to axonal release, DA neurons in midbrain exhibit somatodendritic release by an incompletely understood, but apparently exocytotic, mechanism. Even in striatum, axonal release sites are controversial, with evidence for DA varicosities that lack postsynaptic specialization, and largely extrasynaptic DA receptors and transporters. Moreover, DA release is often assumed to reflect a global response to a population of activities in midbrain DA neurons, whether tonic or phasic, with precise timing and specificity of action governed by other basal ganglia circuits. This view has been reinforced by anatomical evidence showing dense axonal DA arbors throughout striatum, and a lattice network formed by DA axons and glutamatergic input from cortex and thalamus. Nonetheless, localized DA transients are seen in vivo using voltammetric methods with high spatial and temporal resolution. Mechanistic studies using similar methods in vitro have revealed local regulation of DA release by other transmitters and modulators, as well as by proteins known to be disrupted in Parkinson's disease and other movement disorders. Notably, the actions of most other striatal transmitters on DA release also do not conform to the synaptic doctrine, with the absence of direct synaptic contacts for glutamate, GABA, and acetylcholine (ACh) on striatal DA axons. Overall, the findings reviewed here indicate that DA signaling in the basal ganglia is sculpted by cooperation between the timing and pattern of DA input and those of local regulatory factors. PMID:21939738

Rice, M E; Patel, J C; Cragg, S J

2011-09-14

26

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

27

Cerebellar hypoplasia and brainstem thinning associated with severe white matter and basal ganglia abnormalities in a child with an mtDNA deletion.  

PubMed

Cerebellar and brainstem hypoplasia may occur in different conditions, including those disorders designated as pontocerebellar hypoplasia (PCH). In particular, when PCH is combined with severe supratentorial white matter involvement and cerebral atrophy, mutations in the mitochondrial arginyl-tRNA synthethase (RARS2) gene causing PCH6 are possible. We describe a patient with a lethal mitochondrial encephalomyopathy due to a mtDNA deletion and no alterations in RARS2, whose magnetic resonance (MR) findings mimicked PCH6. A thorough diagnostic work-up for mitochondrial disorders should be carried out when facing with a PCH-like and severe white matter and basal ganglia involvement on brain MR imaging in children, even if clinical and laboratory mitochondrial "stigmata" are scant or nonspecific. PMID:21826524

Biancheri, Roberta; Bruno, Claudio; Cassandrini, Denise; Bertini, Enrico; Santorelli, Filippo M; Rossi, Andrea

2011-08-09

28

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

Microsoft Academic Search

Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data\\u000a supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in\\u000a dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the\\u000a basal ganglia dopaminergic system between transgenic mice

Dimitra Giannakopoulou; Ioanna Armata; Ada Mitsacos; Pullani Shashidharan; Panagiotis Giompres

2010-01-01

29

Basal ganglia and cerebellar loops: motor and cognitive circuits  

Microsoft Academic Search

The traditional view that the basal ganglia and cerebellum are simply involved in the control of movement has been challenged in recent years. One of the pivotal reasons for this reappraisal has been new information about basal ganglia and cerebellar connections with the cerebral cortex. In essence, recent anatomical studies have revealed that these connections are organized into discrete circuits

Frank A Middleton; Peter L Strick

2000-01-01

30

Germ cell tumors of the thalamus and the basal ganglia  

Microsoft Academic Search

Two cases of germ cell tumors (GCTs) of the basal ganglia are presented and 40 previously reported cases are reviewed. The incidence of GCTs of the basal ganglia and thalamus was estimated as less than 14% of all intracranial GCTs. All patients except for two (95%) were male, aged 7–19 years. The clinical course was usually slow. The major symptoms

Norihiko Tamaki; Tingkai Lin; Kunio Shirataki; Kohkichi Hosoda; Hiromitsu Kurata; Satoshi Matsumoto; Hiroshi Ito

1990-01-01

31

LEARNING AND MEMORY FUNCTIONS OF THE BASAL GANGLIA  

Microsoft Academic Search

? Abstract Although the mammalian,basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcor- tical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent,hypothesis is that this brain region

Mark G. Packard; Barbara J. Knowlton

2002-01-01

32

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

Microsoft Academic Search

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

Fabio Blandini; Giuseppe Nappi; Cristina Tassorelli; Emilia Martignoni

2000-01-01

33

Mirror-writing and reversed repetition of digits in a right-handed patient with left basal ganglia haematoma.  

PubMed Central

A 57 year old right-handed Chinese man sustained a left basal ganglia haemorrhage resulting in speech disorder and right hemiplegia. He mirror-wrote with his left hand and during speech recovery repeated digits in reverse sequence. The abnormal right to left directionality possibly reflected release of right basal ganglia from left-sided control. Images

Chia, L G; Kinsbourne, M

1987-01-01

34

Functional anatomy: dynamic States in Basal Ganglia circuits.  

PubMed

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

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

2010-11-23

35

Functional Anatomy: Dynamic States in Basal Ganglia Circuits  

PubMed Central

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

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

2010-01-01

36

Interactions between the Midbrain Superior Colliculus and the Basal Ganglia  

PubMed Central

An important component of the architecture of cortico-basal ganglia connections is the parallel, re-entrant looped projections that originate and return to specific regions of the cerebral cortex. However, such loops are unlikely to have been the first evolutionary example of a closed-loop architecture involving the basal ganglia. A phylogenetically older, series of subcortical loops can be shown to link the basal ganglia with many brainstem sensorimotor structures. While the characteristics of individual components of potential subcortical re-entrant loops have been documented, the full extent to which they represent functionally segregated parallel projecting channels remains to be determined. However, for one midbrain structure, the superior colliculus (SC), anatomical evidence for closed-loop connectivity with the basal ganglia is robust, and can serve as an example against which the loop hypothesis can be evaluated for other subcortical structures. Examination of ascending projections from the SC to the thalamus suggests there may be multiple functionally segregated systems. The SC also provides afferent signals to the other principal input nuclei of the basal ganglia, the dopaminergic neurones in substantia nigra and to the subthalamic nucleus. Recent electrophysiological investigations show that the afferent signals originating in the SC carry important information concerning the onset of biologically significant events to each of the basal ganglia input nuclei. Such signals are widely regarded as crucial for the proposed functions of selection and reinforcement learning with which the basal ganglia have so often been associated.

Redgrave, Peter; Coizet, Veronique; Comoli, Eliane; McHaffie, John G.; Leriche, Mariana; Vautrelle, Nicolas; Hayes, Lauren M.; Overton, Paul

2010-01-01

37

The Basal Ganglia and Chunking of Action Repertoires  

Microsoft Academic Search

The basal ganglia have been shown to contribute to habit and stimulus–response (S–R) learning. These forms of learning have the property of slow acquisition and, in humans, can occur without conscious awareness. This paper proposes that one aspect of basal ganglia-based learning is the recoding of cortically derived information within the striatum. Modular corticostriatal projection patterns, demonstrated experimentally, are viewed

Ann M. Graybiel

1998-01-01

38

Dopamine-glutamate interactions in the basal ganglia  

Microsoft Academic Search

Summary In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of “wanted” and in the suppression of “unwanted” behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill

W. J. Schmidt

1998-01-01

39

Localization of GABA receptors in the basal ganglia.  

PubMed

The majority of neurons in the basal ganglia utilize GABA as their principal neurotransmitter and, as a consequence, most basal ganglia neurons receive extensive GABAergic inputs derived from multiple sources. In order to understand the diverse roles of GABA in the basal ganglia it is necessary to define the precise localization of GABA receptors in relation to known neuron subtypes and known afferents. In this chapter, we summarize data on the ultrastructural localization of ionotropic GABA(A) receptors and metabotropic GABA(B) receptors in the basal ganglia. In each of the regions of the basal ganglia that have been studied, GABA(A) receptor subunits are located primarily at symmetrical synapses formed by GABAergic boutons, where they display a several-hundred-fold enrichment over extrasynaptic sites. In contrast, GABA(B) receptors are widely distributed at synaptic and extrasynaptic sites on both presynaptic and postsynaptic membranes. Presynaptic GABA(B) receptors are localized on striatopallidal, striatonigral and pallidonigral afferent terminals, as well as glutamatergic terminals derived from the cortex, thalamus and subthalamic nucleus. It is concluded that fast GABA transmission mediated by GABA(A) receptors in the basal ganglia occurs primarily at synapses whereas GABA transmission mediated by GABA(B) receptors is more complex, involving receptors located at presynaptic, postsynaptic and extrasynaptic sites. PMID:17499117

Boyes, Justin; Bolam, J Paul

2007-01-01

40

Loss of specificity in Basal Ganglia related movement disorders.  

PubMed

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

Bronfeld, Maya; Bar-Gad, Izhar

2011-06-03

41

Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster  

Microsoft Academic Search

Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output

Arthur Leblois; René Reese; David Labarre; Melanie Hamann; Angelika Richter; Thomas Boraud; Wassilios G. Meissner

2010-01-01

42

Evidence for segregated and integrative connectivity patterns in the human Basal Ganglia.  

PubMed

Detailed knowledge of the anatomy and connectivity pattern of cortico-basal ganglia circuits is essential to an understanding of abnormal cortical function and pathophysiology associated with a wide range of neurological and neuropsychiatric diseases. We aim to study the spatial extent and topography of human basal ganglia connectivity in vivo. Additionally, we explore at an anatomical level the hypothesis of coexistent segregated and integrative cortico-basal ganglia loops. We use probabilistic tractography on magnetic resonance diffusion weighted imaging data to segment basal ganglia and thalamus in 30 healthy subjects based on their cortical and subcortical projections. We introduce a novel method to define voxel-based connectivity profiles that allow representation of projections from a source to more than one target region. Using this method, we localize specific relay nuclei within predefined functional circuits. We find strong correlation between tractography-based basal ganglia parcellation and anatomical data from previously reported invasive tracing studies in nonhuman primates. Additionally, we show in vivo the anatomical basis of segregated loops and the extent of their overlap in prefrontal, premotor, and motor networks. Our findings in healthy humans support the notion that probabilistic diffusion tractography can be used to parcellate subcortical gray matter structures on the basis of their connectivity patterns. The coexistence of clearly segregated and also overlapping connections from cortical sites to basal ganglia subregions is a neuroanatomical correlate of both parallel and integrative networks within them. We believe that this method can be used to examine pathophysiological concepts in a number of basal ganglia-related disorders. PMID:18614684

Draganski, Bogdan; Kherif, Ferath; Klöppel, Stefan; Cook, Philip A; Alexander, Daniel C; Parker, Geoff J M; Deichmann, Ralf; Ashburner, John; Frackowiak, Richard S J

2008-07-01

43

Osteopontin (Eta-1) is present in the rat basal ganglia.  

PubMed

Osteopontin (OPN) is a secreted glycosylated phosphoprotein that is responsive to oxidative stress and inflammation and controls cytokine production, inducible nitric oxide synthase (iNOS) expression and apoptotic cell death. In this study, we demonstrate the presence of OPN in the rat basal ganglia. Using reverse transcriptase polymerase chain reaction (RT-PCR), OPN cDNA was found in the substantia nigra, and striatum. The presence of OPN mRNA was demonstrated in the same areas of the basal ganglia, using in situ hybridisation. OPN protein was found in the SN, using Western blotting and confirmed by immunohistochemistry. The protein was localised to neurones but not to microglia or astroglia. This is the first report of the presence of OPN in the basal ganglia where it may be involved in the maintenance of neuronal viability. PMID:15548430

Iczkiewicz, Joanna; Rose, Sarah; Jenner, Peter

2004-12-01

44

Covert skill learning in a cortical-basal ganglia circuit.  

PubMed

We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning; influential 'actor-critic' models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire. Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit, contributes to skill learning even when it does not contribute to such 'exploratory' variation in behavioural performance during training. Blocking the output of the AFP while training Bengalese finches to modify their songs prevented the gradual improvement that normally occurs in this complex skill during training. However, unblocking the output of the AFP after training caused an immediate transition from naive performance to excellent performance, indicating that the AFP covertly gained the ability to implement learned skill performance without contributing to skill practice. In contrast, inactivating the output nucleus of the AFP during training completely prevented learning, indicating that learning requires activity within the AFP during training. Our results suggest a revised model of skill learning: basal ganglia circuits can monitor the consequences of behavioural variation produced by other brain regions and then direct those brain regions to implement more successful behaviours. The ability of the AFP to identify successful performances generated by other brain regions indicates that basal ganglia circuits receive a detailed efference copy of premotor activity in those regions. The capacity of the AFP to implement successful performances that were initially produced by other brain regions indicates precise functional connections between basal ganglia circuits and the motor regions that directly control performance. PMID:22699618

Charlesworth, Jonathan D; Warren, Timothy L; Brainard, Michael S

2012-05-20

45

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

2013-02-28

46

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

PubMed Central

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.

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

2013-01-01

47

Are periodic movements in sleep a basal ganglia dysfunction?  

Microsoft Academic Search

Summary Muscle activity during sleep is a new area of interest in sleep research. No precise brain structures are known to be involved in sleep movement. The etiology of periodic movements during sleep is unknown. The present study was dedicated to evaluate involvement of basal ganglia in periodic movements of the legs during sleep (PMS) in Parkinson's diseased patients. Sleep

J. J. M. Askenasy; E. D. Weitzman; M. D. Yahr

1987-01-01

48

Toward a Functional Analysis of the Basal Ganglia  

Microsoft Academic Search

Parkinson patients were tested in two paradigms to test the hypothesis that the basal ganglia are involved in the shifting of attentional set. Set shifting means a respecification of the conditions that regulate responding, a process sometimes referred to as an executive process. In one paradigm, upon the appearance of each stimulus, subjects were instructed to respond either to its

Amy E. Hayes; Matthew C. Davidson; Steven W. Keele; Robert D. Rafal

1998-01-01

49

Injuries of Basal Ganglia following Head Trauma in Children  

Microsoft Academic Search

7 pediatric patients with injuries of basal ganglia following head trauma were reported. They ranged in age from 10 months to 10 years. 5 boys and 2 girls comprised the patients. Cases 1–4 are mild cases in which the children fell down backward while playing, followed by a minimum loss of consciousness. In every case there was hemiparesis, but all

Yutaka Maki; Hiroshi Akimoto; Takao Enomoto

1980-01-01

50

The role of the basal ganglia in data processing.  

PubMed

Complex cerebral activities are likely to be composed of massively repeated simple data processing tasks since the cortical data processing unit, the cortical mini-column, is found throughout the cortex with only minor variations. It has been proposed that one task performed by the cortical mini-column may be to match afferent sensory data to learnt datasets in a process known as automatic association. We hypothesize that basal ganglia circuits, through the relative signal of the nigro-striatal and striato-pallidal pathways, determine the matching threshold for dataset matching within cortical mini-columns. Basal ganglia circuits are in a unique position to use parallel information to modulate the parameters of auto-association to increase the speed of data processing tasks. This hypothesis can explain motor symptoms in Parkinson's disease and also predicts that over and underactivity of basal ganglia circuits (the 'on' and 'off' states) will lead to characteristic errors in sensory data interpretation in all modalities - false negative data recognition when 'off' and false positive data recognition when 'on'. As a preliminary exploration of this hypothesis 16 patients with advanced Parkinson's disease were tested in voice and face recognition when 'off' and 'on'. Each patient exhibited errors in the recognition task according to basal ganglia activity as predicted by our hypothesis. Further experiments to test the hypothesis are proposed. PMID:18410994

Leyden, James; Kleinig, Tim

2008-04-14

51

Computed tomography of germinomas in basal ganglia and thalamus  

Microsoft Academic Search

CT findings of 6 cases with germinoma originating in the basal ganglia and thalamus are reported. The early finding of germinoma in this region on plain CT, was an irregularly defined, slightly high density area without mass effect. Repeated CT scanning showed enlarging iso-density lesion accompanied by mass effect to high. Intratumorous cysts and calcifications were frequently observed. The tumor

T. Soejima; I. Takeshita; H. Yamamoto; Y. Tsukamoto; M. Fukui; S. Matsuoka

1987-01-01

52

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

Microsoft Academic Search

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

Michael T. Ullman

2006-01-01

53

Glutamate–dopamine–GABA interactions in the aging basal ganglia  

Microsoft Academic Search

The study of neurotransmitter interactions gives a better understanding of the physiology of specific circuits in the brain. In this review we focus mostly on our own results on the interaction of the neurotransmitters glutamate, dopamine and GABA in the basal ganglia during the normal process of aging. We review first the studies on the action of endogenous glutamate on

Francisco Mora; Gregorio Segovia; Alberto del Arco

2008-01-01

54

Expectation of reward modulates cognitive signals in the basal ganglia  

Microsoft Academic Search

Action is controlled by both motivation and cognition. The basal ganglia may be the site where these kinds of information meet. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual and memory responses of caudate neurons are modulated by expectation of reward so profoundly that a neuron's preferred direction often changed with the change in

Reiko Kawagoe; Yoriko Takikawa; Okihide Hikosaka

1998-01-01

55

The effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkey.  

PubMed

Manganese (Mn) may produce neurotoxicity in man through inhalation of Mn dust. Animals exposed to excessive Mn develop neurological abnormalities, and neuropathological lesions in the brain mainly in the globus pallidus with decreased concentrations of the neurotransmitter, dopamine (DA), in the brain. Monkeys exposed to Mn by inhalation did not produce any abnormal movements. After two years, the animals were sacrificed and certain brain areas were compared to controls. There were significant decreases in DA concentration in caudate and globus pallidus, and there was a 60-80% increase in Mn concentration in the basal ganglia of the brain. The DA system in the basal ganglia is vulnerable to the effects of Mn, but the amount of Mn inhaled and the period of exposure would appear to determine whether abnormal neurological signs develop. PMID:6538950

Bird, E D; Anton, A H; Bullock, B

1984-01-01

56

Canceling actions involves a race between basal ganglia pathways.  

PubMed

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 exhibited low-latency responses to 'Stop' cues, irrespective of whether actions were canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) only responded to Stop cues 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 stopping requiring Stop-cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return. PMID:23852117

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

2013-07-14

57

Centrality of Striatal Cholinergic Transmission in Basal Ganglia Function  

PubMed Central

Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction. Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson's disease and dystonia. Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

Bonsi, Paola; Cuomo, Dario; Martella, Giuseppina; Madeo, Graziella; Schirinzi, Tommaso; Puglisi, Francesca; Ponterio, Giulia; Pisani, Antonio

2011-01-01

58

Modeling Basal Ganglia for Understanding Parkinsonian Reaching Movements  

Microsoft Academic Search

We present a computational model that highlights the role of basal ganglia\\u000a(BG) in generating simple reaching movements. The model is cast within the\\u000areinforcement learning (RL) framework with the correspondence between RL\\u000acomponents and neuroanatomy as follows: dopamine signal of substantia nigra\\u000apars compacta as the Temporal Difference error, striatum as the substrate for\\u000athe Critic, and the motor

K. N. Magdoom; D. Subramanian; V. S. Chakravarthy; B. Ravindran; Shun-ichi Amari; N. Meenakshisundaram

2011-01-01

59

What do the basal ganglia do? A modeling perspective  

Microsoft Academic Search

Basal ganglia (BG) constitute a network of seven deep brain nuclei involved in a variety of crucial brain functions including:\\u000a action selection, action gating, reward based learning, motor preparation, timing, etc. In spite of the immense amount of\\u000a data available today, researchers continue to wonder how a single deep brain circuit performs such a bewildering range of\\u000a functions. Computational models

V. Srinivasa Chakravarthy; Denny Joseph; Raju S. Bapi

2010-01-01

60

Calcium-binding proteins in primate basal ganglia  

Microsoft Academic Search

This paper describes the distribution of the calcium-binding proteins calbindin-D28k, parvalbumin and calretinin in primate basal ganglia. The data derive from immunocytochemical studies undertaken in squirrel monkeys (Saimiri sciureus) and in normal human individuals. In the striatum, calbindin labels medium-sized spiny projection neurons whereas parvalbumin and calretinin mark two separate classes of aspiny interneurons. The striatal matrix compartment is markedly

A. Parent; M. Fortin; P.-Y. Côté; F. Cicchetti

1996-01-01

61

Pure psychic akinesia with bilateral lesions of basal ganglia.  

PubMed Central

Three patients showed dramatic psychic akinesia after recovery from toxic encephalopathy. They had no or only mild motor disorders. The spontaneous psychic akinesia was reversible when the patient was stimulated, as if there was a loss of self psychic activation. Intellectual capacities were normal. Two patients had stereotyped behaviours resembling compulsions. In all patients CT cans showed bilateral lesions in the basal ganglia, mainly within the globus pallidus. Images

Laplane, D; Baulac, M; Widlocher, D; Dubois, B

1984-01-01

62

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

PubMed Central

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

Pamela, Reitsma; Brent, Doiron; Jonathan, Rubin

2011-01-01

63

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

PubMed

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

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

2012-07-13

64

Multi-Neuronal Recordings in the Basal Ganglia in Normal and Dystonic Rats  

PubMed Central

Classical rate-based pathway models are invaluable for conceptualizing direct/indirect basal ganglia pathways, but cannot account for many aspects of normal and abnormal motor control. To better understand the contribution of patterned basal ganglia signaling to normal and pathological motor control, we simultaneously recorded multi-neuronal and EMG activity in normal and dystonic rats. We used the jaundiced Gunn rat model of kernicterus as our experimental model of dystonia. Stainless steel head fixtures were implanted on the skulls and EMG wires were inserted into antagonistic hip muscles in nine dystonic and nine control rats. Under awake, head-restrained conditions, neuronal activity was collected from up to three microelectrodes inserted in the principal motor regions of the globus pallidus (GP), subthalamic nucleus, and entopeduncular nucleus (EP). In normal animals, most neurons discharged in regular or irregular patterns, without appreciable bursting. In contrast, in dystonic animals, neurons discharged in slow bursty or irregular, less bursty patterns. In normal rats, a subset of neurons showed brief discharge bursts coinciding with individual agonist or antagonist EMG bursts. In contrast, in dystonics, movement related discharges were characterized by more prolonged bursts which persist over multiple dystonic co-contraction epics. The pattern of movement related decreases in discharge activity however did not differ in dystonics compared to controls. In severely dystonic rats, exclusively, simultaneously recorded units often showed abnormally synchronized movement related pauses in GP and bursts in EP. In conclusion, our findings support that slow, abnormally patterned neuronal signaling is a fundamental pathophysiological feature of intrinsic basal ganglia nuclei in dystonia. Moreover, from our findings, we suggest that excessive movement related silencing of neuronal signaling in GP profoundly disinhibits EP and in turn contributes to sustained, unfocused dystonic muscle contractions.

Baron, Mark S.; Chaniary, Kunal D.; Rice, Ann C.; Shapiro, Steven M.

2011-01-01

65

Analysis of Candidate Genes at the IBGC1 Locus Associated with Idiopathic Basal Ganglia Calcification (“Fahr’s Disease”)  

Microsoft Academic Search

Basal ganglia calcification (striatopallidodentate calcifications) can be caused by several systemic and neurological disorders.\\u000a Familial Idiopathic Basal Ganglia Calcification (IBGC, “Fahr’s disease”), is characterized by basal ganglia and extrabasal\\u000a ganglia calcifications, parkinsonism and neuropsychiatric symptoms. Because of an increased use of neuroimaging procedures,\\u000a calcifications of the basal ganglia are visualized more often and precociously. In 1999, a major American family

J. R. M. Oliveira; M. J. Sobrido; E. Spiteri; S. Hopfer; G. Meroni; E. Petek; M. Baquero; D. H. Geschwind

2007-01-01

66

Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q  

Microsoft Academic Search

Idiopathic basal ganglia calcification (IBGC) is characterised by radiological, neurological, cognitive and psychiatric abnormalities. The associations between these abnormal phenotypes and abnormal genes remain unclear despite the recent mapping to chromosome 14q of a susceptibility locus for IBGC (IBGC1). We identified two siblings, from a large multigenerational pedigree, who had both been diagnosed with radiological IBGC, dementia, bipolar affective disorder

Henry Brodaty; Philip Mitchell; Georgina Luscombe; John B. J. Kwok; Renee F. Badenhop; Rod McKenzie; Peter R. Schofield

2002-01-01

67

How do the basal ganglia regulate sleep-wake behavior?  

PubMed

The basal ganglia (BG) are involved in motor function, habit formation, and reward or addictive behaviors, but the question as to how the BG integrate arousal with these fundamental striatal functions has only recently received much attention. Findings based on electrophysiology, neurotoxic lesioning, and the use of transgenic animals have established that the striatum and globus pallidus are key structural elements for the control of sleep and wakefulness. Here, we discuss emerging anatomical and molecular mechanisms of sleep-wake regulation at work in the BG. Furthermore, we propose a model whereby adenosine and dopamine receptors in the nucleus accumbens (NAc) are involved in the integration of behavioral processes and the induction of wakefulness through cortical activation. PMID:22858523

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

2012-08-01

68

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

69

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems.  

PubMed

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions. PMID:18614161

Schmahmann, Jeremy D; Pandya, Deepak N

2008-05-23

70

Zonisamide regulates basal ganglia transmission via astroglial kynurenine pathway.  

PubMed

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

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

2013-08-22

71

An ultra-short dopamine pathway regulates basal ganglia output  

PubMed Central

Substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus critical for movement control. Its ?-aminobutyric acid (GABA)-containing projection neurons intermingle with nigral dopamine (DA) neuron dendrites. Here we show that SNr GABA neurons co-express dopamine D1 and D5 receptor mRNAs and also mRNA for TRPC3 channels. Dopamine induced an inward current in these neurons and increased their firing frequency. These effects were mimicked by D1-like agonists, blocked by a D1-like antagonist. D1-like receptor blockade reduced SNr GABA neuron firing frequency and increased their firing irregularity. These D1-like effects were absent in D1 or D5 receptor knockout mice and inhibited by intracellularly applied D1 or D5 receptor antibody. These D1-like effects were also inhibited when the tonically active TRPC3 channels were inhibited by intracellularly applied TRPC3 channel antibody. Furthermore, stimulation of DA neurons induced a direct inward current in SNr GABA neurons that was sensitive to D1-like blockade. Manipulation of DA neuron activity and DA release and inhibition of dopamine reuptake affected SNr GABA neuron activity in a D1-like receptor-dependent manner. Taken together, our findings indicate that dendritically released dopamine tonically excites SNr GABA neurons via D1-D5 receptor co-activation that enhances constitutively active TRPC3 channels, forming an ultra-short SNc?SNr dopamine pathway that regulates the firing intensity and pattern of these basal ganglia output neurons.

Zhou, Fu-Wen; Jin, Ying; Matta, Shannon G.; Xu, Ming; Zhou, Fu-Ming

2009-01-01

72

An Avian Basal Ganglia Pathway Essential for Vocal Learning Forms a Closed Topographic Loop  

Microsoft Academic Search

The mammalian basal ganglia-thalamocortical pathway is im- portant for motor control, motor learning, and cognitive func- tions. It contains parallel, closed loops, at least some of which are organized topographically and in a modular manner. Song- birds have a circuit specialized for vocal learning, the anterior forebrain pathway (AFP), forming a basal ganglia loop with only three stations: the pallial

Minmin Luo; Dj Perkel

2001-01-01

73

Inhibition of Ongoing Responses Following Frontal, Nonfrontal, and Basal Ganglia Lesions  

Microsoft Academic Search

The authors investigated the role of the frontal lobes and the basal ganglia in the inhibition of ongoing responses. Seventeen patients with frontal lesions (FG), 20 patients with lesions outside the frontal cortex (NFG), 8 patients with lesions to the basal ganglia (BG), and 20 orthopedic controls (OG) performed the stop-signal task that allows the estimation of the time it

Martina Rieger; Siegfried Gauggel; Katja Burmeister

2003-01-01

74

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

75

What are the computations of the cerebellum, the basal ganglia and the cerebral cortex?  

Microsoft Academic Search

The classical notion that the cerebellum and the basal ganglia are dedicated to motor control is under dispute given increasing evidence of their involvement in non-motor functions. Is it then impossible to characterize the functions of the cerebellum, the basal ganglia and the cerebral cortex in a simplistic manner? This paper presents a novel view that their computational roles can

Kenji Doya

1999-01-01

76

Complementary roles of basal ganglia and cerebellum in learning and motor control  

Microsoft Academic Search

The classical notion that the basal ganglia and the cerebellum are dedicated to motor control has been challenged by the accumulation of evidence revealing their involvement in non-motor, cognitive functions. From a computational viewpoint, it has been suggested that the cerebellum, the basal ganglia, and the cerebral cortex are specialized for different types of learning: namely, supervised learning, reinforcement learning

Kenji Doya

2000-01-01

77

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

Microsoft Academic Search

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of

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

2010-01-01

78

Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal  

Microsoft Academic Search

The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interesting- ly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning—the ability to adaptively change a response when previously learned stimulus-outcome contingencies are re- versed. Here, we compared the

Daphna Shohamy; Catherine E. Myers; Ramona O. Hopkins; Jake Sage; Mark A. Gluck

2009-01-01

79

Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal  

Microsoft Academic Search

The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning—the ability to adaptively change a response when previously learned stimulus–outcome contingencies are reversed. Here, we compared the contribution of

Daphna Shohamy; Catherine E. Myers; Ramona O. Hopkins; Jake Sage; Mark A. Gluck

2008-01-01

80

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

Microsoft Academic Search

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

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

2010-01-01

81

Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates  

Microsoft Academic Search

There are two views as to the character of basal-ganglia processing – processing by segregated parallel circuits or by information sharing. To distinguish between these views, we studied the simultaneous activity of neurons in the output stage of the basal ganglia with cross-correlation techniques. The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated. However,

Hagai Bergman; Ariela Feingold; Asaph Nini; Aeyal Raz; Hamutal Slovin; Moshe Abeles; Eilon Vaadia

1998-01-01

82

Functional Coupling Between Substantia Nigra and Basal Ganglia Homologues in Amphibians  

PubMed Central

Neuroanatomical and pharmacological experiments support the existence of a homologue of the mammalian substantia nigra–basal ganglia circuit in the amphibian brain. Demarcation of borders between the striatum and pallidum in frogs, however, has been contentious, and direct evidence of functional coupling between the putative nigral and striatal homologues is lacking. To clarify basal ganglia function in anurans, the authors used expression of immediate–early gene egr-1 as a marker of neural activation in the basal ganglia of túngara frogs (Physalaemus pustulosus). Regional variation in egr-1 mRNA levels distinguished striatal and pallidal portions of the basal ganglia and supported the grouping of the striatopallidal transition zone with the dorsal pallidum. As further evidence for a functional coupling between the dopaminergic cells in the posterior tuberculum (the putative substantia nigra homologue) and the basal ganglia, a positive relationship was demonstrated between the size of the dopaminergic cell population and the neural activation levels within the dorsal pallidum.

Hoke, Kim L.; Ryan, Michael J.; Wilczynski, Walter

2008-01-01

83

Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease.  

PubMed

We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases in which it correlates with visible pathology, possibly by its involvement in toxic free-radical reactions. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name 'neuroferritinopathy'. PMID:11438811

Curtis, A R; Fey, C; Morris, C M; Bindoff, L A; Ince, P G; Chinnery, P F; Coulthard, A; Jackson, M J; Jackson, A P; McHale, D P; Hay, D; Barker, W A; Markham, A F; Bates, D; Curtis, A; Burn, J

2001-08-01

84

Humanized Foxp2 specifically affects cortico-basal ganglia circuits.  

PubMed

It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution and influence aspects of speech and language. Recently it was shown that when these substitutions are introduced into the endogenous Foxp2 gene of mice, they increase dendrite length and long-term depression (LTD) in medium spiny neurons of the striatum. Here we investigated if these effects are found in other brain regions. We found that neurons in the cerebral cortex, the thalamus and the striatum have increased dendrite lengths in the humanized mice whereas neurons in the amygdala and the cerebellum do not. In agreement with previous work we found increased LTD in medium spiny neurons, but did not detect alterations of synaptic plasticity in Purkinje cells. We conclude that although Foxp2 is expressed in many brain regions and has multiple roles during mammalian development, the evolutionary changes that occurred in the protein in human ancestors specifically affect brain regions that are connected via cortico-basal ganglia circuits. PMID:21111790

Reimers-Kipping, S; Hevers, W; Pääbo, S; Enard, W

2010-11-25

85

Basal Ganglia Contributions to Motor Control: A Vigorous Tutor  

PubMed Central

SUMMARY OF RECENT ADVANCES The roles of the basal ganglia (BG) in motor control are much debated. Many influential hypotheses have grown from studies in which output signals of the BG were not blocked, but pathologically-disturbed. A weakness of that approach is that the resulting behavioral impairments reflect degraded function of the BG per se mixed together with secondary dysfunctions of BG-recipient brain areas. To overcome that limitation, several studies have focused on the main skeletomotor output region of the BG, the globus pallidus internus (GPi). Using single-cell recording and inactivation protocols these studies provide consistent support for two hypotheses: the BG modulates movement performance (“vigor”) according to motivational factors (i.e., context-specific cost/reward functions) and the BG contributes to motor learning. Results from these studies also add to the problems that confront theories positing that the BG selects movement, inhibits unwanted motor responses, corrects errors online, or stores and produces well-learned motor skills.

Turner, Robert S.; Desmurget, Michel

2010-01-01

86

Medical students' viewpoint regarding the integrated module of basal ganglia.  

PubMed

Integration is an important educational strategy in medical education. Considering this idea, the goal of the present study was to design and implementation of longitudinal and vertical integrated education of anatomy, physiology, pharmacology, neurology and neuropsychiatry subjects of brain's basal ganglia by a multidisciplinary team. Kern's approach to curriculum development was used. Participants were 20 medical students at basic science level who contribute in a 10 stations of pre-test exam at Medical School's Skill Lab. After the implementation of the module by a multidisciplinary team, post-test were done. A structured questionnaire was designed to assess student opinions about adequacy, usefulness of the module using a Likert scale with 5 categories ranging from "completely agreement" to "completely disagreement". The result of pre and post-test were also compared. Twenty questionnaires were completed, giving a 77.63% satisfaction rate. Seventy-five percent of students found it useful and appropriate at basic science level. About fifty percent of students suggested the implementation of this module for other medical students. The score of post-test was significantly (14.52 ± 0.47 vs 6.32 ± 0.62, P < 0.05) higher than pre-test results. The viewpoints of medical students were positive and they value the module highly. Since it is not easy to change the style we teach, these results suggest necessitate of supporting the faculty member's participation in these modules. PMID:22131247

Mehr, Shahram Ejtemaei; Hassanzadeh, Gholamreza; Zahmatkesh, Maryam; Seyedian, Maziar; Arbabi, Mohammad; Mirzazadeh, Azim; Hatami, Farhad

2011-01-01

87

Microcircuitry of the direct and indirect pathways of the basal ganglia.  

PubMed

Our understanding of the organization of the basal ganglia has advanced markedly over the last 10 years, mainly due to increased knowledge of their anatomical, neurochemical and physiological organization. These developments have led to a unifying model of the functional organization of the basal ganglia in both health and disease. The hypothesis is based on the so-called "direct" and "indirect" pathways of the flow of cortical information through the basal ganglia and has profoundly influenced the field of basal ganglia research, providing a framework for anatomical, physiological and clinical studies. The recent introduction of powerful techniques for the analysis of neuronal networks has led to further developments in our understanding of the basal ganglia. The objective of this commentary is to build upon the established model of the basal ganglia connectivity and review new anatomical findings that lead to the refinement of some aspects of the model. Four issues will be discussed. (1) The existence of several routes for the flow of cortical information along "indirect" pathways. (2) The synaptic convergence of information flowing through the "direct" and "indirect" pathways at the single-cell level in the basal ganglia output structures. (3) The convergence of functionally diverse information from the globus pallidus and the ventral pallidum at different levels of the basal ganglia. (4) The interconnections between the two divisions of the pallidal complex and the subthalamic nucleus and the characterization of the neuronal network underlying the indirect pathways. The findings summarized in this commentary confirm and elaborate the models of the direct and indirect pathways of information flow through the basal ganglia and provide a morphological framework for future studies. PMID:9881853

Smith, Y; Bevan, M D; Shink, E; Bolam, J P

1998-09-01

88

Metabolite Alterations in Basal Ganglia Associated with Psychiatric Symptoms of Abstinent Toluene Users: A Proton MRS Study  

Microsoft Academic Search

Long-term toluene abuse causes a variety of psychiatric symptoms. However, little is known about abnormalities at the neurochemical level in the living human brain after long-term exposure to toluene. To detect neurochemical changes in the basal ganglia of subjects with a history of long-term toluene use, proton magnetic resonance spectroscopy (1H MRS) was performed in 12 abstinent toluene users and

Kiyokazu Takebayashi; Yoshimoto Sekine; Nori Takei; Yoshio Minabe; Haruo Isoda; Hiroyasu Takeda; Katsuhiko Nishimura; Kazuhiko Nakamura; Katsuaki Suzuki; Yasuhide Iwata; Harumi Sakahara; Norio Mori

2004-01-01

89

A case of idiopathic basal ganglia calcification associated with membranoproliferative glomerulonephritis.  

PubMed

Idiopathic basal ganglia calcification (IBGC) is a syndrome in which bilateral cerebral calcification occurs despite the absence of abnormal calcium metabolism. A 17-year-old Japanese female was admitted for investigation of intermittent proteinuria from the age of 12 years. On admission, her blood pressure was 126/60 mmHg and her serum creatinine was 0.8 mg/dL. Although computed tomography revealed bilateral striopallidodentate calcinosis, her level of intelligence and neurological findings were normal, as were the results of endocrine tests including parathyroid hormone. Asymptomatic IBGC was diagnosed. Renal biopsy showed membranoproliferative glomerulonephritis. Peritoneal dialysis was started for end-stage renal failure when she was 24 years old. Pyramidal and extrapyramidal signs started to develop at the age of 27 years and progressed, resulting in death from aspiration pneumonia at the age of 32 years. Post-mortem revealed bilateral calcification of the basal ganglia, dentate nucleus, thalamus, and centrum semiovale. On light microscopy, there was circumferential calcification of the media and intima of affected vessels in the brain, including small arteries, small veins, and capillaries, and luminal narrowing was seen. On electron microscopy, layers of differing electron density were arranged in concentric laminae. This is the first report of IBGC with bilateral and symmetrical cerebral calcification accompanied by membranoproliferative glomerulonephritis resulting in end-stage renal failure. PMID:22001464

Tsuchiya, Yoshiki; Ubara, Yoshifumi; Anzai, Makoto; Hiramatsu, Rikako; Suwabe, Tatsuya; Hoshino, Junichi; Sumida, Keiichi; Hasegawa, Eiko; Yamanouchi, Masayuki; Hayami, Noriko; Marui, Yuji; Sawa, Naoki; Hara, Shigeko; Takaichi, Kenmei; Oohashi, Kenichi

2011-10-15

90

Prospects for cannabinoid therapies in basal ganglia disorders  

PubMed Central

Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like ?9-tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB1 and CB2 receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB2 receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB2 receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB2 receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB2 receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB2 receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7

Fernandez-Ruiz, Javier; Moreno-Martet, Miguel; Rodriguez-Cueto, Carmen; Palomo-Garo, Cristina; Gomez-Canas, Maria; Valdeolivas, Sara; Guaza, Carmen; Romero, Julian; Guzman, Manuel; Mechoulam, Raphael; Ramos, Jose A

2011-01-01

91

Cognitive deficits in animal models of basal ganglia disorders.  

PubMed

The two most common neurological disorders of the basal ganglia are Parkinson's disease (PD) and Huntington's disease (HD). The most overt symptoms of these diseases are motoric, reflecting the loss of the striatal medium spiny neurons in HD and ascending substantia nigra dopaminergic cells in PD. However, both disease processes induce insidious psychiatric and cognitive syndromes that can manifest well in advance of the onset of motor deficits. These early deficits provide an opportunity for prophylactic therapeutic intervention in order to retard disease progression from the earliest possible point. In order to exploit this opportunity, animal models of HD and PD are being probed for the specific cognitive deficits represented in the disease states. At the neuronal level, these deficits are typically, but not exclusively, mediated by disruption of parallel corticostriatal loops that integrate motor information with sensory and higher order, "executive" cognitive functions. Dysfunction in these systems can be probed with sensitive behavioural tests that selectively probe these cognitive functions in mouse models with focal lesions of striatal or cortical regions, or of specific neurotransmitter systems. Typically these tests were designed and validated in rats. With the advent of genetically modified mouse models of disease, validated tests provide an opportunity to screen mouse models of disease for early onset cognitive deficits. This review seeks to draw together the literature on cognitive deficits in HD and PD, to determine the extent to which these deficits are represented in the current animal models of disease, and to evaluate the viability of selecting cognitive deficits as potential therapeutic targets. This article is part of a Special Issue entitled 'Animal Models'. PMID:22588013

Brooks, Simon P; Dunnett, Stephen B

2012-05-12

92

Prospects for cannabinoid therapies in basal ganglia disorders.  

PubMed

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

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

2011-08-01

93

Relationship between oscillations in the basal ganglia and synchronization of cortical activity.  

PubMed

The functions of oscillations within the basal ganglia are poorly understood. We discuss in the present paper, the possible physiological or pathological roles of oscillatory activities within the basal ganglia, and their relationship to cortical oscillations. Three aspects are presented: 1. What do we know from animal studies? 2. What do we know from neurophysiological studies in parkinsonian patients? 3. What is the effect of L-dopa treatment and electrical stimulation within basal ganglia circuits on cortical oscillations? Animal studies suggest that neuronal oscillations are spontaneously generated within the basal ganglia system, especially from the GPE and the subthalamic nucleus (STN), but are mainly synchronized by cortical activity via the striatal inputs. Dopamine depletion results in a global increase of oscillations within the whole basal ganglia system, particularly in the GP-NST network. Oscillations within the basal ganglia may, in part, be related to tremor since they are enhanced, especially in the globus pallidus internus (GPI) and the STN, in human and animal dopaminergic depletion. However, they also play a role in the physiology of movement as revealed by coherence analysis between cortex, muscles and GPI/STN in parkinsonian patients undergoing deep brain stimulation. It is known that the basal ganglia may influence cortico-muscular oscillations such as the Piper rhythm and other rhythms in the beta band. In off-drug parkinsonian patients, low frequency oscillations (4-10 Hz) are favoured, presumably resulting in bradykinesia and low force. When medically (Ldopa) or surgically (deep brain stimulation) treated, these low frequency oscillations are replaced by high frequency (70 Hz) oscillations that are important for motor programs to be correctly executed. Studies of cortical reactivity related to planning of voluntary movement in parkinsonian patients provide evidence that it is possible to influence cortical reactivity through the basal ganglia system. PMID:12495873

Cassim, François; Labyt, Etienne; Devos, David; Defebvre, Luc; Destée, Alain; Derambure, Philippe

2002-12-01

94

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 has 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 program 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 programs 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

2013-02-25

95

Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis  

Microsoft Academic Search

Information-processing speed (IPS) slowing is a primary cognitive deficit in multiple sclerosis (MS). Basal ganglia, thalamus\\u000a and neocortex are thought to have a key role for efficient information-processing, yet the specific relative contribution\\u000a of these structures for MS-related IPS impairment is poorly understood. To determine if basal ganglia and thalamus atrophy\\u000a independently contribute to visual and auditory IPS impairment in

Sonia Batista; Robert Zivadinov; Marietta Hoogs; Niels Bergsland; Mari Heininen-Brown; Michael G. Dwyer; Bianca Weinstock-Guttman; Ralph H. B. Benedict

96

Basal ganglia volumetric studies in affective disorder: what did we learn in the last 15 years?  

Microsoft Academic Search

Summary.  Until today, morphometric neuroimaging studies on affective disorders concentrate on the limbic system, especially the hippocampus,\\u000a amygdala, and anterior cingulate. In most of the studies and reviews available today, the basal ganglia are of secondary interest.\\u000a It seems that the basal ganglia are interest of neurologist, whereas the limbic system is reserved for psychiatric neuroimaging\\u000a studies. We follow a different

R. M. Bonelli; H.-P. Kapfhammer; S. S. Pillay; D. A. Yurgelun-Todd

2006-01-01

97

Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia  

PubMed Central

GABA transporter type 1 and 3 (GAT-1 and GAT-3, respectively) are the two main subtypes of GATs responsible for the regulation of extracellular GABA levels in the central nervous system. These transporters are widely expressed in neuronal (mainly GAT-1) and glial (mainly GAT-3) elements throughout the brain, but most data obtained so far relate to their role in the regulation of GABAA receptor-mediated postsynaptic tonic and phasic inhibition in the hippocampus, cerebral cortex and cerebellum. Taking into consideration the key role of GABAergic transmission within basal ganglia networks, and the importance for these systems to be properly balanced to mediate normal basal ganglia function, we analyzed in detail the localization and function of GAT-1 and GAT-3 in the globus pallidus of normal and Parkinsonian animals, in order to further understand the substrate and possible mechanisms by which GABA transporters may regulate basal ganglia outflow, and may become relevant targets for new therapeutic approaches for the treatment of basal ganglia-related disorders. In this review, we describe the general features of GATs in the basal ganglia, and give a detailed account of recent evidence that GAT-1 and GAT-3 regulation can have a major impact on the firing rate and pattern of basal ganglia neurons through pre- and post-synaptic GABAA- and GABAB-receptor-mediated effects.

Jin, Xiao-Tao; Galvan, Adriana; Wichmann, Thomas; Smith, Yoland

2011-01-01

98

A hypothetical role of cortico-basal ganglia-thalamocortical loops in visual processing.  

PubMed

The goal of the present work was to define the mechanisms underlying the contribution of sensory and limbic cortico-basal ganglia-thalamocortical loops to visual processing and its attentional modulation. We proposed that visual processing is promoted by dopamine-dependent long-term modifications of synaptic transmission in the basal ganglia that favour a selection of neocortical patterns representing a visual stimulus. This selection is the result of the opposite sign of modulation of strong and weak cortico-basal ganglia inputs and subsequent activity reorganization in each loop. Reorganization leads to disinhibition/inhibition of cortical neurons strongly/weakly excited by stimulus during dopamine release. Recruitment of the thalamo-basal ganglia-collicular pathway is proposed to be necessary for stimulus-evoked dopamine release that underlies bottom-up attentional effects. Visual excitation of the prefrontal cortex and hippocampus (via the thalamus), their cooperation in control of the basal ganglia and dopaminergic cell firing, and simultaneous modulation of activity in diverse cortico-basal ganglia-thalamocortical loops is proposed to underlie top-down attentional effects. It follows from our model that only those components of cortical responses can be modulated by attention, whose onset exceeds the latency of visual responses of dopaminergic cells (50-110 ms). This and other consequences of the model are in accordance with known experimental data. PMID:17204363

Silkis, Isabella

2006-11-16

99

Information processing, dimensionality reduction and reinforcement learning in the basal ganglia.  

PubMed

Modeling of the basal ganglia has played a major role in our understanding of this elusive group of nuclei. Models of the basal ganglia have undergone evolutionary and revolutionary changes over the last 20 years, as new research in the fields of anatomy, physiology and biochemistry of these nuclei has yielded new information. Early models dealt with a single pathway through the nuclei and focused on the nature of the processing performed within it, convergence of information versus parallel processing of information. Later, the Albin-DeLong "box-and-arrow" model characterized the inter-nuclei interaction as multiple pathways while maintaining a simplistic scalar representation of the nuclei themselves. This model made a breakthrough by providing key insights into the behavior of these nuclei in hypo- and hyper-kinetic movement disorders. The next generation of models elaborated the intra-nuclei interactions and focused on the role of the basal ganglia in action selection and sequence generation which form the most current consensus regarding basal ganglia function in both normal and pathological conditions. However, new findings challenge these models and point to a different neural network approach to information processing in the basal ganglia. Here, we take an in-depth look at the reinforcement driven dimensionality reduction (RDDR) model which postulates that the basal ganglia compress cortical information according to a reinforcement signal using optimal extraction methods. The model provides new insights and experimental predictions on the computational capacity of the basal ganglia and their role in health and disease. PMID:15013228

Bar-Gad, Izhar; Morris, Genela; Bergman, Hagai

2003-12-01

100

Substrates for normal gait and pathophysiology of gait disturbances with respect to the basal ganglia dysfunction.  

PubMed

In this review, we have tried to elucidate substrates for the execution of normal gait and to understand pathophysiological mechanisms of gait failure in basal ganglia dysfunctions. In Parkinson's disease, volitional and emotional expressions of movement processes are seriously affected in addition to the disturbance of automatic movement processes, such as adjustment of postural muscle tone before gait initiation and rhythmic limb movements during walking. These patients also suffer from muscle tone rigidity and postural instability, which may also cause reduced walking capabilities in adapting to various environments. Neurophysiological and clinical studies have suggested the importance of basal ganglia connections with the cerebral cortex and limbic system in the expression of volitional and emotional behaviors. Here we hypothesize a crucial role played by the basal ganglia-brainstem system in the integrative control of muscle tone and locomotion. The hypothetical model may provide a rational explanation for the role of the basal ganglia in the control of volitional and automatic aspects of movements. Moreover, it might also be beneficial for understanding pathophysiological mechanisms of basal ganglia movement disorders. A part of this hypothesis has been supported by studies utilizing a constructive simulation engineering technique that clearly shows that an appropriate level of postural muscle tone and proper acquisition and utilization of sensory information are essential to maintain adaptable bodily functions for the full execution of bipedal gait. In conclusion, we suggest that the major substrates for supporting bipedal posture and executing bipedal gait are 1) fine neural networks such as the cortico-basal ganglia loop and basal ganglia-brainstem system, 2) fine musculoskeletal structures with adequately developed (postural) muscle tone, and 3) proper sensory processing. It follows that any dysfunction of the above sensorimotor integration processes would result in gait disturbance. PMID:18821082

Takakusaki, Kaoru; Tomita, Nozomi; Yano, Masafumi

2008-08-01

101

Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood  

PubMed Central

Background Childhood adversity increases the risk of psychopathology, but the neurobiological mechanisms underlying this vulnerability are not well-understood. In animal models, early adversity is associated with dysfunction in basal ganglia regions involved in reward processing, but this relationship has not been established in humans. Methods Functional magnetic resonance imaging was used to examine basal ganglia responses to (a) cues signaling possible monetary rewards and losses, and (b) delivery of monetary gains and penalties, in 13 young adults who experienced maltreatment before age 14 and 31 non-maltreated controls. Results Relative to controls, individuals exposed to childhood adversity reported elevated symptoms of anhedonia and depression, rated reward cues less positively, and displayed a weaker response to reward cues in the left globus pallidus. There were no group differences in right hemisphere basal ganglia response to reward cues, or in basal ganglia response to loss cues, no-incentive cues, gains, or penalties. Conclusions Results indicate that childhood adversity in humans is associated with blunted subjective responses to reward-predicting cues as well as dysfunction in left basal ganglia regions implicated in reward-related learning and motivation. This dysfunction may serve as a diathesis that contributes to the multiple negative outcomes and psychopathologies associated with childhood adversity. The findings suggest that interventions that target motivation and goal-directed action may be useful for reducing the negative consequences of childhood adversity.

Dillon, Daniel G.; Holmes, Avram J.; Birk, Jeffrey L.; Brooks, Nancy; Lyons-Ruth, Karlen; Pizzagalli, Diego A.

2010-01-01

102

The thalamostriatal system: a highly specific network of the basal ganglia circuitry.  

PubMed

Although the existence of thalamostriatal projections has long been known, the role(s) of this system in the basal ganglia circuitry remains poorly characterized. The intralaminar and ventral motor nuclei are the main sources of thalamic inputs to the striatum. This review emphasizes the high degree of anatomical and functional specificity of basal ganglia-thalamostriatal projections and discusses various aspects of the synaptic connectivity and neurochemical features that differentiate this glutamate system from the corticostriatal network. It also discusses the importance of thalamostriatal projections from the caudal intralaminar nuclei in the process of attentional orientation. A major task of future studies is to characterize the role(s) of corticostriatal and thalamostriatal pathways in regulating basal ganglia activity in normal and pathological conditions. PMID:15331233

Smith, Yoland; Raju, Dinesh V; Pare, Jean-Francois; Sidibe, Mamadou

2004-09-01

103

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

104

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

Microsoft Academic Search

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

H. H. Kornhuber

1971-01-01

105

Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.  

PubMed

Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: <40, 40-60, and >60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression. PMID:24065723

Nicolas, Gaël; Pottier, Cyril; Charbonnier, Camille; Guyant-Maréchal, Lucie; Le Ber, Isabelle; Pariente, Jérémie; Labauge, Pierre; Ayrignac, Xavier; Defebvre, Luc; Maltête, David; Martinaud, Olivier; Lefaucheur, Romain; Guillin, Olivier; Wallon, David; Chaumette, Boris; Rondepierre, Philippe; Derache, Nathalie; Fromager, Guillaume; Schaeffer, Stéphane; Krystkowiak, Pierre; Verny, Christophe; Jurici, Snejana; Sauvée, Mathilde; Vérin, Marc; Lebouvier, Thibaud; Rouaud, Olivier; Thauvin-Robinet, Christel; Rousseau, Stéphane; Rovelet-Lecrux, Anne; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

2013-09-24

106

Teaching NeuroImages: Manganese neurotoxicity of the basal ganglia and thalamus.  

PubMed

A 27-year-old man with cholestasis presented with 4 weeks of progressive spastic quadriparesis and hypophonia. MRI revealed T2/fluid-attenuated inversion recovery hyperintensities in the basal ganglia and thalamus (figure 1). He was treated with IV methylprednisolone for acute disseminated encephalomyelitis. His condition worsened. MRI 4 weeks later showed larger symmetric hyperintensities in the basal ganglia and thalami (figure 2). Blood manganese was elevated (25.4 µg/L, reference 4.4-15.2). There was no known exposure. He was treated with chelation and levodopa with limited response. PMID:24081969

Lakhan, Shaheen E; Abboud, Hesham

2013-10-01

107

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

ERIC Educational Resources Information Center

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

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

2010-01-01

108

A modular neural-network model of the basal ganglia's role in learning and selecting motor behaviours  

Microsoft Academic Search

This work presents a modular neural-network model (based on reinforcement-learning actor-critic methods) that tries to capture some of the most-relevant known aspects of the role that basal ganglia play in learning and selecting motor behavior related to different goals. In particular some simulations with the model show that basal ganglia selects \\

Gianluca Baldassarre

2002-01-01

109

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

ERIC Educational Resources Information Center

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

Alm, Per A.

2004-01-01

110

Fulminant encephalopathy with basal ganglia hyperintensities in HIV-infected drug users  

PubMed Central

Objective: To define a clinical syndrome associated with active drug abuse in HIV-infected individuals. Methods: We performed a retrospective review to identify individuals treated at the Johns Hopkins Hospital from 1993 to 2008 who were HIV-infected and were actively abusing drugs and had bilateral basal ganglia lesions on MRI. They were identified using a key word search in the radiology database, autopsy database, and the Moore HIV clinic database. Clinical, laboratory, and radiographic findings were correlated to define the syndrome. Results: Ten individuals were identified who presented with a change in mental status or seizures, used cocaine or cocaine with heroin, had uncontrolled HIV infection (>190,000 copies/mL of plasma), elevated CSF protein (63–313 mg/dL), and diffuse hyperintense bilateral basal ganglia lesions on imaging. The majority of patients (8/10) had renal failure and despite supportive therapy most (7/9) ultimately died (median survival 21 days). Postmortem examination in one individual showed the presence of overwhelming microglial activation in the basal ganglia. The 2 surviving individuals were started on combined antiretroviral therapy (CART) during hospitalization. Conclusion: We describe a unique clinical syndrome of a fulminant encephalopathy associated with primarily basal ganglia involvement in HIV-infected drug abusers. This syndrome is a rare but serious condition that is associated with a high mortality rate. Early CART institution may be useful and neuroprotective in this disorder, although this requires further investigation.

Newsome, S.D.; Johnson, E.; Pardo, C.; McArthur, J.C.

2011-01-01

111

The basal ganglia, the ideal machinery for the cost-benefit analysis of action plans.  

PubMed

Basal ganglia dysfunction causes profound movement disorders, often attributed to imbalance between direct and indirect pathway activity in the sensorimotor basal ganglia. In the classical view, the direct pathway facilitates movements, whereas the indirect pathway inhibits movements. However, the recent finding of co-activation of the two pathways during movement challenges this view. Reconciling the new finding with the body of evidence supporting the classical view, this perspective proposes that the direct pathway computes the expected benefits of motor plans entering the basal ganglia, while the indirect pathway computes their expected costs. Thus, basal ganglia output combining the two pathway signals in a subtraction manner weighs benefits against costs, and endorses the plan with the best prospective outcome via feedback projections to the cortex. The cost-benefit model, while retaining the antagonistic roles of the two pathways for movements, requires co-activation of the two pathways during movement as both benefit and cost are computed for every movement. The cost-benefit model, though simple, accounts for a number of confounding results, and generates new focus for future research with testable predictions. PMID:23885236

Hwang, Eun Jung

2013-07-22

112

Human basal ganglia and the dynamic control of force during on-line corrections.  

PubMed

Natural movements are corrected in part by the generation of submovements, occurring early in a movement such that they amend an ongoing action. Submovements are associated with activity of the basal ganglia, implying a role for the structures in error correction. In parallel, the basal ganglia are linked to the generation and control of force amplitude, change, and duration. Here, we tested whether activity in human basal ganglia is associated with submovements generally, or was specific to a condition where the submovements only occurred in the face of unexpected proprioceptive error. Submovements were induced by introducing unexpected and variable viscous loads (augmenting the need for trial-specific grip forces) or by reducing target size (augmenting the need for visually guided on-line control) in a one-dimensional target-capture task. In both cases, subjects compensated for the increased task difficulty by generating corrective submovements, which were closely matched in frequency and type. Activity in the internal segment of the globus pallidus and subthalamic nucleus correlated strongly with the number of submovements during the viscous challenge but not with the target challenge. The effects could not be explained by kinematic differences, i.e., movement amplitude or average number of submovements. The results support a specific role for the basal ganglia in error correction under conditions of variable load where there is a need for the dynamic control of force within an ongoing movement. PMID:21289168

Grafton, Scott T; Tunik, Eugene

2011-02-01

113

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

114

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

ERIC Educational Resources Information Center

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

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

2010-01-01

115

Activity propagation in an avian basal ganglia-thalamo-cortical circuit essential for vocal learning  

PubMed Central

In mammalian basal ganglia-thalamo-cortical circuits, GABAergic pallidal neurons are thought to ‘gate’ or modulate excitation in thalamus with their strong inhibitory inputs, and thus signal to cortex by pausing and permitting thalamic neurons to fire in response to excitatory drive. In contrast, in a homologous circuit specialized for vocal learning in songbirds, evidence suggests that pallidal neurons signal by eliciting postinhibitory rebound spikes in thalamus, which could occur even without any excitatory drive to thalamic neurons. To test whether songbird pallidal neurons can also communicate with thalamus by gating excitatory drive, as well as by postinhibitory rebound, we examined the activity of thalamic relay neurons in response to acute inactivation of the basal ganglia structure Area X; Area X contains the pallidal neurons that project to thalamus. Although inactivation of Area X should eliminate rebound-mediated spiking in thalamus, this manipulation tonically increases the firing rate of thalamic relay neurons, providing evidence that songbird pallidal neurons can gate tonic thalamic excitatory drive. We also found that the increased thalamic activity was fed forward to its target in the avian equivalent of cortex, which includes neurons that project to the vocal premotor area. These data raise the possibility that basal ganglia circuits can signal to cortex through thalamus both by generating postinhibitory rebound and by gating excitatory drive, and may switch between these modes depending on the statistics of pallidal firing. Moreover, these findings provide insight into the strikingly different disruptive effects of basal ganglia and ‘cortical’ lesions on songbird vocal learning.

Kojima, Satoshi; Doupe, Allison J.

2009-01-01

116

Activity propagation in an avian basal ganglia-thalamocortical circuit essential for vocal learning.  

PubMed

In mammalian basal ganglia-thalamocortical circuits, GABAergic pallidal neurons are thought to "gate" or modulate excitation in thalamus with their strong inhibitory inputs and thus signal to cortex by pausing and permitting thalamic neurons to fire in response to excitatory drive. In contrast, in a homologous circuit specialized for vocal learning in songbirds, evidence suggests that pallidal neurons signal by eliciting postinhibitory rebound spikes in thalamus, which could occur even without any excitatory drive to thalamic neurons. To test whether songbird pallidal neurons can also communicate with thalamus by gating excitatory drive, as well as by postinhibitory rebound, we examined the activity of thalamic relay neurons in response to acute inactivation of the basal ganglia structure Area X; Area X contains the pallidal neurons that project to thalamus. Although inactivation of Area X should eliminate rebound-mediated spiking in thalamus, this manipulation tonically increased the firing rate of thalamic relay neurons, providing evidence that songbird pallidal neurons can gate tonic thalamic excitatory drive. We also found that the increased thalamic activity was fed forward to its target in the avian equivalent of cortex, which includes neurons that project to the vocal premotor area. These data raise the possibility that basal ganglia circuits can signal to cortex through thalamus both by generating postinhibitory rebound and by gating excitatory drive and may switch between these modes depending on the statistics of pallidal firing. Moreover, these findings provide insight into the strikingly different disruptive effects of basal ganglia and cortical lesions on songbird vocal learning. PMID:19369547

Kojima, Satoshi; Doupe, Allison J

2009-04-15

117

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

118

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

ERIC Educational Resources Information Center

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

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

2006-01-01

119

Basal ganglia–hippocampal interactions support the role of the hippocampal formation in sensorimotor integration  

Microsoft Academic Search

Experiments were carried out to evaluate whether neural activity in the basal ganglia is functionally related to the neural activity underlying mechanisms of theta band oscillation and synchrony in the hippocampal formation. Experiment 1 demonstrated that electrical stimulation administered to the substantia nigra, globus pallidus (GP) and caudate-putamen (CPu) in urethane anesthetized rats elicited theta field activity in the hippocampal

Nicholas E. Hallworth; Brian H. Bland

2004-01-01

120

Basal Ganglia Volume Is Associated with Aerobic Fitness in Preadolescent Children  

Microsoft Academic Search

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

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

2010-01-01

121

Dopamine Modulates Excitability of Spiny Neurons in the Avian Basal Ganglia  

Microsoft Academic Search

The neural substrate of vocal learning in songbirds is an acces- sible system for studying motor learning and motor control in vertebrates. In the so-called song system, the anterior forebrain pathway (AFP), which is essential for song learning, resembles the mammalian basal ganglia-thalamocortical loop in its mac- roscopic organization, neuronal intrinsic properties, and micro- circuitry. Area X, the first station

Long Ding; David J. Perkel

2002-01-01

122

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

ERIC Educational Resources Information Center

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

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

2011-01-01

123

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

Microsoft Academic Search

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

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

1996-01-01

124

Adenosine–dopamine receptor–receptor interactions as an integrative mechanism in the basal ganglia  

Microsoft Academic Search

Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the motor depressant effects of adenosine receptor agonists and the motor stimulant effects of adenosine receptor antagonists, such as caffeine. The GABAergic striatopallidal neurons are regulated by interacting adenosine A2A and dopamine D2 receptors. On the other hand, the

Sergi Ferré; Kjell Fuxe; Bertil B. Fredholm; Micaela Morelli; Patrizia Popoli

1997-01-01

125

Cuprizone effect on myelination, astrogliosis and microglia attraction in the mouse basal ganglia  

Microsoft Academic Search

Multiple sclerosis is the leading cause of neurological disability in young adults affecting more than two million people worldwide. Although multiple sclerosis is generally considered as white matter disease, distinct pathological alterations are also found in the grey matter. Involvement of basal ganglia seems to be related to a set of symptoms such as fatigue, impaired cognition, and movement disturbance.

Friederike Pott; Stefan Gingele; Tim Clarner; Jon Dang; Werner Baumgartner; Cordian Beyer; Markus Kipp

2009-01-01

126

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

ERIC Educational Resources Information Center

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

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

2011-01-01

127

Competition between feedback loops underlies normal and pathological dynamics in the basal ganglia.  

PubMed

Experiments performed in normal animals suggest that the basal ganglia (BG) are crucial in motor program selection. BG are also involved in movement disorders. In particular, BG neuronal activity in parkinsonian animals and patients is more oscillatory and more synchronous than in normal individuals. We propose a new model for the function and dysfunction of the motor part of BG. We hypothesize that the striatum, the subthalamic nucleus, the internal pallidum (GPi), the thalamus, and the cortex are involved in closed feedback loops. The direct (cortex-striatum-GPi-thalamus-cortex) and the hyperdirect loops (cortex-subthalamic nucleus-GPi-thalamus-cortex), which have different polarities, play a key role in the model. We show that the competition between these two loops provides the BG-cortex system with the ability to perform motor program selection. Under the assumption that dopamine potentiates corticostriatal synaptic transmission, we demonstrate that, in our model, moderate dopamine depletion leads to a complete loss of action selection ability. High depletion can lead to synchronous oscillations. These modifications of the network dynamical state stem from an imbalance between the feedback in the direct and hyperdirect loops when dopamine is depleted. Our model predicts that the loss of selection ability occurs before the appearance of oscillations, suggesting that Parkinson's disease motor impairments are not directly related to abnormal oscillatory activity. Another major prediction of our model is that synchronous oscillations driven by the hyperdirect loop appear in BG after inactivation of the striatum. PMID:16571765

Leblois, Arthur; Boraud, Thomas; Meissner, Wassilios; Bergman, Hagai; Hansel, David

2006-03-29

128

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

PubMed Central

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.

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

2007-01-01

129

Effect of high-dose methyl-prednisolone on brainstem encephalopathy and basal ganglia impairment complicating cat scratch disease.  

PubMed

Cat scratch disease (CSD) is a zoonotic illness caused by the Gram negative bacillus Bartonella henselae characterized by a small skin lesion at the site of a bite, lick or scratch by a cat, commonly followed by regional lymphadenopathy 1 or 2 weeks later. We report herein on severe neurological complications of CSD combining brainstem encephalopathy and basal ganglia impairment. This 12-year-old female acutely presented to a local hospital with profound coma and a prolonged tonic posturing of extremities. On the neurological examination she was deeply comatose with pin-point pupils and lack of vestibulo-ocular responses, suggestive of brainstem encephalopathy, along with marked rigid hypertonicity suggestive also of basal ganglia impairment. Initially suspecting Herpes simplex encephalitis or acute disseminated encephalomyelitis she was promptly started with high-dose methyl-prednisolone and acyclovir. Her parents apparently reported that she was scratched by a kitten some 4 weeks prior to her present admission and as such, suspecting CSD, she was begun with doxycycline and rifampicin. Her serology had proven positive for IgM antibodies to Bartonella henselae establishing the diagnosis. She regained consciousness after 4 days and the signs of brainstem and extra-pyramidal impairment also gradually abated and disappeared after 10 days. A follow-up exam after a month disclosed mild extra-pyramidal abnormalities which disappeared after 3 months. Although extremely rare, CSD should be also considered in a patient presenting with a severe encephalopathy and associated basal ganglia impairment. The prompt administration of high-dose methyl-prednisolone upon admission may have contributed to the favorable outcome in our patient and therefore should be advocated in any patient presenting with profound encephalopathy regardless the underlying etiology recovered later. PMID:17174500

Genizi, Jacob; Kasis, Imad; Schif, Aharon; Shahar, Eli

2006-12-15

130

Streptococcus pneumoniae meningoencephalitis with bilateral basal ganglia necrosis: an unusual complication due to vasculitis.  

PubMed

Streptococcus pneumoniae (S pneumoniae) is a common cause of bacterial meningitis, frequently leading to death or severe neurological impairment. We report an exceptional case of a 4-month-old boy with meningitis caused by S pneumoniae. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations of the brain showed bilateral symmetrical necrosis involving the lentiform and caudate nuclei, as well as the thalamus. T1-weighted MR images showed patchy areas of increased signal intensity, consistent with hemorrhagic transformation of the lesions. Autopsy revealed widespread necrosis of the basal ganglia with clear signs of vasculitis. Severe complications of S pneumoniae meningoencephalitis are known in infants but to our knowledge, such lesions in the basal ganglia have only been reported thrice in adults and never in children. PMID:21677202

Magnus, Jessy; Parizel, Paul M; Ceulemans, Berten; Cras, Patrick; Luijks, Marloes; Jorens, Philippe G

2011-06-15

131

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

SciTech Connect

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

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

1989-04-01

132

Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction  

PubMed Central

Serotonin (5-HT)-selective reuptake inhibitors (SSRIs) are widely administered for the treatment of depression, anxiety, and other neuropsychiatric disorders, but response rates are low, and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs inhibit dopaminergic activity, but mechanistic insight remains scarce. Here we show that in mice, chronic 5-HT transporter (5-HTT) blockade during adulthood but not during development impairs basal ganglia-dependent behaviors in a dose-dependent and reversible fashion. Furthermore, chronic 5-HTT blockade reduces striatal dopamine (DA) content and metabolism. A causal relationship between reduced DA signaling and impaired basal ganglia-dependent behavior is indicated by the reversal of behavioral deficits through l-DOPA administration. Our data suggest that augmentation of DA signaling would reduce side effects and increase efficacies of SSRI-based therapy.

Morelli, Emanuela; Moore, Holly; Rebello, Tahilia J.; Gray, Neil; Steele, Kelly; Esposito, Ennio; Ansorge, Mark S.

2011-01-01

133

Basal Ganglia – Cortex Interactions: Regulation of Cortical Function by D1 Dopamine Receptors in the Striatum  

Microsoft Academic Search

This paper reviews recent findings of molecular imaging studies that investigated the role of striatal dopamine in the regulation\\u000a of basal ganglia output and cortical function. These studies employed immediate-early genes such as c-fos and zif 268 as functional markers to determine the effects of dopamine depletion and local dopamine receptor stimulation in the striatum\\u000a on cortical function. The results

Heinz Steiner

134

Substrates for normal gait and pathophysiology of gait disturbances with respect to the basal ganglia dysfunction  

Microsoft Academic Search

\\u000a Abstract\\u000a   In this review, we have tried to elucidate substrates for the execution of normal gait and to understand pathophysiological\\u000a mechanisms of gait failure in basal ganglia dysfunctions. In Parkinson’s disease, volitional and emotional expressions of\\u000a movement processes are seriously affected in addition to the disturbance of automatic movement processes, such as adjustment\\u000a of postural muscle tone before gait initiation

Kaoru Takakusaki; Nozomi Tomita; Masafumi Yano

2008-01-01

135

Preservation of the hyperdirect pathway of basal ganglia in a rodent brain slice.  

PubMed

Basal ganglia are a network of interconnected nuclei, involved in motor control, goal-directed behaviors and procedural learning. Basal ganglia process information from the cerebral cortex through three main pathways. The striatum is the input nucleus of the direct (cortico-striato-nigral) and indirect (cortico-striato-pallido-subthalamo-nigral) pathways while the subthalamic nucleus (STN) is the input structure of the hyperdirect (cortico-subthalamo-nigral) pathway. Despite the fact that the hyperdirect pathway constitutes a central part of most of basal ganglia models, experimental studies concerning its synaptic transmission and plasticity are still lacking. This is mainly because in vitro brain slices do not preserve the hyperdirect pathway. Here, we address this by developing a hyperdirect pathway brain slice where cortico-subthalamo-nigral connections were preserved. We characterized the transmission properties and its monosynaptic features between the frontal cortex and the STN, and between the STN and the substantia nigra pars reticulata (SNr), the output nucleus of the hyperdirect pathway. Cortical stimulation evoked monosynaptic glutamatergic events in STN neurons with a mean latency of 11.3 ms and a mean amplitude of 21 pA. STN stimulations evoked monosynaptic glutamatergic events in SNr neurons with a mean latency of 2.5 ms and a mean amplitude of 116 pA. This brain slice also preserved a part of the direct and indirect pathways such as the cortico-striatal connection. This novel slice configuration containing the hyperdirect pathway is a useful tool to better understand the transmission and plasticity in this pathway and hence the physiology and the pathophysiology of basal ganglia. PMID:22537846

Bosch, C; Mailly, P; Degos, B; Deniau, J-M; Venance, L

2012-04-23

136

Germinoma originating in the basal ganglia and thalamus: MR and CT evaluation  

Microsoft Academic Search

Purpose: to describe MR and CT features of germinoma originating in the basal ganglia and thalamus and to discuss the roles of each modality for its diagnosis. Methods: MR and CT studies of six cases of germinomas, five of which were histologically proved, were retrospectively reviewed. T1-weighted, T2-weighted, and contrast-enhanced T1-weighted conventional spin-echo images, and unenhanced and contrast-enhanced CT images

Shuichi Higano; Shoki Takahashi; Kiyoshi Ishii

1994-01-01

137

Acute effects of the neurotoxin kainic acid on neurons of the pigeon basal ganglia  

Microsoft Academic Search

Kainic acid (KA) is a powerful excitant and neurotoxin of the large nerve cells of the pigeon basal ganglia, and birds treated with KA developed pronounced movement disorders. Sensitive neurons responded to the intracerebrally injected toxin with elevated extracellular unit discharge rates. The rates increased from 3–12 times the base line frequency and remained elevated for 1–2h, followed by a

G. K. Rieke; D. E. Bowers

1982-01-01

138

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

139

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

140

Self-Organization in the Basal Ganglia with Modulation of Reinforcement Signals  

Microsoft Academic Search

Self-organization is one of fundamental brain computations for forming efficient representations of information. Experimental support for this idea has been largely limited to the developmental and reorganizational formation of neural circuits in the sensory cortices. We now propose that self-organization may also play an important role in short-term synaptic changesinreward-drivenvoluntarybehaviors.Ithasrecentlybeenshown that many neurons in the basal ganglia change their sensory

Hiroyuki Nakahara; Shun-ichi Amari; Okihide Hikosaka

2002-01-01

141

Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia  

PubMed Central

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion. We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting. Ketamine induced coherent oscillations in low gamma (50 Hz), high gamma (80 Hz) and high frequency (HFO, 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement. These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of connectivity among the structures analyzed.

Alegre, Manuel; Perez-Alcazar, Marta; Iriarte, Jorge; Artieda, Julio

2011-01-01

142

Ketamine-induced oscillations in the motor circuit of the rat basal ganglia.  

PubMed

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion.We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting.Ketamine induced coherent oscillations in low gamma (~ 50 Hz), high gamma (~ 80 Hz) and high frequency (HFO, ~ 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement.These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of connectivity among the structures analyzed. PMID:21829443

Nicolás, María Jesús; López-Azcárate, Jon; Valencia, Miguel; Alegre, Manuel; Pérez-Alcázar, Marta; Iriarte, Jorge; Artieda, Julio

2011-07-29

143

Progress in understanding basal ganglia dysfunction as a common target for methamphetamine abuse and HIV-1 neurodegeneration.  

PubMed

HIV-1 infection with concurrent methamphetamine (MA) abuse results in exacerbated neurodegenerative changes and rapid progression of a form of sub-cortical dementia termed HIV-1 associated dementia (HAD). A notable feature of HAD is the involvement of the dopaminergic system manifested as parkinsonian like movement abnormalities. The HIV-1 transactivator of transcription (Tat) protein is very often used in experimental studies trying to understand neurotoxic consequences of HIV-1 infection, since the pathophysiological changes induced by Tat mirrors, in part, the means by which HIV-1 infection of the nervous system results in neuronal damage. Understanding the interaction of Tat and MA in the basal ganglia and the resultant injury to the dopaminergic system in rodent models as well as cell culture will shed light on the dopaminergic pathology occurring in HIV-1 infected-MA abusers. The aim of this review is to update the reader on the current knowledge of MA and HIV-1 neurotoxicity, specifically Tat, and discuss the progress in understanding how MA synergizes with the HIV-1 transactivator protein Tat to damage the basal ganglia. PMID:17504172

Theodore, Shaji; Cass, Wayne A; Nath, Avindra; Maragos, William F

2007-05-01

144

[Participation of the basal ganglia in the mechanism of visual memory in the rat].  

PubMed

Studies have been made of the effect of bilateral injury of paleo-, archi- and neostriatum, as well as that of the nucleus ruber on adaptive behaviour in albino rats. It was shown that injury of the basal structures of the brain results in disturbances of optimal visual choice of a food signal. The data obtained are discussed from a standpoint of disturbances in operative memory of visual signals. It is suggested that during evolutionary development, when the higher brain functions pass to neocortex, the basal ganglia do not loose their initial role in the higher analytical-synthetic activity. PMID:7102174

Gambarian, L S; Garibian, A A; Kazarian, G M; Sarkisian, Zh S; Kazarian, A G

145

Evidence for Altered Basal Ganglia-Brainstem Connections in Cervical Dystonia  

PubMed Central

Background There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia. Methodology/Principal Findings In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients. Conclusions/Significance These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

Blood, Anne J.; Kuster, John K.; Woodman, Sandra C.; Kirlic, Namik; Makhlouf, Miriam L.; Multhaupt-Buell, Trisha J.; Makris, Nikos; Parent, Martin; Sudarsky, Lewis R.; Sjalander, Greta; Breiter, Henry

2012-01-01

146

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

2012-06-08

147

The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)  

PubMed Central

The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia.

Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

2010-01-01

148

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

NASA Astrophysics Data System (ADS)

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

Brainard, Michael S.; Doupe, Allison J.

2000-04-01

149

Reinforcement-driven dimensionality reduction--a model for information processing in the basal ganglia.  

PubMed

Although anatomical studies of the basal ganglia show the existence of extensive convergence and lateral inhibitory connections, physiological studies failed to show correlated neural activity or lateral interaction in these nuclei. These seemingly contradictory results could be explained with a model in which the basal ganglia reduce the dimensionality of cortical information using optimal extraction methods. Simulations of this model predict a transient change in the efficacy of the feed-forward and lateral synapses following changes in reinforcement signal, causing an increase in correlated firing rates. This process ultimately restores the steady-state situation with diminished efficacy of lateral inhibition and no correlation of firing. Our experimental results confirm the model's predictions: rate correlations show a drastic decrease between the input stage (cortex) and output stage (pallidum). Moreover, preliminary analysis revealed that pallidal correlations show a transient increase following discrepancies between the animal's predictions and reality. We therefore propose that by using a reinforcement-driven dimensionality reduction process the basal ganglia achieve efficient extraction of cortical salient information that may then be used by the frontal cortex for execution and planning of forthcoming actions. PMID:11248944

Bar-Gad, I; Havazelet-Heimer, G; Goldberg, J A; Ruppin, E; Bergman, H

2000-01-01

150

Contributions of an avian basal ganglia-forebrain circuit to real-time modulation of song.  

PubMed

Cortical-basal ganglia circuits have a critical role in motor control and motor learning. In songbirds, the anterior forebrain pathway (AFP) is a basal ganglia-forebrain circuit required for song learning and adult vocal plasticity but not for production of learned song. Here, we investigate functional contributions of this circuit to the control of song, a complex, learned motor skill. We test the hypothesis that neural activity in the AFP of adult birds can direct moment-by-moment changes in the primary motor areas responsible for generating song. We show that song-triggered microstimulation in the output nucleus of the AFP induces acute and specific changes in learned parameters of song. Moreover, under both natural and experimental conditions, variability in the pattern of AFP activity is associated with variability in song structure. Finally, lesions of the output nucleus of the AFP prevent naturally occurring modulation of song variability. These findings demonstrate a previously unappreciated capacity of the AFP to direct real-time changes in song. More generally, they suggest that frontal cortical and basal ganglia areas may contribute to motor learning by biasing motor output towards desired targets or by introducing stochastic variability required for reinforcement learning. PMID:15703748

Kao, Mimi H; Doupe, Allison J; Brainard, Michael S

2005-02-10

151

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

PubMed Central

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

2013-01-01

152

Sonographic basal ganglia alterations are related to non-motor symptoms in multiple sclerosis.  

PubMed

The anatomical basis of cognitive dysfunction and other non-motor symptoms in multiple sclerosis (MS) is poorly understood. In MS patients, transcranial sonography (TCS) shows neurodegenerative disease-like lesions of the substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation. The present study deals with the question of whether sonographic changes of SN, brainstem raphe, lenticular nucleus (LN) or caudate nucleus are related to non-motor symptoms of MS. We used TCS to investigate 54 MS patients and 54 age- and sex-matched healthy subjects. Degree of cognitive (executive) dysfunction, fatigue, depression, and urinary urge incontinence in MS patients was assessed using the Paced Auditory Serial Addition Test, the Faces Symbol Test, the Modified Fatigue Impact Scale, the Beck Depression Inventory, and the Urinary Distress Inventory. Abnormal TCS findings of SN, brainstem raphe, LN, and caudate nucleus were found in 13, 7, 11, and 6% of the healthy subjects, but in 54, 43, 62, and 41% (each, p < 0.001) of the MS patients, with similar frequency in relapsing-remitting and primary or secondary progressive MS patients. Sonographic alteration of the LN correlated with cognitive dysfunction. Combined alteration of both, LN and SN, was clearly associated with cognitive dysfunction and cognitive fatigue. The combined sonographic alteration of SN and brainstem raphe indicated severe urinary urge incontinence irrespective of the presence of spinal MS lesions. No relation was found between depression and any of the TCS findings. These findings suggest that neurodegenerative processes affecting deep brain structures contribute to cognitive and autonomic dysfunction in MS. PMID:20740288

Horowski, Sebastian; Zettl, Uwe K; Benecke, Reiner; Walter, Uwe

2010-08-26

153

Kearns-Sayre syndrome. A case of the complete syndrome with encephalic leukodystrophy and calcification of basal ganglia  

Microsoft Academic Search

A case of a complete Kearns-Sayre syndrome, of early onset, associated with cerebral and cerebellar leukodystrophy and basal ganglia calcification is reported. The clinical, neurophysiological and morphological findings suggest multisystem involvement.

P. Carboni; M. Giacanelli; G. Porro; G. Sideri; A. Paolella

1981-01-01

154

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

Microsoft Academic Search

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

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

155

Perineuronal nets in the rhesus monkey and human basal forebrain including basal ganglia  

Microsoft Academic Search

Perineuronal nets of extracellular matrix have been shown to characterize the microenvironment of individual neurons and the chemoarchitecture of brain regions such as basal forebrain nuclei. Previous work has also demonstrated that neurons in the human cerebral cortex ensheathed by perineuronal nets rarely undergo cytoskeletal changes in Alzheimer’s disease, suggesting a neuroprotective effect of extracellular matrix components. It is not

I Adams; K Brauer; C Arélin; W Härtig; A Fine; M Mäder; T Arendt; G Brückner

2001-01-01

156

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

PubMed Central

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

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

2013-01-01

157

Redefining functional models of basal ganglia organization: role for the posteroventral pallidum in linguistic processing?  

PubMed

Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical-semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high-level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinson's disease (PD). Commensurate linguistic profiles were also gathered over a 3-month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non-neurologically impaired controls (NC). Nonparametric between-groups comparisons were conducted and reliable change indices calculated, relative to baseline/3-month follow-up difference scores. Group-wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case-by-case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical-semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive postlesional effects. Relative to parkinsonian cohorts, clinically reliable versus statistically significant changes on a case by case basis may provide the most accurate method of characterizing the way in which pathophysiologically divergent basal ganglia linguistic circuits respond to BPVP. PMID:15390054

Whelan, Brooke-Mai; Murdoch, Bruce E; Theodoros, Deborah G; Darnell, Ross; Silburn, Peter; Hall, Bruce

2004-11-01

158

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.; Sejnowski, Terrence J.

2000-10-01

159

Association between a Novel Mutation in SLC20A2 and Familial Idiopathic Basal Ganglia Calcification  

PubMed Central

Familial idiopathic basal ganglia calcification (FIBGC) is a rare, autosomal dominant disorder involving bilateral calcification of the basal ganglia. To identify gene mutations related to a Chinese FIBGC lineage, we evaluated available individuals in the family using CT scans. DNA was extracted from the peripheral blood of available family members, and both exonic and flanking intronic sequences of the SLC20A2 gene were amplified by PCR and then sequenced. Non-denaturing polyacrylamide gel electrophoresis (PAGE) was used to confirm the presence of mutations. Allele imbalances of the SLC20A2 gene or relative quantity of SLC20A2 transcripts were evaluated using qRT-PCR. A novel heterozygous single base-pair deletion (c.510delA) within the SLC20A2 gene was identified. This deletion mutation was found to co-segregate with basal ganglia calcification in all of the affected family members but was not detected in unaffected individuals or in 167 unrelated Han Chinese controls. The mutation will cause a frameshift, producing a truncated SLC20A2 protein with a premature termination codon, most likely leading to the complete loss of function of the SLC20A2 protein. This mutation may also lead to a reduction in SLC20A2 mRNA expression by approximately 30% in cells from affected individuals. In conclusion, we identified a novel mutation in SLC20A2 that is linked to FIBGC. In addition to the loss of function at the protein level, decreasing the expression of SLC20A2 mRNA may be another mechanism that can regulate SLC20A2 function in IBGC individuals. We propose that the regional expression pattern of SLC20A1 and SLC20A2 might explain the unique calcification pattern observed in FIBGC patients.

Zhang, Yang; Guo, Xianan; Wu, Anhua

2013-01-01

160

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

161

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, ; Marder and Goaillard, ; Churchland et al., ). 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., ; Day et al., ). We examined the maturation of cellular activity patterns that underlie these changes. Single unit ensemble recording combined with antidromic identification (Day et al., ) 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 (HVCX 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 HVCX s with coordinated release from inhibition, then the activity of HVCX s in juveniles should be decreased relative to adults due to uncorrelated, tonic inhibition. Consistent with this hypothesis, HVCX s had lower activity in juveniles. These data reveal network changes that shape cortical-to-basal ganglia signaling during motor learning. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 754-768, 2013. PMID:23776169

Day, Nancy F; Nick, Teresa A

2013-07-19

162

Neural representation of a target auditory memory in a cortico-Basal Ganglia pathway.  

PubMed

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

Achiro, Jennifer M; Bottjer, Sarah W

2013-09-01

163

Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder.  

PubMed

We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3- to 4-year-old children with autism spectrum disorder (ASD; n = 77) and developmental delay without autism (DD; n = 34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n = 45), DD (n = 14), and a group of children with typical development (TD; n = 25) were also assessed by magnetic resonance imaging. Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus. PMID:21480545

Estes, Annette; Shaw, Dennis W W; Sparks, Bobbi F; Friedman, Seth; Giedd, Jay N; Dawson, Geraldine; Bryan, Matthew; Dager, Stephen R

2011-04-07

164

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

PubMed

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

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

2013-04-24

165

Enhancing neuroplasticity in the basal ganglia: the role of exercise in Parkinson's disease.  

PubMed

Epidemiological and clinical trials have suggested that exercise is beneficial for patients with Parkinson's disease (PD). However, the underlying mechanisms and potential for disease modification are currently unknown. This review presents current findings from our laboratories in patients with PD and animal models. The data indicate that alterations in both dopaminergic and glutamatergic neurotransmission, induced by activity-dependent (exercise) processes, may mitigate the cortically driven hyper-excitability in the basal ganglia normally observed in the parkinsonian state. These insights have potential to identify novel therapeutic treatments capable of reversing or delaying disease progression in PD. PMID:20187247

Petzinger, Giselle M; Fisher, Beth E; Van Leeuwen, Jon-Eric; Vukovic, Marta; Akopian, Garnik; Meshul, Charlie K; Holschneider, Daniel P; Nacca, Angelo; Walsh, John P; Jakowec, Michael W

2010-01-01

166

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

2013-07-19

167

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

PubMed

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation. PMID:14738287

Crosson, Bruce; Benefield, Hope; Cato, M Allison; Sadek, Joseph R; Moore, Anna Bacon; Wierenga, Christina E; Gopinath, Kaundinya; Soltysik, David; Bauer, Russell M; Auerbach, Edward J; Gökçay, Didem; Leonard, Christiana M; Briggs, Richard W

2003-11-01

168

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

PubMed

Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication--a complex phenotype probably supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene coexpression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ?2,000 singing-regulated genes comprising three coexpression groups unique to area X, the basal ganglia subregion dedicated to learned vocalizations. These contained known targets of human FOXP2 and potential avian targets. We validated biological pathways not previously implicated in vocalization. Higher-order gene coexpression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that probably bear on human motor disorders, especially those affecting speech. PMID:22325205

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

2012-02-01

169

Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia  

PubMed Central

Although retinoic acid (RA) has been implicated as an extrinsic signal regulating forebrain neurogenesis, the processes regulated by RA signaling remain unclear. Here, analysis of retinaldehyde dehydrogenase mutant mouse embryos lacking RA synthesis demonstrates that RA generated by Raldh3 in the subventricular zone of the basal ganglia is required for GABAergic differentiation, whereas RA generated by Raldh2 in the meninges is unnecessary for development of the adjacent cortex. Neurospheres generated from the lateral ganglionic eminence (LGE), where Raldh3 is highly expressed, produce endogenous RA, which is required for differentiation to GABAergic neurons. In Raldh3?/? embryos, LGE progenitors fail to differentiate into either GABAergic striatal projection neurons or GABAergic interneurons migrating to the olfactory bulb and cortex. We describe conditions for RA treatment of human embryonic stem cells that result in efficient differentiation to a heterogeneous population of GABAergic interneurons without the appearance of GABAergic striatal projection neurons, thus providing an in vitro method for generation of GABAergic interneurons for further study. Our observation that endogenous RA is required for generation of LGE-derived GABAergic neurons in the basal ganglia establishes a key role for RA signaling in development of the forebrain.

Chatzi, Christina; Brade, Thomas; Duester, Gregg

2011-01-01

170

A population level computational model of the basal ganglia that generates parkinsonian Local Field Potential activity.  

PubMed

Recordings from the basal ganglia's subthalamic nucleus are acquired via microelectrodes immediately prior to the application of Deep Brain Stimulation (DBS) treatment for Parkinson's Disease (PD) to assist in the selection of the final point for the implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality-effect relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest a pivotal role of both of these parameters to the pathophysiology of PD. PMID:20041261

Tsirogiannis, George L; Tagaris, George A; Sakas, Damianos; Nikita, Konstantina S

2009-12-30

171

Germinoma originating in the basal ganglia and thalamus: MR and CT evaluation  

SciTech Connect

Purpose: to describe MR and CT features of germinoma originating in the basal ganglia and thalamus and to discuss the roles of each modality for its diagnosis. Methods: MR and CT studies of six cases of germinomas, five of which were histologically proved, were retrospectively reviewed. T1-weighted, T2-weighted, and contrast-enhanced T1-weighted conventional spin-echo images, and unenhanced and contrast-enhanced CT images were evaluated. Results: Typically, the tumor consisted of an irregular solid area with contrast enhancement and various-size cysts. Cystic components were found in five cases and calcification in four. Intratumoral hemorrhage was noted in one. Ipsilateral cerebral hemiatrophy and brain stem hemiatrophy were noted in three cases each. MR was superior to CT in evaluating precise tumor extension, cystic components, and intratumoral hemorrhage, although in one case, extension of the tumor was better defined on CT in its early stage. Calcification was difficult to identify by MR alone. The solid components of the tumors generally showed slightly high density on CT, which seemed to be characteristic compared with nonspecific intensity pattern on MR. Conclusion: The combination of CT and MR findings allows early detection and appropriate diagnosis of the mass in the basal ganglia and/or thalamus. 26 refs., 4 figs., 1 tab.

Shuichi Higano; Shoki Takahashi; Kiyoshi Ishii [Tohoku Univ. School of Medicine (Japan)

1994-09-01

172

Modulation by dopamine of human basal ganglia involvement in feedback control of movement.  

PubMed

We learn new motor tasks by trial and error, repeating what works best and avoiding past mistakes. To repeat what works best we must register a satisfactory outcome, and in a study [1] we showed the existence of an evoked activity in the basal ganglia that correlates with accuracy of task performance and is associated with reiteration of successful motor parameters in subsequent movements. Here we report evidence that the signaling of positive trial outcome relies on dopaminergic input to the basal ganglia, by recording from the subthalamic nucleus (STN) in patients with nigrostriatal denervation due to Parkinson's Disease (PD) who have undergone functional neurosurgery. Correlations between subthalamic evoked activities and trial accuracy were weak and behavioral performance remained poor while patients were untreated; however, both improved after the dopamine prodrug levodopa was re-introduced. The results suggest that the midbrain dopaminergic system may be important, not only in signaling explicit positive outcomes or rewards in tasks requiring choices between options [2,3], but also in trial-to-trial learning and in reinforcing the selection of optimal parameters in more automatic motor control. PMID:17686426

Kempf, Florian; Brücke, Christof; Kühn, Andrea A; Schneider, Gerd-Helge; Kupsch, Andreas; Chen, Chiung Chu; Androulidakis, Alexandros G; Wang, Shouyan; Vandenberghe, Wim; Nuttin, Bart; Aziz, Tipu; Brown, Peter

2007-08-01

173

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

PubMed

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

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

2012-08-18

174

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

PubMed Central

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

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

2012-01-01

175

Increase of glucose consumption in basal ganglia, thalamus and frontal cortex of patients with spasmodic torticollis  

SciTech Connect

The pathophysiology of spasmodic torticollis, a focal dystonia involving neck muscles, is still unclear. Positron emission tomography (PET) studies showed either an increase as well as a decrease of regional cerebral metabolic rate of glucose (rCMRglu) in basal ganglia. In the present study, [18F]FDG and PET was used to measure rCMRglu in 10 patients with spasmodic torticollis (mean age 50.37 {plus_minus} 11.47) and 10 age matched controls. All cases with a short disease duration, were untreated. A factorial analysis of variance revealed a significant bilateral increase of glucose consumption in caudate nucleus and pallidum/putamen complex (p>0.004) and in the cerebellum (p>0.001). The rCMRglu increase in the motor/premotor cortex and in the thalamus reached a trend towards significance (p<0.05). These preliminary data show enhanced metabolism in basal ganglia and cerebellum as the functional correlate of focal dystonia. A recently proposed model suggests that dystonia would be the consequence of a putaminal hyperactivity, leading to the breakdown of the pallidal inhibitory control on thalamus and thalamo-cortical projections.

Grassi, F.; Bressi, S.; Antoni, M. [Univ. of Milan (Italy)] [and others

1994-05-01

176

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

PubMed Central

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

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

2011-01-01

177

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

178

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

2013-07-05

179

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

180

The Basal Ganglia is necessary for learning spectral, but not temporal, features of birdsong.  

PubMed

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

Ali, Farhan; Otchy, Timothy M; Pehlevan, Cengiz; Fantana, Antoniu L; Burak, Yoram; Olveczky, Bence P

2013-09-26

181

Extrapyramidal symptoms in a BMT recipient with hyperintense basal ganglia and elevated manganese.  

PubMed

Neurologic syndromes attributed to conditioning or medications have been reported in BMT recipients. A patient is presented who developed extrapyramidal symptoms on day +56 after allogeneic BMT. Brain magnetic resonance images of this patient demonstrated hyperintense basal ganglia, which has been associated with manganese (Mn) toxicity. The patient had received total parenteral nutrition (TPN) with standard trace element supplementation and had been cholestatic. Serum Mn was elevated, and continued to be so 5 months after BMT, long after discontinuation of TPN. Cholestatic patients and those on long-term TPN have been found to have high blood or serum levels of Mn, but generally are asymptomatic. When other cholestatic BMT patients were reviewed, all had elevated serum Mn. Manganese supplementation in TPN requires evaluation for BMT recipients. PMID:7581103

Fredstrom, S; Rogosheske, J; Gupta, P; Burns, L J

1995-06-01

182

Learning to Select Actions with Spiking Neurons in the Basal Ganglia  

PubMed Central

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

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

2012-01-01

183

Distinct Neurogenomic States in Basal Ganglia Subregions Relate Differently to Singing Behavior in Songbirds  

PubMed Central

Both avian and mammalian basal ganglia are involved in voluntary motor control. In birds, such movements include hopping, perching and flying. Two organizational features that distinguish the songbird basal ganglia are that striatal and pallidal neurons are intermingled, and that neurons dedicated to vocal-motor function are clustered together in a dense cell group known as area X that sits within the surrounding striato-pallidum. This specification allowed us to perform molecular profiling of two striato-pallidal subregions, comparing transcriptional patterns in tissue dedicated to vocal-motor function (area X) to those in tissue that contains similar cell types but supports non-vocal behaviors: the striato-pallidum ventral to area X (VSP), our focus here. Since any behavior is likely underpinned by the coordinated actions of many molecules, we constructed gene co-expression networks from microarray data to study large-scale transcriptional patterns in both subregions. Our goal was to investigate any relationship between VSP network structure and singing and identify gene co-expression groups, or modules, found in the VSP but not area X. We observed mild, but surprising, relationships between VSP modules and song spectral features, and found a group of four VSP modules that were highly specific to the region. These modules were unrelated to singing, but were composed of genes involved in many of the same biological processes as those we previously observed in area X-specific singing-related modules. The VSP-specific modules were also enriched for processes disrupted in Parkinson's and Huntington's Diseases. Our results suggest that the activation/inhibition of a single pathway is not sufficient to functionally specify area X versus the VSP and support the notion that molecular processes are not in and of themselves specialized for behavior. Instead, unique interactions between molecular pathways create functional specificity in particular brain regions during distinct behavioral states.

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

2012-01-01

184

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

185

Song tutoring triggers CaMKII phosphorylation within a specialized portion of the avian basal ganglia.  

PubMed

In several songbird species, a specialized anterior forebrain pathway (AFP) that includes part of the avian basal ganglia has been implicated specifically in song learning. To further elucidate cellular mechanisms and circuitry involved in vocal learning, we used quantitative immunoblot analysis to determine if early song tutoring promotes within the AFP phosphorylation of calcium/calmodulin-dependent kinase II (CaMKII), a multifunctional kinase whose phosphorylation at threonine 286 is critical for many forms of neural plasticity and behavioral learning. We report that in young male zebra finches likely to have begun the process of song acquisition, brief tutoring by a familiar conspecific adult promotes a dramatic increase in levels of phosphorylated CaMKII (pCaMKII) in Area X, the striatal/pallidal component of the AFP. In contrast, pCaMKII levels in this region were not elevated if 1) the tutor did not sing, 2) the tutor sang but was visually isolated from the pupil, or 3) the tutor was an unfamiliar adult. In young males that had not previously heard any conspecific song, first exposure to a song tutor produced a more modest, but significant rise in pCaMKII levels. Young females (who do not develop song behavior) did not exhibit any effect of tutoring on pCaMKII levels in that portion of the basal ganglia that corresponds to Area X in males. These data are consistent with the hypothesis that Area X participates in encoding and/or attaching reward value to a representation of tutor song that is accessed later to guide motor learning. PMID:16114029

Singh, Tryambak D; Nordeen, Ernest J; Nordeen, Kathy W

2005-11-01

186

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

PubMed

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

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

2008-04-24

187

The role of exercise in facilitating basal ganglia function in Parkinson's disease  

PubMed Central

SUMMARY Epidemiological and clinical studies have suggested that exercise is beneficial for patients with Parkinson’s disease (PD). Through research in normal (noninjured) animals, neuroscientists have begun to understand the mechanisms in the brain by which behavioral training and exercise facilitates improvement in motor behavior through modulation of neuronal function and structure, called experience-dependent neuroplasticity. Recent studies are beginning to reveal molecules and downstream signaling pathways that are regulated during exercise and motor learning in animal models of PD and that are important in driving protective and/or adaptive changes in neuronal connections of the basal ganglia and related circuitry. These molecules include the neurotransmitters dopamine and glutamate (and their respective receptors) as well as neurotrophic factors (brain-derived neurotrophic factor). In parallel, human exercise studies have been important in revealing ‘proof of concept’ including examining the types and parameters of exercise that are important for behavioral/functional improvements and brain changes; the feasibility of incorporating and maintaining an exercise program in individuals with motor disability; and, importantly, the translation and investigation of exercise effects observed in animal studies to exercise effects on brain and behavior in individuals with PD. In this article we highlight findings from both animal and human exercise studies that provide insight into brain changes of the basal ganglia and its related circuitry and that support potentially key parameters of exercise that may lead to long-term benefit and disease modification in PD. In addition, we discuss the current and future impact on patient care and point out gaps in our knowledge where continuing research is needed. Elucidation of exercise parameters important in driving neuroplasticity, as well as the accompanying mechanisms that underlie experience-dependent neuroplasticity may also provide insights towards new therapeutic targets, including neurorestorative and/or neuroprotective agents, for individuals with PD and related neurodegenerative disorders.

Petzinger, Giselle M; Fisher, Beth E; Akopian, Garnik; Holschneider, Daniel P; Wood, Ruth; Walsh, John P; Lund, Brett; Meshul, Charles; Vuckovic, Marta; Jakowec, Michael W

2012-01-01

188

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

189

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

2013-05-17

190

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

PubMed Central

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

Gale, Samuel D.; Perkel, David J.

2010-01-01

191

Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis.  

PubMed

Information-processing speed (IPS) slowing is a primary cognitive deficit in multiple sclerosis (MS). Basal ganglia, thalamus and neocortex are thought to have a key role for efficient information-processing, yet the specific relative contribution of these structures for MS-related IPS impairment is poorly understood. To determine if basal ganglia and thalamus atrophy independently contribute to visual and auditory IPS impairment in MS, after controlling for the influence of neocortical volume, we enrolled 86 consecutive MS patients and 25 normal controls undergoing 3T brain MRI and neuropsychological testing. Using Sienax and FIRST software, neocortical and deep gray matter (DGM) volumes were calculated. Neuropsychological testing contributed measures of auditory and visual IPS using the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), respectively. MS patients exhibited significantly slower IPS relative to controls and showed reduction in neocortex, caudate, putamen, globus pallidus, thalamus and nucleus accumbens volume. SDMT and PASAT were significantly correlated with all DGM regions. These effects were mitigated by controlling for the effects of neocortical volume, but all DGM volumes remained significantly correlated with SDMT, putamen (r = 0.409, p < 0.001) and thalamus (r = 0.362, p < 0.001) having the strongest effects, whereas for PASAT, the correlation was significant for putamen (r = 0.313, p < 0.01) but not for thalamus. We confirm the significant role of thalamus atrophy in MS-related IPS slowing and find that putamen atrophy is also a significant contributor to this disorder. These DGM structures have independent, significant roles, after controlling for the influence of neocortex atrophy. PMID:21720932

Batista, Sonia; Zivadinov, Robert; Hoogs, Marietta; Bergsland, Niels; Heininen-Brown, Mari; Dwyer, Michael G; Weinstock-Guttman, Bianca; Benedict, Ralph H B

2011-07-01

192

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

2012-12-28

193

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

Microsoft Academic Search

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

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

1999-01-01

194

Investigating the effect of different targets in deep brain stimulation on symptoms of Parkinson's disease using a mean-field model of the basal ganglia-thalamocortical system  

Microsoft Academic Search

In this paper, we investigated effects of deep brain stimulation (DBS) on Parkinson's disease (PD) when different target sites in the basal ganglia are stimulated. The targets which are investigated are subthalamic nucleus (STN), globus pallidus interna (GPi), and globus pallidus externa (GPe). For this purpose we used a computational model of the basal ganglia- thalamocortical system (BGTCS) with parameters

Alireza Nahvi; Fariba Bahrami

2011-01-01

195

Immunocytochemical localization of D 1 and D 2 dopamine receptors in the basal ganglia of the rat: Light and electron microscopy  

Microsoft Academic Search

The modulatory actions of dopamine on the flow of cortical information through the basal ganglia are mediated mainly through two subtypes of receptors, the D1 and D2 receptors. In order to examine the precise cellular and subcellular location of these receptors, immunocytochemistry using subtype specific antibodies was performed on sections of rat basal ganglia at both the light and electron

K. K. L. Yung; J. P. Bolam; A. D. Smith; S. M. Hersch; B. J. Ciliax; A. I. Levey

1995-01-01

196

A study of the switching function of the Subthalamic Nucleus in saccade generation using a computational model of Basal Ganglia  

Microsoft Academic Search

Saccades are rapid, frequent eye movements that shift the fovea onto objects of interest. Several areas of the brain, including the frontal cortical areas, Lateral Intraparietal (LIP) cortex, Basal Ganglia (BG), Superior Colliculus (SC) and the brainstem reticular formation are believed to be involved in saccade generation. Models of saccade generation, however, tend to focus heavily on the determination of

Maithreye Rengaswamy; V. Srinivasa Chakravarthy

2010-01-01

197

Basal Ganglia, Dopamine and Temporal Processing: Performance on Three Timing Tasks on and off Medication in Parkinson's Disease  

ERIC Educational Resources Information Center

|A pervasive hypothesis in the timing literature is that temporal processing in the milliseconds and seconds range engages the basal ganglia and is modulated by dopamine. This hypothesis was investigated by testing 12 patients with Parkinson's disease (PD), both "on" and "off" dopaminergic medication, and 20 healthy controls on three timing tasks.…

Jones, Catherine R. G.; Malone, Tim J. L.; Dirnberger, Georg; Edwards, Mark; Jahanshahi, Marjan

2008-01-01

198

How preparation changes the need for top-down control of the basal ganglia when inhibiting premature actions.  

PubMed

Goal-oriented signals from the prefrontal cortex gate the selection of appropriate actions in the basal ganglia. Key nodes within this fronto-basal ganglia action regulation network are increasingly engaged when one anticipates the need to inhibit and override planned actions. Here, we ask how the advance preparation of action plans modulates the need for fronto-subcortical control when a planned action needs to be withdrawn. Functional magnetic resonance imaging data were collected while human participants performed a stop task with cues indicating the likelihood of a stop signal being sounded. Mathematical modeling of go trial responses suggested that participants attained a more cautious response strategy when the probability of a stop signal increased. Effective connectivity analysis indicated that, even in the absence of stop signals, the proactive engagement of the full control network is tailored to the likelihood of stop trial occurrence. Importantly, during actual stop trials, the strength of fronto-subcortical projections was stronger when stopping had to be engaged reactively compared with when it was proactively prepared in advance. These findings suggest that fronto-basal ganglia control is strongest in an unpredictable environment, where the prefrontal cortex plays an important role in the optimization of reactive control. Importantly, these results further indicate that the advance preparation of action plans reduces the need for reactive fronto-basal ganglia communication to gate voluntary actions. PMID:22875921

Jahfari, Sara; Verbruggen, Frederick; Frank, Michael J; Waldorp, Lourens J; Colzato, Lorenza; Ridderinkhof, K Richard; Forstmann, Birte U

2012-08-01

199

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

200

Presynaptic Depression of Glutamatergic Synaptic Transmission by D1Like Dopamine Receptor Activation in the Avian Basal Ganglia  

Microsoft Academic Search

Vocal behavior in songbirds exemplifies a rich integration of motor, cognitive, and social functions that are shared among vertebrates. As a part of the underlying neural substrate, the song system, the anterior forebrain pathway (AFP) is required for song learning and maintenance. The AFP resembles the mammalian basal ganglia-thalamocortical loop in its macroscopic organization, neuronal intrinsic properties, and microcircuitry. Area

Long Ding; David J. Perkel; Michael A. Farries

2003-01-01

201

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

202

Regional distribution of cholecystokinin binding sites in macaque basal ganglia determined by in vitro receptor autoradiography.  

PubMed

Cholecystokinin binding sites were labeled with [3H]cholecystokinin-8, [125I]cholecystokinin-33, and [125I]cholecystokinin-8 in major structures of macaque basal ganglia by in vitro receptor autoradiography. Analysis of autoradiograms revealed areas of heavy cholecystokinin binding in the neostriatum and substantia nigra that were set off, often quite sharply, from the adjacent globus pallidus and subthalamic nucleus where labeling was, by contrast, very light. Heavy label characterized the ventromedial and posterior parts of the caudate nucleus and adjacent putamen, binding was of moderate intensity in central areas of these regions, while, the dorsolateral margin of the head of the caudate and precommissural putamen, the dorsolateral one-third of the body of the caudate, and all but the most medial and ventral portions of the posterior putamen lateral to the pallidum were sparsely labeled. The pattern of cholecystokinin binding within the neostriatum was mottled; patches of reduced label stood out from the background of more prominent binding. However, those patches were only imperfectly correlated with the striosomal organization of both the caudate nucleus and putamen as revealed by acetylcholinesterase staining. Cholecystokinin binding in the substantia nigra was also intricately patterned. Moderately dense, vertically orientated bands of label were found in the dorsal one-third to half of the pars reticulata, providing a marked contrast to the near background levels in the ventral pars reticulata and overlying pars compacta. The present study shows that heavy cholecystokinin binding is confined to particular areas within the primate basal ganglia; the pattern of label within the substantia nigra and neostriatum can be linked to intrinsic and afferent connections of these structures. The confinement of binding sites to the dorsal pars reticulata suggests an association with dendrites of pars compacta neurons which invade this region; this interpretation is consistent with recent evidence of depletion of nigral cholecystokinin binding sites in macaques following chemical lesion of dopaminergic cells of the par compacta. In the neostriatum the distribution of binding shows overlap with its topographically organized corticostriatal innervation; portions of heavily labeled striatum coincide with regions innervated by association cortex of the frontal and temporal lobes, whereas regions of diminished binding correspond to areas innervated mainly by sensory and motor cortex. These latter findings suggest that cholecystokinin may have a particularly strong influence on cognitive aspects of striatal function. PMID:2255400

Kritzer, M F; Innis, R B; Goldman-Rakic, P S

1990-01-01

203

A computational model of inhibitory control in frontal cortex and basal ganglia.  

PubMed

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 model informed by behavioral and electrophysiological data collected on various response inhibition paradigms. This model extends a well-established model of action selection in the basal ganglia by including a frontal executive control network that integrates information about sensory input and task rules to facilitate well-informed decision making via the oculomotor system. Our simulations of the anti-saccade, Simon, and saccade-override tasks ensue in conflict between a prepotent and controlled response that causes the network to pause action selection via projections to the subthalamic nucleus. Our model reproduces key behavioral and electrophysiological patterns and their sensitivity to lesions and pharmacological manipulations. Finally, we show how this network can be extended to include the inferior frontal cortex to simulate key qualitative patterns of global response inhibition demands as required in the stop-signal task. PMID:23586447

Wiecki, Thomas V; Frank, Michael J

2013-04-01

204

Different susceptibility of medial temporal lobe and basal ganglia atrophy rates to vascular risk factors.  

PubMed

Atrophy of the medial temporal lobe (MTL) and basal ganglia (BG) are characteristic of various neurodegenerative diseases in older people. In search of potentially modifiable factors that lead to atrophy in these structures, we studied the association of vascular risk factors with atrophy of the MTL and BG in 368 nondemented men and women (born, 1907-1935) who participated in the Age, Gene/Environment, Susceptibility-Reykjavik Study. A fully automated segmentation pipeline estimated volumes of the MTL and BG from whole-brain magnetic resonance imaging performed at baseline and 2.4 years later. Linear regression models showed higher systolic and diastolic blood pressures and the presence of Apo E ?4 were independently associated with increased atrophy of the MTL but no association of vascular risk factors with atrophy of the BG. The different susceptibility of MTL and BG atrophy to the vascular risk factors suggests perfusion of the BG is relatively preserved when vascular risk factors are present. PMID:23992618

de Jong, Laura W; Forsberg, Lars E; Vidal, Jean-Sébastien; Sigurdsson, Sigurdur; Zijdenbos, Alex P; Garcia, Melissa; Eiriksdottir, Gudny; Gudnason, Vilmundur; van Buchem, Mark A; Launer, Lenore J

2013-08-28

205

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

206

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

PubMed Central

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

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

2011-01-01

207

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

PubMed Central

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

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

2008-01-01

208

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

209

Linkage studies in familial idiopathic basal ganglia calcification: separating the wheat from the chaff.  

PubMed

Idiopathic Basal Ganglia Calcification (IBGC) is a neuropsychiatric condition characterized by brain calcinosis, heterogeneous motor impairment and behavioral symptoms. The IBGC1 locus was the first region linked to this phenotype in an American family, but another kindred from Spain was also reported as possibly associated with this locus. Our group excluded this locus in additional families together with an independent study of an Australian pedigree with IBGC, but without clinical symptoms. Recently, a large Italian family from a population isolate was excluded from IBGC1. However, there are unusual aspects concerning this Tyrolean family, especially if we consider that almost all the clinically affected subjects manifested symptoms and signs suggestive of a dysmorphic syndrome, associated with neuropsychiatric symptoms. Curiously, some of the clinical features in this kindred match with the autosomal dominant chromosomal instability syndrome reported in Japan. Previous studies show that the definition of an autosomal dominant pattern of inheritance is an assumption that might be considered cautiously in familial IBGC, due to the limited clinical penetrance for the brain calcifications and especially when there is no access to all the parents neuroimaging data. Families from an Italian isolate, such as Tyrol, with high inbreeding rates, are more likely to manifest recessive syndromes. Nevertheless, the current debate regarding the nosology of this heterogeneous phenotype demands the establishment of standard diagnostic criteria. The current identification of loci or mutations responsible for FIBGC might help to elucidate this intriguing neuropsychiatric condition. PMID:18663732

Oliveira, J R M; Lemos, R R

2009-06-01

210

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

2013-09-23

211

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

PubMed

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

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

2005-01-01

212

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

213

Discrete sequence production with and without a pause: the role of cortex, basal ganglia, and cerebellum  

PubMed Central

Our sensorimotor experience unfolds in sequences over time. We hypothesize that the processing of movement sequences with and without a temporal pause will recruit distinct but cooperating neural processes, including cortico-striatal and cortico-cerebellar networks. We thus, compare neural activity during sequence learning in the presence and absence of this pause. Young volunteer participants learned sensorimotor sequences using the discrete sequence production (DSP) task, with Pause, No-Pause, and Control sequences of four elements in an event related fMRI protocol. The No-Pause and Pause sequences involved a more complex sequential structure than the Control sequence, while the Pause sequences involved insertion of a temporal pause, relative to the No-Pause sequence. The Pause vs. No-Pause contrast revealed extensive fronto-parietal, striatal, thalamic and cerebellar activations, preferentially for the Pause sequences. ROI analysis indicated that the cerebellum displays an early activation that was attenuated over successive runs, and a significant preference for Pause sequences when compared with caudate. These data support the hypothesis that a cortico-cerebellar circuit plays a specific role in the initial processing of temporal structure, while the basal ganglia play a more general role in acquiring the serial response order of the sequence.

Jouen, Anne-Lise; Verwey, Willem B.; van der Helden, Jurjen; Scheiber, Christian; Neveu, Remi; Dominey, Peter F.; Ventre-Dominey, Jocelyne

2013-01-01

214

Calcification of basal ganglia in a patient with partial trisomy 5q and partial monosomy 18q.  

PubMed

A patient with partial trisomy for the distal segment of the long arm of chromosome 5 (q35.1-->qter) with partial 18q monosomy is presented. The mother of the patient was phenotypically normal and was proved to be a carrier of a reciprocal translocation of the long arm of chromosomes 5 and 18 46,XX,t(5;18)(q35.1;q23). The patient shows mild mental retardation, short stature, mild obesity, dysmorphic face, eczema, minor malformations of the extremities, and bilateral intracranial calcification in the basal ganglia. Most of the clinical manifestations of the patient are compatible with the previously reported clinical features of partial trisomy of the distal segment of 5q. However, the calcification of bilateral basal ganglia has not been reported for this chromosomal anomaly. PMID:8379328

Nakayama, T; Sakakihara, Y; Hanaoka, S; Akagi, K; Kamoshita, S

1993-08-01

215

Reduced Leucine-Enkephalin-Like Immunoreactive Substance in Hamster Basal Ganglia after Long-Term Ethanol Exposure  

Microsoft Academic Search

Golden Syrian hamsters were placed individually in cages with three drinking bottles--one empty, one containing water, and the third containing water and ethanol. Control hamsters received water only. After 1 year the experimental hamsters showed a significantly lower concentration of leucine-enkephalin-like immunoreactive substance in the basal ganglia than the control hamsters. This finding indicates that the action of ethanol involves

Kenneth Blum; Arthur H. Briggs; Steven F. A. Elston; Leonard Delallo; Peter J. Sheridan; Madhabananda Sar

1982-01-01

216

Interactions between Cortical Rhythms and Spiking Activity of Single Basal Ganglia Neurons in the Normal and Parkinsonian State  

Microsoft Academic Search

In order to evaluate the specific interactions between cortical oscillations and basal ganglia--spiking activity under normal and parkinsonian conditions, we examined the relationship between frontal cortex electroencephalographic (EEG) signals and simulta- neously recorded neuronal activity in the internal and external segmentsofthepallidumorthesubthalamicnucleus(STN)in3rhesus monkeys. After we made recordings in the normal state, hemi- parkinsonism was induced with intracarotid injections of the dopaminergicneurotoxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Plamen Gatev; Thomas Wichmann

2009-01-01

217

Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: an fMRI study.  

PubMed

Semantic event sequencing is the ability to plan ahead and order meaningful events chronologically. To investigate the neural systems supporting this ability, an fMRI picture sequencing task was developed. Participants sequenced a series of four pictures presented in random order based on the temporal relationship among them. A control object discrimination task was designed to be comparable to the sequencing task regarding semantic, visuospatial, and motor processing requirements but without sequencing demands. fMRI revealed significant activation in the dorsolateral prefrontal cortex and globus pallidus internal part in the picture sequencing task compared with the control task. The findings suggest that circuits involving the frontal lobe and basal ganglia output nuclei are important for picture sequencing and more generally for the sequential ordering of events. This is consistent with the idea that the basal ganglia output nuclei are critical not only for motor but also for high-level cognitive function, including behaviors involving meaningful information. We suggest that the interaction between the frontal lobes and basal ganglia output nuclei in semantic event sequencing can be generalized to include the sequential ordering of behaviors in which the selective updating of neural representations is the key computation. PMID:16360121

Tinaz, Sule; Schendan, Haline E; Schon, Karin; Stern, Chantal E

2005-12-19

218

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

PubMed Central

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

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

2010-01-01

219

Interactions between Cortical Rhythms and Spiking Activity of Single Basal Ganglia Neurons in the Normal and Parkinsonian State  

PubMed Central

In order to evaluate the specific interactions between cortical oscillations and basal ganglia–spiking activity under normal and parkinsonian conditions, we examined the relationship between frontal cortex electroencephalographic (EEG) signals and simultaneously recorded neuronal activity in the internal and external segments of the pallidum or the subthalamic nucleus (STN) in 3 rhesus monkeys. After we made recordings in the normal state, hemiparkinsonism was induced with intracarotid injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in one animal, followed by additional recordings. Spiking activity in the pallidum and STN was associated with significant shifts in the level of EEG synchronization. We also found that the spectral power of beta- and gamma-band EEG rhythms covaried positively before the basal ganglia spikes but did not covary or covaried negatively thereafter. In parkinsonism, changes in cortical synchronization and phase coherence were reduced in EEG segments aligned to STN spikes, whereas both were increased in data segments aligned to pallidal spikes. Spiking-related changes in beta/gamma-band covariance were reduced. The findings indicate that basal ganglia and cortex interact in the processing of cortical rhythms that contain oscillations across a broad range of frequencies and that this interaction is severely disrupted in parkinsonism.

Gatev, Plamen

2009-01-01

220

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

PubMed

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

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

2010-12-16

221

Age-related changes in HSP25 expression in basal ganglia and cortex of F344/BN rats  

PubMed Central

Normal aging is associated with chronic oxidative stress. In the basal ganglia, oxidative stress may contribute to the increased risk of Parkinson's disease in the elderly. Neurons are thought to actively utilize compensatory defense mechanisms, such as heat shock proteins (HSPs), to protect from persisting stress. Despite their protective role, little is known about HSP expression in the aging basal ganglia. The purpose of this study was to examine HSP expression in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month-old Fischer 344/Brown Norway rats. We found robust age-related increases in phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72 (the inducible form of HSP70) was reduced with age, but only in the striatum. p38 MAPK, a protein implicated in activating HSP25, did not change with age, nor did HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that HSP25 is especially responsive to age-related stress in the basal ganglia.

Gupte, Anisha A.; Morris, Jill K.; Zhang, Hongyu; Bomhoff, Gregory L.; Geiger, Paige C.; Stanford, John A.

2010-01-01

222

Disturbance of delayed match-to-sample in macaques by tetanization of anterior commissure versus limbic system or basal ganglia.  

PubMed

Three pig-tailed macaques were trained to select ("match") from a pair of colored images that which they had seen ("sample") and responded to 5--15 s previously. The anterior commissure (AC) and/or its radiation, various loci in basal ganglia, hippocampal formation and "control" areas, (splenium of corpus callosum, precentral gyrus, insular cortex), totalling 40 loci, were each tetanized for 4 s during presentation of the "sample" image, during the delay period, or when the monkey was required to select the "matching" image. For several loci in the hippocampal formation tetanization at any phase of the task reduced "matching" to chance levels and gave evidence of electrical after-discharge; but other comparable hippocampal loci had little or no effect. Response to "sample" or "match" stimuli were absent during tetanization of basal ganglia or anterior commissure. When finally made, upon cessation of tetanization, responses were equally correct for basal ganglia and "control" sites, but for AC were at chance levels. PMID:118045

Overman, W H; Doty, R W

1979-01-01

223

Surgical treatment for large spontaneous basal ganglia hemorrhage: retrospective analysis of 253 cases.  

PubMed

Abstract Objectives. Spontaneous intracerebral hemorrhage (ICH) is a challenge to both neurologists and neurosurgeons. We aim to summarize the surgical treatment of ICH based on retrospective analysis of our patients. Methods. Two hundred and fifty-three patients with spontaneous ICH from August 2008 to August 2011 were retrospectively analyzed. Clinical data, including preoperative ICH score, pre- and postoperative GCS score, hematoma volume, postoperative brain infarction, 30-day mortality, and GOS 3 months postictus, were collected. One hundred and fifty patients had their intracranial pressure (ICP) monitored, and data were recorded and analyzed. All patients underwent craniotomy and clot removal under general anesthesia. Outcome analysis was stratified using hematoma volume, ICH score, preoperative GCS score, and decompressive craniectomy (DC). Results. The mean hematoma volume was 70.8 mL, and 68 patients (26.9%) underwent DC. The mean postoperative ICP was 28.8 ± 6.7 mmHg for patients without DC, and only 17.5 ± 8.6 mmHg for patients with DC. Twenty-five patients (9.9%) died within 30 days of operation, and 88 patients (34.8%, GOS ? 4) had good outcome 3 months after surgery. ICH volume > 50 mL, preoperative GCS score ? 8, and ICH score ? 3 are risk factors for unfavorable outcomes. Conclusions. DC can be used for patients with low preoperative GCS score, and it effectively reduces ICP and 30-day mortality. Hematoma volume, preoperative GCS score, and ICH score are of predictive value for surgical outcome of large basal ganglia hemorrhage. PMID:23406426

Li, Q; Yang, C H; Xu, J G; Li, H; You, C

2013-02-14

224

The Arbitration-Extension Hypothesis: A Hierarchical Interpretation of the Functional Organization of the Basal Ganglia  

PubMed Central

Based on known anatomy and physiology, we present a hypothesis where the basal ganglia motor loop is hierarchically organized in two main subsystems: the arbitration system and the extension system. The arbitration system, comprised of the subthalamic nucleus, globus pallidus, and pedunculopontine nucleus, serves the role of selecting one out of several candidate actions as they are ascending from various brain stem motor regions and aggregated in the centromedian thalamus or descending from the extension system or from the cerebral cortex. This system is an action-input/action-output system whose winner-take-all mechanism finds the strongest response among several candidates to execute. This decision is communicated back to the brain stem by facilitating the desired action via cholinergic/glutamatergic projections and suppressing conflicting alternatives via GABAergic connections. The extension system, comprised of the striatum and, again, globus pallidus, can extend the repertoire of responses by learning to associate novel complex states to certain actions. This system is a state-input/action-output system, whose organization enables it to encode arbitrarily complex Boolean logic rules using striatal neurons that only fire given specific constellations of inputs (Boolean AND) and pallidal neurons that are silenced by any striatal input (Boolean OR). We demonstrate the capabilities of this hierarchical system by a computational model where a simulated generic “animal” interacts with an environment by selecting direction of movement based on combinations of sensory stimuli, some being appetitive, others aversive or neutral. While the arbitration system can autonomously handle conflicting actions proposed by brain stem motor nuclei, the extension system is required to execute learned actions not suggested by external motor centers. Being precise in the functional role of each component of the system, this hypothesis generates several readily testable predictions.

Kamali Sarvestani, Iman; Lindahl, Mikael; Hellgren-Kotaleski, Jeanette; Ekeberg, Orjan

2011-01-01

225

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

226

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

227

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

228

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

PubMed Central

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

Desmurget, M.; Turner, R.S.

2010-01-01

229

Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds  

PubMed Central

The basal ganglia-recipient thalamus receives inhibitory inputs from the pallidum and excitatory inputs from cortex, but it is unclear how these inputs interact during behavior. We recorded simultaneously from thalamic neurons and their putative synaptically connected pallidal inputs in singing zebra finches. We find, first, that each pallidal spike produces an extremely brief (?5 ms) pulse of inhibition that completely suppresses thalamic spiking. As a result, thalamic spikes are entrained to pallidal spikes with submillisecond precision. Second, we find that the number of thalamic spikes that discharge within a single pallidal interspike interval (ISI) depends linearly on the duration of that interval but does not depend on pallidal activity prior to the interval. In a detailed biophysical model, our results were not easily explained by the postinhibitory “rebound” mechanism previously observed in anesthetized birds and in brain slices, nor could most of our data be characterized as “gating” of excitatory transmission by inhibitory pallidal input. Instead, we propose a novel “entrainment” mechanism of pallidothalamic transmission that highlights the importance of an excitatory conductance that drives spiking, interacting with brief pulses of pallidal inhibition. Building on our recent finding that cortical inputs can drive syllable-locked rate modulations in thalamic neurons during singing, we report here that excitatory inputs affect thalamic spiking in two ways: by shortening the latency of a thalamic spike after a pallidal spike and by increasing thalamic firing rates within individual pallidal ISIs. We present a unifying biophysical model that can reproduce all known modes of pallidothalamic transmission—rebound, gating, and entrainment—depending on the amount of excitation the thalamic neuron receives.

Goldberg, Jesse H.; Farries, Michael A.

2012-01-01

230

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

231

The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer's cramp  

Microsoft Academic Search

Writer's cramp is a focal hand dystonia that specifically affects handwriting. Though writer's cramp has been attributedto adysfunctionof thebasal ganglia,theroleof thebasal ganglia inthepathogenesisofwriter'scramp remains to be determined. Seventeen patients with writer's cramp (nine females; age range: 24-71 years) and 17 healthy individuals (six females; age range: 27-68 years) underwent functional MRI (fMRI) while they dis- criminated the orientation of gratings

M. Peller; K. E. Zeuner; A. Munchau; A. Quartarone; M. Weiss; A. Knutzen; M. Hallett; G. Deuschl; H. R. Siebner

2006-01-01

232

[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

233

Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice  

PubMed Central

Background Methylphenidate (MPH) is a psychostimulant that exerts its pharmacological effects via preferential blockade of the dopamine transporter (DAT) and the norepinephrine transporter (NET), resulting in increased monoamine levels in the synapse. Clinically, methylphenidate is prescribed for the symptomatic treatment of ADHD and narcolepsy; although lately, there has been an increased incidence of its use in individuals not meeting the criteria for these disorders. MPH has also been misused as a “cognitive enhancer” and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of MPH in mice at either 1 mg/kg or 10 mg/kg, affects cell number and gene expression in the basal ganglia. Methodology/Principal Findings Through the use of stereological counting methods, we observed a significant reduction (?20%) in dopamine neuron numbers in the substantia nigra pars compacta (SNpc) following chronic administration of 10 mg/kg MPH. This dosage of MPH also induced a significant increase in the number of activated microglia in the SNpc. Additionally, exposure to either 1 mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopaminergic neurons to the parkinsonian agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Unbiased gene screening employing Affymetrix GeneChip® HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1 mg/kg and 10 mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the substantia nigra (SN) were observed with both acute and chronic dosing of 10 mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes il-6 and tnf-? in the striatum, although these were seen only at an acute dose of 10 mg/kg and not following chronic dosing. Conclusion Collectively, our results suggest that chronic MPH usage in mice at doses spanning the therapeutic range in humans, especially at prolonged higher doses, has long-term neurodegenerative consequences.

Sadasivan, Shankar; Pond, Brooks B.; Pani, Amar K.; Qu, Chunxu; Jiao, Yun; Smeyne, Richard J.

2012-01-01

234

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

PubMed

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. PMID:22832400

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; Tézenas du Montcel, S; Bastian, A; Langbour, N; Teillant, A; Haynes, W; Yelnik, J; Karachi, C; Mallet, L

2011-05-03

235

[Basal ganglia deep-brain stimulation for treatment of drug-resistant epilepsy: review and current data].  

PubMed

The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience. PMID:18452956

Chabardès, S; Minotti, L; Chassagnon, S; Piallat, B; Torres, N; Seigneuret, E; Vercueil, L; Carron, R; Hirsch, E; Kahane, P; Benabid, A L

2008-05-02

236

Characterization of multifocal T2*-weighted MRI hypointensities in the basal ganglia of elderly, community-dwelling subjects.  

PubMed

Multifocal T2*-weighted (T2*w) hypointensities in the basal ganglia, which are believed to arise predominantly from mineralized small vessels and perivascular spaces, have been proposed as a biomarker for cerebral small vessel disease. This study provides baseline data on their appearance on conventional structural MRI for improving and automating current manual segmentation methods. Using a published thresholding method, multifocal T2*w hypointensities were manually segmented from whole brain T2*w volumes acquired from 98 community-dwelling subjects in their early 70s. Connected component analysis was used to derive the average T2*w hypointensity count and load per basal ganglia nucleus, as well as the morphology of their connected components, while nonlinear spatial probability mapping yielded their spatial distribution. T1-weighted (T1w), T2-weighted (T2w) and T2*w intensity distributions of basal ganglia T2*w hypointensities and their appearance on T1w and T2w MRI were investigated to gain further insights into the underlying tissue composition. In 75/98 subjects, on average, 3 T2*w hypointensities with a median total volume per intracranial volume of 50.3ppm were located in and around the globus pallidus. Individual hypointensities appeared smooth and spherical with a median volume of 12mm(3) and median in-plane area of 4mm(2). Spatial probability maps suggested an association between T2*w hypointensities and the point of entry of lenticulostriate arterioles into the brain parenchyma. T1w and T2w and especially the T2*w intensity distributions of these hypointensities, which were negatively skewed, were generally not normally distributed indicating an underlying inhomogeneous tissue structure. Globus pallidus T2*w hypointensities tended to appear hypo- and isointense on T1w and T2w MRI, whereas those from other structures appeared iso- and hypointense. This pattern could be explained by an increased mineralization of the globus pallidus. In conclusion, the characteristic spatial distribution and appearance of multifocal basal ganglia T2*w hypointensities in our elderly cohort on structural MRI appear to support the suggested association with mineralized proximal lenticulostriate arterioles and perivascular spaces. PMID:23769704

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

2013-06-12

237

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

PubMed

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

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

2003-06-01

238

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

239

A case of traumatic hematoma in the basal ganglia that showed deterioration after arrival at the hospital.  

PubMed

A case of traumatic hematoma in the basal ganglia that showed deterioration after arrival at the hospital was reported. A 65-year-old man crashed into the wall while riding a motorcycle. His Glasgow coma scale was E3V4M6 and showed retrograde amnesia and slight right motor weakness. Because head CT in the secondary trauma survey showed subarachnoid hemorrhage in the right Sylvian fissure and multiple gliding contusions in the left frontal and parietal lobe, he was entered into the intensive care unit for diagnosis of diffuse brain injury. He showed complete muscle weakness of left upper and lower limbs 5 h after the accident. Head CT newly showed hematoma, 2 cm in diameter, in the right basal ganglia. The patient vomited following the CT scan, and so his consciousness suddenly deteriorated into a stupor. We performed head CT again. The hematoma had enlarged to 5 cm at the same lesion and partially expanded into midbrain. The patient died on the 13th day of trauma. Based on retrospective interpretation, we conclude that clinical examinations, follow-up CT scans and blood examinations should be performed frequently as part of ICU management for all TBI patients in the early phase after trauma. PMID:23564122

Moriya, Takashi; Tagami, Rumi; Furukawa, Makoto; Sakurai, Atsushi; Kinoshita, Kosaku; Tanjoh, Katsuhisa

2013-01-01

240

Early onset of deafening-induced song deterioration and differential requirements of the pallial-basal ganglia vocal pathway  

PubMed Central

Similar to humans, songbirds rely on auditory feedback to maintain the acoustic and sequence structure of adult learned vocalizations. When songbirds are deafened, the learned features of song, such as syllable structure and sequencing, eventually deteriorate. However, the time-course and initial phases of song deterioration have not been well studied, particularly in the most commonly studied songbird, the zebra finch. Here, we observed previously uncharacterized subtle but significant changes to learned song within a few days following deafening. Syllable structure became detectably noisier and silent intervals between song motifs increased. Although song motif sequences remained stable at 2 weeks, as previously reported, pronounced changes occurred in longer stretches of song bout sequences. These included deletions of syllables between song motifs, changes in the frequency at which specific chunks of song were produced and stuttering for birds that had some repetitions of syllables before deafening. Changes in syllable structure and song bout sequence occurred at different rates, indicating different mechanisms for their deterioration. The changes in syllable structure required an intact lateral part but not the medial part of the pallial-basal ganglia vocal pathway, whereas changes in the song bout sequence did not require lateral or medial portions of the pathway. These findings indicate that deafening-induced song changes in zebra finches can be detected rapidly after deafening, that acoustic and sequence changes can occur independently, and that, within this time period, the pallial-basal ganglia vocal pathway controls the acoustic structure changes but not the song bout sequence changes.

Horita, Haruhito; Wada, Kazuhiro; Jarvis, Erich D.

2010-01-01

241

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

PubMed

Bilinguals must focus their attention to control competing languages. In bilingual aphasia, damage to the fronto-subcortical loop may lead to pathological language switching and mixing and the attrition of the more automatic language (usually L1). We present the case of JZ, a bilingual Basque-Spanish 53-year-old man who, after haematoma in the left basal ganglia, presented with executive deficits and aphasia, characterised by more impaired language processing in Basque, his L1. Assessment with the Bilingual Aphasia Test revealed impaired spontaneous and automatic speech production and speech rate in L1, as well as impaired L2-to-L1 sentence translation. Later observation led to the assessment of verbal and non-verbal executive control, which allowed JZ's impaired performance on language tasks to be related to executive dysfunction. In line with previous research, we report the significant attrition of L1 following damage to the left basal ganglia, reported for the first time in a Basque-Spanish bilingual. Implications for models of declarative and procedural memory are discussed. PMID:21453016

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

2011-03-31

242

External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network  

PubMed Central

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson’s disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the MPTP monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in GPi and STN and increased in VPLo. Effective GPe DBS also reduced bursting in STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD.

Vitek, Jerrold L.; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary; Baker, Kenneth B.

2011-01-01

243

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

2013-10-02

244

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

245

Loss of function of slc20a2 associated with familial idiopathic Basal Ganglia calcification in humans causes brain calcifications in mice.  

PubMed

Familial idiopathic basal ganglia calcification (FIBGC) is a neurodegenerative disorder with neuropsychiatric and motor symptoms. Deleterious mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), were recently linked to FIBGC in almost 50 % of the families reported worldwide. Here, we show that knockout of Slc20a2 in mice causes calcifications in the thalamus, basal ganglia, and cortex, demonstrating that reduced PiT2 expression alone can cause brain calcifications. PMID:23934451

Jensen, Nina; Schrøder, Henrik Daa; Hejbøl, Eva Kildall; Füchtbauer, Ernst-Martin; de Oliveira, João Ricardo Mendes; Pedersen, Lene

2013-08-10

246

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

247

Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson's Disease and related disorders  

Microsoft Academic Search

The basal ganglia (BG) are a set of interconnected subcortical structures that play a critical role in motor control. The BG are thought to control movements by a delicate balance of transmission through two BG circuits that connect the input and output nuclei: the direct and the indirect pathways. The BG are also involved in a number of movement disorders.

Susan T Rouse; Michael J Marino; Stefania R Bradley; Hazar Awad; Marion Wittmann; P. Jeffrey Conn

2000-01-01

248

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

249

Topographic projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta of the cat with special reference to pallidal projections  

Microsoft Academic Search

Projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta (TPC) were studied by using anterograde and retrograde tracing techniques with horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the cat. Following WGA-HRP injections into the medial TPC area, a substantial number of retrogradely labeled cells were seen in the entopeduncular nucleus (EP) and medial half of

T. Moriizumi; Y. Nakamura; H. Tokuno; Y. Kitao; M. Kudo

1988-01-01

250

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

ERIC Educational Resources Information Center

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

Wilkinson, Leonora; Khan, Zunera; Jahanshahi, Marjan

2009-01-01

251

Movement-related modulation of neural activity in human basal ganglia and its L DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease  

Microsoft Academic Search

Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinson's disease, we recorded the electrical activity from the human basal ganglia before, during and after voluntary contralateral finger movements, before and after L-DOPA. We analysed the movement-related spectral changes in the electroencephalographic signal from the subthalamic nucleus (STN) and from the internal globus pallidus (GPi). Before,

A. Priori; G. Foffani; A. Pesenti; A. Bianchi; V. Chiesa; G. Baselli; E. Caputo; F. Tamma; P. Rampini; M. Egidi; M. Locatelli; S. Barbieri

2002-01-01

252

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

253

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

Microsoft Academic Search

Summary: The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride vari- ability of gait cycle timing and its subphases, would be dimin- ished with both Parkinson's disease (PD) and Huntington's disease

Jeffrey M. Hausdorff; Merit E. Cudkowicz; Renée Firtion; Jeanne Y. Wei; Ary L. Goldberger

2004-01-01

254

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

255

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

256

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

PubMed

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

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

2013-10-08

257

Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.  

PubMed

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. PMID:22845853

Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

2012-07-30

258

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

PubMed Central

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

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

2013-01-01

259

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

Microsoft Academic Search

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

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

2010-01-01

260

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

261

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

262

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

PubMed Central

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

Sperlagh, Beata; Vizi, E. Sylvester

2011-01-01

263

An avian basal ganglia-forebrain circuit contributes differentially to syllable versus sequence variability of adult Bengalese finch song.  

PubMed

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

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

2009-04-08

264

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

265

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

266

Subthalamic nucleus evokes similar long lasting glutamatergic excitations in pallidal, entopeduncular and nigral neurons in the basal ganglia slice.  

PubMed

The subthalamic nucleus (STN) modulates the activity of globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) neurons via its direct glutamatergic projections. To investigate the mechanism by which STN affects activity in these structures and whether STN induced activity is comparable among STN target neurons, we performed patch clamp recordings in a tilted, parasagittal, basal ganglia slice (BGS) that preserves these functional connections. We report that single, brief stimulation of the STN generates a brief monosynaptic AMPA-mediated excitatory postsynaptic current (EPSC) in GP, EP and SNr neurons. A higher intensity, supra-threshold activation evokes a compound EPSC consisting of an early monosynaptic component followed by a slow inward NMDA-mediated current with an overlying barrage of AMPA-mediated EPSCs. These late EPSCs were polysynaptic and gave rise to bursts of spikes that lasted several hundreds of milliseconds. They were eliminated by surgical removal of the STN from the BGS slice, indicating that the STN is required for their generation. Reconstruction of biocytin-filled STN neurons revealed that a third of STN neurons project intra-STN axon collaterals that may underlie polysynaptic activity. We propose that activation of the STN yields comparable long lasting excitations in its target neurons by means of a polysynaptic network. PMID:20074618

Ammari, R; Lopez, C; Bioulac, B; Garcia, L; Hammond, C

2010-01-13

267

Multiple sclerosis and the accumulation of iron in the Basal Ganglia: quantitative assessment of brain iron using MRI t(2) relaxometry.  

PubMed

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 T(2) relaxometry was used for the measurement. 970 patients with clinically definite MS and 117 controls were examined. Patients were divided into three subgroups according to LL and BPF. This work provides quantitative evidence of increased iron accumulation in the basal ganglia in MS patients in comparison to healthy controls. We also found that in the subgroup with small LL value, iron accumulation is higher than in the subgroup with large LL value. The hypothesis of a neurodegenerative component of MS is supported by the changes in iron content in the brain. PMID:20130410

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

2010-01-30

268

Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3  

Microsoft Academic Search

Summary Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I were subjected to a genotype- phenotype correlation analysis using molecular genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3 (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and basal ganglia nuclei. There was significant atrophy of the cerebellum and brainstem in all

T. Klockgether; M. Skalej; D. Wedekind; A. R. Luft; D. Welte; J. B. Schulz; M. Abele; K. Burk; F. Laccone; A. Brice; J. Dichgans

1998-01-01

269

Intrastriatal injection of D 1 or D 2 dopamine agonists affects glucose utilization in both the direct and indirect pathways of the rat basal ganglia  

Microsoft Academic Search

Two distinct pathways are thought to connect the striatum to the basal ganglia output nuclei: a direct pathway, originating from neurons bearing dopamine, D1 receptors and an indirect pathway, originating from neurons expressing D2 receptors. It has been recently suggested, however, that dopamine receptor sub-types may co-localize and co-operate in the striatum. We sought to verify the functional segregation of

Giuseppe Conti; Fabio Blandini; Cristina Tassorelli; Franco Giubilei; Francesco Fornai; Alessandro Zocchi; Francesco Orzi

2001-01-01

270

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

271

Dopamine transporter density in the basal ganglia assessed with [ 123 I]IPT SPET in children with attention deficit hyperactivity disorder  

Microsoft Academic Search

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder in childhood that is known to be associated with dopamine dysregulation. In this study, we investigated dopamine transporter (DAT) density in children with ADHD using iodine-123 labelled N-(3-iodopropen-2-yl)-2#-carbomethoxy-3#-(4-chlorophenyl) tropane ([123I]IPT) single-photon emission tomography (SPET) and postulated that an alteration in DAT density in the basal ganglia is responsible for dopaminergic dysfunction

Keun-Ah Cheon; Young Hoon Ryu; Young-Kee Kim; Kee Namkoong; Chan-Hyung Kim; Jong Doo Lee

2003-01-01

272

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

Microsoft Academic Search

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

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

2007-01-01

273

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

Microsoft Academic Search

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

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

1993-01-01

274

Changes in metabotropic glutamate receptor 1-8 gene expression in the rodent basal ganglia motor loop following lesion of the nigrostriatal tract  

Microsoft Academic Search

Metabotropic glutamate (mGlu) receptors in the basal ganglia motor loop may increase cell excitability (Group I) or modulate neurotransmitter release (Group I, II and III). Nigrostriatal tract degeneration in Parkinson’s disease (PD) produces downstream pathological disturbances in glutamate and GABA transmission. The present study examined whether changes in mGlu receptor gene expression may either contribute to, or compensate for these

M. J Messenger; L. G Dawson; S Duty

2002-01-01

275

[Organization of the projections of the structures of the basal ganglia morpho-functional system to the individual substructures of the deep mesencephalic nucleus complex of dog brain].  

PubMed

The method of retrograde axonal transport of horseradish peroxidase was used to study the organization of the projections of the morpho-functional system of the basal ganglia nuclei to the individual substructures of the of deep mesencephalic nucleus complex (DMNC) of dog brain (n = 9). It was found that the nucleus accumbens was the only striatum structure containing the neurons that sent projection fibers to the subcuneate nucleus. The projections of the output structures of the basal ganglia--pallidum, substantia nigra, zona incerta, pedunculopontine nucleus were more numerous in DMNC. It was demonstrated that not all DMNC substructures received projection fibers from the neurons of all the nuclei of the basal ganglia structures mentioned. Thus, the fibers from the neurons of the globus pallidus and the ventral pallidum innervated the cuneiform and the subcuneiform nuclei, while those from the entopeduncular nucleus projected to all the DMNC substructures. The projection fibers from the zona incerta neurons were directed to the subcuneate nucleus and to the deep mesencephalic nucleus, while those from the pedunculopontine nucleus projected to the cuneate and the subcuneate nuclei. The projections from the substantia nigra neurons were directed to all the substructures of DMNC. PMID:23659032

Gorbachevskaya, A I

2012-01-01

276

Endoscopic surgery versus conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage (ECMOH): study protocol for a randomized controlled trial  

PubMed Central

Background Spontaneous intracerebral hemorrhage is a disease with high morbidity, high disability rate, high mortality, and high economic burden. Whether patients can benefit from surgical evacuation of hematomas is still controversial, especially for those with moderate-volume hematomas in the basal ganglia. This study is designed to compare the efficacy of endoscopic surgery and conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage. Methods Patients meet the criteria will be randomized into the endoscopic surgery group (endoscopic surgery for hematoma evacuation and the best medical treatment) or the conservative treatment group (the best medical treatment). Patients will be followed up at 1, 3, and 6?months after initial treatment. The primary outcomes include the Extended Glasgow Outcome Scale and the Modified Rankin Scale. The secondary outcomes consist of the National Institutes of Health Stroke Scale and the mortality. The Barthel Index(BI) will also be evaluated. The sample size is 100 patients. Discussion The ECMOH trial is a randomized controlled trial designed to evaluate if endoscopic surgery is better than conservative treatment for patients with moderate-volume hematomas in the basal ganglia. Trial registration Chinese Clinical Trial Registry: ChiCTR-TRC-11001614 (http://www.chictr.org/en/proj/show.aspx?proj=1618)

2012-01-01

277

The Dopamine D1-D2 Receptor Heteromer in Striatal Medium Spiny Neurons: Evidence for a Third Distinct Neuronal Pathway in Basal Ganglia  

PubMed Central

Dopaminergic signaling within the basal ganglia has classically been thought to occur within two distinct neuronal pathways; the direct striatonigral pathway which contains the dopamine D1 receptor and the neuropeptides dynorphin (DYN) and substance P, and the indirect striatopallidal pathway which expresses the dopamine D2 receptor and enkephalin (ENK). A number of studies have also shown, however, that D1 and D2 receptors can co-exist within the same medium spiny neuron and emerging evidence indicates that these D1/D2-coexpressing neurons, which also express DYN and ENK, may comprise a third neuronal pathway, with representation in both the striatonigral and striatopallidal projections of the basal ganglia. Furthermore, within these coexpressing neurons it has been shown that the dopamine D1 and D2 receptor can form a novel and pharmacologically distinct receptor complex, the dopamine D1–D2 receptor heteromer, with unique signaling properties. This is indicative of a functionally unique role for these neurons in brain. The aim of this review is to discuss the evidence in support of a novel third pathway coexpressing the D1 and D2 receptor, to discuss the potential relevance of this pathway to basal ganglia signaling, and to address its potential value, and that of the dopamine D1–D2 receptor heteromer, in the search for new therapeutic strategies for disorders involving dopamine neurotransmission.

Perreault, Melissa L.; Hasbi, Ahmed; O'Dowd, Brian F.; George, Susan R.

2011-01-01

278

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

279

Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons.  

PubMed

The GABA projection neurons in the substantial nigra pars reticulata (SNr) are key output neurons of the basal ganglia motor control circuit. These neurons fire sustained high-frequency, short-duration spikes that provide a tonic inhibition to their targets and are critical to movement control. We hypothesized that a robust voltage-activated K(+) conductance that activates quickly and resists inactivation is essential to the remarkable fast-spiking capability in these neurons. Semi-quantitative RT-PCR (qRT-PCR) analysis on laser capture-microdissected nigral neurons indicated that mRNAs for Kv3.1 and Kv3.4, two key subunits for forming high activation threshold, fast-activating, slow-inactivating, 1 mM tetraethylammonium (TEA)-sensitive, fast delayed rectifier (I(DR-fast)) type Kv channels, are more abundant in fast-spiking SNr GABA neurons than in slow-spiking nigral dopamine neurons. Nucleated patch clamp recordings showed that SNr GABA neurons have a strong Kv3-like I(DR-fast) current sensitive to 1 mM TEA that activates quickly at depolarized membrane potentials and is resistant to inactivation. I(DR-fast) is smaller in nigral dopamine neurons. Pharmacological blockade of I(DR-fast) by 1 mM TEA impaired the high-frequency firing capability in SNr GABA neurons. Taken together, these results indicate that Kv3-like channels mediating fast-activating, inactivation-resistant I(DR-fast) current are critical to the sustained high-frequency firing in SNr GABA projection neurons and hence movement control. PMID:21160004

Ding, Shengyuan; Matta, Shannon G; Zhou, Fu-Ming

2010-12-15

280

Neural encoding of auditory temporal context in a songbird basal ganglia nucleus, and its independence of birds' song experience.  

PubMed

Some of the most complex auditory neurons known are found in the songbird forebrain, throughout the 'song system', including its basal ganglia nucleus Area X. These cells are selective for the temporal order of the bird's own song (BOS): they typically respond strongly to BOS, but more weakly when the syllable sequence of BOS is played in reverse order (roBOS), indicating that they integrate auditory information over more than single syllables. Here, studying the zebra finch Area X, we found that order selectivity strongly depends on the mean syllable duration of individual songs, decreasing markedly as this duration approaches 150-200 ms. Simply segmenting the same songs differently, creating an increase in average syllable length towards 150 ms, caused a similar decrease in order selectivity. This suggests that song neurons integrate acoustic information over a relatively limited time window, predominantly less than 150 ms. We provided further support for this by showing that a significant fraction of Area X order selectivity was accounted for by the acoustic similarity between each BOS and roBOS, measured using cross-correlation with fixed window sizes, but only when the correlation windows were at least 50 ms and no more than 200 ms long. All the same findings were evident in birds raised without tutor exposure, indicating that tutor learning has little effect on neural mechanisms underlying song temporal selectivity. Our results suggest that song-selective neurons encode much of the temporal context of song using a short, constant time window that is conserved across differences in songs, birds and learning. PMID:18364039

Kojima, Satoshi; Doupe, Allison J

2008-03-01

281

Neural encoding of auditory temporal context in a songbird basal ganglia nucleus, and its independence of birds' song experience  

PubMed Central

Some of the most complex auditory neurons known are found in the songbird forebrain, throughout the ‘song system’, including its basal ganglia nucleus Area X. These cells are selective for the temporal order of the bird's own song (BOS): they typically respond strongly to BOS, but more weakly when the syllable sequence of BOS is played in reverse order (roBOS), indicating that they integrate auditory information over more than single syllables. Here, studying the zebra finch Area X, we found that order selectivity strongly depends on the mean syllable duration of individual songs, decreasing markedly as this duration approaches 150–200 ms. Simply segmenting the same songs differently, creating an increase in average syllable length towards 150 ms, caused a similar decrease in order selectivity. This suggests that song neurons integrate acoustic information over a relatively limited time window, predominantly less than 150 ms. We provided further support for this by showing that a significant fraction of Area X order selectivity was accounted for by the acoustic similarity between each BOS and roBOS, measured using cross-correlation with fixed window sizes, but only when the correlation windows were at least 50 ms and no more than 200 ms long. All the same findings were evident in birds raised without tutor exposure, indicating that tutor learning has little effect on neural mechanisms underlying song temporal selectivity. Our results suggest that song-selective neurons encode much of the temporal context of song using a short, constant time window that is conserved across differences in songs, birds and learning.

Kojima, Satoshi; Doupe, Allison J.

2008-01-01

282

Activity in a cortical-basal ganglia circuit for song is required for social context-dependent vocal variability.  

PubMed

Variability in adult motor output is important for enabling animals to respond to changing external conditions. Songbirds are useful for studying variability because they alter the amount of variation in their song depending on social context. When an adult zebra finch male sings to a female ("directed"), his song is highly stereotyped, but when he sings alone ("undirected"), his song varies across renditions. Lesions of the lateral magnocellular nucleus of the anterior nidopallium (LMAN), the output nucleus of a cortical-basal ganglia circuit for song, reduce song variability to that of the stereotyped "performance" state. However, such lesions not only eliminate LMAN's synaptic input to its targets, but can also cause structural or physiological changes in connected brain regions, and thus cannot assess whether the acute activity of LMAN is important for social modulation of adult song variability. To evaluate the effects of ongoing LMAN activity, we reversibly silenced LMAN in singing zebra finches by bilateral reverse microdialysis of the GABA(A) receptor agonist muscimol. We found that LMAN inactivation acutely reduced undirected song variability, both across and even within syllable renditions, to the level of directed song variability in all birds examined. Song variability returned to pre-muscimol inactivation levels after drug washout. However, unlike LMAN lesions, LMAN inactivation did not eliminate social context effects on song tempo in adult birds. These results indicate that the activity of LMAN neurons acutely and actively generates social context-dependent increases in adult song variability but that social regulation of tempo is more complex. PMID:20884763

Stepanek, Laurie; Doupe, Allison J

2010-09-08

283

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

284

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

285

Sleep-related neural activity in a premotor and a basal-ganglia pathway of the songbird.  

PubMed

During singing, neurons in premotor nucleus RA (robust nucleus of the arcopallium) of the zebra finch produce complex temporal sequences of bursts that are recapitulated during sleep. RA receives input from nucleus HVC via the premotor pathway, and also from the lateral magnocellular nucleus of the anterior nidopallium (LMAN), part of a basal ganglia-related circuit essential for vocal learning. We explore the propagation of sleep-related spike patterns in these two pathways and their influences on RA activity. We promote sleep in head-fixed birds by injections of melatonin and make single-neuron recordings from the three major classes of neurons in HVC: RA-projecting neurons, Area X-projecting neurons, and interneurons. We also record LMAN neurons that project to RA. In paired recordings, spike trains from identified HVC neuron types are strongly coherent with spike trains in RA neurons, whereas LMAN projection neurons on average exhibit only a weak coherency with neurons in HVC and RA. We further examine the relative roles of HVC and LMAN in generating RA burst sequences with reversible inactivation. Lidocaine inactivation of HVC completely abolishes bursting in RA, whereas inactivation of LMAN has no effect on burst rates in RA. In combination, our data suggest that in adult birds, RA burst sequences in sleep are driven via the premotor pathway from HVC. We present a simple generative model of spike trains in HVC, RA, and LMAN neurons that is able to qualitatively reproduce observed coherency functions. We propose that commonly observed coherency peaks at positive and negative time lags are caused by sequentially correlated HVC activity. PMID:16495362

Hahnloser, Richard H R; Kozhevnikov, Alexay A; Fee, Michale S

2006-02-22

286

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

PubMed Central

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

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

2011-01-01

287

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

288

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

PubMed Central

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

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

2013-01-01

289

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

290

Effects on turning of microinjections into basal ganglia of D 1 and D 2 dopamine receptors agonists and the cannabinoid CB 1 antagonist SR141716A in a rat Parkinson's model  

Microsoft Academic Search

Brain cannabinoid CB1 receptors are expressed in neural areas that contribute to movement such as basal ganglia, where they co-localize with dopamine D1 and D2 receptors. The objective of the present study was to further study the functional role of CB1 receptors along with D1 and D2 dopamine receptors of basal ganglia by local injections of SR141716A (CB1 receptor antagonist),

Fadwa El Banoua; Isabel Caraballo; Juan A Flores; Beatriz Galan-Rodriguez; Emilio Fernandez-Espejo

2004-01-01

291

Basal ganglia dysfunction  

MedlinePLUS

Lang AE. Parkinsonism. In: Goldman L, Schafer AI, eds. Cecil Medicine . 24th ed. Philadelphia, Pa: Saunders Elsevier; ... ed. Philadelphia, Pa: Saunders Elsevier; 2012:chap 71. Lang AE. Other movement disorders. In: Goldman L, SchaferAI, ...

292

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

293

Adenosine A2A Receptor in the Monkey Basal Ganglia: Ultrastructural Localization and Colocalization With the Metabotropic Glutamate Receptor 5 in the Striatum  

PubMed Central

The adenosine A2A receptor (A2AR) is a potential drug target for the treatment of Parkinson’s disease and other neurological disorders. In rodents, the therapeutic efficacy of A2AR modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A2AR localization in the primate basal ganglia and to assess the degree of A2AR/mGluR5 colocalization in the striatum. A2AR immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A2AR immunoreactivity. At the electron microscopic level, striatal A2AR labeling was most commonly localized in postsynaptic elements (58% ± 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% ± 5%) or glial (27% ± 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A2AR immunoreactivity. Striatal A2AR/mGluR5 colocalization was commonly found; 60–70% of A2AR-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A2AR in the primate basal ganglia and demonstrate that A2AR and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A2AR could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism.

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

2012-01-01

294

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

Microsoft Academic Search

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

Mehdi Khamassi; Louis-Emmanuel Martinet; AgnÃs Guillot

2006-01-01

295

The dorsal root ganglia in adrenomyeloneuropathy: neuronal atrophy and abnormal mitochondria.  

PubMed

Adrenomyeloneuropathy (AMN), a disease of spinal cord, brain, adrenal, and testis, mostly affects men with spastic paraparesis or ataxia beginning in their second or third decade. The spinal cord displays bilateral, usually symmetrical, long tract degeneration particularly of the gracile tract in a "dying-back" pattern. The available data strongly indicate that the fundamental lesion in AMN is an axonopathy or neuronopathy. We compared lumbar dorsal root ganglia (DRG) from 3 AMN patients to 6 age-matched controls histologically, morphometrically, immunohistochemically, and ultrastructurally. There was no apparent neuronal loss, necrosis or apoptosis, nor obvious atrophy; nodules of Nageotte were sparse in both groups. The morphometric studies, however, did reveal neuronal atrophy with a decrease in the number of large neurons and a corresponding increase in neurons less than 2,000 microm2, especially in the 1,500-1,999 microm2 range. No consistent immunohistochemical differences were observed, and no specific cell type appeared to be lost. Many mitochondria in the AMN neurons demonstrated lipidic inclusions; this raises the possibility that, in addition to the well-known peroxisomal defect, impaired mitochondrial function may lead to a failure of ATP-dependent axoplasmic transport in AMN spinal tracts with consequent "dying-back" axonal degeneration. The observation that the DRG parent neurons of the degenerate gracile tracts in AMN undergo atrophy and do not display appreciable evidence of cell death, even at autopsy, provides a wide window of opportunity for the development of therapeutic strategies to combat or prevent this myeloneuropathy. PMID:11379824

Powers, J M; DeCiero, D P; Cox, C; Richfield, E K; Ito, M; Moser, A B; Moser, H W

2001-05-01

296

Role of 5-HT2C receptors in the enhancement of c-Fos expression induced by a 5-HT2B/2C inverse agonist and 5-HT 2 agonists in the rat basal ganglia.  

PubMed

Some non-selective serotonin2C (5-HT2C) agonists or inverse agonists enhance the product of the proto-oncogene c-Fos within the basal ganglia, a group of brain regions involved in motor behavior and in the ability of these drugs to promote abnormal movements. The role of 5-HT2C receptors in these effects is unclear. The 5-HT2C antagonist SB243,213 (1 mg/kg), which enhanced Fos per se in the striatum and the subthalamic nucleus (STN) only, was used to study the implication of 5-HT2C receptors. The agonists Ro 60-0175 (3 mg/kg) and m-CPP (1 mg/kg) and the inverse agonist SB206,553 (10 mg/kg) enhanced Fos expression in the STN and faintly in the entopeduncular nucleus (EPN, the internal globus pallidus in primate). The effects of these drugs differed mainly in the striatum regarding the magnitude (m-CPP > Ro 60-0175> SB243,213 > SB206,553) or the striatal quadrants (faint to no labeling in lateral striatum) and in the substantia nigra. None of these compounds enhanced Fos expression by themselves in the globus pallidus or in the EPN when combined with SB243,213. Their Fos effect in the STN was reduced significantly by SB243,213 only in the case of m-CPP. In the ventromedial striatum, SB243,213 reduced the effects of m-CPP while SB206,553 reduced the effects of SB243,213. The results show that opposite pharmacological agents alter similarly Fos expression in the EPN or the STN. Although some of the effects of 5-HT agents are related to targets other than 5-HT2C receptors, the study confirms the existence of multiple 5-HT2C receptor-dependent controls recruited by these drugs upon basal ganglia activity. PMID:23681297

Navailles, S; Lagière, M; Le Moine, C; De Deurwaerdère, P

2013-05-17

297

An evaluation of distinct volumetric and functional MRI contributions toward understanding age and task performance: A study in the basal ganglia  

PubMed Central

Prior work by our group and others has implicated the basal ganglia as important in age-related differences in tasks involving motor response control. The present study used structural and functional MRI approaches to analyze this region of interest (ROI) toward better understanding the contributions of structural and functional MRI measures to understanding age-related and task performance-related cognitive differences. Eleven healthy elders were compared with 11 healthy younger adults while they completed the “go” portion of a complex Go/No-go task. Separate ROI’s in the bilateral caudate (C) and putamen/globus pallidus (PGp) were studied based upon previous findings of age-related functional MRI differences in basal ganglia for this portion of the task. Structural volumes and functional activation (in percent area under the curve during correct responses) were independently extracted for these ROI’s. Results showed that age correlated with ROI volume in bilateral PGp and C, while multiple task performance measures correlated with functional activation in the left PGp. The Go/No-go task measures were also significantly correlated with traditional attention and executive functioning measures. Importantly, fMRI activation and volumes from each ROI were not significantly inter-correlated. These findings suggest that structural and functional MRI make unique contributions to the study of performance changes in aging.

Langenecker, Scott A.; Briceno, Emily M.; Hamid, Najat M.; Nielson, Kristy A.

2007-01-01

298

[Changes in neural networks by conditional transgenic approach: a key to our comprehension of neuro-psychiatric disorders in the basal ganglia system].  

PubMed

The striatum, the first relay of the basal ganglia system, is critically involved in motor functions and motivational processes. The dorsal striatum is central to the motor control and motor learning and the ventral striatum or nucleus accumbens is essential for motivation, the reward system and reinforcement by drugs. This system is dysfunctional in movement disorders such as Parkinson's disease and Huntington's disease and in psychiatric disorders including drug addiction. The striatum consists of two populations of neurons projecting at the origin of two distinct paths in the circuit of basal ganglia, and of different populations of interneurons. These two populations of efferent neurons, striatopallidal and striatonigral neurons, are characterized by their projection sites and their differential expression in dopamine receptors and neuropeptides. Their roles in motor control and motivational processes and in the mechanisms of neuroadaptation in the system's pathologies remain mostly unknown. To identify these specific functions, we have developed new animal models wearing molecular or cell "lesions" by a conditional transgenic approach to target a specific population of neurons. By this approach, we demonstrated the inhibitory role of the population of striatopallidal neurons in the motor control and in the process of drug addiction, identified new genes selectively expressed by striatopallidal neurons that could be the target for future therapies and identified the potential role of this population of neurons disturbances in attention-deficit hyperactivity disorder (ADHD). PMID:20218186

Schiffmann, S N

2009-01-01

299

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

300

Phase Relationships Support a Role for Coordinated Activity in the Indirect Pathway in Organizing Slow Oscillations in Basal Ganglia Output after Loss of Dopamine  

PubMed Central

The goal of the present study was to determine the phase relationships of the slow oscillatory activity that emerges in basal ganglia nuclei in anesthetized rats after dopamine cell lesion in order to gain insight into the passage of this oscillatory activity through the basal ganglia network. Spike train recordings from striatum, subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNpr) were paired with simultaneous local field potential (LFP) recordings from SNpr or motor cortex ipsilateral to a unilateral lesion of substantia nigra dopamine neurons in urethane anesthetized rats. Dopamine cell lesion induced a striking increase in incidence of slow oscillations (0.3-2.5 Hz) in firing rate in all nuclei. Phase relationships assessed through paired recordings using SNpr LFP as a temporal reference showed that slow oscillatory activity in GP spike trains is predominantly antiphase with oscillations in striatum, and slow oscillatory activity in STN spike trains is in-phase with oscillatory activity in cortex but predominantly antiphase with GP oscillatory activity. Taken together, these results imply that after dopamine cell lesion in urethane anesthetized rats, increased oscillatory activity in GP spike trains is shaped more by increased phasic inhibitory input from the striatum than by phasic excitatory input from STN. In addition, results show that oscillatory activity in SNpr spike trains is typically antiphase with GP oscillatory activity and in-phase with STN oscillatory activity. While these observations do not rule out additional mechanisms contributing to the emergence of slow oscillations in the basal ganglia after dopamine cell lesion in the anesthetized preparation, they are compatible with 1) increased oscillatory activity in the GP facilitated by an effect of dopamine loss on striatal ‘filtering’ of slow components of oscillatory cortical input, 2) increased oscillatory activity in STN spike trains supported by convergent antiphase inhibitory and excitatory oscillatory input from GP and cortex, respectively, and 3) increased oscillatory activity in SNpr spike trains organized by convergent antiphase inhibitory and excitatory oscillatory input from GP and STN, respectively.

Walters, Judith R.; Hu, Dan; Itoga, Christy A.; Parr-Brownlie, Louise C.; Bergstrom, Debra A.

2007-01-01

301

Chronic treatment with MPEP, an mGlu5 receptor antagonist, normalizes basal ganglia glutamate neurotransmission in l-DOPA-treated parkinsonian monkeys.  

PubMed

Metabotropic glutamate 5 (mGlu5) receptor antagonists reduce l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesias (LID) in Parkinson's disease (PD). The aim of this study was to investigate the long-term effect of the prototypal mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on glutamate receptors known to be involved in the development of LID in the de novo chronic treatment of monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP monkeys were treated for one month with l-DOPA and developed dyskinesias while those treated with l-DOPA and MPEP (10 mg/kg) developed significantly less. Normal control and saline-treated MPTP monkeys were also included. All MPTP monkeys were extensively and similarly denervated. The basal ganglia [(3)H]ABP688 specific binding (mGlu5 receptors) was elevated in l-DOPA-treated MPTP monkeys compared to controls but not in those treated with l-DOPA and MPEP; dyskinesia scores of these monkeys correlated positively with their [(3)H]ABP688 specific binding. Striatal density (Bmax) of [(3)H]ABP688 specific binding increased in l-DOPA-treated MPTP monkeys compared to other groups and affinity (Kd) remained unchanged. Striatal mGlu5 receptor mRNA remained unchanged following treatments. Elevated basal ganglia specific binding of [(3)H]Ro 25-6981 (NMDA NR1/NR2B receptors), [(3)H]Ro 48-8587 (AMPA receptors) but not [(3)H]CGP-39653 (NMDA NR1/NR2A receptors) was observed only in l-DOPA-treated MPTP monkeys; dyskinesias scores correlated with binding. By contrast, basal ganglia [(3)H]LY341495 specific binding (mGlu2/3 receptors) decreased in l-DOPA-treated MPTP monkeys compared to controls, saline and l-DOPA + MPEP treated MPTP monkeys; dyskinesias scores correlated negatively with this binding. Hence, chronic MPEP treatment reduces the development of LID and is associated with a normalization of glutamate neurotransmission. PMID:23756168

Morin, Nicolas; Morissette, Marc; Grégoire, Laurent; Gomez-Mancilla, Baltazar; Gasparini, Fabrizio; Di Paolo, Thérèse

2013-06-10

302

Fos expression following activation of the ventral pallidum in normal rats and in a model of Parkinson's Disease: implications for limbic system and basal ganglia interactions.  

PubMed

The circuit-related consequences of activating the ventral pallidum (VP) are not well known, and lacking in particular is how these effects are altered in various neuropathological states. To help to address these paucities, this study investigated the brain regions affected by VP activation by quantifying neurons that stain for Fos-like immunoreactivity (ir). Fos-ir was assessed after intra-pallidal injections of the excitatory amino acid agonist, NMDA, or the GABA(A) antagonist, bicuculline in normal rats and in those rendered Parkinsonian-like by lesioning dopaminergic neurons with the neurotoxin, 6-OHDA. We hypothesized that activation of the VP will alter the activity state of brain regions associated with both the basal ganglia and limbic system, and that this influence would be modified in the Parkinsonian state. Blocking tonically activated GABA(A) receptors with bicuculline (50 ng/0.5 microl) elevated Fos-ir in the VP to 423% above the contralateral, vehicle-injected side. Likewise, intra-VP NMDA (0.23 microg or 0.45 microg/0.5 microl), dose-dependently increased the number of pallidal neurons expressing Fos-ir by 224 and 526%, respectively. At higher NMDA doses, the density of Fos-ir neurons was not elevated above control levels. This inverted U-shaped profile was mirrored by a VP output structure, the medial subthalamic nucleus (mSTN). The mSTN showed a 289% increase in Fos-ir neurons with intra-VP injections of 0.45 microg NMDA, and this response was halved following intra-VP injections of 0.9 microg NMDA. Of the 12 other brain regions measured, three showed VP NMDA-induced enhancements in Fos-ir: the frontal cortex, entopeduncular nucleus and substantia nigra pars reticulata, all regions associated with the basal ganglia. In a second study, we evaluated the NMDA activation profile in a rat model of Parkinson's Disease (PD) which was created by a unilateral injection of 6-OHDA into the rostral substantia nigra pars compacta. Comparisons of responses to intra-VP NMDA between the hemispheres ipsilateral and contralateral to the lesion revealed that Fos-ir cells in the pedunculopontine nucleus was reduced by 62%, whereas Fos-ir for the basolateral amygdala and STN was reduced by 32 and 42%, respectively. These findings support the concept that the VP can influence both the basal ganglia and the limbic system, and that that the nature of this influence is modified in an animal model of PD. As the VP regulates motivation and cognition, adaptations in this system may contribute to the mood and mnemonic disorders that can accompany PD. PMID:18663473

Turner, Michael S; Gray, Thackery S; Mickiewicz, Amanda L; Napier, T Celeste

2008-07-29

303

Calcification of basal ganglia and cerebellar roof nuclei in mentally defective patient with hidrotic ectodermal dysplasia. Analysis of intracranial concretions by electon microprobe.  

PubMed

This report describes, for the first time, an analysis by electron microprobe of concretions in the brain of an individual with striopallidodentate calcification. We also report the unique association of this intracranial syndrome with hidrotic ectodermal dysplasia. An institutionalized male with impaired intellectual function and hidrotic ectodermal dysplasia was known since the age of 3 years to have bilateral radiopaque densities in the region of the basal ganglia on skull roentgenogram. He died at age 29 in congestive heart failure from rheumatic pancarditis. At autopsy, concretions were identified in globus pallidus, caudate nuclei, thalamus, and dentate nuclei. Mineral deposits within the brain, analyzed by energy dispersive x-ray microanalysis, consisted predominately of calcium and phosphorus. Trace amounts of magnesium, iron, and silicon also were detected. PMID:562997

Copeland, D D; Lamb, W A; Klintworth, G K

1977-11-01

304

Anti-basal ganglia antibodies and Tourette's syndrome: a voxel-based morphometry and diffusion tensor imaging study in an adult population.  

PubMed

Anti-basal ganglia antibodies (ABGAs) have been suggested to be a hallmark of autoimmunity in Gilles de la Tourette's syndrome (GTS), possibly related to prior exposure to streptococcal infection. In order to detect whether the presence of ABGAs was associated with subtle structural changes in GTS, whole-brain analysis using independent sets of T(1) and diffusion tensor imaging MRI-based methods were performed on 22 adults with GTS with (n = 9) and without (n = 13) detectable ABGAs in the serum. Voxel-based morphometry analysis failed to detect any significant difference in grey matter density between ABGA-positive and ABGA-negative groups in caudate nuclei, putamina, thalami and frontal lobes. These results suggest that ABGA synthesis is not related to structural changes in grey and white matter (detectable with these methods) within frontostriatal circuits. PMID:18303105

Martino, D; Draganski, B; Cavanna, A; Church, A; Defazio, G; Robertson, M M; Frackowiak, R S J; Giovannoni, G; Critchley, H D

2008-02-26

305

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

2013-03-15

306

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

PubMed

Cannabinoid receptor 1 (CB(1) receptor) controls several neuronal functions, including neurotransmitter release, synaptic plasticity, gene expression and neuronal viability. Downregulation of CB(1) 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 CB(1) signaling is thought to contribute to HD symptoms and neurodegeneration. Here we determined whether CB(1) 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 CB(1) expression is downregulated in medium spiny neurons of the indirect pathway, and found that CB(1) is also downregulated in neuropeptide Y (NPY)/neuronal nitric oxide synthase (nNOS)-expressing interneurons while remaining unchanged in parvalbumin- and calretinin-expressing interneurons. CB(1) downregulation in striatal NPY/nNOS-expressing interneurons occurs in R6/2 mice, Hdh(Q150/Q150) mice and the caudate nucleus of patients with HD. In R6/2 mice, CB(1) 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 CB(1) signaling in NPY/nNOS-expressing interneurons could contribute to the impairment of basal ganglia functions linked to HD. PMID:23167744

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

2012-11-21

307

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

PubMed Central

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.

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

2013-01-01

308

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

Microsoft Academic Search

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

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

2006-01-01

309

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

Microsoft Academic Search

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

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

2007-01-01

310

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

SciTech Connect

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

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

1991-06-01

311

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

312

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

PubMed Central

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.

2011-01-01

313

Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.  

PubMed

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

Vuckovi?, Marta G; Wood, Ruth I; Holschneider, Daniel P; Abernathy, Avery; Togasaki, Daniel M; Smith, Alexandra; Petzinger, Giselle M; Jakowec, Michael W

2008-08-05

314

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

Microsoft Academic Search

In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification\\u000a (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally\\u000a examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications\\u000a in six family members

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

315

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

SciTech Connect

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

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

1991-06-01

316

The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for Basal Ganglia models and deep brain stimulation.  

PubMed

The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurologic and psychiatric disorders. Our experiments were designed to demonstrate the existence and organization of prefrontal-STN projections, help delineate the "limbic" STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate, and dorsal prefrontal cortices of Macaca nemestrina and Macaca fascicularis to analyze the organization of terminals and passing fibers in the STN. Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior. PMID:23486951

Haynes, William I A; Haber, Suzanne N

2013-03-13

317

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

318

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

PubMed Central

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

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

2009-01-01

319

Microdialysis in Parkinsonian Patient Basal Ganglia: Acute Apomorphine-Induced Clinical and Electrophysiological Effects Not Paralleled by Changes in the Release of Neuroactive Amino Acids  

Microsoft Academic Search

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

Ernesto Fedele; Paolo Mazzone; Alessandro Stefani; Andrea Bassi; Maria Antonia Ansaldo; Maurizio Raiteri; Maria Grazia Altibrandi; Mariangela Pierantozzi; Patrizia Giacomini; Giorgio Bernardi; Paolo Stanzione

2001-01-01

320

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.  

PubMed

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry. PMID:22745463

Brun, Yohann; Karachi, Carine; Fernandez-Vidal, Sara; Jodoin, Nicolas; Grabli, David; Bardinet, Eric; Mallet, Luc; Agid, Yves; Yelnik, Jerome; Welter, Marie-Laure

2012-06-27

321

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

322

Functional anatomy of thalamus and basal ganglia  

Microsoft Academic Search

Thalamus. The human thalamus is a nuclear complex located in the diencephalon and comprising of four parts (the hypothalamus, the epythalamus, the ventral thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one or a few well-defined cortical areas. Multiple cortical areas receive afferents from a

María-Trinidad Herrero; Carlos Barcia; Juana Mari Navarro

2002-01-01

323

Cortico-Basal Ganglia Reward Network: Microcircuitry  

Microsoft Academic Search

Many of the brain's reward systems converge on the nucleus accumbens, a region richly innervated by excitatory, inhibitory, and modulatory afferents representing the circuitry necessary for selecting adaptive motivated behaviors. The ventral subiculum of the hippocampus provides contextual and spatial information, the basolateral amygdala conveys affective influence, and the prefrontal cortex provides an integrative impact on goal-directed behavior. The balance

Susan R Sesack; Anthony A Grace; AA Grace

2010-01-01

324

White matter abnormalities in dystonia normalize after botulinum toxin treatment  

PubMed Central

The pathophysiology of dystonia is still poorly understood. We used diffusion tensor imaging to screen for white matter abnormalities in regions between the basal ganglia and the thalamus in cervical and hand dystonia patients. All patients exhibited an abnormal hemispheric asymmetry in a focal region between the pallidum and the thalamus. This asymmetry was absent 4 weeks after the same patients were treated with intramuscular botulinum toxin injections. These findings represent a new systems-level abnormality in dystonia, which may lead to new insights about the pathophysiology of movement disorders. More generally, these findings demonstrate central nervous system changes following peripheral reductions in muscle activity. This raises the possibility that we have observed activity-dependent white matter plasticity in the adult human brain.

Blood, Anne J.; Tuch, David S.; Makris, Nikos; Makhlouf, Miriam L.; Sudarsky, Lewis R.; Sharma, Nutan

2011-01-01

325

Extragenic bypass suppressors of mutations in the essential gene BLD2 promote assembly of basal bodies with abnormal microtubules in Chlamydomonas reinhardtii.  

PubMed Central

bld2-1 mutant Chlamydomonas reinhardtii strains assemble basal bodies with singlet microtubules; bld2-1 cells display flagellar assembly defects as well as positioning defects of the mitotic spindle and cleavage furrow. To further understand the role of the BLD2 gene, we have isolated three new bld2 alleles and three partially dominant extragenic suppressors, rgn1-1, rgn1-2, and rgn1-3. bld2 rgn1-1 strains have phenotypes intermediate between those of bld2 and wild-type strains with respect to flagellar number, microtubule rootlet organization, cleavage furrow positioning, and basal body structural phenotypes. Instead of the triplet microtubules of wild-type cells, bld2 rgn1-1 basal bodies have mixtures of no, singlet, doublet, and triplet microtubules. The bld2-4 allele was made by insertional mutagenesis and identified in a noncomplementation screen in a diploid strain. The bld2-4 allele has a lethal phenotype based on mitotic segregation in diploid strains and in haploid strains generated by meiotic recombination. The lethal phenotype in haploid strains is suppressed by rgn1-1; these suppressed strains have similar phenotypes to other bld2 rgn1-1 double mutants. It is likely that BLD2 is an essential gene that is needed for basal body assembly and function.

Preble, A M; Giddings, T H; Dutcher, S K

2001-01-01

326

Humanized Foxp2 specifically affects cortico-basal ganglia circuits  

Microsoft Academic Search

It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution and influence aspects of speech and language. Recently it was shown that when these substitutions are introduced into the endogenous Foxp2 gene of mice, they increase dendrite length and long-term depression (LTD) in medium spiny neurons of the striatum.

S. Reimers-Kipping; W. Hevers; S. Pääbo; W. Enard

2011-01-01

327

Dissociations in Processing Derivational Morphology: The Right Basal Ganglia Involvement  

ERIC Educational Resources Information Center

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

Marangolo, Paola; Piras, Fabrizio

2008-01-01

328

Developmental aspects of the basal ganglia and therapeutic perspectives.  

PubMed

Development and sex hormones play an important role in the expression of seizures. Sex-specific differences in the development of seizure suppressing neuronal networks may account, at least in part, for age- and sex related susceptibility to seizures. The substantia nigra pars reticulata is a site involved in the control of seizures. In adult male rats, there are two distinct GABAA sensitive regions within the substantia nigra pars reticulata, which mediate opposite effects in flurothyl seizures. Muscimol infused into the anterior region is anticonvulsant while similar infusions into the posterior region are proconvulsant. These two regions differ morphologically, and utilize different efferent networks. In contrast, in postnatal day 15 male rats, there is no such differentiation and muscimol infusions have only proconvulsant effects. The hallmark of the female substantia nigra pars reticulata is the fact that muscimol- mediated proconvulsant effects cannot be demonstrated in any region at any age. The sex-related difference in nigral seizure control may be related to the lack of testosterone in females. Accordingly, neonatal castration of males results in the loss of the proconvulsant region. The male type of the substantia nigra pars reticulata effects can be induced by exogenous testosterone administration in neonatally castrated male or in female rats. The phenotype of nigral GABAergic neurons, as characterized by GABAA receptor subunit composition, muscimol-induced electrophysiological responses, and connectivity of output networks may each be altered by the presence of testosterone. Better understanding of the influence of the endocrine system on brain development and neuronal activity may provide new insight into the treatment of age- and sex-dependent seizure disorders. PMID:12495877

Velísková, Jana; Claudio, Olga I; Galanopoulou, Aristea S; Kyrozis, Andreas; Lado, Fred A; Ravizza, Teresa; Velísek, Libor; Moshé, Solomon L

2002-12-01

329

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems  

Microsoft Academic Search

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion.First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas,

Jeremy D. Schmahmann; Deepak N. Pandya

2008-01-01

330

Dopamine visualized in the basal ganglia of living man  

Microsoft Academic Search

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease1, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of

E. S. Garnett; G. Firnau; C. Nahmias

1983-01-01

331

Basal Ganglia Hypermetabolism and Symptoms of Fatigue during Interferon-? Therapy  

Microsoft Academic Search

Interferon (IFN)-? is a cytokine of the innate immune response that is well known for inducing behavioral alterations and has been used to study effects of cytokines on the nervous system. Limited data, however, are available on the sites of action of IFN-? within the brain and their relationship with specific IFN-?-induced symptoms. Using a longitudinal design, whole-brain metabolic activity

Lucile Capuron; Giuseppe Pagnoni; Marina F Demetrashvili; David H Lawson; Fiona B Fornwalt; Bobbi Woolwine; Gregory S Berns; Charles B Nemeroff; Andrew H Miller

2007-01-01

332

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

333

Neural Correlates of Anticipation in Cerebellum, Basal Ganglia, and Hippocampus  

Microsoft Academic Search

Animals anticipate the future in a variety of ways. For instance: (a) they make motor actions that are timed to a reference\\u000a stimulus and motor actions that anticipate future movement dynamics; (b) they learn to make choices that will maximize reward\\u000a they receive in the future; and (c) they form memories of behavioral episodes such that the animal’s future actions

Jason G. Fleischer; John Jay

2006-01-01

334

Synaptic Transmission in Sympathetic Ganglia.  

National Technical Information Service (NTIS)

Properties of the atropine-sensitive slow synaptic responses in mammalian sympathetic ganglia were further analysed as to their 1) postsynaptic origin, 2) transmitter substances, and 3) durations of synaptic delays for each. Intracellular studies on singl...

B. Libet

1965-01-01

335

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

336

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

PubMed Central

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

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

2010-01-01

337

Physiology of mammalian prevertebral ganglia.  

PubMed

When assessing the physiological role of the prevertebral ganglia, the following should be considered. Ganglion cells in these ganglia receive continuous excitatory synaptic input from peripheral sensory mechanoreceptors and central preganglionic neurons. The latter may result from sensory afferents projecting from the gastrointestinal tract to spinal preganglionic neurons or as a result of endogenous oscillator activity located in the spinal cord (18) or within the ganglion (45). Peripheral and spinal reflex pathways probably do not operate as separate, independent pathways. Rather, they must be considered functionally integrated in the prevertebral ganglia. Because of continuous synaptic input, the prevertebral neuron operates at some level of "neurogenic tone" that provides capabilities for bi-directional responses. An increase in spinal or peripheral synaptic input will be matched by a proportional increase in output firing. The functional effect of spatial summation of peripheral and central input is to prime the prevertebral neuron so that adjustments in its firing frequency can be made without the lag inherent in building up a response in a quiescent system. Not all prevertebral ganglia participate in reflex activity. It may be that reflex activity between prevertebral ganglia and visceral smooth muscle depends upon the nature of the mechanical activity of the muscle. For example, the mechanical activity of smooth muscle of the vas deferens is not characterized by spontaneous, myogenic, regularly occurring contractions. Mechanical activity in this organ occurs in bursts. There is no evidence to suggest that sensory fibers project from the wall of the vas deferens to the hypogastric plexus thereby forming a peripheral reflex arc. Contraction of th smooth muscle of the vas deferens is brought about by bursts of nerve impulses through simple relay connections in the pelvic plexus. Smooth muscles supplied by this ganglion have a direct line to the central nervous system and are secured by a "fail-safe" system. In contrast, the mechanical activity of the gastrointestinal system is characterized by slow spontaneous myogenic activity. Pattern formation of motor activity is achieved by reflex activity within the enteric plexuses. Extrinsic alteration of the nature and pattern of contraction of smooth muscle of the gastrointestinal tract would be best served by prevertebral ganglia that modulate and adjust motor function by continuous integration of convergent weak synaptic input emanating from the peripheral and central nervous systems. When a prevertebral neuron is part of a peripheral reflex loop, its physiological role may be to modulate end organ activity; when it does not participate in a peripheral reflex loop, its role may be to relay CNS input and initiate end organ activity. PMID:6260023

Szurszewski, J H

1981-01-01

338

Fifty percent reduced-dose cerebral CT perfusion imaging of Alzheimer's disease: regional blood flow abnormalities.  

PubMed

To evaluate the value of 50% reduced-dose cerebral computed tomography (CT)perfusion imaging (CTPI) to show the perfusion abnormalities in Alzheimer's disease (AD), as an attempt to develop a new imaging protocol with lower radiation dose to track the correlation of AD with regional blood flow abnormalities. A total of 52 patients with AD were assigned to the AD group and 28 healthy volunteers served as the control group. All participants were given a 50% reduced-dose cerebral CTPI (current was reduced from 160 to 80 mA) test by a multislice spiral CT scanner. Perfusion parameters of the bilateral frontal cortex, temporal cortex, hippocampus, and basal ganglia were measured, including the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). Both the CBV and CBF values of the measured regions were significantly higher in the healthy control group than in the AD group (P < .05), while the MTT and TTP values of these cerebral areas were significantly lower in the healthy control group than in the AD group (P < .05). Four perfusion parameters, namely the MTT of the left frontal cortex, right temporal cortex, right basal ganglia, and right hippocampus, had the greatest sensitivity and a striking correlation with the incidence of AD. The blood flow per unit of time in the regions of interest was significantly lower in the AD group, which provides new evidence for the existence of microcirculation disturbance and ischemia in AD. The 50% reduced-dose cerebral CTPI scan is valuable to show the regional perfusion abnormalities in the patients with AD. PMID:22615483

Tang, Zhen; Pi, Xiaoling; Chen, Feng; Shi, Linghua; Gong, Haiting; Fu, Hongmei; Qu, Zhengwan

2012-05-20

339

[Traumatic basal subarachnoid hemorrhage].  

PubMed

Massive subarachnoid hemorrhage may occur on a traumatic basis. The injury is most often sustained by a blow with a clenched fist against the posterolateral part of the cranial basis, but the injury may also occur in relation to an accident. The condition is rare, most often occurring in alcohol intoxicated men. The victim typically collapses immediately and usually dies within a few minutes. The origin of the bleeding may be the vertebral artery on the neck or the intercranial basal brain arteries. In some cases the origin of the bleeding cannot be located. The pathogenetic mechanisms have been a subject of discussion. The damage to the artery may occur in relation to a fracture of the transverse process of the atlas or in relation to subluxations in the cervical vertebral column. The arterial rupture may occur in both normal and abnormal arteries. In many of the cases the trauma may be very slight. This has, of course, important legal implications. PMID:12772392

Lundgaard, Peter; Leth, Peter Mygind; Gregersen, Markil

2003-04-28

340

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

341

Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.  

PubMed

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 [(11)C]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. PMID:24027271

Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

2013-09-11

342

[Changes in the adrenergic structures of the human stellate ganglia in pathological states].  

PubMed

Stellate ganglia from patients who had succumbed to various diseases were examined by a fluorescent histochemical technique using 2% glyoxylic acid. Catecholamines were detectable in the major neurons, in small intensely fluorescent cells, and in adrenergic fibers with varicosities at levels that varied with the patient's age, cause of death, duration of the agonal period, the treatment administered, and the time when the material had been taken after death. All adrenergic structures of the ganglia were clearly demonstrable after early autopsies of those who had died suddenly from pulmonary artery thromboembolism in the absence of other abnormalities. The ganglia were found to be greatly depleted of catecholamines in cases of sudden cardiac death in the presence of ischemic heart disease before the development of myocardial infarction as well as in those of rapid death from stroke. PMID:3446109

Amvros'ev, A P; Rogov, Iu I

1987-01-01

343

Antibasal Ganglia Antibodies and Antistreptolysin O in Noncomorbid ADHD.  

PubMed

Objective: An association between streptococcal infections, ABGA positivity, and no comorbidity ADHD (nc-ADHD) has been little investigated. The aim of this study was to evaluate the streptococcal infection frequency, defined entitled serum antistreptolysin O (ASO), and frequency of serum ABGA positivity in a sample of patients with nc-ADHD. Method: In all 40 participants were investigated the ASO titer and ABGA. Results: The results showed that ABGA positivity was statistically significantly higher in patients affected by ADHD than in patients of a control group, and pathological values of ASO were statistically more frequent in the ADHD group than the control group. Conclusion: These data suggest that streptococcal infections and autoimmune reactions against the basal ganglia are more frequent in ADHD patients than patients in a control group. PMID:22956712

Toto, Maddalena; Margari, Francesco; Simone, Marta; Craig, Francesco; Petruzzelli, Maria Giuseppina; Tafuri, Silvio; Margari, Lucia

2012-09-24

344

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities.  

PubMed

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p=0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p=0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention. PMID:23787273

Cianfoni, A; Caulo, M; Cerase, A; Della Marca, G; Falcone, C; Di Lella, G M; Gaudino, S; Edwards, J; Colosimo, C

2013-06-17

345

Basal Cell Carcinoma (BCC)  

MedlinePLUS

... technique is particularly useful for basal cell carcinomas located on the nose, the ears, and the lips. ... technique is particularly useful for basal cell carcinomas located on the nose, the ears, and the lips. ...

346

Growth Basal Area Handbook.  

National Technical Information Service (NTIS)

Growth basal area (GBA) is that basal area at which dominant trees grow at 1.0 inch in diameter per decade at age 100. Diameter growth rate of 1.0 inch per decade is a constant used to compare sites; basal area is a variable used to express stockability. ...

F. C. Hall

2003-01-01

347

Abnormal posturing  

MedlinePLUS

People with abnormal posturing almost always have reduced consciousness. Anyone who shows symptoms of abnormal posturing should ... Elsevier; 2008:chap 5. Bleck T. Levels of consciousness and attention. In: Goetz, CG, ed. Textbook of ...

348

Walking abnormalities  

MedlinePLUS

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

349

Abuse of Amphetamines and Structural Abnormalities in Brain  

PubMed Central

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 that include 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.

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

2009-01-01

350

Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.  

PubMed

Resting state functional brain networks have been widely studied in brain disease research. However, it is currently unclear whether abnormal resting state functional brain network metrics can be used with machine learning for the classification of brain diseases. Resting state functional brain networks were constructed for 28 healthy controls and 38 major depressive disorder patients by thresholding partial correlation matrices of 90 regions. Three nodal metrics were calculated using graph theory-based approaches. Nonparametric permutation tests were then used for group comparisons of topological metrics, which were used as classified features in six different algorithms. We used statistical significance as the threshold for selecting features and measured the accuracies of six classifiers with different number of features. A sensitivity analysis method was used to evaluate the importance of different features. The result indicated that some of the regions exhibited significantly abnormal nodal centralities, including the limbic system, basal ganglia, medial temporal, and prefrontal regions. Support vector machine with radial basis kernel function algorithm and neural network algorithm exhibited the highest average accuracy (79.27 and 78.22%, respectively) with 28 features (P<0.05). Correlation analysis between feature importance and the statistical significance of metrics was investigated, and the results revealed a strong positive correlation between them. Overall, the current study demonstrated that major depressive disorder is associated with abnormal functional brain network topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms. PMID:23044496

Guo, Hao; Cao, Xiaohua; Liu, Zhifen; Li, Haifang; Chen, Junjie; Zhang, Kerang

2012-12-01

351

Abnormal low frequency drive in myoclonus-dystonia patients correlates with presence of dystonia.  

PubMed

The pathophysiology of Myoclonus-Dystonia (M-D), an autosomal dominantly inherited movement disorder is largely unknown. In different forms of dystonia abnormal intermuscular coherence is present. The objective of this study was to investigate whether the myoclonic and dystonic features are the result of an abnormal common drive to the muscles in M-D. Coherence analysis was performed in 20 DYT11 mutation carriers (MC) and 13 healthy controls during resting condition and during weak isometric contraction of the arm and neck. The EMG-EMG coherence analysis showed significantly increased intermuscular 3 to 10 Hz coherence in 4 DYT11 MC with clinical pronounced (mobile and static) dystonia. This coherence was not present in DYT11 MC with mild (static) dystonia and/or predominating myoclonus. The EEG-EMG analysis showed significant 15 to 30 Hz coherence during weak isometric contraction of the arm in five healthy controls, but in none of the DYT11 MC. The intermuscular coherence in the low frequency band in DYT11 MC with predominant dystonia is concordant with the previously described coherence in dystonia and suggests that the pathophysiology of M-D shares common pathophysiological features with dystonia. The absence of 15 to 30 Hz EEG-EMG coherence in DYT11 MC may reflect abnormal motor activation caused by an altered cortical drive because of the basal ganglia dysfunction. PMID:17486590

Foncke, Elisabeth M J; Bour, Lo J; van der Meer, Johan N; Koelman, Johannes H T M; Tijssen, Marina A J

2007-07-15

352

White matter abnormalities in gene-positive myoclonus-dystonia.  

PubMed

Myoclonus-dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic movements of the upper body. Functional imaging and structural gray matter imaging studies in M-D suggest defective sensorimotor integration and an association between putaminal volume and severity of dystonia, possibly because of neuronal plasticity. As we expect changes in the connections between the cortical and subcortical regions, we performed a combination of white matter voxel-based morphometry (wVBM) and diffusion tensor imaging (DTI) to detect macro- and microstructural white matter changes, respectively, in DYT-11 mutations carriers (M-D). Sixteen clinically affected DYT-11 mutation carriers and 18 control subjects were scanned with 3-Tesla MRI to compare white matter volume, fractional anisotropy, and mean diffusivity between groups. In DYT11 mutation carriers, increased white matter volume and FA and decreased mean diffusivity were found in the subthalamic area of the brain stem, including the red nucleus. Furthermore, decreased mean diffusivity was found in the subgyral cortical sensorimotor areas. The white matter changes found in the subthalamic area of the brain stem, connecting the cerebellum with the thalamus, are compatible with the hypothesis that abnormal function in M-D involves a network that includes the cerebellum, brain stem, and basal ganglia. Whether these changes are causative or an effect of M-D requires further study. PMID:23114862

van der Meer, Johan N; Beukers, Richard J; van der Salm, S M A; Caan, Matthan W A; Tijssen, Marina A J; Nederveen, Aart J

2012-10-31

353

Abnormal temporal dynamics of visual attention in spatial neglect patients.  

PubMed

When we identify a visual object such as a word or letter, our ability to detect a second object is impaired if it appears within 400ms of the first. This phenomenon has been termed the attentional blink or dwell time and is a measure of our ability to allocate attention over time (temporal attention). Patients with unilateral visual neglect are unaware of people or objects contralateral to their lesion. They are considered to have a disorder of attending to a particular location in space (spatial attention). Here we examined the non-spatial temporal dynamics of attention in patients, using a protocol for assessing the attentional blink. Neglect patients with right parietal, frontal or basal ganglia strokes had an abnormally severe and protracted attentional blink When they identified a letter, their awareness of a subsequent letter was significantly diminished for a length of time that was three times as long as for individuals without neglect. Our results demonstrate for the first time that visual neglect is a disorder of directing attention in time, as well as space. PMID:8990117

Husain, M; Shapiro, K; Martin, J; Kennard, C

1997-01-01

354

Noradrenergic innervation of rabbit pancreatic ganglia  

Microsoft Academic Search

Sympathetic nerve stimulation indirectly regulates pancreatic endocrine and exocrine secretion, in part, through actions on the cholinergic parasympathetic innervation of the secretory tissues. Earlier work identified noradrenergic nerves in pancreatic ganglia and demonstrated the effects of exogenous norepinephrine (NE) on synaptic transmission but no quantitative studies of ganglionic NE content and release exist. Therefore, the distribution and density of catecholamine

Eunyoung Yi; Tina G. Smith; Jeffrey A. Love

2005-01-01

355

ARTHROSCOPIC RESECTION OF DORSAL WRIST GANGLIA AND TREATMENT OF RECURRENCES  

Microsoft Academic Search

From 1995 to 1998, 30 patients with dorsal wrist ganglia and four with recurrent dorsal ganglia underwent arthroscopic resection. At a mean follow-up of 16 months, no complications were seen, but minimal pain persisted in three patients. Two recurrences were seen after arthroscopic resection of primary ganglia.

R. LUCHETTI; A. BADIA; M. ALFARANO; J. ORBAY; I. INDRIAGO; B. MUSTAPHA

2000-01-01

356

Craniofacial Abnormalities  

MedlinePLUS

... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

357

Congenital Abnormalities  

MedlinePLUS

... only. Girls may carry the abnormal gene that causes these disorders but not show the actual disease. (Examples of this problem include hemophilia, color blindness, and the common forms of muscular ...

358

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

PubMed

Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. "What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia?" and "how do tissue or nerve injuries affect the communication?" are the main questions addressed in this review. GLIA 2013;61:1571-1581. PMID:23918214

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

2013-08-05

359

Basal Cell Carcinoma  

MedlinePLUS

... forms on skin that has received years of sun exposure. Basal cell carcinoma (BCC) is the most common ... skin cancer usually develops on skin that gets sun exposure, such as on the head, neck, and back ...

360

Amphibian sympathetic ganglia in tissue culture  

Microsoft Academic Search

1.A culture medium has been developed for amphibian sympathetic nervous tissue but it is suggested that the ionic values should be adjusted to correspond to the concentrations of salts in the plasma of particular species.2.The morphology, monoamine fluorescence, growth and differentiation of sympathetic ganglia of the frog, Limnodynastes dumerili, have been studied in culture.3.Two types of neuron could be distinguished

C. E. Hill; G. Burnstock

1975-01-01

361

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

362

Abnormal Plasminogen  

PubMed Central

A patient who suffered a recurring thrombosis over the last 15 yr has been investigated. The only abnormality found in this patient was a significantly depressed level of plasminogen activity in plasma. In spite of the depressed plasminogen activity, the patient was found to have a normal level of plasminogen antigen concentration. It was calculated that the activity per milligram of plasminogen of the patient was approximately one-half the values of normal subjects. The same discrepancy between biological activity and antigen concentration was found in the other members of the kindred. A niece was found to have practically no plasminogen activity but possessed a normal concentration of plasminogen antigen. Both her parents were found to have approximately half the normal plasminogen activity and normal antigen levels. These studies suggested that the molecular abnormality was inherited as an autosomal characteristic, and the family members who had half the normal levels of activity with normal plasminogen antigen were heterozygotes whereas the one with practically no plasminogen activity was homozygote. Subsequent studies showed that the pattern of gel electrofocusing of purified plasminogen of the heterozygotes consisted of 10 normal bands and 10 additional abnormal bands, each of which had a slightly higher isoelectric point than each corresponding normal component. This indicates that plasminogen of the heterozygote is a mixture of normal and abnormal molecules in an approximately equal amount, which was substantiated by active site titration of purified plasminogen preparations obtained from the propositus and a normal individual. The gel electrofocusing pattern of the homozygote consisted of abnormal bands only. The defect is a hereditary abnormality of plasminogen. Images

Aoki, Nobuo; Moroi, Masaaki; Sakata, Yoichi; Yoshida, Nobuhiko; Matsuda, Michio

1978-01-01

363

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., &…

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

2008-01-01

364

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

Microsoft Academic Search

Most daily tasks are performed almost automatically, but occasionally it is necessary to alter a routine if something changes in the environment and the routine behavior becomes inappropriate. Such behavioral switching can occur either retroactively based on error feedback or proactivelybydetectingacontextualcue.Recentimaging and electrophysiological data in humans and monkeys supporttheviewthatthefrontalcorticalareasplayexecu- tive roles in behavioral switching. The anterior cingulate cortex acts retroactively

Okihide Hikosaka; Masaki Isoda

2010-01-01

365

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

Microsoft Academic Search

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

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

2007-01-01

366

Basal ganglia phantom simulation: improvement of relative quantitation in SPECT [I-123] dynamic neuroreceptor imaging  

Microsoft Academic Search

[I-123] labeled radiopharmaceuticals are being used to study neuroreceptor in monkey and human brain with a triple headed SPECT system. To optimize quantitative accuracies in monkey dynamic neuroreceptor studies, a combination of collimators (high-resolution fan-beam collimators (HRF), ultrahigh-resolution fan-beam collimators (UHRF)) with various filters including a Butterworth filtering, a count rate dependent 2-D Wiener (2-DW) prefiltering, 3-D Wiener postfiltering techniques

Hee-Joung Kim; Will McElgin; P. David Mozley; Hank F Kung

1994-01-01

367

Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice  

Microsoft Academic Search

BackgroundMethylphenidate (MPH) is a psychostimulant that exerts its pharmacological effects via preferential blockade of the dopamine transporter (DAT) and the norepinephrine transporter (NET), resulting in increased monoamine levels in the synapse. Clinically, methylphenidate is prescribed for the symptomatic treatment of ADHD and narcolepsy; although lately, there has been an increased incidence of its use in individuals not meeting the criteria

Shankar Sadasivan; Brooks B. Pond; Amar K. Pani; Chunxu Qu; Yun Jiao; Richard J. Smeyne

2012-01-01

368

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

ERIC Educational Resources Information Center

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

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

2010-01-01

369

Dysfunction of the basal ganglia, but not the cerebellum, impairs kinaesthesia  

Microsoft Academic Search

Summary Precise knowledge about limb position and orientation is essential for the ability of the nervous system to plan and control voluntary movement. While it is well established that proprioceptive signals from peripheral receptors are necessary for sensing limb position and motion, it is less clear which supraspinal structures mediate the sig- nals that ultimately lead to the conscious awareness

Matthias Maschke; Christopher M. Gomez; Paul J. Tuite; Jurgen Konczak

2003-01-01

370

Exploring neurocircuitries of the basal ganglia by intracerebral administration of selective neurotoxins  

Microsoft Academic Search

The detailed anatomy of the monoamine pathways of the rat, first described by the students of Nils-Åke Hillarp in Sweden,\\u000a provided the basis for a neurocircuitry targeted pharmacology, leading to important therapeutic breakthroughs. Progress was\\u000a achieved by the introduction of accurate lesion techniques based on selective neurotoxins. Systematic intracerebral injections\\u000a of 6-hydroxydopamine let Urban Ungerstedt at the Karolinska Institutet, Stockholm,

Mario Herrera-Marschitz; Diego Bustamante; Paola Morales; Michel Goiny

2007-01-01

371

Long-Term Potentiation in an Avian Basal Ganglia Nucleus Essential for Vocal Learning  

Microsoft Academic Search

Vocal learning in songbirds provides an excellent model for sensorimotor learning in vertebrates, with an accessible, well-defined behavior and discrete neural substrate. The rich behavioral plasticity exhibited by songbirds, however, contrasts starkly with the scarcity of candidate cellular mechanisms. Here, we report for the first time on an activity-dependent form of synaptic plasticity in area X, a component of the

Long Ding; David J. Perkel

2004-01-01

372

Preliminary observation of elevated levels of nanocrystalline iron oxide in the basal ganglia of neuroferritinopathy patients  

PubMed Central

Magnetometry analysis of brain tissue sub-samples from two neuroferritinopathy patients provides a preliminary indication that the amount of magnetic iron compounds associated with this rare disease is significantly larger than in age/sex-matched controls from the same region of the brain. The primary iron compounds contributing to the remanant magnetization of the tissue above 50 K and at body temperature, are both blocked and superparamagnetic (SPM) biogenic magnetite (Fe3O4) and/or maghemite (?-Fe2O3). The concentration of SPM magnetite is significant and appears to be proportional to the concentration of ferritin, which varies with progression of the disease. The mutated ferritin protein appears to be responsible for the presence of iron oxide nano-particules, which in turn could be responsible for extensive damage in the brain.

Hautot, Dimitri; Pankhurst, Quentin A.; Morris, Chris M.; Curtis, Andrew; Burn, John; Dobson, Jon

2007-01-01

373

Preliminary observation of elevated levels of nanocrystalline iron oxide in the basal ganglia of neuroferritinopathy patients.  

PubMed

Magnetometry analysis of brain tissue sub-samples from two neuroferritinopathy patients provides a preliminary indication that the amount of magnetic iron compounds associated with this rare disease is significantly larger than in age/sex-matched controls. The primary iron compounds contributing to the remnant magnetization of the tissue above 50 K and at body temperature are both blocked and superparamagnetic (SPM) biogenic magnetite (Fe3O4) and/or maghemite (gamma-Fe2O3). The concentration of SPM magnetite is significant and appears to be proportional to the concentration of ferritin, which varies with progression of the disease. The mutated ferritin protein appears to be responsible for the presence of iron oxide nano-particules, which in turn could be responsible for extensive damage in the brain. PMID:17097860

Hautot, Dimitri; Pankhurst, Quentin A; Morris, Chris M; Curtis, Andrew; Burn, John; Dobson, Jon

2006-10-06

374

Reduced basal ganglia ?-opioid receptor availability in trigeminal neuropathic pain: A pilot study  

PubMed Central

Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional ?-opioid receptor (?OR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the ?OR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced ?OR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the ?OR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous ?-opioid system, rather than only to the peripheral pathology. The decreased availability of ?ORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

2012-01-01

375

Projections from the primary somatosensory cortex to basal ganglia and thalamus in the monkey  

Microsoft Academic Search

Radioactive amino acids were injected into the postcentral cortex (areas 3, 1 and 2) in 6 monkeys (Macaca fascicularis). Fibers were traced to the ipsilateral putamen, to Olszewski's n. ventralis posterior lateralis pars caudalis, n. ventralis posterior medialis and inferior, to n. pulvinaris oralis, n. suprageniculatus and corpus geniculatum mediale pars magnocellularis. Furthermore, there were faint postcentral projections to claustrum,

H. Künzle

1977-01-01

376

Dopamine-Angiotensin interactions in the basal ganglia and their relevance for Parkinson's disease.  

PubMed

Renin-angiotensin systems are known to act in many tissues, for example, the blood vessel wall or kidney, where a close interaction between angiotensin and dopamine has been demonstrated. Regulatory interactions between the dopaminergic and renin-angiotensin systems have recently been described in the substantia nigra and striatum. In animal models, dopamine depletion induces compensatory overactivation of the local renin-angiotensin system, which primes microglial responses and neuron vulnerability by activating NADPH-oxidase. Hyperactivation of the local renin-angiotensin system exacerbates the inflammatory microglial response, oxidative stress, and dopaminergic degeneration, all of which are inhibited by angiotensin receptor blockers and inhibitors of angiotensin-converting enzymes. In this review we provide evidence suggesting that the renin-angiotensin system may play an important role in dopamine's mediated neuroinflammation and oxidative stress changes in Parkinson's disease. We suggest that manipulating brain angiotensin may constitute an effective neuroprotective strategy for Parkinson's disease. © 2013 International Parkinson and Movement Disorder Society. PMID:23925977

Labandeira-Garcia, Jose L; Rodriguez-Pallares, Jannette; Dominguez-Meijide, Antonio; Valenzuela, Rita; Villar-Cheda, Begoña; Rodríguez-Perez, Ana I

2013-08-07

377

Conditional visuo-motor learning in primates: a key role for the basal ganglia  

Microsoft Academic Search

Sensory guidance of behavior often involves standard visuo-motor mapping of body movements onto objects and spatial locations. For example, looking at and reaching to grasp a glass of wine requires the mapping of the eyes and hand to the location of the glass in space, as well as the formation of a hand configuration appropriate to the shape of the

Fadila Hadj-Bouziane; Martine Meunier; Driss Boussaoud

2003-01-01

378

Indirect basal ganglia pathway mediation of repetitive behavior: Attenuation by adenosine receptor agonists  

Microsoft Academic Search

Repetitive behaviors are diagnostic for autism and common in related neurodevelopmental disorders. Despite their clinical importance, underlying mechanisms associated with the expression of these behaviors remain poorly understood. Our lab has previously shown that the rates of spontaneous stereotypy in deer mice (Peromyscus maniculatus) were negatively correlated with enkephalin content, a marker of striatopallidal but not striatonigral neurons. To investigate

Yoko Tanimura; Sasha Vaziri; Mark H. Lewis

2010-01-01

379

The influence of excitotoxic basal ganglia lesions on motor performance in the common marmoset  

Microsoft Academic Search

Summary Huntington's disease is a genetically inherited neurodegenerative disorder for which currently there is no effective treatment or cure. In order to gauge the potential therapeutic benefits of neuroprotective or restorative treatments, it is necessary to create an animal model that is associated with readily measurable and long-lasting functional impairments. The undifferentiated neostriatum and limited behavioural repertoire of rodents have

A. Lisa Kendall; F. David; G. Rayment; Eduardo M. Torres; Lucy E. Annett; Stephan B. Dunnett

2000-01-01

380

Basal Ganglia Activity in Pathological Gambling: A Fluorodeoxyglucose-Positron Emission Tomography Study  

Microsoft Academic Search

Background: Pathological gambling (PG) is a disorder classified as an impulse control disorder (DSM-IV) bridging impulsive, compulsive and addictive behaviors. The striatum and thalamus are supposed to be involved in the pathophysiological substrate of these behaviors. An increased relative glucose metabolic rate (rGMR) in patients with a diagnosis of PG had previously been reported in the medial and orbitofrontal cortex.

Stefano Pallanti; M. Mehmet Haznedar; Eric Hollander; Elizabeth M. LiCalzi; Silvia Bernardi; Randall Newmark; Monte S. Buchsbaum

2010-01-01

381

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

382

Hierarchical learning induces two simultaneous, but separable, prediction errors in human basal ganglia.  

PubMed

Studies suggest that dopaminergic neurons report a unitary, global reward prediction error signal. However, learning in complex real-life tasks, in particular tasks that show hierarchical structure, requires multiple prediction errors that may coincide in time. We used functional neuroimaging to measure prediction error signals in humans performing such a hierarchical task involving simultaneous, uncorrelated prediction errors. Analysis of signals in a priori anatomical regions of interest in the ventral striatum and the ventral tegmental area indeed evidenced two simultaneous, but separable, prediction error signals corresponding to the two levels of hierarchy in the task. This result suggests that suitably designed tasks may reveal a more intricate pattern of firing in dopaminergic neurons. Moreover, the need for downstream separation of these signals implies possible limitations on the number of different task levels that we can learn about simultaneously. PMID:23536092

Diuk, Carlos; Tsai, Karin; Wallis, Jonathan; Botvinick, Matthew; Niv, Yael

2013-03-27

383

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

384

Physiology of the normal and dopamine-depleted basal ganglia: insights into levodopa pharmacotherapy.  

PubMed

Dopamine (DA) neurons exist in two activity states; either spontaneously firing or quiescent and nonfiring. When faced with a behavioral demand, the quiescent DA neurons can be activated to facilitate normal motor output. Levodopa appears to increase DA output by activating these nonfiring neurons; as a consequence, DA release is increased, but behavioral demand can now overwhelm the system, potentially leading to the inactivation and on/off phenomena. Levodopa administered in a pulsatile manner may also lead to the induction of synaptic plasticity within the DA systems. In the ventral mesolimbic system, this could lead to the loss of behavioral flexibility, impulsive behavior, and cognitive impairment, whereas in the dorsal nigrostriatal system, this may underlie Levodopa-induced dyskinesia. Continuous administration of Levodopa may circumvent this sensitization process, enabling a therapeutic response without limbic and motor side effects. PMID:18781673

Grace, Anthony A

2008-01-01

385

Impaired source memory in huntington's disease and its relation to basal ganglia atrophy  

Microsoft Academic Search

Memory for contrived facts and the source of those facts was assessed in a group of early-stage HD patients and an age- and education-equated group of healthy control subjects. Fact recall did not differ significantly between the groups, but erroneous source attributions were more common among the HD patients. Like individuals with frontal lobe damage, HD patients have impaired memory

Jason Brand; Frederick W. Bylsma; Elizabeth H. Aylward; Johannes Rothlind; Catherine A. Gow

1995-01-01

386

Persistent denial of handicap after infarction of the right basal ganglia: a case study.  

PubMed Central

A case is reported of persistent denial of handicap following stroke. Hemiplegia was due to infarction involving only sub-cortical structures, and there was no associated visual or sensory neglect or inattention, and no evidence of dementia. Images

House, A; Hodges, J

1988-01-01

387

Avoidance of swallowing saliva: A symptom related to aberrant basal ganglia functions?  

Microsoft Academic Search

We report two patients with avoidance of swallowing saliva despite intact swallowing functions. One, with mild, de novo Parkinson's disease, had a fear that his saliva was contaminated and would harm him. The other, with a history of CNS germinoma in remission for 3 years following chemotherapy, expectorated because his saliva was distasteful and disgusting. He had a lesion involving

Hideto Miwa; Kaoru Tsuruta; Tomoyoshi Kondo

2012-01-01

388

Study of spindle-spike interactions: features of basal ganglia control.  

PubMed

Changes in cortical spindle distribution following penicillin (PCN) injections were studied in feline generalized PCN epilepsy. PCN activation caused no substantial changes in spindle duration, frequency and intraburst frequency, while significant reductions in the amplitude of the negative waves were noted. At the same time combinations of spindle waves and epileptic complexes were recorded with one or more spikes randomly occurring at the beginning, in the middle, or at the end of a spindle envelope. Low frequency stimulation of the caudate nucleus induced a certain degree of enhancement in cortical precruciate spike frequency while high frequency activation of the entopeduncular nucleus caused significant inhibition of cortical spike frequency. The results are discussed in the light of the reciprocal interrelationship between spindles and spikes. Furthermore, the role played by the caudate and the entopeduncular nucleus in the control of the cortico-thalamo-cortical circuit is also emphasized. PMID:3685577

Sabatino, M; La Grutta, V; Savatteri, V; La Grutta, G

1987-09-01

389

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

390

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

2011-04-04

391

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

392

Neuroimaging of nevoid basal cell carcinoma syndrome (NBCCS) in children.  

PubMed

Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant condition with a wide range of manifestations, including multiple basal cell carcinomas, medulloblastoma, odontogenic keratocysts (OKC) and skeletal abnormalities. Children with NBCCS also have a predisposition for secondary cancers after exposure to ionising radiation. In children undergoing imaging for posterior fossa mass and/or maxillofacial cysts, certain additional findings can raise the possibility of NBCCS. Making the diagnosis can significantly impact patient management, especially for children with medulloblastoma. PMID:23151728

Sartip, Kamyar; Kaplan, Adam; Obeid, George; Kadom, Nadja

2012-11-14

393

Immunohistochemical analysis of intracardiac ganglia of the rat heart  

Microsoft Academic Search

The neurochemistry of intracardiac neurons in whole-mount preparations of the intrinsic ganglia was investigated. This technique allowed the study of the morphology of the ganglionated nerve plexus found within the atria as well as of individual neurons. Intracardiac ganglia formed a ring-like plexus around the entry of the pulmonary veins and were interconnected by a series of fine nerve fibres.

R. J. Richardson; I. Grkovic; C. R. Anderson

2003-01-01

394

Protocadherin 17 regulates presynaptic assembly in topographic corticobasal Ganglia circuits.  

PubMed

Highly topographic organization of neural circuits exists for the regulation of various brain functions in corticobasal ganglia circuits. Although neural circuit-specific refinement during synapse development is essential for the execution of particular neural functions, the molecular and cellular mechanisms for synapse refinement are largely unknown. Here, we show that protocadherin 17 (PCDH17), one of the nonclustered ?2-protocadherin family members, is enriched along corticobasal ganglia synapses in a zone-specific manner during synaptogenesis and regulates presynaptic assembly in these synapses. PCDH17 deficiency in mice causes facilitated presynaptic vesicle accumulation and enhanced synaptic transmission efficacy in corticobasal ganglia circuits. Furthermore, PCDH17(-/-) mice exhibit antidepressant-like phenotypes that are known to be regulated by corticobasal ganglia circuits. Our findings demonstrate a critical role for PCDH17 in the synaptic development of specific corticobasal ganglia circuits and suggest the involvement of PCDH17 in such circuits in depressive behaviors. PMID:23684785

Hoshina, Naosuke; Tanimura, Asami; Yamasaki, Miwako; Inoue, Takeshi; Fukabori, Ryoji; Kuroda, Teiko; Yokoyama, Kazumasa; Tezuka, Tohru; Sagara, Hiroshi; Hirano, Shinji; Kiyonari, Hiroshi; Takada, Masahiko; Kobayashi, Kazuto; Watanabe, Masahiko; Kano, Masanobu; Nakazawa, Takanobu; Yamamoto, Tadashi

2013-05-16

395

Subthalamic Nucleus Stimulation Reduces Abnormal Motor Cortical Overactivity in Parkinson Disease  

Microsoft Academic Search

Background: Based on the basal ganglia model, it has been hypothesized that the efficacy of high-frequency stimulation of the subthalamic nucleus (STN) against par- kinsonian symptoms relies on the activation of cortical premotor regions. In previous positron emission tomog- raphy activation studies, STN high-frequency stimula- tion was associated with selective activation of midline premotor areas during hand movements but mainly

Pierre Payoux; Philippe Remy; Philipe Damier; Malika Miloudi; Isabelle Loubinoux; Bernard Pidoux; Véronique Gaura; Olivier Rascol; Yves Samson; Yves Agid

2004-01-01

396

Subthalamic nucleus lesion reverses motor abnormalities and striatal glutamatergic overactivity in experimental parkinsonism  

Microsoft Academic Search

Subthalamic nucleus (STN) is a target of choice for the neurosurgical treatment of Parkinson’s disease (PD). The therapeutic effect of STN lesion in PD is classically ascribed to the rescue of physiological activity in the output structures of the basal ganglia, and little is known about the possible involvement of the striatum. In the present study, therefore, we electrophysiologically recorded

D. Centonze; P. Gubellini; S. Rossi; B. Picconi; A. Pisani; G. Bernardi; P. Calabresi; C. Baunez

2005-01-01

397

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

398

UNMEDULLATED FIBERS ORIGINATING IN DORSAL ROOT GANGLIA  

PubMed Central

The compound action potential of the unmedullated fibers arising from dorsal root ganglia, as recorded in cat skin nerves after conduction of simultaneously initiated impulses, shows among its components a temporal dispersion corresponding to velocities between 2.3 and 0.7 M.P.S. The maximum representation of the component velocities is at about 1.2 M.P.S. On both sides of the maximum the representation falls off irregularly, in such a way that groupings in the distribution produce in the action potential a configuration in which successive features appear always in the same positions at a given conduction distance. Through this demonstration of a characteristic configuration the system of the unmedullated fibers is brought into analogy with that of the medullated fibers. The unmedullated fibers originating in the dorsal root ganglia have distinctive physiological properties, among which is a large positive potential which reaches its maximum immediately after the spike and decrements to half relaxation in about 50 msec., at 37°C. The positive phases of the unit potentials in the compound action potential, owing to their duration, sum to a much greater extent than the temporally dispersed spikes; and, since they have sizes such that one equivalent to 25 per cent of the spike height would not be at the limit, in the summation process the major portion of the compound action potential is caused to be written at a potential level positive to the starting base line. The position of the spikes in the sequence can be seen in the analyses in Section III. The course of the activity in unit fibers is subject to variation in ways affecting the positive potential. Preliminary descriptions, based on orienting experiments, of how these variations are conditioned are given in Section I. Two of the findings are particularly noteworthy. One is the high sensitivity of the dimensions of the postspike positivity to temperature in the range of temperatures at which skin nerves may be expected to function, even when the environmental temperatures of an animal are moderate. The other is the high sensitivity to conditioning by previous activity. The positivity is first decreased, then replaced by a negative potential of similar duration. Reasons have been given why it is inadvisable at the present time to call the postspike potential an after-potential. A comparison has been made of the properties of the unmedullated fibers arising from dorsal root ganglia with those of fibers arising from sympathetic ganglia. The differences are so great that, in the interest of precision in designation, a division of the C group of fibers into two subgroups is indicated. It is suggested that the two subgroups be named respectively d.r.C and s.C. Measurements have been made of the diameters of the d.r.C fibers in a saphenous nerve stained with silver. Graphs showing the number of fibers at each diameter are presented in Section II. In Section III there are shown constructions, from histological data, of the action potential as it would appear, after 3 cm. of conduction, with the correlation between diameter and velocity in strict linearity. The degree of fit between the constructed and recorded potentials can be seen in Fig. 18.

Gasser, Herbert S.

1950-01-01

399

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia  

Microsoft Academic Search

Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion\\u000a of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation\\u000a of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the\\u000a separation of survival and

Uwe Ernsberger

2009-01-01

400

Paced finger-tapping abnormalities in bipolar disorder indicate timing dysfunction  

PubMed Central

Background Theoretical and empirical evidence suggests that impaired time perception and the neural circuitry contributing to internal timing mechanisms may contribute to severe psychiatric disorders, including mood disorders. The structures that are involved in subsecond timing, i.e., cerebellum and basal ganglia,