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PubMed1993

Primate basal ganglia activity in a precued reaching task: preparation for movement.

Single cell activity was recorded from the primate putamen, caudate nucleus, and globus pallidus during a precued reaching movement task. Two monkeys were trained to touch one of several target knobs mounted in front of them after an LED was lighted on the correct target. A precue was presented prior to this target "go cue" by a randomly varied delay interval, giving the animals partial or complete advance information about the target for the movement task. The purpose of this design was to examine neuronal activity in the major structures of the basal ganglia during the preparation phase of limb movements when varying amounts of advance information were provided to the animals. The reaction times were shortest with complete precues, intermediate with partial precues, and longest with precues containing no information, demonstrating that the animals used precue information to prepare partly or completely for the reaching movement before the target go cue was given. Changes in activity were seen in the basal ganglia during the preparatory period in 30% of neurons in putamen, 31% in caudate nucleus, and 27% in globus pallidus. Preparatory changes were stronger and more closely linked to the time of movement initiation in putamen than in caudate nucleus. Although the amount of information contained in the precues had no significant effect on preparatory activity preceding the target go cue, a directional selectivity during this period was observed for a subset of neurons with preparatory changes (15% in putamen, 11% in caudate nucleus, 14% in globus pallidus) when the precue contained information about the upcoming direction of movement. A smaller subset of neurons showed selectivity for the preparation of movement amplitude. A larger number of preparatory changes showed selectivity for the direction or amplitude of movement following the target go cue than in the delay period before the cue. The intensity of preparatory changes in activity in many cases depended on the length of the delay interval preceding the target go cue. Even following the target go cue, the intensity of the preparatory changes in activity continued to be significantly influenced by the length of the preceding delay interval for 11% of changes in putamen, 8% in caudate nucleus, and 18% in globus pallidus. This finding suggests that preparatory activity in the basal ganglia takes part in a process termed motor readiness. Behaviorally, this process was seen as a shortening of reaction time regardless of precue information for trials in which the delay interval was long and the animals showed an increased readiness to move.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Synchronized neuronal discharge in the basal ganglia of parkinsonian patients is limited to oscillatory activity.

It has been proposed that an increase in synchronization between neurons in the basal ganglia contributes to the clinical features of Parkinson's disease (PD). To examine this hypothesis, we looked for correlations in the discharge activity of pairs of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and the substantia nigra pars reticulata (SNr). Recordings were performed in PD patients undergoing functional stereotactic mapping for pallidotomy (eight patients) or subthalamic nucleus deep brain stimulation (four patients). A double-microelectrode setup was used to simultaneously record from neurons separated by distances as small as 250 microm. In the five pallidotomy patients without limb tremor during the procedure, none of the 73 GPi pairs and 15 GPe pairs displayed synchronous activity. In the three pallidotomy patients with limb tremor, 6 of 21 GPi pairs and 5 of 29 GPe pairs displayed oscillatory synchronization in the frequency range of the ongoing limb tremor (3-6 Hz) or at higher frequencies (15-30 Hz). Synchronized activity was not observed in the SNr (10 pairs). The findings indicate that oscillatory synchronization between pairs of GPi or GPe neurons is found in patients with limb tremor. These results also suggest that overt neuronal synchronization, which may be attributable to an increase in direct synaptic connections or common collateral afferent inputs, is not present in the basal ganglia of patients with PD.

Action Potentials↗
PubMed2001

Basal ganglia hematomas in severely head injured patients: clinicoradiological analysis of 37 cases.

OBJECT: The authors analyzed the clinicoradiological presentation of traumatic basal ganglia hematomas (TBGHs) in severely head injured (SHI) patients. METHODS: The records of 37 patients (28 male and nine female patients with a mean age of 28 years) in whom computerized tomography (CT) scans revealed TBGHs 2 ml or more in volume were retrospectively reviewed. These cases represented 2.4% of the total series of 1526 SHI patients admitted to the authors' institution between 1979 and 1998. Thirty-five patients (94%) were involved in traffic accidents and only two exhibited a period of lucidity. Associated extracranial injuries were seen in 21 patients (57%) and coagulation disorders in 32 (86%). Skull fracture was present in 10 (43%) of the 23 patients in whom skull x-ray films were obtained. Computerized tomography findings indicated diffuse axonal injury in 27 patients (73%), intraventricular hemorrhage in 22 patients (59%), and subarachnoid hemorrhage in 16 patients (43%). In all but two patients, the TBGHs were visible on the initial CT scan, and in 28 cases (76%) these hematomas were contralateral to the side of impact. Hematoma enlargement over the first few posttraumatic days was noted in 65% of the patients in whom control CT scans had been obtained (22 of 34 patients). Four patients (11%) underwent surgery to remove their TBGHs. Final outcomes were poor: 22 patients (59%) died, two (5%) became vegetative, seven (19%) experienced severe disabilities, and only six patients (16%) made a favorable recovery. CONCLUSIONS: Traumatic basal ganglia hematomas are dynamic lesions that tend to enlarge during the acute posttraumatic period. The overall prognosis in this series was poor. Patients in whom the volume of the hematoma was larger than 25 ml and those in whom hematoma volume enlargement or raised intracranial pressure occurred had the worst outcomes, perhaps indicating the need for a more aggressive surgical treatment.

Adolescent↗
PubMed2003

Opposing basal ganglia processes shape midbrain visuomotor activity bilaterally.

The manner in which the nervous system allocates limited motor resources when confronted with conflicting behavioural demands is a crucial issue in understanding how sensory information is transformed into adaptive motor responses. Understanding this selection process is of particular concern in current models of functions of the basal ganglia. Here we report that the basal ganglia use simultaneous enhancing and suppressing processes synergistically to modulate sensory activity in the superior colliculi, which are bilaterally paired midbrain structures involved in the control of visual orientation behaviours. These complementary processes presumably ensure accurate gaze shifts mediated by the superior colliculi despite the presence of potential distractors.

Animals↗
PubMed1985

The basal ganglia in chlordecone-induced neurotoxicity in the mouse.

This overview summarizes the available data concerning the neurotoxic effects of chlordecone on the basal ganglia in mice. Included are the effects of chlordecone on motor coordination, levels of biogenic amines, uptake of catecholamines and GABA, release of 3H-dopamine from striatal slices, newly synthesized dopamine, levels of dopamine metabolites in striatum, total and protein-bound Ca++ in discrete areas of brain, and distribution of chlordecone in discrete areas of brain. These data suggest that the basal ganglia may be the brain site at which chlordecone acts to produce its neurotoxic effects.

Animals↗
PubMed1984

Evidence for a dopaminergic innervation of the cat lateral habenula: its role in controlling serotonin transmission in the basal ganglia.

The presence of a dopaminergic innervation of the cat lateral habenula and its possible role in modulating serotonin transmission within the basal ganglia were investigated using both in vitro and in vivo approaches. A high density of [3H]spiroperidol binding sites with similar affinities for domperidone and apomorphine as those present in the cat striatum were found in the habenula. By means of the push-pull cannula technique, a substantial release of [3H]dopamine continuously formed from [3H]tyrosine was detected in the lateral habenula of halothane-anesthetized cats since the amount of [3H]catecholamines was enhanced in the presence of benztropine, an inhibitor of dopamine uptake into dopaminergic nerve terminals. Furthermore, in anesthetized animals with a push-pull cannula implanted in each caudate nucleus and substantia nigra habenular applications of dopamine (10(-7) M) reduced nigral but not striatal release of [3H]serotonin continuously formed from [3H]tryptophan. This change was prevented either by the delivery of domperidone to the lateral habenula or by the blockade of GABAergic transmission (picrotoxin 10(-5) M) in the dorsal raphe. These data support the involvement of habenulo-raphe pathways in the regulation of serotonin transmission in the cat basal ganglia and indicate that dopaminergic inputs to the lateral habenula participate in such a control.

Animals↗
PubMed2002

Bilateral lesions of thalamus and basal ganglia: origin and outcome.

Twenty-seven MRI examinations from 17 children (7 females, 10 males) with bilateral lesions of the basal ganglia and thalamus, presenting over a period of 8 years, were reevaluated, and correlated with the type of cerebral palsy (CP) as well as motor and cognitive impairment. Children were between 1 year 6 months and 17 years old at last examination (mean 5 years 9 months). Brain damage had occurred as a consequence of birth asphyxia in nine patients and of neonatal shock in four patients. No adverse event could be identified in four children. In these, late prenatal compromise is assumed, as extensive screening (including MR spectroscopy in two patients) did not yield an underlying metabolic disorder. Three different degrees of MRI lesion patterns could be defined: a mild pattern (involvement of nucleus lentiformis and ventro-lateral thalamus only; n=7), an intermediate pattern (involvement of nucleus lentiformis, ventro-lateral thalamus, and pericentral region; n=3), and a severe pattern (involvement of nucleus lentiformis, entire thalamus, pericentral region, and hippocampus; n=7). This grading of MRI findings correlated significantly with the severity of both cognitive and motor impairment and type of CP. Normal cognitive development and mild motor delay was only seen with the mild pattern. All children developed CP: purely dyskinetic CP was only seen with the mild pattern, whereas the dyskinetic-spastic or spastic CP types could be seen in all three lesion patterns, with dyskinetic-spastic CP more related to the moderate, and purely spastic CP more related to the severe pattern.

Adolescent↗
PubMed2004

Reduced basal ganglia volumes after switching to olanzapine in chronically treated patients with schizophrenia.

OBJECTIVE: A follow-up study of patients with schizophrenia was conducted to examine change in striatal volumes and extrapyramidal symptoms after a change in medication. METHOD: Thirty-seven patients with schizophrenia and 23 healthy volunteers were examined. Patients at baseline receiving typical antipsychotics (N=10) or risperidone but exhibiting limited response (N=13) were switched to treatment with olanzapine. Patients receiving risperidone and exhibiting a good response (N=14) continued treatment with risperidone. Caudate, putamen, and pallidal volumes were assessed with magnetic resonance imaging. The Extrapyramidal Symptoms Rating Scale was used to assess clinical signs and symptoms. RESULTS: At baseline, basal ganglia volumes in patients treated with typical antipsychotics were greater than in healthy subjects (putamen: 7.0% larger; globus pallidus: 20.7% larger). After the switch to olanzapine, putamen and globus pallidus volumes decreased (9.8% and 10.7%, respectively) and did not differ from those of healthy subjects at the follow-up evaluation. Akathisia was also reduced. In the patients receiving risperidone at baseline, basal ganglia volumes did not differ between those exhibiting good and poor response, and no significant volume changes were observed in subjects with poor risperidone response after the switch to olanzapine treatment. CONCLUSIONS: Olanzapine reversed putamen and globus pallidus enlargement induced by typical antipsychotics but did not alter volumes in patients previously treated with risperidone. Changes in striatal volumes related to typical and atypical antipsychotics may represent an interactive effect between individual medications and unique patient characteristics.

Adolescent↗
PubMed2001

[Chronic hepatic encephalopathy: the role of high serum manganese levels and its relation with basal ganglia lesions in nuclear magnetic resonance of the brain. Clinical case].

Chronic hepatic encephalopathy (CHE) is a disabling complication of chronic liver failure and porto-systemic shunt. The pathogenesis of CHE remains unclear but increased levels of ammonia are a basic feature. Several clinical and experimental observations support a role for manganese (Mn) in the pathogenesis of this disorder. Increased blood levels of Mn have been described in patients with CHE and this could lead to its accumulation on the basal ganglia and characteristic hyperintensities of basal ganglia as seen on magnetic resonance imaging (MRI) of the brain. We report on the clinical features and characteristic radiologic findings of a patient who presented with the neurologic syndrome of CHE and who had very high blood levels of Mn in the absence of an occupational exposure to this metal. Our report supports the hypothesis that Mn has a role in the pathogenesis of CHE and also suggests that brain MRI is a useful marker of the brain metabolic repercussion due to CHE.

Ammonia↗
PubMed1996

Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: a stereological study using the cavalieri and optical disector methods.

The total number of neurons within six subdivisions of the rat basal ganglia was estimated using unbiased stereological counting methods and systematic random sampling techniques. Six young adult rats were perfuse-fixed, their right cerebral hemispheres were embedded in glycolmethacrylate, and a complete set of serial 40-mu m sections was cut through each hemisphere. After a random start, a systematic subset (e.g., every tenth) of these sections was used to estimate the total volume of each subdivision using Cavalieri's method. The same set of sampled sections was used to estimate the number of neurons in a known subvolume (i.e., the Nv) by the optical disector method. The product of the total volume and the Nv by these methods yields an unbiased estimate of the total number of neurons. It was found that the right basal ganglia consisted, on average, of 2.79 million neostriatal or caudate-putamen neurons (with a coefficient of variation of 0.07), 46,000 external globus pallidus neurons (0.11), 3,200 entopeduncular/internal globus pallidus neurons (0.10), 13,600 subthalamic neurons (0.10), 7,200 substantial nigra pars compacta neurons (0.15), and 26,300 substantia nigra pars reticulata neurons (0.07).

Animals↗
PubMed1986

Chronic haloperidol and clozapine differentially affect dynorphin peptides and substance P in basal ganglia of the rat.

The effect of chronic neuroleptic treatment, using haloperidol or clozapine, on immunoreactive dynorphin peptide and substance P levels in basal ganglia of rats was examined. The drugs were administered i.p. in daily doses for 10 days (haloperidol 1 mg/kg and clozapine 10 mg/kg). Dynorphin A, dynorphin B and substance P were measured in substantia nigra, striatum, globus pallidus and hypothalamus using specific radioimmunoassays. The most prominent effects were observed with with clozapine which increased levels of all measured peptides in substantia nigra. Haloperidol only affected nigral substance P levels which declined, while nigral dynorphin peptide levels remained unchanged. In striatum, haloperidol slightly reduced dynorphin peptides while substance P was unaffected. Clozapine increased striatal substance P but the dynorphin peptides were not affected. Minor changes in dynorphin peptides found in globus pallidus and hypothalamus were not statistically reliable. Substance P was not changed in these structures after either of the two drugs. High molecular weight fragments (greater than or equal to 5,000) from the dynorphin precursor, proenkephalin B, were measured in substantia nigra and striatum using trypsin digestion and subsequent analysis of generated Leu-enkephalin-Arg6. These high molecular weight fragments were found to be affected in the same manner as the dynorphin peptides. This study indicates that the two types of neuroleptic drugs have different modes of interaction on peptide systems in basal ganglia of rats. Dynorphin peptides and substance P were also differentially affected.

Animals↗
PubMed2001

New aspects of physiological and pathophysiological functions of adenosine A2A receptor in basal ganglia.

There is now growing interest in the functional role of adenosine A2A receptors. Their distribution within the brain is restricted in the basal ganglia, particularly abundant in the striatum, which are thought to play a crucial role in the control of motor behavior. Indeed, newly developed A2A receptor selective antagonists have a profound influence on motor functions, with anti-Parkinsonian activities in several animal models. Striatal spiny neurons serve as a major anatomical locus for the relay of cortical information flow through the basal ganglia. The GABA releasing projection neurons represent the A2A receptor-mediated main target of adenosine. The GABAergic synaptic neurotransmission is regulated by adenosine via A2A receptors on the presynaptic terminals. Blockade of this modulatory function by A2A antagonists could repair striatopallidal abnormal neuronal activities provoked by striatal dopamine depletion in the Parkinsonian state. A2A receptor antagonists provide a novel therapeutic potential for the treatment of Parkinson's disease.

Adenosine↗
PubMed1997

Basal ganglia organization in amphibians: efferent connections of the striatum and the nucleus accumbens.

As a further step in unraveling the organization of the basal ganglia of amphibians, the efferent connections of the striatum and the nucleus accumbens have been studied in the brains of the anurans, Rana perezi and Xenopus laevis, and the urodele, Pleurodeles waltl, by using biotinylated or fluorescent dextran amines as anterograde tracers. A common pattern of efferent connections was observed in both groups of amphibians, but those in the anurans were more elaborate. Striatal efferent fibers were found to reach the lateral and medial amygdala, the anterior and posterior entopeduncular nuclei, several thalamic nuclei, the dorsomedial posterior tubercle, the pretectum, the optic tectum, the torus semicircularis, the pontomesencephalic reticular formation, and the caudal brainstem. Efferent fibers of the nucleus accumbens project to the medial amygdala, the preoptic area, the ventral hypothalamic nucleus, the dorsomedial posterior tubercle, the medial tegmental area, the pontomesencephalic reticular formation, and the raphe. In addition, the study has revealed the existence of intrinsic connections within the ventral telencephalic wall, suggesting a possible further compartmentalization of the amphibian basal forebrain. In conclusion, the results of the present study corroborate the notion that the basal ganglia of amphibians share many features with their presumed homologues in amniotes.

Animals↗
PubMed1996

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

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

Adenosine↗
PubMed1995

Epidemiological, genetic, pharmacological, kinesiological, nuclear medical (IBZM-SPECT), standard and functional MRI studies on Parkinson's disease and related disorders and economic evaluation of Parkinson's disease therapy--clinical projects in the BMFT-research program Munich: "Parkinson's disease and other basal ganglia disorders".

The results of selected clinical research projects related to epidemiological, genetic, pharmacological, kinesiological, and neuroimaging aspects (SPECT, PET, MRI, functional MRI) of basal ganglia disorders such as Parkinson's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and Wilson's disease are summarized. A retrospective pharmacoeconomic analysis of Parkinson's disease is presented. These studies are part of a nationwide research program of the German ministry of research and technology (BMFT) entitled "Parkinson's disease and other basal ganglia disorders" and were carried out at the Department of Neurology, LMU München.

Basal Ganglia Diseases↗