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PubMed1996

Metabolic activity of the basal ganglia in parkinsonian syndromes in human and non-human primates: a cytochrome oxidase histochemistry study.

In order to examine the consequences of nigrostriatal denervation on metabolic and functional activity of the basal ganglia, we analysed the distribution of cytochrome oxidase, a metabolic marker for neuronal functional activity, throughout the different basal ganglia structures in parkinsonian syndromes. The study was performed using enzyme histochemistry and densitometric measurements in patients with Parkinson's disease and in monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrydine (MPTP) intoxication. In MPTP-intoxicated monkeys compared to control animals, enzyme activity was significantly increased in the subthalamic nucleus and in the output nuclei of the basal ganglia, e.g. the internal segment of the globus pallidus and the substantia nigra pars reticulata, but remained unchanged in the external segment of the globus pallidus and the striatum. L-DOPA treatment reversed the increased enzyme activity in all of the affected structures studied. In contrast, in parkinsonian patients, who had all been chronically treated with L-DOPA, no changes in enzyme activity were detected compared to control subjects. The results in MPTP-intoxicated monkeys are in agreement with the accepted model of basal ganglia organization, in which the output nuclei of the basal ganglia are considered to be overactive after nigrostriatal denervation, partly due to increased activity of excitatory afferents from the subthalamic nucleus. Since the increased enzyme activity in MPTP-intoxicated monkeys was reversed by L-DOPA therapy, the unchanged cytochrome oxidase activity observed in parkinsonian patients might result from L-DOPA treatment, combined with the chronicity of nigrostriatal denervation.

Aged↗
PubMed2003

Basal ganglia lesions and the theory of fronto-subcortical loops: neuropsychological findings in two patients with left caudate lesions.

Basal ganglia lesions have a high prevalence for associated behavioural impairments. However, the exact pattern of cognitive impairments and its relationship to individual basal ganglia lesion have rarely been investigated by means of a detailed neuropsychological and lesion study. Furthermore, different mechanisms have been proposed as relevant for the observed cognitive deficits; among these, the hypothesis of fronto-subcortical loops (Alexander et al., 1986) has made predictions regarding the relationship between the damage of particular striato-frontal circuits and the resulting behavioural impairment which await clinical confirmation. We present a study of two subjects who suffered a MRI-documented focal left basal ganglia hematoma. The two patients differed in their lesions; in one patient (PJ) large parts of the caudate nucleus were destroyed whereas in the other (AS) mainly the pallidum and putamen were lesioned and the caudate suffered only minor damage. In the acute phase, the behavioural and neuropsychological abnormalities were similar in both cases and included mainly abulia, an impairment of executive and attentional functions, and a severe amnestic syndrome. After several months many functions were restored in AS, whereas PJ's abilities remained largely defective. Based on these data and on previous case studies several conclusions are drawn. Left caudate lesions induce marked and long-lasting behavioural and neuropsychological impairments comprising predominantly drive, executive control, attention, and memory. The extent of lesion in the head of the caudate nucleus is the critical factor regarding the severity and the outcome of the syndrome, whereas damage to the putamen and pallidum is less crucial for cognitive functions. A subset of behavioural alterations, among them abulia, attentional and frontal-executive dysfunctions, can well be attributed to lesions of the anterior cingulate circuit and the dorsolateral-frontal circuit at the basal ganglia level. Other impairments, most importantly the prominent amnestic syndrome, are more difficult to interpret on the grounds of this hypothesis and may be related to other pathomechanisms.

Basal Ganglia↗
PubMed2004

Acute bilateral basal ganglia lesions in patients with diabetic uremia: an FDG-PET study.

PURPOSE: Head CT and MRI show characteristic changes in the syndrome of acute bilateral basal ganglia lesions in patients with diabetic uremia. However, they do not provide further insight into the underlying pathophysiology. To further clarify the biologic mechanism of the syndrome, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in 2 patients. METHODS: PET studies were performed in 2 diabetic uremic patients with acute movement disorders. The cerebral glucose metabolic rates in these 2 patients were compared with 11 normal age-matched controls. The images were further analyzed with statistical parametric mapping to identify regions of significant metabolic abnormality. RESULTS: The cases showed markedly reduced glucose metabolism in the bilateral basal ganglia, especially in the bilateral putamens, where the glucose uptake was nearly absent. CONCLUSIONS: FDG-PET correlates better with the clinical conditions and provides more pathophysiological information than head CT or MRI scans in bilateral basal ganglia lesions in patients with diabetic uremia. We propose that acute exacerbation of a long-term glucose utilization failure in the basal ganglia cells produced these lesions.

Acute Disease↗
PubMed2000

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

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 and unsupervised learning, respectively. This idea of learning-oriented specialization is helpful in understanding the complementary roles of the basal ganglia and the cerebellum in motor control and cognitive functions.

Animals↗
PubMed2005

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

The effects of Delta-9-tetrahydrocannabinole (Delta-9-THC) on locomotor activities and related basal ganglia neural responses were investigated in rats. A multiple-channel, single unit recording method was used to record neuronal activity in the dorsal lateral striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra pars reticulata simultaneously during spontaneous movement and treadmill locomotion. Delta-9-THC treatment (0.05-2.0 mg/kg, i.p.) dose-dependently decreased spontaneous motor activity and altered walking patterns in treadmill locomotion in that stance time was increased and step number was decreased. In parallel with the behavioral effects, Delta-9-THC treatment inhibited neural activity across all four basal ganglia areas recorded during both motor tests. Further, this inhibition of basal ganglia neural activity was behavioral context-dependent. Greater inhibition was found during resting than during walking periods in the treadmill locomotion test. Delta-9-THC treatment also changed firing patterns in the striatum and globus pallidus. More neurons in these regions discharged in an oscillatory pattern during treadmill walking with Delta-9-THC, and the oscillatory frequency was similar to that of the step cycle. Synchronized firing patterns were found in few basal ganglia neurons in the control condition (approximately 1%). Synchronized firing patterns increased during the treadmill resting phase after Delta-9-THC treatment, but still represented a very small proportion of the total neural population (1.9%). The drug treatment did not change neural responses to the tone cue proceeding treadmill locomotion. This study demonstrates dose-dependent inhibitory effects of cannabinoid injection on motor activity. This effect may be related to the behavioral context-dependent inhibition observed in the basal ganglia system where CB1 receptors are densely distributed.

Action Potentials↗
PubMed2005

Third pathway in the cortico-basal ganglia loop: Neurokinin B-producing striatal neurons modulate cortical activity via striato-innominato-cortical projection.

In the cortico-basal ganglia loop, striatal regions serve as 'entrances' to the basal ganglia, receiving massive inputs from the cerebral cortex and sending 'direct' and 'indirect' pathways to the output nuclei of the basal ganglia. However, we have recently identified a new striatofugal subgroup which produces neurokinin B (NKB). Although NKB-producing neurons constitute a minority of striatal neurons, this subgroup is distinguished by the unique distribution and chemical characteristics. NKB-producing striatal neurons are distributed in association with mu-opioid receptor localization, and rarely express DARPP32, which is produced by the major striatofugal neurons and coupled with dopaminergic signaling. Further interestingly NKB-producing striatal neurons send axons to basal forebrain regions, but not to the main target regions of striatal outflow, pallidal or mesencephalic regions. In the basal forebrain, some GABAergic inhibitory neurons express NK3 receptor, selective receptor for NKB, and directly send axons to the cerebral cortex. The NK3-expressing neurons show different electrical properties from cholinergic basal forebrain neurons, and display facilitatory responses to stimulation of NK3 receptor. These findings strongly suggest that NKB-producing striatal neurons and NK3-expressing basal forebrain neurons constitute a third pathway which bypasses the common output nuclei of the basal ganglia, and more directly control or modulate cortical activity.

Animals↗
PubMed1991

Basal ganglia calcifications in postoperative hypoparathyroidism: a case with unusual characteristics.

A patient is described with post-thyroidectomy hypoparathyroidism and basal ganglia calcifications. The patient presented with a tonic-clonic seizure. The calcifications shown on CT scan were extensive in the basal ganglia, the bifrontal periventricular white matter and even in the brainstem. The white matter with calcifications displayed a high signal intensity on MRI, probably due to a different stage of the calcifying process in the white matter than in the basal ganglia. A severe dystonic reaction was observed after phenothiazine therapy and is discussed.

Basal Ganglia↗
PubMed2004

123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia.

RATIONALE: The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. OBJECTIVES: The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. METHODS: Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. RESULTS: The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). CONCLUSIONS: There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade.

Adult↗
PubMed2002

The distribution of copper, zinc- and manganese-superoxide dismutase, and glutathione peroxidase messenger ribonucleic acid in rat basal ganglia.

Oxidative stress may contribute to the progression of Parkinson's disease, and while the status of antioxidant enzymes is thus important, little data on their regional distribution in basal ganglia exist. We now report on the distribution and levels of messenger ribonucleic acid (m-RNA) for the antioxidant enzymes copper, zinc-superoxide dismutase (Cu,Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and glutathione peroxidase in rat basal ganglia using in situ hybridisation histochemistry with complementary deoxyribonucleic acid probes specific for these enzymes. The m-RNA for Cu,Zn-SOD, Mn-SOD, and glutathione peroxidase was expressed throughout basal ganglia. Levels of m-RNA were significantly higher in substantia nigra pars compacta than in all other regions of basal ganglia for both Cu,Zn-SOD (53-62%, P<0.001) and Mn-SOD (37-45%, P<0.05). Mn-SOD m-RNA levels were also significantly higher in SN pars reticulata than in the nucleus accumbens (10%, P<0.05) and striatum (12%, P<0.01). In contrast, glutathione peroxidase m-RNA levels were only significantly higher in SN pars compacta when compared with SN pars reticulata (23%, P<0.05), and in the striatum when compared with the nucleus accumbens (21%, P<0.05). The data suggest that SN pars compacta may be vulnerable to oxidative stress and thus dependent on the high antioxidant capacity provided by these cytoprotective enzymes. In conclusion, this study demonstrates the relative distribution of antioxidant enzymes in rat basal ganglia and forms the basis for further study in rodent models of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain.

Glutamate is the principal excitatory transmitter of the mammalian brain and plays a particularly important role in the physiology of the basal ganglia structures responsible for movement regulation. Using in situ hybridization with oligonucleotide probes, we examined the expression patterns of the five known kainate type glutamate receptor subunit genes, KA1, KA2 and GluR5-7, in the basal ganglia of adult and developing rat brain. In the adult rat, a highly organized and selective pattern of expression of the kainate subunits was observed in the basal ganglia and associated structures as well as in other regions of the brain. KA2 mRNA was abundant in the striatum, nucleus accumbens, subthalamic nucleus and substantia nigra pars compacta, and was present at lower levels in the globus pallidus and substantia nigra pars reticulata. Neither KA1 nor GluR5 expression was observed in the basal ganglia of adult rats, although these messages were present in other regions. GluR6 was highly expressed in the striatum and subthalamic nucleus and to a lesser extent in the substantia nigra pars reticulata, while no hybridization signal was detectable in the large, presumably dopaminergic neurons of the substantia nigra pars compacta. In contrast, GluR7 was strongly expressed in the substantia nigra pars compacta, was present at lower levels in the striatum, globus pallidus and substantia nigra pars reticulata, and was not detectable in the subthalamic nucleus. During postnatal development, expression of the kainate receptor subunits was characteristically highest on postnatal day 1 and declined to adult levels by day 20; however, in the globus pallidus we did observe the transient expression of KA1 and GluR5 between day 1 and day 10. These results demonstrate that the neuronal structures comprising the basal ganglia express a distinct combination of kainate receptor subunit genes, suggesting that the pharmacological properties of the resultant glutamate receptors are likely to be regionally specific. The organization of expression of these genes is established early in life, which is consistent with the important role they may play in establishing the functions of the motor system.

Animals↗
PubMed1995

Effect of subthalamic nucleus lesion on mitochondrial enzyme activity in rat basal ganglia.

The subthalamic nucleus (STN) plays a major role in the control of basal ganglia output, and its overactivity may be central to the symptoms of Parkinson's disease. In order to elucidate the functional relationship between STN and its projection nuclei, we studied the short-term (1 week) effect of a selective lesion of STN on the activity of succinate dehydrogenase (SDH) and cytochrome oxidase (CO), two markers of neuronal activity, in the basal ganglia of rats. STN ablation induced a discrete reduction of oxidative metabolism, ipsilaterally to the lesion, in substantia nigra pars reticulata and globus pallidus, the rodent homologue of lateral globus pallidus. Such changes, ascribable to the interruption of the STN excitatory output to these nuclei, were present after 24 h and remained stable, or increased, throughout the observation period. A transitory, ipsilateral decrease was also observed in the caudate-putamen and the somato-sensory cortex, likely due to involvement of polysynaptic pathways. SDH and CO activity were always altered in the same areas, but SDH changes were more pronounced and occurred more rapidly. These results shed further light on the role played by STN in the control of basal ganglia output.

Animals↗
PubMed2005

Motor control in basal ganglia circuits using fMRI and brain atlas approaches.

In this study, we examined how the motor, premotor and associative basal ganglia territories process movement parameters such as the complexity and the frequency of movement. Twelve right-handed volunteers were studied using EPI BOLD contrast (3 T) while performing audio-paced finger tapping tasks designed to differentiate basal ganglia territories. Tasks varied movement complexity (repetitive index tapping, simple sequence of finger movements and complex sequence of 10 moves) and frequency (from 0.5 to 3 Hz). Activation maps were coregistered onto a 3-D brain atlas derived from post-mortem brains. Three main patterns of activation were observed. In the posterior putamen and the sensorimotor cortex, signal increased with movement frequency but not with movement complexity. In premotor areas, the anterior putamen and the ventral posterolateral thalamus, signal increased regularly with increasing movement frequency and complexity. In rostral frontal areas, the caudate nucleus, the subthalamic nucleus and the ventral anterior/ventrolateral thalamus, signal increased mainly during the complex task and the high frequency task (3 Hz). These data show the different roles of motor, premotor and associative basal ganglia circuits in the processing of motor-related operations and suggest that activation can be precisely located within the entire circuitry of the basal ganglia.

Adolescent↗
PubMed1988

Immunocytochemical studies on the basal ganglia and substantia nigra in Parkinson's disease and Huntington's chorea.

The basal ganglia and substantia nigra, taken from control human brain and from patients dying with a diagnosis of Parkinson's disease or Huntington's chorea, were analysed with histochemical and biochemical techniques. The pigmented neurons of the substantia nigra pars compacta possess tyrosine hydroxylase immunoreactivity and are disposed in three major layers, alpha, beta and gamma. This pattern became obscured in choreic brains by the severe shrinkage of the nigra, but total numbers of pigmented neurons were within the normal range. In contrast, pigmented neurons were lost from all layers of the substantia nigra in Parkinson's disease, although examination of cases with minimal cell loss suggested that an internal part of the lateral alpha sub-layer was most severely and consistently affected. A dopaminergic projection between this internal part of the alpha sub-layer and the putamen was suggested by the preferential loss of catecholamines from the putamen in Parkinson's disease. The distribution of the peptides, substance P, methionine-enkephalin and dynorphin 1-17 were mapped immunohistochemically within the substantia nigra. The different patterns of immunoreactive axons and terminals were found to be extensive, at least partially overlapping, and largely avoided the region of the pigmented perikarya of the alpha sub-layer and nucleus paranigralis. All peptides were depleted in choreic substantia nigra, reflecting the degeneration of the striatonigral pathway. However, concentrations of enkephalin-like immunoreactivity were increased within the interpeduncular nucleus. In Parkinson's disease there was a loss of enkephalin- and dynorphin-like immunoreactivity from the substantia nigra but a fall in substance P-like immunoreactivity was only detected by radioimmunoassay, not by immunocytochemistry. Peptide immunoreactivity was also reduced within choreic basal ganglia. However, no gross changes were found in peptide staining of the parkinsonian basal ganglia. In summary we have reported a number of changes in peptide-containing pathways in human degenerative disorders that may reflect the degeneration of neuronal pathways either as a primary event or secondary to initial lesion. We have also emphasized the sensitivity of the alpha sub-layer of nigral neurons to damage in Parkinson's disease. We suggest that the lower density of peptidergic fibres in the area of the perikarya may contribute to the susceptibility of these neurons to damage.

Adult↗
PubMed1987

Cognition and the basal ganglia: a possible substrate for procedural knowledge.

Disruption of neural activity within the basal ganglia of experimental animals causes selective learning deficits in tasks requiring switching between response strategies. These data along with reports of both general and specific intellectual impairment in patients with neurodegenerative disorders such as Parkinson's disease, appear to support the theory of cognitive functions of the basal ganglia. Recent studies have failed to confirm general cognitive or memory deficits in parkinsonian patients, but have identified deficiencies in devising and executing certain cognitive strategies. Following the lead of theorists such as Squire and Mishkin, this brief review emphasizes the distinction between procedural and declarative knowledge and examines the possible role of the basal ganglia in the acquisition and retention of procedural knowledge.

Animals↗
PubMed1996

Basal ganglia and thalamo-cortical hypermetabolism in patients with spasmodic torticollis.

UNLABELLED: The basal ganglia are thought to be involved in the primary dystonias, largely because of the repeated demonstration of neuropathological changes in these nuclei in the secondary dystonias. A hyperactivity of a network involving basal ganglia has been suggested in experimental animal dystonia. To test this hypothesis in humans, we studied the functional correlates of primary cervical dystonia using [18F]FDG and PET. MATERIAL AND METHODS: Regional cerebral glucose metabolism (rCMRglc) was measured in 10 patients with idiopathic torticollis (6 drug-free and 4 drug-naive) and in 15 normal controls, using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). RESULTS: A significant hypermetabolism in the basal ganglia, thalamus, premotor-motor cortex and cerebellum in the patients compared with normal controls was found. The patients were correctly assigned to their clinical category by a discriminant function analysis with a total accuracy of 96%. CONCLUSION: The results support the hypothesis that a dysfunction of a subcortical-cortical motor network may play a role in the pathogenesis of focal dystonia, in agreement with the experimental dystonia models.

Adult↗
PubMed1991

Basal ganglia--possible role in motor coordination and learning.

The basal ganglia, with their inhibitory efferents, control motor outputs either directly by their projections to the midbrain motor regions or indirectly through the thalamic nuclei. Neural mechanisms in the basal ganglia act selectively to remove or enhance the inhibition so that different combinations of motor signals, which may act as neural templates for motor learning, are formed.

Animals↗
PubMed1982

Basal ganglia calcification on computer tomographic scan. A clinical and radiological correlation.

Computerised tomography of the brain was used to demonstrate basal ganglia calcification which may be of an insufficient degree to be seen on skull X-ray. Cases referred for CT scan from hospitals in Singapore for various reasons over a period of 12 months were studied for basal ganglia calcification. There was a startlingly high incidence of 1.5%, as 47 cases (all except 2 were Chinese) showed such calcification. In 42 cases there was no evidence of basal ganglia calcification on skull X-ray. 16 cases showed neurological affection, fits being the commonest manifestation. An unexpected finding was that no case had abnormality of calcium metabolism or evidence of hypoparathyroidism or pseudohypoparathyroidism. The CT scan is very sensitive in demonstrating minimal basal ganglia calcification and our impression is that such calcification is common.

Adolescent↗
PubMed1994

[Cisplatin-etoposide chemotherapy of an embryonal carcinoma arising in the basal ganglia of the cerebrum: a case report].

Cases of embryonal carcinoma arising in the basal ganglia are rarely reported. According to the literature available, only 5 cases of embryonal carcinoma, arising from the basal ganglia, have been reported to date. This paper reports one such case we recently encountered. The patient was a 15-year-old boy. He was first admitted to another hospital because of occasional headache and vomiting. During the hospital stay, CT scans revealed abnormalities. For this reason, the patient was referred to our critical care center. Upon admission to our center, a physical examination revealed no abnormalities, but neurological examination disclosed left hemiparesis. CT scans revealed a large mass lesion of a low to high density in the right basal ganglia, accompanied by midline shift and ventricular dilatation. Elevation of human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP) in both serum and cerebrospinal fluid (CSF) was observed. The tumor with multiple cysts was removed totally by craniotomy. The removed tissue was rated histopathologically as mixed-type germ cell tumor composed of germinoma and embryonal carcinoma. The removed tumor cells were found immunohistologically to contain HCG and AFP. Postoperative CT scans showed complete disappearance of the tumor. Taking into account a recent report that a combined cisplatin and etoposide therapy (PE chemotherapy) was effective in treating intracranial germ cell tumors, we used this chemotherapy for postoperative management of this patient. The patient underwent 3 cycles of PE chemotherapy during the 3 months after surgery. The elevated HCG and AFP levels in serum and CSF returned to their normal range within 2 months after surgery. CT and tumor markers revealed no signs of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗