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PubMed2001

MRI follow-up of basal ganglia involvement in subacute sclerosing panencephalitis.

A 12-year-old male with subacute sclerosing panencephalitis is presented. Magnetic resonance imaging revealed basal ganglia involvement without white matter changes for several months. Basal ganglia changes are not infrequent in subacute sclerosing panencephalitis, but they tend to appear in advanced clinical stages. Prominent basal ganglia involvement may occur very rarely in subacute sclerosing panencephalitis. In our patient, serial magnetic resonance imaging demonstrated the involvement of white matter after 2 years of magnetic resonance imaging follow-up. In contrast with the neuroradiologic progression, our patient's clinical status remained stable.

Basal Ganglia↗

PubMed2005

Parkinsonism with basal ganglia lesions in a patient with uremia: Evidence of vasogenic edema.

Parkinsonian syndromes associated with basal ganglia pathology have very rarely been reported in patients with end-stage renal failure. The nature and pathophysiology of the basal ganglia lesion responsible for parkinsonism were unknown. A 48-year-old man who had advanced renal failure developed disturbance of balance and gait and decreased spontaneity. Brain magnetic resonance (MR) imaging disclosed bilateral basal ganglia lesions. By the finding of diffusion-weighted image, the apparent diffusion coefficient map, MR angiography, and SPECT, we suggest that the basal ganglia lesions may be the result of vasogenic edema attributable to focal hyperemia secondary to abnormal dilatation of small vessels.

Brain Edema↗

PubMed2006

Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity.

In addition to its involvement in motor control and in encoding reward value, increasing evidence also implicates basal ganglia dopaminergic mechanisms in responses to stress and aversive stimuli. Basal ganglia dopamine (DA) neurotransmission may then respond to environmental events depending on their saliency, orienting the subsequent responses of the organism to both positive and negative stimuli. Here we examined the involvement of DA neurotransmission in the human response to pain, a robust physical and emotional stressor across species. Positron emission tomography with the DA D2 receptor antagonist radiotracer [11C]raclopride detected significant activation of DA release in dorsal and ventral regions of the basal ganglia of healthy volunteers. Activation of nigrostriatal (dorsal nucleus caudate and putamen) DA D2 receptor-mediated neurotransmission was positively associated with individual variations in subjective ratings of sensory and affective qualities of the pain. In contrast, mesolimbic (nucleus accumbens) DA activation, which may impact on both D2 and D3 receptors, was exclusively associated with variations in the emotional responses of the individual during the pain challenge (increases in negative affect and fear ratings). These data demonstrate that basal ganglia dopamine D2 receptor-mediated neurotransmission is involved in responses to pain and that it contributes to individual variations in the pain experience at the levels of physical and emotional elements, albeit with different neuroanatomical substrates.

Adult↗

PubMed2006

Pathways of neurodegeneration and experimental models of basal ganglia disorders: downstream effects of mitochondrial inhibition.

The basal ganglia circuit plays a key role in the regulation of voluntary movements as well as in behavioural control and cognitive functions. The main pathogenic role of mitochondrial dysfunctions is now accepted in the neurodegenerative process and the mitochondria have been successfully used as subcellular targets to obtain relevant experimental models of basal ganglia neurodegenerative disorders. Mitochondrial toxins act through an inhibition of the respiratory chain complexes. These toxins, by uncoupling cellular respiration, shift the cell into a state of oxidative stress and trigger several bidirectional links with the excitotoxic process. Moreover, the in vitro inhibition of the respiratory chain complexes alters the electrophysiological properties of the neurons. The downstream effects triggered by mitochondrial complexes inhibition provide a model integrating genetic and environmental pathogenic factors to explain the selective neuronal vulnerability.

Animals↗

PubMed2000

Electrophysiological properties of avian basal ganglia neurons recorded in vitro.

The forebrains of mammals and birds appear quite different in their gross morphology, making it difficult to identify homologies between them and to assess how far they have diverged in organization. Nevertheless one set of forebrain structures, the basal ganglia, has been successfully compared in mammals and birds. Anatomical, histochemical, and molecular data have identified the avian homologues of the mammalian basal ganglia and indicate that they are very similar in organization, suggesting that they perform similar functions in the two classes. However, the physiological properties of the avian basal ganglia have not been studied, and these properties are critical for inferring functional similarity. We have used a zebra finch brain slice preparation to characterize the intrinsic physiological properties of neurons in the avian basal ganglia, particularly in the input structure of the basal ganglia, the striatum. We found that avian striatum contains a cell type that closely resembles the medium spiny neuron, the principal cell type of mammalian striatum. Avian striatum also contains a rare cell type that is very similar to an interneuron class found in mammalian striatum, the low-threshold spike cell. On the other hand, we found an aspiny, fast-firing cell type in avian striatum that is distinct from all known classes of mammalian striatal neuron. These neurons usually fired spontaneously at 10 Hz or more and were capable of sustained firing at very high rates when injected with depolarizing current. The existence of this cell type represents an important difference between avian striatum and mammalian dorsal striatum. Our data support the general idea that the organization and functional properties of the basal ganglia have been largely conserved in mammals and birds, but they imply that avian striatum is not identical to mammalian dorsal striatum.

4-Aminopyridine↗

PubMed1997

Consequences of nigrostriatal denervation on the functioning of the basal ganglia in human and nonhuman primates: an in situ hybridization study of cytochrome oxidase subunit I mRNA.

To examine the consequences of nigrostriatal denervation and chronic levodopa (L-DOPA) treatment on functional activity of the basal ganglia, we analyzed, using in situ hybridization, the cellular expression of the mRNA encoding for cytochrome oxidase subunit I (COI mRNA), a molecular marker for functional neuronal activity, in the basal ganglia. This analysis was performed in monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Intoxication, some of which had been receiving L-DOPA, and in patients with Parkinson's disease (PD). In MPTP-intoxicated monkeys compared with control animals, COI mRNA expression was increased in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia, i.e., the internal segment of the globus pallidus and the substantia nigra pars reticulata. This increase was partially reversed by L-DOPA treatment. COI mRNA expression remained unchanged in the external segment of the globus pallidus (GPe). In PD patients, all of whom had been treated chronically by L-DOPA, COI mRNA expression in the analyzed basal ganglia structures was similar to that in control subjects. These results are in agreement with the accepted model of basal ganglia organization, to the extent that the output nuclei of the basal ganglia are considered to be overactive after nigrostriatal denervation, partly because of increased activity of excitatory afferents from the STN. Yet, our results would also seem to contradict this model, because the overactivity of the STN does not seem to be attributable to a hypoactivation of the GPe.

Aged↗

PubMed2001

Magnetization transfer and diffusion tensor MR imaging of basal ganglia from patients with multiple sclerosis.

Although post-mortem studies have shown that lesions of multiple sclerosis (MS) can be detected in the basal ganglia, conventional T2-weighted magnetic resonance (MR) imaging is poorly sensitive for detecting such abnormalities. This study was performed to investigate whether magnetization transfer (MT) and diffusion tensor MR imaging are able to detect in vivo basal ganglia changes in patients with MS. After image coregistration, MT ratio (MTR) and mean diffusivity (&Dmacr;) maps were obtained and MTR and &Dmacr; values of the putamen, head of the caudatus and thalamus measured from 31 patients with clinically definite MS and 14 age- and sex-matched healthy volunteers using region of interest analysis. Although we found slightly decreased MTR and increased &Dmacr; in the basal ganglia from patients compared to controls, suggesting increased extra-cellular water and reduced amount of 'barriers' restricting water molecular motion in the basal ganglia of patients with MS, none of the differences was statistically significant. These data suggest that the more sophisticated MR probes of tissue disruption and cellular integrity are no more sensitive than current conventional imaging for detecting basal ganglia abnormalities in patients with MS.

Adult↗

PubMed2005

Cannabinoid CB(1) receptors in the basal ganglia and motor response to activation or blockade of these receptors in parkin-null mice.

The endocannabinoid transmission becomes overactive in the basal ganglia in Parkinson's disease (PD), as reported in patients and animal models of this disease. In the present study, we examined the status of cannabinoid CB(1) receptors in the basal ganglia of female and male Park-2 knockout mice, a genetic model of PD that progresses with no neuronal death and that may be considered representative of early and presymptomatic parkinsonian deficits. We found an increase in the density of CB(1) receptors in the substantia nigra compared to wild-type animals with no changes in other basal ganglia, although this occurred only in females. Despite this increase, the motor inhibition caused by the acute administration of the cannabinoid agonist Delta(9)-tetrahydrocannabinol to Park-2 knockout female mice was markedly of lesser magnitude compared with the response found in wild-type animals. By contrast, the administration of the CB(1) receptor antagonist SR141716 resulted in a hyperkinetic response in parkin-null mice, response that was almost absent in wild-type animals and that was accompanied by a decrease in tyrosine hydroxylase activity in the caudate-putamen. However, parkin-null male mice exhibited normal levels of CB(1) receptors in the substantia nigra and the remaining basal ganglia, with the only exception of a small decrease in the lateral part of the caudate-putamen. This was associated with an increase in mRNA levels for superoxide dismutase in this structure. In addition, the administration of Delta(9)-tetrahydrocannabinol to parkin-null male mice caused a motor inhibition that was significantly greater than in the case of their wild-type counterparts, and that was accompanied by an increase in tyrosine hydroxylase activity in the caudate-putamen. In summary, extending the data obtained in humans and animal models of basal ganglia neurodegeneration, changes in CB(1) receptors were also observed in parkin-null mice, a model of PD that may be considered representative of early stages of this disease. These changes are associated with differences in behavioral responses to cannabinoid agonists or antagonists between Park-2 knockout and wild-type mice, although parkin-null mice exhibited evident gender-dependent differences for both levels of CB(1) receptors and motor responses to agonists or antagonists.

Analysis of Variance↗

PubMed1991

MRI in schizophrenia: basal ganglia and white matter T1 times.

The T1 relaxation time of the basal ganglia (putamen, globus pallidus and head of caudate) and of the frontoparietal centrum semiovale was compared between 49 schizophrenic patients and 36 healthy controls. Previous reports of increased T1 time in the basal ganglia were not confirmed, and group differences were not detected within the white matter. Within patients T1 values could not be related to tardive dyskinesia or other clinical features. Normal variation seen in basal ganglia T1 times is described for the first time: lowest values occur in the globus pallidus and highest in the caudate, and values within the putamen increase rostrally.

Adult↗

PubMed2002

Metabolic changes in the basal ganglia of patients with Huntington's disease: an in situ hybridization study of cytochrome oxidase subunit I mRNA.

On the basis of the functional model of the basal ganglia developed in the 1980s and the neuropathological findings in Huntington's disease (HD), changes in the neuronal activity of the basal ganglia have previously been proposed to explain the abnormal movements observed in this pathology. In particular, it has been stated that the neurodegenerative process affecting the basal ganglia in the disease should provoke a hypoactivity in the internal segment of the pallidum (GPi) that could explain choreic movements observed in the disease. To test this functional hypothesis, we performed an in situ hybridization study on control and HD brains postmortem, taking cytochrome oxidase subunit I (COI) mRNAs expression as index of neuronal activity. As most of the HD patients studied were under chronic neuroleptic (NL) treatment, we also studied the brains of non-HD patients under chronic NL treatment. Our results show that in HD brain the number of neurons expressing COI mRNA tends to be lower in the striatum, GPe and GPi, suggesting a severe involvement of these structures during the neurodegenerative process. Moreover, COI mRNA level of expression was markedly reduced within neurons of the putamen and GPe. Surprisingly, COI mRNA expression was not modified in the GPi in HD brains compared with controls. This paradoxical result in the GPi may be explained by the antagonistic effect of GPe hypoactivity and the degenerative process involving neurons of GPi. Our results indicate that the functional modifications, and consequently the pathophysiology of abnormal movements, observed in HD basal ganglia are more complex than expected from the currently accepted model of the basal ganglia organization.

Adult↗

PubMedDate not supplied

The neurophysiologic basis of abnormal movements in basal ganglia disorders.

Recent anatomical and physiological studies have shed new light on the functional organization of the basal ganglia and the contributions of these structures to movement. While the striatum receives input from the entire neocortex, this information appears to remain segregated in the basal ganglia along lines established at the cortical level. There appears to be, in the broadest sense, a maintained segregation of information relevant to motor and "complex" functions. The concept of segregated parallel subcortical loops subserving "motor" and "complex" functions is discussed. Single cell studies in the basal ganglia of behaving animals have revealed specific relations of neuronal activity to movements of individual body parts and a relation to specific parameters of movement, particularly direction, amplitude, and velocity. The pathophysiologic basis of akinesia tremor, rigidity, and diskinesias is discussed in light of recent findings.

Animals↗

PubMed1994

Basal ganglia lacunes and parkinsonism.

'Arteriosclerotic' parkinsonism is still a subject of debate. The aim of this study was to investigate whether parkinsonism associated with basal ganglia lacunes possesses peculiar clinical features and a clinical course which enables its distinction from idiopathic Parkinson's disease (IPD). 106 consecutive ambulatory patients with the clinical diagnosis of parkinsonism were referred for CT examination. Patients in whom isolated basal ganglia lacunes were found were interviewed and examined, and their clinical characteristics were compared to those of patients suffering from IPD without lacunes (controls). In 20 patients, isolated basal ganglia lacunes were detected; all had risk factors for stroke (significantly more than controls) and 7 of them had had clinically diagnosed strokes. The extrapyramidal disability evolved slowly in all. The clinical picture was indistinguishable from IPD in individual patients. However, tremor was significantly less frequent in this group. Lower body parkinsonism was not observed. Extra-pyramidal signs were frequently asymmetrical (55%), with no consistent relationship to the side of the lacune. Asymmetrical pyramidal signs were present in 30% of those with unilateral lacunes, always on the appropriate side. Only 1 patient was an L-dopa nonresponder. Patients with parkinsonism associated with basal ganglia lacunes showed tremor less frequently than other IPD patients; otherwise, clinical features and course of the disease were indistinguishable from IPD. In these cases, parkinsonism and basal ganglia lacunes might have occurred independently of each other and tremor might have been prevented by ischemic events.

Aged↗

PubMed1984

Functional organization of the basal ganglia: contributions of single-cell recording studies.

Studies of single-cell discharge in the basal ganglia of behaving primates have revealed: characteristic patterns of spontaneous discharge in the striatum, external (GPe) and internal (GPi) globus pallidus, pars reticulata and pars compacta of the substantia nigra, and the subthalamic nucleus (STN); phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face); short-latency (sensory) neural responses to passive joint rotation; a somatotopic organization of movement-related neurons in GPe, GPi, and STN; a clustering of functionally similar neurons in the putamen and globus pallidus; greater representation of the proximal than of the distal portion of the limb; changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force; a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity. Some of these findings suggest that the basal ganglia may play a role in the control of movement parameters rather than (or independent of) the pattern of muscular activity. Loss of basal ganglia output related to amplitude may account for the bradykinesia in Parkinson's disease. The presence of somatotopic organization in the putamen and globus pallidus, together with known topographic striopallidal connections, suggests that segregated, parallel cortico-subcortical loops subserve 'motor' and 'complex' functions.

Animals↗

PubMed2006

Expression of protein kinase C-substrate mRNAs in the basal ganglia of adult and infant macaque monkeys.

We performed in situ hybridization histochemistry on the monkey basal ganglia to investigate the mRNA localization of three protein kinase C substrates (GAP-43, MARCKS, and neurogranin), of which expression plays a role in structural changes in neurites and synapses. Weak hybridization signals for GAP-43 mRNA and intense signals for both MARCKS and neurogranin mRNAs were observed in the adult neostriatum. All three of the mRNAs were expressed in both substance P-positive direct pathway neurons and enkephalin-positive indirect pathway neurons. In the nucleus accumbens, the hybridization signals for the three mRNAs were weaker than those in the neostriatum. Double-label in situ hybridization histochemistry in the neostriatum revealed that GAP-43 and neurogranin mRNAs were expressed in a subset of MARCKS-positive neurons. While intense hybridization signals for MARCKS mRNA were observed in all of the other basal ganglia regions such as the globus pallidus, substantia innominata, subthalamic nucleus, and substantia nigra, intense signals for GAP-43 mRNA were restricted to the substantia innominata and substantia nigra pars compacta. No signal for neurogranin mRNA was observed in the basal ganglia regions outside the neostriatum and the nucleus accumbens. These results indicate that the protein kinase C substrates are abundant in some specific connections in cortico-basal ganglia circuits. Developmental analysis showed that the expression level in the putamen and nucleus accumbens, but not in the caudate nucleus, was higher in the infant than in the adult, suggesting that synaptic maturation in the caudate nucleus occurs earlier than that in the putamen and nucleus accumbens.

Age Factors↗

PubMed2005

Tertiary microvascular territories define lacunar infarcts in the basal ganglia.

Lacunar infarcts are commonly found in the basal ganglia, though little is known about the organization of small-scale microvascular territories that presumably subtend lacunae. We investigated microvascular territories of the lenticulostriate arteries, the recurrent artery of Heubner, the anterior choroidal artery, and striate branches of the anterior cerebral and anterior communicating arteries in perfusion-fixed human brains by simultaneous injection of fluorescent dyes and a radio-opaque substance in 5% gelatin. Territories were defined by ultraviolet illumination of dye and high-resolution mammography of radio-opaque substance. Brains were sectioned coplanar with the Talairach proportional grid system and vascular data were plotted, allowing for application to any human brain. The data suggest first that the lenticulostriate artery, recurrent artery of Heubner, and anterior choroidal artery supply distinct territories of the basal ganglia with minimal overlap and sparse anastomoses between major penetrating vessels. Individual territories are spatially consistent across brains and match the extent of major/minor infarcts. Second, branching patterns of parental, second-, and third-order vessels leading to circumscribed terminal vascular beds could account structurally for "lacunar" infarcts.

Artifacts↗

PubMed1999

Hemichorea and hemiballism associated with contralateral hemiparesis and ipsilateral basal ganglia lesions.

We report on two patients with unilateral hyperkinetic movement disorders associated with contralateral hemiparesis and ipsilateral basal ganglia lesions. The first patient, a 47-year-old woman, had a low-grade astrocytoma located in the right basal ganglia extending into the subthalamic area and the cerebral peduncle. She presented with left hemiparesis, right hemichorea, and intermittent right-sided tremor at rest. The second patient, a 85-year-old woman, had hypertensive hemorrhage to the right posterior basal ganglia, the posterior limb of the internal capsule, the lateral thalamus, and the subthalamic region with accompanying intraventricular bleeding. She developed right-sided transient hemichorea-hemiballism. A videotape illustration of one of the patients is provided. The literature on the rare occurrence of ipsilateral hemichorea-hemiballism is discussed and possible pathomechanisms are reviewed. We postulate that hemiparesis contralateral to basal ganglia lesions might have a conditioning effect on the appearance of ipsilateral dyskinetic movement disorders.

Aged↗

PubMed2006

Temporal dynamics of basal ganglia response and connectivity during verbal working memory.

Research on the neural basis of working memory (WM) has generally focused on neocortical regions; comparatively little is known about the role of subcortical structures. There is growing evidence that the basal ganglia are involved in WM, but their contribution to different component processes of WM is poorly understood. We examined the temporal dynamics of basal ganglia response and connectivity during the encoding, maintenance and response phases of a Sternberg WM task. During the encoding and maintenance phases, WM-load-dependent activation was observed in the left anterior caudate, anterior putamen and globus pallidus; activation in the right anterior caudate was observed only during the maintenance phase. During the response phase, the basal ganglia were equally active in both the high-load and low-load WM conditions. Caudate and putamen activations were primarily localized to the (rostral) associative parts of the basal ganglia, consistent with the putative role of these regions in cognitive processing. Effective connectivity analyses revealed increased WM-load-dependent interaction of the left anterior caudate with the left posterior parietal cortex during all three phases of the task; with the visual association cortex, including the fusiform gyrus and inferior temporal gyrus, only during the encoding phase; with the ventrolateral prefrontal cortex during the encoding and maintenance phases; with the pre-supplementary motor area during the maintenance and response phases; and with the dorsolateral prefrontal and anterior cingulate cortices only during the response phase. Taken together with known neuroanatomy of the basal ganglia, these results suggest that the anterior caudate helps to link signals in distinct functional networks during different phases of the WM task. Our study offers new insight into the integrative and adaptive role of the basal ganglia in higher cognitive function.

Adolescent↗

PubMed1998

A computational model of how the basal ganglia produce sequences.

We propose a systems-level computational model of the basal ganglia based closely on known anatomy and physiology. First, we assume that the thalamic targets, which relay ascending information to cortical action and planning areas, are tonically inhibited by the basal ganglia. Second, we assume that the output stage of the basal ganglia, the internal segment of the globus pallidus (Gpi), selects a single action from several competing actions via lateral interactions. Third, we propose that a form of local working memory exists in the form of reciprocal connections between the external globus pallidus (Gpe) and the subthalamic nucleus (STN). As a test of the model, the system was trained to learn a sequence of states that required the context of previous actions. The striatum, which was assumed to represent a conjunction of cortical states, directly selected the action in the GP during training. The STN-to-GP connection strengths were modified by an associative learning rule and came to encode the sequence after 20 to 40 iterations through the sequence. Subsequently, the system automatically reproduced the sequence when cued to the first action. The behavior of the model was found to be sensitive to the ratio of the striatal-nigral learning rate to the STN-GP learning rate. Additionally, the degree of striatal inhibition of the globus pallidus had a significant influence on both learning and the ability to select an action. Low learning rates, which would be hypothesized to reflect low levels of dopamine, as in Parkinson's disease, led to slow acquisition of contextual information. However, this could be partially offset by modeling a lesion of the globus pallidus that resulted in an increase in the gain of the STN units. The parameter sensitivity of the model is discussed within the framework of existing behavioral and lesion data.

Basal Ganglia↗