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PubMed1985

Influences of pyramidal tract on the subthalamic nucleus in the cat.

In adult cats, with mesencephalic decerebration sparing the cerebral peduncles and ablation of the sensorimotor cortex, changes in firing of single cells of subthalamic nucleus (STN) were analyzed upon stimulation of ipsilateral medullary pyramidal tract (PT). Twenty-two out of 44 of the STN cells exhibited, following PT stimulation, discharge changes that in the greatest part of cases (91%) were excitatory in nature. Excitations, always followed by inhibitory rebound, appeared with latency values compatible with a monosynaptic linkage.

Animals↗

PubMed2000

Double blinded evaluation of the effects of pallidal and subthalamic nucleus stimulation on daytime activity in advanced Parkinson's disease.

The results of a double blinded evaluation of the effects of globus pallidus (GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with advanced Parkinson's disease are summarized. The patients were evaluated at 6-8months after surgery. In order to determine the benefits afforded by the stimulation to the actual daily activities, the patients were maintained on-medication with optimal doses and schedules. The stimulation was turned off overnight for at least 12h. It was turned on in the morning (or maintained turned off), and the best and worst scores during daytime activity were recorded, as on-period and off-period scores, respectively. A reduction in total motor score on the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN stimulation at both the off-period (-57 and -29%, respectively) and the on-period (-36 and -25%, respectively). The difference in effects between GPi and STN stimulation appeared to be due largely to an unintended difference in the patients' preoperative symptoms. The benefits provided by stimulation to the actual daily activities appears to be limited in patients who have become unresponsive to a large dose of levodopa. Two advantages of GPi and STN stimulation were identified. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia. Clinically important improvement was observed in severe gait freezing in 2 patients following unilateral anterodorsal GPi stimulation on the right side alone.

Journal Article↗

PubMed2002

Deep brain stimulation of both subthalamic nucleus and internal globus pallidus restores intracortical inhibition in Parkinson's disease paralleling apomorphine effects: a paired magnetic stimulation study.

OBJECTIVE: We investigated the effect of bilateral subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on intracortical inhibition (ICI) in patients with advanced Parkinson's disease (PD). METHODS: The activity of intracortical inhibitory circuits was studied in 4 PD patients implanted with stimulating electrodes both in STN and GPi by means of paired-pulse transcranial magnetic stimulation, delivered in a conditioning-test design at short (1-6 ms) interstimulus intervals (ISI). The effect of apomorphine on the same PD patients was also investigated. RESULTS: We observed that implanted PD patients showed a significant increase in ICI during either bilateral STN or GPi DBS at 3 ms ISI, and during bilateral STN DBS at 2 ms ISI in comparison to their off DBS condition. The same statistical improvement was observed during apomorphine infusion at 3 and 2 ms ISI. In each condition, the electrophysiological changes were associated with a significant clinical improvement as measured by the Unified Parkinson's Disease Rating Scale motor examination. CONCLUSIONS: These results are consistent with the hypothesis that basal ganglia DBS can mimic the effects of pharmacological dopaminergic therapy on PD patients cortical activity. We propose that in PD patients, the basal ganglia DBS-induced improvement of ICI may be related to a recovery in modulation of thalamo-cortical motor pathway.

Antiparkinson Agents↗

PubMed2004

Unilateral battery depletion in Parkinson's disease patients treated with bilateral subthalamic nucleus deep brain stimulation may require urgent surgical replacement.

We describe 2 patients with advanced Parkinson's disease (PD) treated with bilateral deep brain stimulation of the subthalamic nucleus in whom unilateral stimulator battery depletion resulted in the rapid appearance of disabling PD symptoms (severe rigidity, bradykinesia and gait difficulty). Both patients did not respond to high doses of dopaminergic medications and were restored to their previous level of function only with battery replacement. One patient developed a deep vein thrombosis and pulmonary emboli as a result of prolonged immobility. Although extreme worsening of PD secondary to battery depletion may be rare, such patients should have their stimulators replaced promptly.

Aged↗

PubMed1987

The fine structure of the subthalamic nucleus in the cat. II. Synaptic organization. Comparisons with the synaptology and afferent connections of the pallidal complex and the substantia nigra.

The synaptic organization of the subthalamic nucleus (Sth) of the cat has been investigated by means of electron microscopy. On the basis of the following criteria: the size and the shape of the synaptic boutons, their origin, the size and the shape of the synaptic vesicles, the distribution and density of the vesicular population, and the characteristics of the active synaptic zones, several types of synaptic boutons have been discriminated: F1, F2, SR, LR1, LR2, d.c.v., and "d" profiles. The F1 and F2 types have pleomorphic vesicles and form symmetrical synapses with the neuronal perikarya, the proximal dendrites and their spines, as well as with the initial axonal segments. The SR, LR1 and LR2 types contain round or oval vesicles and form asymmetrical synapses mainly with middle sized and small dendrites, and their spines. The d.c.v. boutons contain a mixed population of clear synaptic vesicles and dense core vesicles. The d.c.v. type forms asymmetrical synapses. The "d" profiles share identical features with the vesicle containing dendrites. The F2, SR, LR1, LR2, and "d" profiles take part in synaptic diads and/or triads, and occasionally participate in the synaptic glomeruli. The LR1 and LR2 take part in glomeruluslike formations. The Sth has a distinct synaptic pattern that permits its discrimination as a separate ultrastructural entity. The Sth seems to share some common ultrastructural features with the thalamic nuclei. On the other hand, the ultrastructural aspects of the Sth are much more different from its closest embryological allies: the both pallidal segments, and the zona reticulata of the substantia nigra.

Afferent Pathways↗

PubMedDate not supplied

Systemic administration of ephedrine induces Fos protein expression in caudate putamen and subthalamic nucleus of rats.

Systemic administration of ephedrine, an anti-hypotensive agent with central effects, induced dramatic expression of Fos protein in the caudate putamen (CPu) and subthalamic nucleus (STN) of rats. This may be related to dopaminergic agonist properties that have been attributed to this compound, dopamine receptors being present in both CPu and STN. This finding seems to suggest that central effects of ephedrine might be mediated by changes in basal ganglia outflow.

Adrenergic Agonists↗

PubMed2004

Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: The goal of this project was to develop a quantitative understanding of the volume of axonal tissue directly activated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). METHODS: The 3-dimensionally inhomogeneous and anisotropic tissue medium surrounding DBS electrodes complicates our understanding of the electric field and tissue response generated by the stimulation. We developed finite element computer models to address the effects of DBS in a homogeneous isotropic medium, and a medium with tissue conductivity properties derived from human diffusion tensor magnetic resonance data. The second difference of the potential distribution generated in the tissue medium was used as a predictor of the volume of tissue supra-threshold for axonal activation. RESULTS: The model predicts that clinically effective stimulation parameters (-3 V; 0.1 ms; 150 Hz) result in activation of large diameter (5.7 microm) myelinated axons over a volume that spreads outside the borders of the STN. The shape of the activation volume was dependent on the strong dorsal-ventral anisotropy of the internal capsule, and the moderate anterior-posterior anisotropy of the region around zona incerta. CONCLUSIONS: Small deviations ( approximately 1 mm) in the electrode position within STN can substantially alter the shape of the activation volume as well as its spread to neighboring structures. SIGNIFICANCE: STN DBS represents an effective treatment for medically refractory movement disorders such as Parkinson's disease. However, stimulation induced side effects such as tetanic muscle contraction, speech disturbance and ocular deviation are not uncommon. Quantitative characterization of the spread of stimulation will aid in the development of techniques to maximize the efficacy of DBS.

Artifacts↗

PubMed1994

Characterization of dopamine receptor binding sites in the subthalamic nucleus.

Experiments were undertaken to determine the distribution and binding profile of dopamine (DA) receptors within a key extra-striatal region of the rat basal ganglia, the subthalamic nucleus (STh). Analysis of [125I]NCQ-298 autoradiograms showed that binding sites of the D2-receptor family are abundant in the STh. Competition studies indicated that these sites were specifically of the D2 subtype. However, contrary to previously published data, [125I]SCH-23982 autoradiograms failed to reveal D1 receptor binding in the STh. These data suggest that DA acting at D2 receptors may directly modulate STh neural activity and furthermore that the antagonism of STh D2 receptor binding by neuroleptics may be involved in the expression of extrapyramidal motor disturbances.

Animals↗

PubMed1999

Ablation of the subthalamic nucleus supports the survival of nigral dopaminergic neurons after nigrostriatal lesions induced by the mitochondrial toxin 3-nitropropionic acid.

We investigated the role of the excitatory afferents from the subthalamic nucleus (STN) in the death of nigral dopamine (DA) neurons after nigrostriatal axon terminal lesions. Nigral DA neurons were detected by use of both tyrosine hydroxylase immunolabeling or retrograde labeling of nigral cells with fluorogold. Sprague-Dawley rats were subjected to unilateral, quinolinic acid-induced destruction of the STN. Sham lesions of the STN were made by injecting phosphate-buffered saline. Two weeks after STN ablation, lesions of nigrostriatal DA neurons were induced by intrastriatal injections of either the mitochondrial toxin 3-nitropropionic acid (3-NP) or the catecholamine toxin 6-hydroxydopamine (6-OHDA). Intrastriatal injections of 3-NP or 6-OHDA caused a progressive loss of nigral tyrosine hydroxylase-positive or fluorogold-labeled DA neurons in a dose-dependent manner. Previous ablation of the STN significantly attenuates the loss of DA neurons in rats receiving 3-NP but not 6-OHDA. Sham lesions of the STN did not affect DA neuron death induced by the toxins. The results indicate that the excitatory inputs from the STN may contribute to the death of nigral DA neurons under a condition of 3-NP-induced metabolic impairment.

Animals↗

PubMed1985

Topographical projections of the cerebral cortex to the subthalamic nucleus.

Corticosubthalamic projections in the rat were investigated using the autoradiographic anterograde axonal tracing technique. After unilateral injections of tritiated amino acids in the cerebral cortex, projections to the ipsilateral subthalamic nucleus (STH) could be found arising only from the frontal agranular cortex and the zone of MI-SI overlap. Injections into granular areas of the cortex (e.g., somatosensory and visual areas) did not result in labeling in STH. Following injections in the frontal agranular cortex, labeling was present in the ipsilateral but not the contralateral STH. In general, injections that involved the lateral agranular field of frontal cortex, as defined by Donoghue and Wise ('82), resulted in a greater amount of labeling in STH than injections within the medial agranular area or the zone of MI-SI overlap. The projection from the frontal agranular areas to STH is topographically organized. The rostral part of the lateral agranular cortex projects to the lateral portion of the rostral two-thirds of STH, and the caudal part of this field projects to the ventral aspect of the middle third of STH. Injections in the rostral part of the medial agranular cortex resulted in labeling throughout the ventral two-thirds of the medial half of STH. The caudal part of the medial agranular cortex projects to the dorsolateral part of the caudal two-thirds of STH. The present results reveal projections from only the frontal agranular cortex and the zone of MI-SI overlap to STH in the rat. The cortico-STH projection is ipsilateral and terminates in a topographical manner in all parts of STH.

Animals↗

PubMed2000

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: methodologic aspects and clinical criteria.

The technique of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) is evolving very rapidly. The subthalamic nucleus (STN) has become the preferred target in the past few years since our group demonstrated that high-frequency stimulation in this nucleus improves all cardinal features of PD, including resting tremor. This benefit in the parkinsonian symptoms allows a drastic reduction in daily levodopa requirements. Dyskinesias become drastically attenuated, possibly as a consequence of reduced dopaminergic medication but also because STN DBS may stabilize basal ganglia output activity, thus avoiding the problems associated with standard levodopa replacement therapy. DBS of the STN is associated with a marked improvement of motor function even in patients with advanced PD. Such a large degree of benefit in parkinsonian features relies on two crucial points that must be taken into consideration for achieving the best possible results with this technique: proper selection of patients and accuracy in targeting the STN. From a neurosurgical point of view, we believe that the most precise localization of the STN is obtained by using ventriculography to determine the stereotactic coordinates of the STN. This is complemented with intraoperative neuronal microrecording to define physiologically the sensorimotor region of the nucleus. Future advances in neuroimaging techniques may well lead to modifications of our current methodology.

Adult↗

PubMed1999

A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity.

BACKGROUND: Long-term high-frequency stimulation of the subthalamic nucleus (STN) improves akinesia in Parkinson disease. The neural correlates of STN stimulation are not well understood. Positron emission tomography can be applied to the in vivo study of the mechanisms of deep brain stimulation. OBJECTIVE: To study changes in regional cerebral blood flow as an index of synaptic activity in patients with Parkinson disease with effective STN stimulation on and off during rest and movement. METHODS: Eight patients with Parkinson disease who had electrodes implanted in the STN underwent 12 measurements of regional cerebral blood flow with water O 15 positron emission tomography at rest and during performance of paced freely selected joystick movements, both with and without STN stimulation (3 scans per experimental condition). Motor performance and reaction and movement times were monitored. Statistical parametric mapping was used to compare changes in regional cerebral blood flow between conditions and differences in activation. RESULTS: All patients showed improvement in reaction and movement times during scans with the stimulator on. As predicted, increases in activation of rostral supplementary motor area and premotor cortex ipsilateral to stimulation were observed when stimulation was on during contralateral movement (P<.001). Unpredicted observations included decreases in regional cerebral blood flow in primary motor cortex at rest induced by STN stimulation. CONCLUSION: Stimulation of the STN reduces the movement-related impairment of frontal motor association areas and the inappropriate motor cortex resting activity in Parkinson disease.

Adult↗

PubMed1994

Nitric oxide synthase mRNA expression in human subthalamic nucleus, striatum and globus pallidus: implications for basal ganglia function.

The distribution of NOS mRNA within human basal ganglia was investigated using in situ hybridisation histochemistry (ISHH). Greater than 95% of subthalamic nucleus neurons were NOS mRNA-positive, between 1.5% and 2% of striatal neurons were positive and scattered NOS mRNA-positive neurons were detected in the medial, but not lateral globus pallidus. Levels of NOS mRNA expression per neuron were considerably higher in the striatum than in the pallidum or subthalamus. These findings have implications for basal ganglia function and disease states.

Amino Acid Oxidoreductases↗

PubMed1976

The neurons in the primate subthalamic nucleus: a Golgi and electron microscopic study.

In Golgi preparations of the adult monkey (Macaca mulatta) local interneurons and two varieties of principal neurons, radiating and elongated fusiform, are found in the subthalamic nucleus. The cell bodies of the radiating neurons have a few delicate, somatic spines some of which are occasionally bilobed and trilobed. Five to eight dendritic trunks give rise to branching, tapering dendrites, which may extend for over 400 microns. These dendrites are much thinner than the dendrites in the globus pallidus and the substantia nigra. Some neurons have many and some neurons have few dendritic spines. When numerous the dendritic spines are concentrated on the dendritic trunks and proximal dendrites. The relatively few elongated fusiform neurons are found not only in the capsule but also in the center of the nucleus. Most dendrites emerge from the opposite poles of their smooth surfaced cell bodies. They have a few dendritic spines. Some of these dendrites extend for more than 750 microsn. In 1-micron thick plastic sections lipofuscin granules are present in some but not all principal neuron cell bodies of the monkey (Macaca mulatta); but these granules are present in all principal neuron cell bodies of the pig-tail monkey (Macaca nemestrina) and of the squirrel monkey (Saimiri sciureus). The local interneurons have small cell bodies and a few relatively long undulating dendrites. The dendrites have bulbous dendritic appendages of varying complexity and beaded axon-like processes. The dendritic appendages and axon-like processes are more numerous distally and on the distal ends of the dendrites they form complex entanglements. Axons coming from the cell body have not been observed. The cell bodies of the local interneurons are identified in cresyl violet stained sections of the monkey (Macaca mulatta), in 1-micron thick plastic sections and electron micrographs of the squirrel monkey (Saimiri sciureus). They have relatively large nuclei surrounded by a thin rim of cytoplasm rich in polyribosomes.

Animals↗

PubMed1998

Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation.

The recent resurgent interest in functional surgery for the treatment of Parkinson's disease (PD) has focused on the effects on akinesia and levodopa-induced dyskinesia. Stimulation of the subthalamic nucleus (STN) improves akinesia and rigidity but its effects on tremor have not been studied. The objective of this study was to assess the efficacy of STN stimulation on tremor in patients with the complete parkinsonian triad with motor fluctuations. Of 27 consecutive patients with STN stimulation (26 bilateral), 15 exhibited tremor rated at least 2/4 according to item 20 (rest tremor) of the Unified Parkinson's Disease Rating Scale (UPDRS) in at least one limb. The mean preoperative tremor score was 11.3+/-5.6 in off-drug and 1.2+/-2.4 in on-drug conditions. The postoperative tremor scores at the last follow up (from 1-12 months) were 2.2+/-2.2 off-drug/on-stimulation and 0.2+/-0.4 on-drug/on-stimulation. Both rest and action tremors were improved in all patients. The UPDRS tremor score was reduced by 80%, rigidity score by 65%, and akinesia score by 51% on average. For the three symptoms, the stimulation effect was close to that induced before surgery by a suprathreshold dose of levodopa given in the morning. STN stimulation can be considered an interesting alternative to thalamic or internal pallidal surgery even in PD patients with severe high-amplitude tremor. In keeping with electrophysiological data in monkeys rendered parkinsonian by MPTP injections, our results emphasize the importance of the oscillation of a neuronal loop involving the STN in the pathophysiology of parkinsonian tremor.

Adult↗

PubMed1993

Projections of the anterior coronal gyrus to the subthalamic nucleus in the cat: a combined retrograde and anterograde WGA-HRP study.

In order to re-examine the corticosubthalamic projections in the cat, WGA-HRP was injected into the subthalamic nucleus (STN). Following WGA-HRP injections into the lateral STN, a small number of retrogradely labeled neurons were found in the anterior coronal gyrus (ACG) as well as the anterior sigmoid gyrus. To confirm the projection of the ACG to the lateral STN, which had not been reported previously, WGA-HRP was injected into the ACG. Anterogradely labeled fiber terminals were found in the dorsolateral part of the STN. These results indicate that the ACG influences the STN activity through its direct projections.

Animals↗

PubMed1998

Excitotoxic lesions of the subthalamic nucleus ameliorate asymmetry induced by striatal dopamine depletion in the rat.

We investigated the effect of unilateral dorsal striatal dopamine depletion (by intrastriatal infusion of 6-OHDA), ibotenic acid lesions of the subthalamic nucleus (STN) and combined dopamine depletion and STN lesions on sensorimotor asymmetry using a test of somatosensory asymmetry [T. Schallert et al., Pharmacol. Biochem. Behav. 16 (1982) 455-462]. The unilateral striatal dopamine depletion resulted in a somatosensory asymmetry. This asymmetry was ameliorated in the rats with combined dopamine depletion and STN lesion. indicating the potential beneficial nature of STN inactivation in rats with striatal dopamine depletion.

Animals↗

PubMed1996

Calretinin as a marker of specific neuronal subsets in primate substantia nigra and subthalamic nucleus.

Neurons immunoreactive for the calcium-binding protein calretinin (CR) were visualized in the substantia nigra (SN) pars compacta (SNc), reticulata (SNr) and lateralis (SNl), the ventral tegmental area (VTA) and the subthalamic nucleus (STN) of squirrel monkeys. The density of CR perikarya was high in VTA, moderate in SNc, low in SNr/SNl, and very low in STN. The SNc/VTA complex also displayed a CR-rich neuropil. Some CR perikarya and fibers occurred in specific sectors of STN. These data suggest that CR may play a role in specific neuronal subpopulations in all components of primate basal ganglia.

Animals↗