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Results for “Subthalamic Nucleus”

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PubMed2003

Involvement of the human subthalamic nucleus in movement preparation.

BACKGROUND: Although it has long been recognized that the basal ganglia play a major role in motor control, their precise functions remain unclear. As patients with Parkinson's disease (PD) have difficulties initiating movement, the basal ganglia may be involved in movement preparation. The subthalamic nucleus (STN) is particularly suited to play a role in movement preparation because it receives direct input from the supplementary motor area through the corticosubthalamic pathway. METHODS: Taking advantage of the electrodes surgically implanted in the STN for deep brain stimulation (DBS) treatment in 13 PD patients, we recorded from the DBS electrodes and the scalp simultaneously while the patients were performing self-paced wrist extension movements. RESULTS: Scalp recordings showed a slow, negative movement-related potential (MRP) in all patients studied (onset 1,690 +/- 336 milliseconds before electromyography onset). STN recordings showed premovement MRP in 11 of 13 patients. The STN activity occurred with both ipsilateral and contralateral hand movement. The onset time for STN MRP (contralateral 2,095 +/- 1,005 milliseconds, ipsilateral 2,020 +/- 920 milliseconds) was not significantly different from that for cortical MRP. CONCLUSION: The STN or nearby structures are active before self-paced movement in humans.

Action Potentials↗

PubMed2002

Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety.

OBJECT: Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD. METHODS: In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods. CONCLUSIONS: This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.

Aged↗

PubMed2005

Deep brain stimulation of the subthalamic nucleus reversibly deteriorates stuttering in advanced Parkinson's disease.

The etiology of developmental stuttering is still unknown. In some patients, stuttering re-emerges or is aggravated with the onset of Parkinson's disease (PD). We here report on a patient with PD treated by deep brain stimulation of the subthalamic nucleus and severe deterioration of stuttering under effective stimulation. Positron emission tomography (PET) of regional cerebral blood flow (rCBF) in stimulation on- and off-conditions showed overactivation of cerebral and cerebellar motor systems during speech activation and was in line with recent PET studies investigating brain activation during stuttering. The abnormal rCBF pattern increased in the stimulation on-condition and was associated with a marked worsening of stuttering. Clinical and imaging findings in this patient support the hypothesis that the basal ganglia circuitry plays an important role in the pathophysiology of stuttering.

Antiparkinson Agents↗

PubMed2004

Effects of bilateral subthalamic nucleus stimulation on resting-state cerebral glucose metabolism in advanced Parkinson's disease.

BACKGROUND: The major neuropathological symptoms of Parkinson's disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism in advanced PD, and investigate the mechanism of deep brain stimulation (DBS). METHODS: Seven consecutive advanced PD patients (4 men and 3 women, mean age 64 +/- 4 years, mean H-Y disability rating 4.4 +/- 0.65) receiving bilateral STN DBS underwent 18F-fluorodeoxyglucose (18F-FDG)/positron-emission tomography (PET) examinations at rest both preoperatively and one month postoperatively, with STN stimulation still on. The unified PD rating scale was used to evaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to investigate the regional cerebral metabolic rates of glucose (rCMRGlu) during STN stimulation, and to compare these values to rCMRGlu preoperation. RESULTS: STN stimulation clearly improved clinical symptoms in all patients. A significant increase in rCMRGlu was found in the bilateral lentiform nucleus, brainstem (midbrain and pons), bilateral premotor area (BA6), parietal-occipital cortex, and anterior cingulated cortex, and a marked decrease in rCMRGlu was noted in the left limbic lobe and bilateral inferior frontal cortex (P < 0.05). CONCLUSION: Bilateral STN stimulation may activate the projection axon from the STN, improving clinical symptoms in advanced PD patients by improving both ascending and descending pathways from the basal ganglia and increasing the metabolism of higher-order motor control in the frontal cortex.

Brain↗

PubMed1999

Effect of bilateral subthalamic nucleus stimulation and dopatherapy on oral control in Parkinson's disease.

This study focuses on the speech organs of a parkinsonian patient who initially had been treated with levodopa for 13 years, and had become severely disabled by motor fluctuations. This patient has been treated with bilateral chronic stimulation of the subthalamic nucleus (STN) for the last 2 years. Upper lip, lower lip and tongue force production were examined before surgery under off and on medication conditions, and 2 years after surgery under off and on stimulation conditions. We compared the effect of stimulation and dopatherapy on the speech organs. L-Dopa had a poor effect whereas bilateral stimulation improved oral control and speech intelligibility. These results suggest that STN stimulation influences speech organs in a different way from the dopaminergic system and similarly affects oral and limb motor systems.

Analysis of Variance↗

PubMed2006

Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson's disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus.

BACKGROUND: The clinical condition of advanced Parkinson's disease (PD) patients is often complicated by motor fluctuations and dyskinesias which are difficult to control with available oral medications. OBJECTIVE: To compare clinical and neuropsychological 12 month outcome following subcutaneous apomorphine infusion (APO) and chronic deep brain stimulation of the subthalamic nucleus (STN-DBS) in advanced PD patients. METHODS: Patients with advanced PD and medically untreatable fluctuations underwent either APO (13 patients) or STN-DBS (12 patients). All patients were clinically (UPDRS-III, AIMS, 12 h on-off daily) and neuropsychologically (MMSE, Hamilton-17 depression, NPI) evaluated at baseline and at 12 months. APO was discontinued at night. RESULTS: At 12 months APO treatment (74.78+/-24.42 mg/day) resulted in significant reduction in off time (-51%) and no change in AIMS. Levodopa equivalent medication doses were reduced from 665.98+/-215 mg/day at baseline to 470+/-229 mg/day. MMSE, NPI, and Hamilton depression scores were unchanged. At 12 months STN-DBS resulted in significant clinical improvement in terms of reduction in daily off time (-76%) and AIMS (-81%) as well as levodopa equivalent medication doses (980+/-835 to 374+/-284 mg/day). Four out of 12 patients had stopped oral medications. MMSE was unchanged (from 28.6+/-0.3 to 28.4+/-0.6). Hamilton depression was also unchanged, but NPI showed significant worsening (from 6.58+/-9.8 to 18.16+/-10.2; p<0.02). Category fluency also declined. CONCLUSIONS: Both APO and STN-DBS resulted in significant clinical improvement in complicated PD. STN-DBS resulted in greater reduction in dopaminergic medications and provided 24 h motor benefit. However, STN-DBS, unlike APO, appears to be associated with significant worsening on NPI resulting from long term behavioral problems in some patients.

Aged↗

PubMed2000

Bilateral subthalamic nucleus stimulation in a parkinsonian patient with preoperative deficits in speech and cognition: persistent improvement in mobility but increased dependency: a case study.

We report a patient with advanced Parkinson's disease, including severe and frequent off periods with freezing of gait, moderate dysphonia, and some cognitive impairment, who underwent bilateral subthalamic nucleus (STN) stimulation. The patient was followed for 1 year after surgery, showing persistent good mobility without off periods and without freezing, which reverted completely when stopping the stimulation. There was deterioration of cognition as well as increased aphonia and drooling, all of which remained when the stimulation was turned off. The striking improvement in motor symptoms following STN stimulation was not paralleled by improvement in disability, probably as a result of a cognitive decline, suggesting a diagnosis of Parkinson's disease with dementia. We conclude that chronic STN stimulation is efficient in alleviating akinetic motor symptoms including gait freezing; this surgery should be offered before patients start to exhibit speech or cognitive disturbances.

Dementia↗

PubMed2002

Neuropsychological sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a critical review.

Neuropsychologists are increasingly involved in surgical candidacy evaluations and postoperative neurobehavioral assessments of patients with movement disorders, most notably those with Parkinson's disease (PD). We review here the initial studies regarding neuropsychological outcomes of deep brain stimulation (DBS) within the subthalamic nucleus (STN) for treatment of PD. Overall, these initial investigations provide preliminary support for the cognitive and neurobehavioral safety of STN DBS. Improvements in self-reported symptoms of depression and diminished verbal fluency were the most common findings, whereas changes in global cognitive abilities, memory, attention, and frontal/executive functions were inconsistent and most often described as nominal and/or transient. The generalizability of this literature is hindered by several methodological limitations, including small samples and the absence of appropriate control participants. The clinical and theoretical implications of these initial studies are highlighted and recommendations are offered to guide future research.

Cognition Disorders↗

PubMed1998

Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease.

OBJECTIVE: To examine objectively the clinical effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in advanced PD. METHODS: Our initial seven consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic STN DBS underwent a standardized preoperative evaluation followed by a 2-day double-blind evaluation of efficacy 6 to 12 months after electrode implantation. Diaries documenting motor fluctuations and dyskinesias were also completed preoperatively and postoperatively. RESULTS: In the medication-off state, turning the stimulators on resulted in improvement in mean total Unified Parkinson's Disease Rating Scale (UPDRS) motor score by 58% including the following improvements in composite scores: akinesia 57%, rigidity 52%, tremor 82%, and gait and postural stability 49%. Additionally, the medication-off state improved 17% without stimulation, possibly as a result of electrode insertion alone or carry-over of chronic stimulation. In the medication-on, stimulation-on state, all major features of parkinsonism improved and total UPDRS motor score improved 41% compared with before surgery. Activities of daily living were improved while off medication 30%, and levodopa-induced dyskinesias were reduced 83% while total drug dosage was decreased 40%. With chronic stimulation, patients reported that the percentage of time spent in the "on" state (without dyskinesias) increased from 26% to 52% and "off" time decreased from 30% to 6%. Operative complications including cognitive worsening were not uncommon. CONCLUSIONS: STN DBS is a promising new surgical option for the treatment of advanced PD. The marked clinical benefits obtained in these severely disabled patients outweighed the adverse effects.

Aged↗

PubMed1997

The response of subthalamic nucleus neurons to dopamine receptor stimulation in a rodent model of Parkinson's disease.

Overactivity in the subthalamic nucleus (STN) is believed to contribute to the pathophysiology of Parkinson's disease. It is hypothesized that dopamine receptor agonists reduce neuronal output from the STN. The present study tests this hypothesis by using in vivo extracellular single unit recording techniques to measure neuronal activity in the STN of rats with 6-hydroxydopamine-induced lesions of the nigrostriatal pathway (a model of Parkinson's disease). As predicted, firing rates of STN neurons in lesioned rats were tonically elevated under basal conditions and were decreased by the nonselective dopamine receptor agonists apomorphine and L-3, 4-dihydroxyphenylalanine (L-DOPA). STN firing rates were also decreased by the D2 receptor agonist quinpirole when administered after the D1 receptor agonist (+/-)- 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393). Results of the present study challenge the prediction that dopaminergic agonists reduce STN activity predominantly through actions at striatal dopamine D2 receptors. Firing rates of STN neurons were not altered by selective stimulation of D2 receptors and were increased by selective stimulation of D1 receptors. Moreover, there was a striking difference between the responses of the STN to D1/D2 receptor stimulation in the lesioned and intact rat; apomorphine inhibited STN firing in the lesioned rat and increased STN firing in the intact rat. These findings support the premise that therapeutic efficacy in the treatment of Parkinson's disease is associated with a decrease in the activity of the STN, but challenge assumptions about the roles of D1 and D2 receptors in the regulation of neuronal activity of the STN in both the intact and dopamine-depleted states.

Animals↗

PubMed2007

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.

Aged↗

PubMed2006

Somatotopically arranged inputs from putamen and subthalamic nucleus to primary motor cortex.

Employing retrograde transsynaptic transport of rabies virus, we investigated the organization of basal ganglia inputs to hindlimb, proximal and distal forelimb, and orofacial representations of the macaque primary motor cortex (MI). Four days after rabies injections into these MI regions, neuronal labeling occurred in the striatum and the subthalamic nucleus (STN) through the cortico-basal ganglia loop circuits. In the striatum, two distinct sets of the labeling were observed: one in the dorsal putamen, and the other in the ventral striatum (ventromedial putamen and nucleus accumbens). The dorsal striatal labeling was somatotopically arranged and its distribution pattern was in good accordance with that of the corticostriatal inputs, such that the hindlimb, orofacial, or forelimb area was located in the dorsal, ventral, or intermediate zone of the putamen, respectively. The distribution pattern of the ventral striatal labeling was essentially the same in all cases. In the STN, the somatotopic arrangement of labeled neurons was in register with that of corticosubthalamic inputs. The present results suggest that the cortico-basal ganglia motor circuits involving the dorsal putamen and the STN may constitute separate closed loops based on the somatotopy, while the ventral striatum provides common multisynaptic projections to all body-part representations in the MI.

Afferent Pathways↗

PubMed2006

Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation.

Pathological gambling (PG) related to dopaminergic treatment in Parkinson's disease (PD) is part of a spectrum of behavioral disorders called the dopamine dysregulation syndrome (DDS). We describe a series of PD patients with preoperative active PG due to dopaminergic treatment from a total of 598 patients who have undergone surgery for subthalamic nucleus stimulation for disabling motor fluctuations. The patients had systematic open assessment of behavioral symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven patients (6 men, 1 woman; age, 54 +/- 9 years; levodopa equivalent dose, 1,390 +/- 350 mg/day) had preoperative PG over a mean of 7 years, intolerant to reduction in medication. Six had nonmotor fluctuations and four had other behavioral symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms improved, allowing for 74% reduction of dopaminergic treatment, below the dosage of gambling onset. In all patients, PG resolved postoperatively after 18 months on average (range, 0-48), although transient worsening occurred in two. Improvement paralleled the time course and degree of reduction in dopaminergic treatment. Nonmotor fluctuations, off period dysphoria, and other symptoms of the DDS improved. Two patients developed persistent apathy. In conclusion, PG and other symptoms of the DDS-associated dopaminergic treatment improved in our patients following surgery. Dopaminergic dysregulation commonly attributed to pulsatile overstimulation of the limbic dopaminergic system may be subject to desensitization on chronic subthalamic stimulation, which has a relative motor selectivity and allows for decrease in dopaminergic treatment.

Adult↗

PubMed2001

Non-motor effects of deep brain stimulation of the subthalamic nucleus in Parkinson's disease: preliminary physiological results.

Although deep brain stimulation (DBS) is a clinically effective therapy for patients with advanced Parkinson's disease (PD), its physiological effects on the brain and possible actions on non-motor functional systems remain largely unknown. This study evaluated the effects of DBS of the subthalamic nucleus (STN) on neurophysiological variables and on cardiovascular physiology. Nine patients affected by PD undergoing chronic DBS of the STN have been studied. We performed electroencephalography (EEG), somatosensory (SEPs) and visual evoked potentials (VEPs), exteroceptive masseteric silent period and sympathetic skin response (SSR) studies with DBS ON and OFF. To assess the effects of stimulation on the cardiovascular system the tilt test and plasma renin activity were studied. When we turned the DBS OFF, both SEP N20 and the VEP P100 component increased significantly in amplitude whereas the SSR decreased in amplitude and increased in latency. Although plasma renin activity tended to increase with DBS OFF, its modification induced by postural changes and blood pressure values did not significantly differ with DBS ON and OFF. We conclude that DBS of the STN in PD, besides inducing a clinical improvement, induces several non-motor effects.

Afferent Pathways↗

PubMed2004

Bilateral subthalamic nucleus stimulation results in reversal of alopecia in Parkinson's disease.

Alopecia is a rare but important side effect of anti-parkinsonian medications. Our patient was a 72-year-old man with advanced Parkinson's disease (PD) who received levodopa and anti-cholinergic drugs and whose head had become almost completely bald. As bilateral subthalamic nucleus (STN) stimulation produced improvement in his motor symptoms, his drug dosages were reduced postoperatively. At 8 months after surgery, hair again covered his entire head. Our study presents a new aspect of the benefit of STN stimulation with regard to drug-induced non-motor symptoms in patient with PD.

Aged↗

PubMed2001

Lesioning the subthalamic nucleus in the treatment of Parkinson's disease.

Ever since it was demonstrated about twenty years ago by two independent groups (Aziz et al. and Bergman et al.) that the cardinal clinical features of MPTP-induced Parkinson's disease (PD) in non-human primate models can be alleviated by lesions of the subthalamic nucleus (STN), this structure has been the focus of interest for functional neurosurgeons involved in the treatment of PD. Initially lesioning and later chronic high frequency stimulation of the STN has become the standard surgical target of akinetic PD. In this brief report we present our experience with 14 STN lesions (8 unilateral and 3 bilateral) confirmed by post-operative imaging. We found significant improvement in OFF rigidity and in ON tremor following unilateral lesions. The major complications were speech disturbance and L-Dopa resistant limb dystonia. Functional disability scores showed inconsistent reduction. There was insufficient data to comment on the significance of bilateral lesions; however, there was a similar pattern of improvement in tremor and speech disturbance. In addition, there was worsening of gait. We comment on the lower degree of improvement in motor scores in our series compared to the few others in recent literature and stress that even in these studies the UPDRS benefits did not translate directly into functional benefit for the patients.

Electrodes, Implanted↗

PubMed2006

Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson's disease.

Deep brain stimulation is generally a safe and effective method of alleviating motor impairment in advanced-stage Parkinson's disease patients. However, adverse events of surgery have been noted, such as hemorrhage, infection, seizures, and device failure. In this report, we describe 2 cases of the unusual adverse event of ischemia associated with subthalamic nucleus stimulator implantation. We present the intraoperative neurological symptoms, microelectrode recording data, imaging findings, and other correlated events. In the first case, the clinical effects of ischemia were evident intraoperatively and coincided with silence during microelectrode recording from the ischemic region. In the second case, the timing of the ischemic event could not be determined precisely but also was associated with a difficult mapping. Subcortical ischemia may be an underrecognized event that confounds neurophysiological mapping of deep brain structures and affects clinical outcomes.

Aged↗

PubMed2001

Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson's disease.

The extent of synchronization within and between the nuclei of the basal ganglia is unknown in Parkinson's disease. The question is an important one because synchronization will increase postsynaptic efficacy at subsequent projection targets. We simultaneously recorded local potentials (LPs) from the globus pallidus interna (GPi) and subthalamic nucleus (STN) in four awake patients after neurosurgery for Parkinson's disease. Nuclei from both sides were recorded in two patients so that a total of six ipsilateral GPi-STN LP recordings were made. Without medication, the power within and the coherence between the GPi and STN was dominated by activity with a frequency <30 Hz. Treatment with the dopamine precursor levodopa reduced the low-frequency activity and resulted in a new peak at approximately 70 Hz. This was evident in the power spectrum from STN and GPi and in the coherence between these nuclei. The phase relationship between the nuclei varied in a complex manner according to frequency band and the presence of exogenous dopaminergic stimulation. Synchronization of activity does occur between pallidum and STN, and its pattern is critically dependent on the level of dopaminergic activity.

Biological Clocks↗