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PubMed2001

Bilateral subthalamic nucleus stimulation does not improve prolonged P300 latencies in Parkinson's disease.

Bilateral deep brain stimulation is an effective treatment for most motor signs of Parkinson's disease (PD), but the effects on cognitive functions are less clear. We therefore examined the effects of bilateral deep brain stimulation on central information processing, using the event-related auditory P300 potential as an electrophysiological index of mental chronometry. Eight PD patients with bilateral stimulators within the subthalamic nuclei (STN) and eight age-matched controls participated. Patients were examined after overnight withdrawal of antiparkinson medication, both "on" and "off" stimulation (in random sequence). The P300 and reaction times were recorded using an auditory oddball paradigm. P300 latencies were prolonged in PD patients off stimulation (440 +/- 45 ms) compared to controls (397 +/- 16 ms; P < 0.05). STN stimulation significantly reduced clinical disease severity (as indexed by the Unified Parkinson's Disease Rating Scale) and markedly improved reaction times, but did not improve the prolonged P300 latencies in PD patients (429 +/- 36 ms). These results confirm that P300 latencies are prolonged in PD. Significantly, bilateral STN stimulation did not improve this electrophysiological measure of cognitive impairment, even though motor disability was markedly reduced. This suggests that some dopa-responsive features are resistant to STN stimulation, possibly due to involvement of dopaminergic deficits outside the nigrostriatal pathway, which are not influenced by outflow from the STN.

Aged↗
PubMed1992

Visual and oculomotor functions of monkey subthalamic nucleus.

1. Single-unit recordings were obtained from the subthalamic nuclei of three monkeys trained to perform a series of visuooculomotor tasks. The monkeys were trained to fixate on a spot of light on the screen (fixation task). When the spot was turned off and a target spot came on, they were required to fixate on the target quickly by making a saccade. Visually guided saccades were elicited when the target came on without a time gap (saccade task). Memory-guided saccades were elicited by delivering a brief cue stimulus while the monkey was fixating; after a delay, the fixation spot was turned off and the monkey made a saccade to the remembered target (delayed saccade task). 2. Of 265 neurons tested, 95 showed spike activity that was related to some aspects of the visuooculomotor tasks, whereas 66 neurons responded to active or passive limb or body movements. The task-related activities were classified into the following categories: eye fixation-related, saccade-related, visual stimulus-related, target- and reward-related, and lever release-related. 3. Activity related to eye fixation (n = 22) consisted of a sustained spike discharge that occurred while the animal was fixating on a target light during the tasks. The activity increased after the animal started fixating on the target and abruptly ceased when the target went off. The activity was unrelated to eye position. It was not elicited during eye fixation outside the tasks. The activity decreased when the target spot was removed. 4. Activity related to saccades (n = 22) consisted of a phasic increase in spike frequency that was time locked with a saccade made during the tasks. The greatest increases occurred predominantly after saccade onset. This activity usually was unrelated to spontaneous saccades made outside the task. The changes in activity typically were optimal in one direction, generally toward the contralateral side. 5. Visual responses (n = 14) consisted of a phasic excitation in response to a visual probe stimulus or target. Response latencies usually were 70-120 ms. The receptive fields generally were centered in the contralateral hemifield, sometimes extending into the ipsilateral field. The receptive fields included the foveal region in seven neurons; most of these neurons responded best to parafoveal stimulation. Peripheral stimuli sometimes suppressed the activity of visually responsive neurons. 6. Activity related to target and reward (n = 29) consisted of sustained spike discharge that occurred only when the monkey could expect a reward by detecting the dimming of the light spot that he was fixating.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a therapy approaching evidence-based standards.

DBS of the STN is one of the most promising new therapies for the treatment of PD. However - like many other therapies for PD - the present stage of the scientific assessment does not yet suffice the rigid criteria of evidence-based medicine. Further studies should specifically address the questions of efficacy and side effects as well as the impact on quality of life.

Dyskinesias↗
PubMed2005

Effect of subthalamic nucleus stimulation patterns on motor performance in Parkinson's disease.

We studied different patterns of deep brain stimulation (DBS), but same average rate, in seven Parkinson disease patients performing a wrist flexion/extension task. Movement times were shorter with regular (continuous) stimulation than cycled 'on' and 'off' for 0.1s (mean difference 0.129 s; 95% confidence interval [CI], 0.228-0.029 s; P < 0.007) and tended to be shorter than cycling at 0.5s (mean difference 0.076 s, 95% CI, 0.171 to -0.020 s; P < 0.6). Movement times under stimulation cycling at 0.5 s tended to be shorter than cycling at 0.1 s (mean difference, 0.083 s, 95% CI, 0.188 to -0.022 s, P < 0.12). Any therapeutic mechanisms of action of DBS must account for patterns of stimulation.

Adult↗
PubMed2001

Targeting the subthalamic nucleus.

The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.

Electric Stimulation Therapy↗
PubMed2003

Lateralized effects of subthalamic nucleus stimulation on different aspects of speech in Parkinson's disease.

In this report, we have analyzed the effects of left and right STN stimulation separately on different aspects of speech. Significant differences were found between left and right stimulation. It appears that selective left-sided stimulation has a profoundly negative effect on prosody, articulation and hence intelligibility. Right-sided stimulation does not display this side-effect. There is no significant difference in speech characteristics between bilateral stimulation on and off. We suggest that a balanced tuning of bilateral basal ganglia networks is necessary for speech, and that the left circuit is probably dominant.

Adult↗
PubMed2004

Monopolar versus bipolar high frequency stimulation in the rat subthalamic nucleus: differences in histological damage.

The aim of the present study was to determine the effects of monopolar and bipolar high frequency stimulation (HFS) on histological damage and current flow using a commonly applied stimulus amplitude (300 microA). Bipolar HFS resulted in a large amount of histological damage whereas with monopolar HFS no damage was observed except for the electrode trajectory. Oscilloscopic readings confirmed that this was due to the application of twice as much current to the target with bipolar HFS. Our results demonstrate that there are differences in tissue damage dependent of polarity. In order to create a better comparison to the clinical condition, we suggest that the present rodent models for studying the effect of chronic HFS require further adjustment. This can be achieved by decreasing the present current densities to a level comparable to the human situation.

Animals↗
PubMed2001

Which target for DBS in Parkinson's disease? Subthalamic nucleus versus globus pallidus internus.

We selected 14 patients with advanced idiopathic Parkinson's disease (PD) and examined the clinical effects of STN DBS versus GPi DBS. Nine patients underwent bilateral STN DBS and five underwent bilateral GPi patients. All patients were followed for at least 12 months. The evaluation was performed on and off drug before surgery; on-drug/on-DBS and off-drug/on-DBS at 1, 3, 6 and 12 months after stereotactic surgery. At 1 and 3 months after surgery in off-drug/on-DBS condition, both groups showed an improvement in motor score (UPDRS III). Nevertheless, the results changed after long-term stimulation in the two groups. Chronic STN DBS is superior to GPi DBS in the amelioration of the clinical features and in the decrease of time spent in the off state. The efficacy in reduction of LID was comparable at 1 and 3 months after surgery, but the results were better in STN DBS after chronic stimulation. The L-dopa dose was reduced only in the STN group.

Electric Stimulation Therapy↗
PubMed2003

[Bilateral subthalamic nucleus deep-brain stimulation (STN-DBS) in Parkinson's disease: initial experience in Cruces Hospital].

INTRODUCTION: Clinical outcomes of Parkinson's disease patients treated for 12 months with STN-DBS were analyzed. PATIENTS ADN METHODS: Twelve patients were selected using the CAPSIT protocol criteria and placement of electrodes in the appropriate target was performed according to results of fusion image techniques and intraoperative microrecording. RESULTS: A reduction in motor UPDRS (44 %) and activities of daily living (58 %) scores during < > phases were observed. < > time with dyskinesias was reduced (86 %), while severe dyskinesias disappeared. Levodopa dosage was also lowered (44 %). Patients and caregivers showed a clear-cut benefit on quality of life (58 % and 61 % respectively). No cognitive deterioration was observed and morbidity was in the same range as that published by other teams. CONCLUSION: Bilateral STN-DBS is an effective symptomatic therapy for complicated Parkinsońs disease patients. It improves the quality of life of patients and their caregivers and allows a reduction of levodopa dosage.

Aged↗
PubMed2001

Stereotactic subthalamic nucleus lesioning for the treatment of Parkinson's disease.

This study was performed to evaluate the effectiveness and safety of unilateral STN lesioning in 23 patients with PD. L-Dopa intake and dyskinesia, Hoehn & Yahr, Schwab & England, and UPDRS motor scores were recorded pre- and postoperatively. Stereotactic MRI and CT and macrostimulation were used to establish target coordinates. A single RF lesion was performed. All patients underwent postoperative MRI. Contralateral tremor arrest and decrease of rigidity and bradykinesia should be regarded as hallmarks to STN stimulation. All recorded parameters were significantly improved after a mean follow-up of 13.5 months. Patients with STN lateral territory lesioning (alpha <0.05), younger than 61 years and with a duration of the disease between 6 and 9 years (alpha >0.05) did better than the others. The recurrence rate was 10%. Two patients developed dyskinesias which were completely resolved by a Vim/VOp lesion. Other significant complications were rare. The authors conclude that unilateral STN lesioning is a safe and very effective procedure to treat PD.

Antiparkinson Agents↗
PubMed2005

The beneficial effects of subthalamic nucleus stimulation on manipulative finger force control in Parkinson's disease.

We investigated the differential effects of levodopa medication and STN stimulation on finger force control in Parkinson subjects grasping to lift an object and performing vertical point-to-point movements of a hand-held object. The experiments were conducted in four treatment conditions: off-drug/off-stimulation, off-drug/on-stimulation, on-drug/off-stimulation and on-drug/on-stimulation. We found that the bradykinesia in Parkinsonian subjects improved by both levodopa medication and STN stimulation. As compared to healthy subjects, excessive grip force was observed in all Parkinson subjects, regardless of the treatment condition. This force excess was most pronounced in the on-drug condition and ameliorated by STN stimulation. We observed reliable correlations between the amount of force overflow and the severity of levodopa-induced dyskinesias in the on-drug condition. Despite some similarities regarding therapeutic effects on bradykinesia, our findings contrast with earlier observations with respect to the differential effects of levodopa and STN stimulation on the scaling of fingertip forces in Parkinson's disease. While levodopa causes an overshoot of fingertip forces, STN stimulation appears to be sufficient to alleviate, but not normalise the force excess. STN stimulation enables Parkinson subjects to scale grip force more accurately to the loads arising from voluntary manipulation of hand-held objects.

Adult↗
PubMed2006

Saccade-related potentials recorded from human subthalamic nucleus.

OBJECTIVE: To investigate an ocular motor role for the STN in Parkinson's disease (PD) patients. METHODS: Potentials were recorded from deep brain stimulation (DBS) electrodes implanted in the vicinity of STN in five PD patients, while patients simultaneously performed visually cued saccades, self-paced saccades and in two patients self-paced wrist extensions. RESULTS: Premovement potentials related to visually cued saccades were found in 4/5 patients and 56% (5/9) of potentials showed phase reversal indicating a local generator. Onsets of these potentials began closer to saccade initiation from STN contacts (0.88+/-0.30s) than thalamic ones (1.39+/-0.28 s). Self-paced saccade-related potentials were found in 4/4 patients. Self-paced saccade potential onsets (1.82+/-0.88 s) were not different from self-paced wrist extension onsets (1.27+/-0.98 s), suggesting a non-specific mechanism could be responsible for both potentials. 50% (3/6) of potentials to self-paced saccades and 66% (2/3) of potentials to self-paced wrist extensions showed phase reversal. Potentials could be found either ipsilaterally or contralaterally with respect to saccade direction. CONCLUSIONS: These subcortical premovement potentials to saccades are similar to Bereitschaftspotentials and contingent negative variations to limb movements recorded in cortical and subcortical regions. SIGNIFICANCE: These studies further support a role of STN in ocular motor control and suggest a common mechanism of motor preparation for both eye and limb movements in the basal ganglia.

Adult↗
PubMed2004

Re-appraising contemporary theories of subcortical participation in language: proposing an interhemispheric regulatory function for the subthalamic nucleus (STN) in the mediation of high-level linguistic processes.

Apropos the basal ganglia, the dominant striatum and globus pallidus internus (GPi) have been hypothesized to represent integral components of subcortical language circuitry. Working subcortical language theories, however, have failed thus far to consider a role for the STN in the mediation of linguistic processes, a structure recently defined as the driving force of basal ganglia output. The aim of this research was to investigate the impact of surgically induced functional inhibition of the STN upon linguistic abilities, within the context of established models of basal ganglia participation in language. Two males with surgically induced'lesions'of the dominant and non-dominant dorsolateral STN, aimed at relieving Parkinsonian motor symptoms, served as experimental subjects. General and high-level language profiles were compiled for each subject up to 1 month prior to and 3 months following neurosurgery, within the drug-on state (i.e., when optimally medicated). Comparable post-operative alterations in linguistic performance were observed subsequent to surgically induced functional inhibition of the left and right STN. More specifically, higher proportions of reliable decline as opposed to improvement in post-operative performance were demonstrated by both subjects on complex language tasks, hypothesised to entail the interplay of cognitive-linguistic processes. The outcomes of the current research challenge unilateralised models of functional basal ganglia organisation with the proposal of a potential interhemispheric regulatory function for the STN in the mediation of high-level linguistic processes.

Aged↗
PubMed2005

Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study.

In this study we aimed to investigate the effects of bilateral STN HFS in patients with advanced Parkinson disease (PD) at long-term, with a minimum follow-up of 4 years. Twenty patients (15 men, five women) were included, with a mean age of 60.9+/-8.1 years. Surgery was performed under local anesthesia. The target was defined on computerized tomography (CT). At 3 months, significant improvements were found on the total Unified Parkinson disease rating scale (UPDRS) III (motor) score, in the medication. off (from 42.3+/-9.3 to 19.5+/-6.4), as well as the medication on (from 18.6+/-12.1 to 10.1+/-5.9) phase. The UPDRS IVa (dyskinesias) and IVb (motor fluctuations) scores decreased significantly. At long-term follow-up, there were still significant improvements on the total UPDRS III motor score (from 42.3+/-9.3 to 24.2+/-13.2), as well as in all motor subscores, in the off phase, during stimulation. In the on phase, the only significant improvement was seen for rigidity. Complications included hypomania to mania in four patients. Our results indicate that HFS STN results in long-lasting improvement of the motor symptoms, ADL activities and functional performance in patients suffering from advanced PD. The stimulation induced behavioural changes need special consideration.

Activities of Daily Living↗
PubMed2004

Reappraising contemporary theories of subcortical participation in language: proposing an interhemispheric regulatory function for the subthalamic nucleus (STN) in the mediation of high-level linguistic processes.

Apropos the basal ganglia, the dominant striatum and globus pallidus internus (GPi) have been hypothesised to represent integral components of subcortical language circuitry. Working subcortical language theories, however, have failed thus far to consider a role for the STN in the mediation of linguistic processes, a structure recently defined as the driving force of basal ganglia output. The aim of this research was to investigate the impact of surgically induced functional inhibition of the STN upon linguistic abilities, within the context of established models of basal ganglia participation in language. Two males with surgically induced 'lesions' of the dominant and non-dominant dorsolateral STN, aimed at relieving Parkinsonian motor symptoms, served as experimental subjects. General and high-level language profiles were compiled for each subject up to 1 month prior to and 3 months following neurosurgery, within the drug-on state (i.e., when optimally medicated). Comparable post-operative alterations in linguistic performance were observed subsequent to surgically induced functional inhibition of the left and right STN. More specifically, higher proportions of reliable decline as opposed to improvement in post-operative performance were demonstrated by both subjects on complex language tasks, hypothesised to entail the interplay of cognitive-linguistic processes. The outcomes of the current research challenge unilateralised models of functional basal ganglia organisation with the proposal of a potential interhemispheric regulatory function for the STN in the mediation of high-level linguistic processes.

Aged↗