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PubMed2006

Stimulation of subthalamic nucleus inhibits emotional activation of fusiform gyrus.

In patients with Parkinson's disease, deep brain stimulation of the subthalamic nucleus is known to impair their ability to correctly identify facial expressions of negative emotions. This difficulty exists only when the stimulator is active. The reason for the impairment is unknown. To test the hypothesis that the stimulation itself is responsible, we used positron emission tomography to compare functional activations of brain regions in nine patients with Parkinson's disease treated with surgically implanted electrodes into both subthalamic nuclei, and 22 healthy volunteers. Both groups viewed images with neutral or emotional content from Aarhus University's standard Empathy Picture System () with 360 images of people in pleasant, unpleasant or neutral real-life situations, presenting either the situations or close-ups of the facial expressions of the people involved. Both groups, the patients with stimulation OFF and the healthy volunteers, had raised regional blood flow rates (rCBF) in the right fusiform gyrus when they viewed emotionally expressive faces compared to neutral faces. With stimulation turned on, this response was significantly inhibited in the patients because of a raised rCBF at baseline during the neutral faces. Stimulation of the STN did not alter fusiform reaction to emotionally pregnant scenes; nor did healthy volunteers and patients react differently to these stimuli regardless of stimulation status. Also, STN stimulation raised the emotional activation of the anterior cingulate and lowered the activity of the putamen. The findings suggest that the stimulation of the subthalamic nucleus interferes with the integration of specific neocortical networks involved in the recognition of facial expressions.

Adult↗

PubMed2003

Pulse width is associated with cognitive decline after thalamic stimulation for essential tremor.

The present study sought to identify predictors of cognitive decline after thalamic deep brain stimulation (DBS) for essential tremor (ET). Twenty-seven patients (55%) with ET demonstrated mild cognitive decrements relative to pre-surgical baseline (ET-D), whereas 22 patients (45%) were classified as neuropsychologically stable (ET-S). The ET-D and ET-S groups were comparable in terms of baseline demographic, disease, and neuropsychological characteristics, as well as post-surgical motor outcomes. However, the ET-D group had significantly higher pulse width (PW) stimulator settings, and a greater proportion of ET-D than ET-S patients underwent left in comparison to right thalamic stimulation. A subsequent step-wise discriminant function analysis revealed that disease onset after age 37 years and higher PW settings (>or=120 micros) were the strongest predictors of post-surgical cognitive decline in this sample. Findings indicate that although relatively higher PW settings might afford optimal tremor control in some patients, the corresponding risk of mild, probably often subclinical, cognitive morbidity must be weighed accordingly.

Aged↗

PubMed2003

MRI directed bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease.

OBJECTIVE: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson's disease refractory to medical therapy. Advances in neuroimaging and neurophysiology have led to the development of varied targeting methods for the delivery of this treatment. Intraoperative neurophysiological and clinical monitoring is regarded by many to be mandatory for accurate STN localisation. We have examined efficacy of bilateral STN stimulation using a predominantly magnetic resonance imaging (MRI)-directed technique. METHODS: DBS leads were stereotactically implanted into the STN using an MRI directed method, with intraoperative macrostimulation used purely for adjustment. The effects of DBS were evaluated in 16 patients followed up to 12 months, and compared with baseline assessments. Assessments were performed in both off and on medication states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. Functional status outcomes were examined using the PDQ-39 quality of life questionnaire. A battery of psychometric tests was used to assess cognition. RESULTS: After 12 months, stimulation in the off medication state resulted in significant improvements in Activities of Daily Living and Motor scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests were significantly improved in the off medication state. Motor scores (UPDRS part III) were significantly improved by 40% in the on medication state. Dyskinesias and off duration were significantly reduced and the mean dose of L-dopa equivalents was reduced by half. Psychometric test scores were mostly unchanged or improved. Adverse events were few. CONCLUSIONS: An MRI directed targeting method for implantation of DBS leads into the STN can be used safely and effectively, and results are comparable with studies using intraoperative microelectrode neurophysiological targeting. In addition, our method was associated with an efficient use of operating time, and without the necessary costs of microelectrode recording.

Aged↗

PubMed2005

Differential effects of subthalamic nucleus stimulation in advanced Parkinson disease on reaction time performance.

The aim of the present study was to assess the effect of bilateral subthalamic nucleus (STN) stimulation and dopaminergic medication on speed of mental processing and motor function. Thirty-nine patients suffering from advanced Parkinson disease (PD) were operated on. Motor function and reaction time (RT) performance [simple RT (SRT) and complex RT (CRT)] were evaluated under four experimental conditions with stimulation (stim) and medication (med) on and off: stim-on/med-on, stim-on/med-off, stim-off/med-off and stim-off/med-on. In the last condition, the patients received either low medication (usual dose) or high medication (suprathreshold dose). STN stimulation improved the motor performance in the SRT and CRT tasks. Furthermore, STN deep brain stimulation (DBS) also improved response preparation as shown by the significant improvement of the RT performance in the SRT task. This effect of STN DBS on the RT performance in the SRT task was greater as compared with the CRT task. This is due to the more complex information processing that is required in the CRT task as compared to the SRT task. These data suggest that treatment of STN hyperactivity by DBS improves motor function, confirming earlier reports, but has a differential effect on cognitive functions. The STN seems to be an important modulator of cognitive processing and STN DBS can differentially affect motor and associative circuits.

Activities of Daily Living↗

PubMed2000

Chronaxie calculated from current-duration and voltage-duration data.

To determine the rheobase and the chronaxie of excitable cells from strength-duration curves both constant-current pulses and constant-voltage pulses are applied. Since the complex impedance of the electrode-tissue interface varies with both the pulsewidth and the stimulation voltage, chronaxie values estimated from voltage-duration measurements will differ from the proper values as determined from current-duration measurements. To allow a comparison of chronaxie values obtained by the two stimulation methods, voltage-duration curves were measured in human subjects with a deep brain stimulation electrode implanted, while the current and the load impedance of the stimulation circuit were determined in vitro as a function of both stimulation voltage and pulsewidth. Chronaxie values calculated from voltage-duration data were shown to be 30-40% below those estimated from current-duration data. It was also shown that in the normal range of stimulation amplitudes (up to 7 V) the load impedance increases almost linearly with the pulsewidth. This result led us to present a simple method to convert voltage-duration data into current-duration data, thereby reducing the error in the calculated chronaxie values to approximately 6%. For this purpose voltage-duration data have to be measured for pulses up to 10-20 times the expected chronaxie.

Brain↗

PubMed1986

Compulsive thalamic self-stimulation: a case with metabolic, electrophysiologic and behavioral correlates.

A 48-year-old woman with a stimulating electrode implanted in the right thalamic nucleus ventralis posterolateralis developed compulsive self-stimulation associated with erotic sensations and changes in autonomic and neurologic function. Stimulation effects were evaluated by neuropsychologic testing, endocrine studies, positron emission tomographic measurements of regional cerebral metabolic rate for glucose, EEG and evoked potentials. During stimulation, vital signs and pupillary diameter increased and a left hemiparesis and left hemisensory loss developed. Verbal functions deteriorated and visuospatial processing improved. Plasma growth hormone concentrations decreased, and adrenocorticotrophic hormone and cortisol levels rose. With stimulation, glucose metabolism increased in both thalami and both hemispheres, reversing baseline right-sided hypometabolism and right-left asymmetries. EEG and both somatosensory and brain-stem auditory evoked potentials remained unchanged during stimulation, while visual evoked potentials revealed evidence of anterior visual pathway dysfunction in the left eye. This case establishes the potential for addiction to deep brain stimulation and demonstrates that widespread behavioral and physiological changes, with concomitant alteration in the regional cerebral metabolic rate for glucose, may accompany unilateral thalamic stimulation.

Brain↗

PubMed1984

Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and beta-endorphin immunoreactivity in the cerebrospinal fluid.

Deep brain stimulation (thalamic relay nucleus, periaqueductal gray and internal capsule) was applied to various cases of intractable pain, and the resulting degree of pain reduction and alteration in beta-endorphin immunoreactivity in the cerebrospinal fluid (CSF) were compared. The following results were obtained. (1) The studies on intractable pain revealed that the levels of beta-endorphin immunoreactivity in the CSF were lower than those in the control group. (2) Thalamic relay nucleus stimulation proved effective not only for deafferentiation pain, but also for somatogenic pain. No relationship was, however, noted between pain reduction and the rate of increase of beta-endorphin immunoreactivity in the CSF. (3) The incidence of stimulation tolerance following prolonged stimulation of the thalamic relay nucleus can be reduced to a minimum by administration of L-DOPA. It is concluded that the increase in beta-endorphin in the CSF is not the direct and major cause of pain reduction during treatment by thalamic relay nucleus stimulation. It may be assumed that neuronal facilitation on the monoaminergic descending pain inhibitory system plays a role in reducing pain.

Adult↗

PubMed2004

High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions.

Deep brain stimulation (DBS) is a widely used clinical treatment for Parkinson's disease (PD). A rodent model of DBS is a necessary tool for understanding the neural mechanisms of this method. Our previous study showed that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) improved treadmill locomotion in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of nigrostriatal dopamine (DA) neurons. The present study tested DBS effects on limb-use asymmetry (LUA) during vertical/lateral exploration in a cylindrical chamber in rats with similar unilateral nigrostriatal DA lesions. Limb-use asymmetry assessment has been used to detect functional capacity over a wide range of dopamine depletion. Before lesioning, rats exhibited regular rearing activity and used both forelimbs equally often to support weight during exploration of the walls of the cylinder. After unilateral nigrostriatal DA lesioning, rats displayed reduced rearing activity and predominant use of the ipsilateral (good) forelimb to touch the wall. HFS of the STN, but not of other nearby regions surrounding the STN, in the lesioned rats restored normal rearing activity and reversed the limb-use asymmetry caused by the unilateral DA depletion. This study is consistent with the possibility that there can be beneficial effects of STN-DBS on behavioral impairments in unilateral DA-depleted rats and may suggest an appropriate rodent model for DBS study.

Animals↗

PubMed2004

Pseudobulbar crying induced by stimulation in the region of the subthalamic nucleus.

We describe a case of pseudobulbar crying associated with deep brain stimulation (DBS) in the region of the subthalamic nucleus (STN). Patients with pseudobulbar crying show no other evidence of subjective feelings of depression such as dysphoria, anhedonia, or vegetative signs. This may be accompanied by other symptoms of pseudobulbar palsy and has been reported to occur with ischaemic or structural lesions in both cortical and subcortical regions of the brain. Although depression has been observed to result from DBS in the region of the STN, pseudobulbar crying has not been reported. A single patient who reported the symptoms of pseudobulbar crying after placement of an STN DBS was tested in the off DBS and on DBS conditions. The patient was tested using all four DBS lead contacts and the observations and results of the examiners were recorded. The Geriatric Depression Scale was used to evaluate for depression in all of the conditions. The patient exhibited pseudobulbar crying when on monopolar stimulation at all four lead contacts. The pseudobulbar crying resolved off stimulation. This case describes another type of affective change that may be associated with stimulation in the region of or within the STN. Clinicians should be aware of this potential complication, the importance of differentiating it from stimulation induced depression, and its response to a serotonin reuptake inhibitor, such as sertraline.

Crying↗

PubMed2004

Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson's disease.

The pattern of neuronal discharge within the basal ganglia is disturbed in Parkinson's disease (PD). In particular, there is a tendency for neuronal elements to synchronise at around 20 Hz in the absence of dopaminergic treatment, whereas this activity can be replaced by spontaneous synchronisation at much higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21 (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at similar frequencies in the globus pallidus interna, the major output structure of the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the subthalamic area at similar high frequencies reverses parkinsonism and forms the basis of therapeutic deep brain stimulation in PD. The results point to a possible common mechanism by which both dopaminergic treatment associated synchronisation of subthalamic activity at very high frequency and synchronisation imposed by therapeutic stimulation of the subthalamic area inhibit an abnormal and potentially deleterious synchronisation of basal ganglia output at around 20 Hz. If this activity is unchecked by synchronisation at higher frequency, then pathological 20-Hz oscillations may cascade through the basal ganglia, increasing at subsequent levels of processing.

Aged↗

PubMed2003

Disappearance of self-mutilating behavior in a patient with lesch-nyhan syndrome after bilateral chronic stimulation of the globus pallidus internus. Case report.

Lesch-Nyhan syndrome (LNS) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. Patients with this syndrome are characterized by hyperuricemia, self-mutilation, developmental retardation, and movement disorders such as spasticity and dystonia. The authors performed bilateral chronic stimulation of the globus pallidus internus for control of dystonic movements in a 19-year-old man with LNS. His self-mutilating behavior unexpectedly disappeared after chronic stimulation. This is the first case of LNS that has been successfully treated with deep brain stimulation. The findings indicate that neurobehavioral features of this syndrome are either mediated in the basal ganglia pathways or secondary to the dystonia.

Adult↗

PubMed2004

Subthalamic nucleus stimulation in advanced Parkinson's disease: blinded assessments at one year follow up.

OBJECTIVE: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease. DESIGN: Open label follow up using blinded ratings of videotaped neurological examinations. PATIENTS: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. MAIN OUTCOME MEASURES: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. RESULTS: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. CONCLUSIONS: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.

Activities of Daily Living↗

PubMed2004

Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a double-blind 12-month evaluation study.

OBJECT: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been established as an effective treatment for Parkinson disease (PD). Nevertheless, bilateral surgical procedures can be associated with frequent and severe complications. The aim in the present study was to assess the safety and efficacy of unilateral STN stimulation, and the need for a second procedure. METHODS: Twelve patients with PD underwent unilateral DBS of the STN and were followed up for 12 months. Patients were assessed at baseline and at each visit in a double-blind fashion by analyzing the Unified PD Rating Scale (UPDRS), ambulation speed, and home diaries. Levodopa-off/stimulation-on UPDRS motor scores were improved by 26 +/- 8% (p < 0.05, mean +/- standard deviation [SD]) compared with the baseline levodopa-off score; there was a 50% improvement in contralateral features, a 17% improvement ipsilaterally, and a 36% improvement in axial features. The mean ambulation speed increased by 83 +/- 44% (p < 0.01, mean +/- SD). The medication-on time with dyskinesias was significantly reduced (p < 0.01) and the daily levodopa dose was reduced by 19 +/- 6% (p < 0.05, mean +/- SD). There were no clinically significant side effects. CONCLUSIONS: Unilateral DBS of the STN is safe and well tolerated, and may provide sufficient benefit so that additional surgery is not required.

Adult↗

PubMed1988

Immunocytochemical localization of pro-opiomelanocortin neurons in human brain areas subserving stimulation analgesia.

The distribution of pro-opiomelanocortin (beta-endorphin, adrenocorticotropic hormone, and 16-K) neurons and fiber projections was evaluated immunocytochemically in 50-mu thick cryostat sections of human diencephalon and midbrain. Specific attention was focused upon regions in which deep brain stimulation has been most effective in the relief of selected chronic pain syndromes. This study revealed a remarkable, nearly point-to-point correlation between clinically effective stimulation sites and the distribution of pro-opiomelanocortin fibers in the human brain. Of particular interest was the dense innervation of the periventricular stratum along the third ventricle, the parafascicular centromedian region of the thalamus, and the periaqueductal gray matter of the midbrain. This study provides anatomical support for the hypothesis that beta-endorphin-containing neuronal systems may contribute to stimulation analgesia in the human.

Adolescent↗

PubMed2004

Brain stimulation for epilepsy.

Neural stimulation is a promising new technology for the treatment of medically-intractable seizures. Vagus-nerve stimulation (VNS) is licensed in several countries as an adjunctive therapy. VNS is as effective as antiepileptic drug therapy, and serious complications are rare. Transcranial magnetic stimulation is simple, non-invasive, and widely used in neurophysiology. Therapeutic results in a few studies are equivocal at best. Deep brain stimulation, although experimental, has been applied to the cerebellum, caudate nucleus, centromedian thalamus, anterior thalamus, subthalamus, hippocampus, and neocortical seizure foci. Preliminary results are encouraging, but not conclusive. Electrode implantation in the brain for indications other than seizures has been associated with a 5% risk for intracranial haemorrhage and 5% for infection. A controlled study of anterior thalamic stimulation in patients with intractable partial and secondarily generalised seizures has been started. Future investigations are likely to study extrathalamic sites of stimulation, and effects of stimulation contingent upon detection of or prediction of EEG patterns of epileptiform activity.

Adult↗

PubMed2002

Bilateral subthalamic nucleus stimulation and quality of life in advanced Parkinson's disease.

We examined the impact of the subthalamic nuclei (STN) deep brain stimulation (DBS) on the health-related quality of life (QoL) of patients with advanced Parkinson's disease (PD). Seventeen consecutive patients with refractory motor fluctuations and dyskinesia were included in the study (mean age, 60.9 +/- 7.7 years [range, 43-74 years]; disease duration, 16.4 +/- 8.5 years [range, 7-38 years]; mean off-medication Hoehn and Yahr stage, 4.23 +/- 0.66 [range, 2.5-5]). Each patient's assessment was carried out using common rating scales, following the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol. Dyskinesia and emotional state were evaluated through the Abnormal Involuntary Movement Scale (AIMS) and the Hospital Anxiety and Depression Scale (HAD). QoL was assessed by means of the Parkinson's Disease Questionnaire Spanish version (PDQ-39). Significant benefit was obtained in the motor manifestations and complications of disease, as well as in the functional state and mood (P < 0.001). Some QoL dimensions (mobility and activities of daily living) and the PDQ-39 Summary Index (PDQ-39SI) showed a significant improvement (P < 0.001). Benefit was modest (P < 0.05) for three other domains (emotional well-being, stigma, bodily discomfort) and nil for the rest. There was no correlation between the change obtained in the QoL (PDQ-39SI) and in the other variables. As measured by the PDQ-39, STN-DBS significantly improves important aspects of QoL in patients with advanced PD.

Adult↗

PubMed2003

Thalamic stimulation in patients with multiple sclerosis: long-term follow-up.

BACKGROUND: We assessed the long-term effect of deep brain stimulation (DBS) in patients with multiple sclerosis (MS). METHODS: Nine patients with MS-induced tremor underwent placement of a DBS electrode in the thalamus. All patients were referred from the tertiary MS center at the New Jersey Medical School. Intraoperative macrostimulation was performed under local anesthesia before permanent implantation. Preoperative and postoperative evaluation included magnetic resonance imaging (MRI), the Extended Disability Status Scale (EDSS), the Bain-Finchley tremor scale, neuropsychological testing and patient assessment of the benefit from surgery. RESULTS: There were no surgical complications. Follow-up ranged from 9 to 48 months (mean 32 months). EDSS scores averaged 7.2 before surgery, 6.8 at 6 months after surgery and 7.8 at late follow-up. Tremor scores averaged 5.4 before surgery, 1.7 at 6 months after surgery and 2.1 at late follow-up. Four patients who had significant tremor reduction at 6 months had severe MS progression afterwards, and one was lost to late follow-up. Another patient, in whom excellent tremor control was obtained, developed increasing stimulation-induced fatigue, and the implant was removed at his request. The 3 other patients have maintained a worthwhile benefit from DBS. MRI scans did not show any new MS plaques in relation to the electrode, although imaging was consistent with disease progression in all patients. Neuropsychological testing showed a mild to moderate decline in cognitive function consistent with disease progression. CONCLUSIONS: Chronic thalamic stimulation decreases tremor in patients with MS. However, this improvement does not correlate with improvement in objective measures of function. Any actual benefit may be limited in most patients by the progression of underlying disease. DBS for relief of tremor in patients with MS should be considered only in carefully selected patients with relatively stable disease, in whom upper extremity tremor is a disabling symptom.

Adult↗

PubMed2002

Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging.

OBJECT: The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD). METHODS: Fifty-four DBS electrodes were localized in and adjacent to the subthalamic nucleus (STN) postoperatively by using magnetic resonance (MR) imaging in a series of 29 patients in whom electrodes were implanted for the treatment of medically refractory PD, and for whom quantitative clinical assessments were available both pre- and postoperatively. A novel MR imaging sequence was developed that optimized visualization of the STN. The coordinates of the tips of these electrodes were calculated three dimensionally and the results were normalized and corrected for individual differences by using intraoperative neurophysiological data (mean 5.13 mm caudal to the midcommissural point [MCP], 8.46 mm inferior to the anterior commissure-posterior commissure [AC-PC], and 10.2 mm lateral to the midline). Despite reported concerns about distortion on the MR image, reconstructions provided consistent data for the localization of electrodes. The neurosurgical procedures used, which were guided by combined neuroimaging and neurophysiological methods, resulted in the consistent placement of DBS electrodes in the subthalamus and mesencephalon such that the electrode contacts passed through the STN and dorsally adjacent fields of Forel (FF) and zona incerta (ZI). The mean location of the clinically effective contacts was in the anterodorsal STN (mean 1.62 mm posterior to the MCP, 2.47 mm inferior to the AC-PC, and 11.72 mm lateral to the midline). Clinically effective stimulation was most commonly directed at the anterodorsal STN, with the current spreading into the dorsally adjacent FF and ZI. CONCLUSIONS: The anatomical localization of clinically effective electrode contacts provided in this study yields useful information for the postoperative programming of DBS electrodes.

Adult↗