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Bart Nuttin

Publications and source records attributed to Bart Nuttin.

17 recordsLinked to original sources
PubMed2006

Involvement of human basal ganglia in offline feedback control of voluntary movement.

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.

Aged↗
PubMed2006

Non-invasive imaging of neuropathology in a rat model of alpha-synuclein overexpression.

Parkinson's disease is a neurodegenerative disorder affecting the dopaminergic neurons in the substantia nigra. Aggregation of alpha-synuclein appears to play a central role in the pathogenesis. Novel animal models for neurodegeneration have been generated by lentiviral vector-mediated locoregional overexpression of disease-associated genes in the adult brain. We have used lentiviral vectors to overexpress a clinical mutant of alpha-synuclein, A30P, in the rat substantia nigra. This overexpression induced time-dependent cytoplasmic and neuritic accumulation of alpha-synuclein and neurodegeneration. A subgroup of the rats developed asymmetric rotational behavior after administration of amphetamine. In addition, these animals displayed reduced dopamine transporter binding visualized by 123I-FP-CIT microSPECT imaging. The behavioral and microSPECT data were validated by histological analysis. There was a strong correlation between the reduction of dopaminergic neurons in the substantia nigra and the reduction of dopamine transporter binding in the striatum. MicroSPECT imaging enables non-invasive imaging of the neurodegeneration allowing longitudinal follow-up in this new animal model for Parkinson's disease and the evaluation of neuroprotective drugs.

Animals↗
PubMed2006

Online movement control in multiple sclerosis patients with tremor: effects of tendon vibration.

Patients with intention tremor due to multiple sclerosis (MS) exhibit an increased reliance on visual feedback in the sensorimotor control of slow goal-directed movements. In the present study, the use of proprioceptive information was investigated in MS patients with intention tremor compared to MS patients without tremor and healthy controls. Tendon vibration was applied to the wrist extensor muscles during a memory-guided slow wrist step-tracking task to investigate the use of muscle spindle afferent information in online movement control. A significant reduction of movement amplitude was induced by tendon vibration in all three groups, but the effect was found to be smaller in MS patients with tremor (28%) than in subjects without tremor (50%). Vibration also induced an increase of overall tremor amplitude in the MS tremor group; however, its effect on movement amplitude was not directly related to (changes in) tremor severity. The results suggest that the decreased online use of proprioceptive information in MS patients with tremor reflects an adaptation over time to cope with a tremor-related noisy background. Abnormalities in proprioceptive processing may explain why MS patients with tremor show an increased reliance on visual feedback for online motor control.

Adult↗
PubMed2006

Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: a key role for the subgenual anterior cingulate and ventral striatum.

UNLABELLED: High-frequency anterior capsular stimulation is a new, promising, and reversible neuromodulatory treatment in the research stage for patients with refractory obsessive-compulsive disorder (OCD). The mechanism of action is unknown but hypothesized to be secondary to interruption of the corticothalamostriatocortical circuit. METHODS: (18)F-FDG PET was performed on 6 consecutive OCD patients preoperatively and after stimulation. The results were compared with those of 20 age- and sex-matched healthy volunteers by using both a standardized volume-of-interest-based approach for subcortical areas and statistical parametric mapping. Correlations were investigated with Yale-Brown Obsessive Compulsive Scale scores (Y-BOCS) and Hamilton Depression Rating Scale scores (HAM-D). RESULTS: Chronic anterior capsular electrostimulation resulted in a further decrease of prefrontal metabolic activity, especially in the subgenual anterior cingulate (P < 0.001). Correlation analysis demonstrated that decreases in Y-BOCS and HAM-D with anterior capsular electrostimulation were inversely related to the metabolic activity changes in the left ventral striatum, left amygdala, and left hippocampus (P < 0.01). Preoperative resting metabolic activity in the subgenual anterior cingulate was predictive of therapeutic response (P = 0.001). CONCLUSION: These observations provide evidence that the subgenual anterior cingulate and ventral striatum have a key role in the neuronal circuitry involved in the pathophysiology of OCD with associated major depression and in the neuromodulatory mechanism of anterior capsular stimulation.

Adult↗
PubMed2005

The effect of changed visual feedback on intention tremor in multiple sclerosis.

In patients with multiple sclerosis (MS), intention tremor amplitude is enhanced during the visually guided compared to the memory guided motor tasks. In the present study, the effect of visual feedback on intention tremor was investigated during visually guided wrist step-tracking tasks. Specifically, visual feedback of the hand was provided either instantly or averaged over different time windows. Thirteen MS patients with intention tremor and 14 healthy controls performed the wrist step-tracking task, while the visual representation of the actual hand position was displayed instantly or averaged over time windows of 150, 250 and 350 ms. It has been found in the patient group that, in association with a decreased initial error and decreased tremor amplitude on the screen, the amplitude of the actual performed tremor also decreased when visual feedback was changed. The tremor reduction was not different between conditions with manipulated feedback, although delays in presenting visual feedback of the hand position increased when the time window was larger. The reduction in overall tremor amplitude was unlikely related to other factors, such as eye fixation deficits or the speed of the primary hand movement. These results suggest that hand tremor severity is dependent on the visual feedback of position and movement errors.

Adult↗
PubMed2005

Relationship between multiple sclerosis intention tremor severity and lesion load in the brainstem.

Intention tremor due to multiple sclerosis is clinically similar to cerebellar tremor. This study investigated, in 14 multiple sclerosis patients, the relationship between intention tremor severity and the lesion load in different infratentorial regions. Tremor amplitude was quantified during step-tracking tasks. The lesion load was measured on magnetic resonance images using an automated segmentation method. Intention tremor amplitude was significantly related to lesion load in the brainstem but not in the cerebellum. Specifically, tremor amplitude correlated with the lesion load in the contralateral pons, and patients with more severe tremor in both arms had a greater lesion load bilaterally in the pons. These results support the view that multiple sclerosis intention tremor is related to dysfunction of cerebellar inflow and/or outflow pathways.

Brain Stem↗
PubMed2005

Interaction between eye and hand movements in multiple sclerosis patients with intention tremor.

Deficient eye and hand movements are present in patients with multiple sclerosis. In the present study, eye and hand movements were simultaneously measured during visually guided wrist step-tracking tasks in 16 patients with intention tremor and 15 healthy controls. The coupling between eye and hand movements was analyzed during simultaneous eye-hand tracking, and interactions were studied by comparing the coordinated eye-hand condition with isolated eye- or hand-tracking conditions. Despite movement abnormalities, the onset of eye and hand movements was highly correlated and an invariant coupling between the saccadic completion time and hand peak velocity was found, suggesting that the temporal coupling was very much preserved. The differences between the experimental tracking conditions suggest that, in MS patients with intention tremor, the ocular system influenced the hand movements. Intention tremor amplitude was reduced when there was no preceding saccadic eye movement, whereas conversely, eye movements were not affected by different hand tremor severity.

Adult↗
PubMed2005

Thalamic stimulation as a treatment for primary erythromelalgia: technical case report.

OBJECTIVE AND IMPORTANCE: We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with immediate and important pain relief for 3 years. CLINICAL PRESENTATION: A 12-year-old boy experiencing primary erythromelalgia had a 4-year history of recurrent attacks of severe burning pain in both feet, accompanied by local reddening, swelling, and heating of the skin. The attacks were triggered by warmth and exercise. The pain was relieved only by elevation and cooling of the lower limbs, which he achieved by immersing his legs in a bucket of ice water, resulting in severe ulceration of the skin. INTERVENTION: Because of the gradual aggravation of the signs and symptoms and resistance of the patient's condition to several medical therapies, the patient received spinal cord stimulation. The implants were removed twice because of recurrent infection. Finally, the patient was treated with bilateral electrical stimulation of the ventral posterolateral thalamic nucleus, which resulted in important pain control until 3 years later. The patient was able to avoid water immersions, and all ulcerations disappeared. CONCLUSION: We conclude that thalamic stimulation was successful in this case of primary erythromelalgia.

Child↗
PubMed2004

Effects of vision and arm position on amplitude of arm postural tremor in patients with multiple sclerosis.

OBJECTIVES: To quantify the effects of vision and arm position on arm postural tremor, comparisons were made between flexed and extended arm positions performed with the eyes open and closed. DESIGN: Case-control study. SETTING: National multiple sclerosis (MS) center in Belgium. PARTICIPANTS: Sixteen patients (32 arms) with MS who had intention tremor and 16 healthy controls (32 arms). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The amplitude of postural tremor was assessed by a magnetic position sensor attached to the index finger. RESULTS: The amplitude of postural tremor was not influenced by changes in visual condition or different arm positions. Both healthy controls and MS patients made more directional changes in the flexed, compared with the extended arm position. CONCLUSIONS: The amplitude of the arm postural tremor in MS is independent of vision and arm position. Selecting 1 arm position is sufficient to assess postural tremor amplitude.

Arm↗
PubMed2004

What's in a "smile?" Intra-operative observations of contralateral smiles induced by deep brain stimulation.

OBJECTIVE: To describe smiling and euphoria induced by deep brain stimulation (DBS). BACKGROUND AND SIGNIFICANCE: The brain systems inducing emotional experiences and displays are not entirely known, but the ventral striatum including the nucleus accumbens has been posited to play a critical role in mediating emotions with positive valence. DBS has been successfully employed for the treatment of movement disorders, and most recently obsessive compulsive disorder (OCD). The purpose of this report is to describe the emotional changes associated with stimulation of the ventral striatum. METHODS: A single patient with intractable OCD had electrode arrays placed in the right and left anterior limbs of the internal capsule and region of the nucleus accumbens. Changes in facial movement during stimulation were quantified by video recording. Ten video segments, time locked to the onset of stimulation, were digitized and changes in pixel intensity that occurred over both sides of the lower face, on a frame by frame basis, following stimulation onset were computed. These summed changes in pixel intensity represented the dependent variable of "entropy" and directly corresponded to changes in light reflectance that occur during facial movement. RESULTS: During stimulation on both the right and left side, the patient consistently developed a half smile on the side of the face contralateral to the stimulating electrode, and also became euphoric. The effect ceased when DBS was discontinued. CONCLUSIONS: DBS in the region of the nucleus accumbens produced smile and euphoria suggesting that alterations in the ventral striatum may result in emotional experience and displays. We hypothesize the existence of a limbic-motor network responsible for such changes. This observation suggests that DBS may be useful as a therapy for mood disorders.

Adult↗
PubMed2003

Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain.

RNA interference (RNAi) is an evolutionarily conserved mechanism of posttranscriptional gene-specific silencing. For in vivo applications, RNAi has been hampered until recently by inefficient delivery methods and by the transient nature of the gene suppression. Lentiviral vectors (LVs) hold great promise for gene therapeutic applications, pharmaceutical target validation, and functional genomics because stable gene transfer is mediated both in dividing and nondividing cells. We have used a lentiviral vector-based system for RNAi. We produced human immunodeficiency virus type 1-derived LVs encoding a short hairpin RNA specific for enhanced green fluorescent protein (EGFP) mRNA that were capable of inhibiting EGFP expression in mammalian cells. EGFP knockdown persisted after multiple passages of the cells. Of particular interest, our RNAi LVs were equally effective in suppression and prevention of EGFP expression after stereotactic injection in adult mouse brain. Therefore, we believe that the use of LVs for stable RNAi in brain will become a powerful aid to probe gene function in vivo and for gene therapy of diseases of the central nervous system.

Animals↗
PubMed2003

Effects of electrical stimulation or lesion in nucleus accumbens on the behaviour of rats in a T-maze after administration of 8-OH-DPAT or vehicle.

Electrical brain stimulation may be a therapeutic alternative for irreversible lesions in treatment-resistant patients with obsessive-compulsive disorder (OCD). We compared the effects of electrical stimulation and lesion in the nucleus accumbens (n acc) on the behaviour of rats in a model for OCD. Rats were tested for spontaneous alternation behaviour (AB) in a T-maze and assigned to four groups: an electrode implant group with stimulation 'ON' (stimON) or 'OFF' (stimOFF), a lesion or a sham group. Postoperatively, the number of arm visits and AB were tested after 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT; 2 mg/kg) or saline administration. After 8-OH-DPAT administration, more arm visits were counted in the stimON (92.2%) and lesion groups (79.3%) than in both control groups (stimOFF 54.2; sham 61.2%). AB was significantly decreased in the stimON (10.5%) and lesion groups (10.2%) relative to the sham (22.0%) but not to the stimOFF group (14.7%). After saline administration, rats performed more arm visits in the stimON (81.5% non-significant) and lesion groups (93.6% significant) relative to the stimOFF (70.8%) and the sham groups (74.5%). No significant differences, however, were observed for AB. In conclusion, both treatments resulted in a decreased AB after 8-OH-DPAT administration (modelling an increase in compulsions) and more arm visits.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synuclein.

Two mutations in alpha-synuclein, the main constituent of Lewy bodies, have been identified in familial Parkinson's disease. We have stereotactically injected lentiviral vectors encoding wild-type and A30P mutant human alpha-synuclein in different brain regions (striatum, substantia nigra, amygdala) of mice. Overexpression of alpha-synuclein induced time-dependent neuropathological changes reminiscent of Lewy pathology: abnormal accumulation of alpha-synuclein in cell bodies and neurites, alpha-synuclein-positive neuritic varicosities and cytoplasmic inclusions that stained with ubiquitin antibodies and became larger and more frequent with time. After one year, alpha-synuclein- and ubiquitin-positive neurons displayed a degenerative morphology and a significant loss of alpha-synuclein-positive cells was observed. Similar findings were observed with both the wild-type and the A30P mutant form of alpha-synuclein and this in different brain regions. This indicates that overexpression of alpha-synuclein is sufficient to induce Lewy-like pathology and neurodegeneration and that this effect is not restricted to dopaminergic cells. Our data also demonstrate the use of lentiviral vectors to create animal models for neurodegenerative diseases.

Amygdala↗
PubMed2002

Characterization of lentiviral vector-mediated gene transfer in adult mouse brain.

Lentiviral vectors are promising tools for gene transfer into the central nervous system. We have characterized in detail transduction with human immunodeficiency virus type 1 (HIV-1)-derived vectors encoding enhanced green fluorescent protein (eGFP) in the adult mouse brain. Different brain regions such as the striatum, hippocampus, and the lateral ventricle were targeted. The eGFP protein was transported anterogradely in the nigrostriatal pathway, but we have found no evidence of transport of the lentiviral vector particle. The performance levels of the different generations of packaging and transfer plasmid were compared. Omission of the accessory genes from the packaging plasmid resulted in a modest decrease in transgene expression. Inclusion of the woodchuck hepatitis posttranscriptional regulatory element, on the one hand, and the central polypurine tract and termination sequences, on the other hand, in the transfer vector each resulted in a 4- to 5-fold increase in transgene expression levels. Combination of both elements enhanced expression levels more than the sum of the individual components, suggesting a synergistic effect. In the serum of mice injected with lentiviral vectors a humoral response to vector proteins was detected, but this did not compromise transgene expression. Immune response to the transgene was found only in a minority of the animals.

Animals↗
PubMed1994

Spinal cord stimulation in Belgium: a nation-wide survey on the incidence, indications and therapeutic efficacy by the health insurer.

The present report describes a nation-wide survey on the incidence, the indications and the efficacy of spinal cord stimulation (SCS), as assessed by the Belgian health authorities. The direct motive for this survey was the rapidly growing expenditures resulting from the increasing use of SCS. Between 1983 and 1992, nearly 700 SCS devices were implanted for a population of less than 10 million inhabitants. The most common indication for SCS was failed back survey (61.4%). Whereas SCS was initially only performed in university teaching hospitals, it is now also widely practised in general hospitals. In 3 studies, the efficacy of SCS was assessed. In a first study, success was defined in terms of resumption of professional activities. After a mean follow-up of more than 1 year, less than 5% of the 147 patients treated with SCS had returned to work. A second study investigated the subjective evaluation of the therapy by the patient. Seventy patients with a mean follow-up of 3.5 years were studied. In 52% of the patients, the effect of SCS was judged as good to very good. Men scored better than women. In addition, the results obtained in the teaching hospitals were significantly better than those obtained in general hospitals. In a third study, the impact of psychiatric screening on patient selection was evaluated. Of the 100 candidates, 36 were withheld from implantation with a SCS device because of psychiatric contra-indications. Patients who had received a positive psychiatric advice showed a significantly better therapeutic outcome than patients for whom the psychiatrist had made reservations.

Adolescent↗