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K L Leenders

Publications and source records attributed to K L Leenders.

At least 19 recordsLinked to original sources
PubMed2006

Functional dominance of finger flexion over extension, expressed in left parietal activation.

Sensory stimuli may elicit a widely distributed parietal-premotor circuitry underlying task-related movements such as grasping. These stimuli include the visual presentation of an object to be grasped, as well as the observation of grasping performed by others. In this study, we used functional Magnetic Resonance Imaging (fMRI) to test whether the performance of simple finger flexion, contrasted to extension, might similarly activate higher-order circuitry associated with grasping. Statistical Parametric Mapping (SPM) showed that flexion, compared to extension, was related with significant activation of the left posterior parietal cortex and posterior insula, bilaterally. This pattern supported our hypothesis that simple finger flexion has a specific relation with circuitry involved in preparing manual tasks. Although the two motor conditions showed major overlap in the primary motor cortex, increased flexion-related activation at the precentral motor-premotor junction further supported its association with higher-order motor control.

Adult↗
PubMed2006

Cerebral activation related to implicit sequence learning in a Double Serial Reaction Time task.

Using functional magnetic resonance imaging (fMRI), we examined the distribution of cerebral activations related to implicitly learning a series of fixed stimulus-response combinations. In a novel - bimanual - variant of the Serial Reaction Time task (SRT), simultaneous finger movements of the two hands were made in response to pairs of visual stimuli that were presented in a fixed order (Double SRT). Paired stimulus presentation prevented explicit sequence knowledge occurring during task practice, which implied that a dual task paradigm could be avoided. Extensive prescanning training on randomly ordered stimulus pairs allowed us to focus on the acquisition of implicit sequence knowledge. Activation specifically related to the acquisition of fixed sequence knowledge was highly significant in the right ventrolateral prefrontal cortex. The medial prefrontal and right ventral premotor cortex were more indirectly related with such procedural learning. We conclude that this set of activations reflects a stage of implicit sequence learning constituted by components of (i) spatial working memory (right ventral prefrontal cortex), (ii) response monitoring and selection (medial prefrontal cortex), and (iii) facilitated linkage of visuospatial cues to compatible responses (right ventral premotor). Comparing the random-order stimulus-response actions with fixed sequences showed activations in dorsal premotor and posterior parietal cortices, consistent with a dorsal pathway dominance in real-time visuomotor control. The relative long time during which performance improves in the DoSRT provides an opportunity for future study of various stages in both general skill and fixed sequence learning.

Adult↗
PubMed2006

Chronic stimulation of the subthalamic nucleus increases daily on-time without dyskinesia in advanced Parkinson's disease.

We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved complete daily on-time without dyskinesia at 12 months significantly. In conclusion, our study demonstrates the efficacy of chronic STN-DBS on motor features in a selected population of advanced PD patients. In addition to clinical assessments, patients' diaries serve as an essential tool to evaluate the functional motor status after STN-DBS.

Aged↗
PubMed2005

Corticostriatal covariance patterns of 6-[18F]fluoro-L-dopa and [18F]fluorodeoxyglucose PET in Parkinson's disease.

6-[18F]fluoro-L-dopa (FDOPA) is a common presynaptic dopaminergic tracer used in examinations by positron emission tomography (PET) for patients with Parkinson's disease (PD). The distinct metabolic covariance pattern in the uptake of [18F]fluorodeoxyglucose (FDG) can also be used to investigate PD pathology. Although the two tracers are widely used in PD research and clinical assessment, no thorough comparative studies of the tracers have been made. In this study, 25 PD patients were examined with FDOPA and FDG to investigate relationships and clinical correlates of metabolic and monoaminergic function in the Parkinsonian brain. A VOI (volume-of-interest) analysis was achieved by 3D spatial normalisation and fixed VOI-sets. The hemisphere ipsi- and contralateral to the predominant symptoms of PD was identified in each data set, and data across subjects were related using that laterality, rather than body side. Regional covariance patterns for FDOPA and FDG were derived from principal component analysis (PCA). The results demonstrated hemispheric asymmetries and sex-differences in the striatal FDOPA uptake, which were not seen with FDG. In addition, the PCA analysis identified a positive relationship between a major component in FDOPA uptake (associated with the striatal uptake) and an FDG component, which had positive loadings in the thalamus and the cerebellum. The subject scores for these components correlated positively, and both had a negative association with the clinical severity of the disease. The specific extrastriatal FDG covariance pattern contained the thalamus and the cerebellum, components of the previously reported PD related pattern, but not the striatum. The network correlated with both the severity of clinical symptoms of PD and the severity of nigrostriatal dopaminergic hypofunction. The results indicate that FDG PET, when combined with multivariate network analysis at group-level, can be used as an indicator of PD severity.

Aged↗
PubMed2005

Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson's disease.

PURPOSE: Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system. METHODS: Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the "off state" (UPDRS-III and H&Y stage). RESULTS: Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r = 0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r = 0.84, both p < 0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (rho = -0.52 for both techniques), UPDRS-III (rho = -0.38 for F-DOPA; rho = -0.45 for FP-CIT) and disease duration (rho = -0.59 for F-DOPA; rho = -0.49 for FP-CIT, all p < 0.05). CONCLUSION: FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.

Adult↗
PubMed2005

Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease.

Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the product of age and CAG repeat length (p < 0.0005). Dopamine D2 receptor availability measured by RAC-BP seems the most sensitive indicator of early neuronal impairment in PMC.

Adult↗
PubMed2005

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation.

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.

Aged↗
PubMed2004

PET neuroimaging and mutations in the DJ-1 gene.

Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism. We performed F-DOPA and FDG PET neuroimaging in two parkinsonism patients homozygous for DJ-1 mutations, three relatives heterozygous for a DJ-1 mutation and one non-carrier, all from the originally described kindred from The Netherlands. Their characteristics were compared to those of typical Parkinson's disease patients and healthy controls. Both parkinsonism patients had reduced F-DOPA uptake concordant with typical Parkinson's disease. In the, clinically unaffected, heterozygous relatives, F-DOPA metabolism was unremarkable, thus not suggesting a dosage effect of the DJ-1 gene.

Brain↗
PubMed2004

Cerebral activation related to skills practice in a double serial reaction time task: striatal involvement in random-order sequence learning.

We used functional Magnetic Resonance Imaging (fMRI) to examine the distribution of cerebral activation related to prolonged skill practice. In a bimanual variant of the Serial Reaction Time Task (SRT), simultaneous finger movements of the two hands were made in response to randomly ordered pairs of visual stimuli (Double SRT, DoSRT). Extended practice by a week of daily performance resulted in gradual decrease of reaction times, associated with an increased involvement of the ventral putamen and globus pallidus, reaching statistical significance only on the left side (Statistical Parametric Mapping, SPM99). This increase was complementary to a decrease of cortical activations. The striatal activation after training on random order stimuli indicates that the striatum is not exclusively involved in sequence learning. This extended function implies a role in the acquisition of basic visuomotor skills that includes the specific selection of the appropriate muscles in response to independent stimuli.

Adult↗
PubMed2004

Development of an inexpensive, low attenuation styrofoam primate chair for use in a PET scanner.

Pharmacokinetic modelling of radiotracers for positron emission tomography (PET) imaging of neuroreceptors can be performed with time-activity data for brain and blood. We aimed to develop an alternative to withdrawal of arterial blood samples for acquisition of a blood curve. A supportive primate chair was constructed out of styrofoam and fixed to the head portion of the bed of a PET scanner. A lightly anaesthetised rhesus monkey was positioned in the chair in a sitting position and injected with the radiotracer. The styrofoam chair provided sufficient support for the monkey. The presence of the chair in the PET scanner caused negligible attenuation of radiation, allowing simultaneous acquisition of dynamic data from the subject's brain and heart. We conclude that a styrofoam primate chair is an ideal tool to measure blood and brain data from a rhesus monkey with PET. Invasiveness to the animal is reduced, as well as experimenter time.

Animals↗
PubMed2003

Cerebral reorganisation of human hand movement following dynamic immobilisation.

Surgical treatment of a flexor tendon lesion of the hand is followed by a 6-week period of dynamic immobilisation. This is achieved by the elastic strings of a Kleinert splint, enabling only passive and no active flexor movements. After such immobilisation, the appearance of a temporary clumsy hand indicates decreased efficiency of cerebral motor control. Using PET we identified the recruitment of contralateral parietal and cingulate activations specifically related to the suboptimal character of these hand movements. After 6-8 weeks, normalised movement was related with contralateral putamen activation. Activations of the sensorimotor cortex and cerebellum were present during both scanning sessions. Changes in the pattern of cerebral activations reflect functional reorganisation. The shift from cortical to striatal involvement, observed in the group of four patients, generates the concept of unlearned movements being relearned.

Cerebellum↗
PubMed2003

Evidence of enhancement of spatial attention during inhibition of a visuo-motor response.

A visuo-motor task was used as the setting for a study into inhibition in six healthy volunteers using fMRI. The task involved responding to colored stimuli, which appeared at random positions in the left and right visual field, with the corresponding hand. The volunteers were asked to respond to green colored stimuli ("go" response) and to inhibit responses to red stimuli ("no-go" response). The task was presented in a block design with blocks of three types; only "go" trials, a pseudo-random mixture of "go" and "no-go" tasks ("go/no-go" block), and "visual control." ANCOVA analysis of the fMRI data was performed within the framework of SPM99. Increased activation in the go vs visual control comparison was found in the bilateral motor and medial premotor cortices associated with the action of the button press response, as well as parietal regions attending to the task of identifying the visual field. The go/no-go vs visual control comparison showed a similar pattern, plus additional prefrontal areas that have previously been shown to be associated with inhibition. The direct comparison of the go and go/no-go blocks highlighted large differences not only in the prefrontal cortices, associated with inhibition, but also particularly in the right parietal cortex. We interpret the increased parietal activation, during inhibition, as representing a heightened spatial attention required for the correct execution of the inhibition task.

Adult↗
PubMed2003

Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers.

This study investigated the processing of increasing monetary reward in nonsmoking and smoking subjects. The choice of the subject populations has been motivated by the observation of differences between nonsmokers and smokers in response to rewarding stimuli in a previous study. Subjects performed a pattern recognition task with delayed response, while rCBF was measured with [H215O] PET. Correct responses to the task were reinforced with three different amounts of monetary reward. The subjects received the sum of the rewards at the end of the experiment. The results show that a cortico-subcortical loop, including the dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus and the thalamus is involved in processing increasing monetary reward. Furthermore, the striatal response differentiates nonsmokers from smokers. Thus, we found significant correlations between rCBF increases in striatum and increasing monetary reward and between striatal rCBF increases and mood in nonsmokers, but not in smokers. Moreover, no significant mood changes among the different monetary rewards could be observed in smokers. We infer that the response of the striatum to reward is related to changes in subjective feelings. The differences between smokers and nonsmokers confirm our previous conclusions that the association between blood flow, performance, mood and amount of reward is more direct in nonsmokers.

Adult↗
PubMed2003

Whole body [O-15]water pharmacokinetics measured in blood.

A simple pharmacokinetic model to explain the time course of [O-15] water in human whole blood after bolus injection is described. The model has been derived from measurements in twelve healthy volunteers who were measured repeatedly, resulting in 67 datasets, made in the context of PET blood flow studies. In contrast to traditional volume of distribution estimates of total body water (TBW) which rely on measurements after many hours, the model and data provide insights into the fast uptake components in the distribution of water in the body. Data fitting shows that the volume of distribution of fast exchanging tissues is 21 l. TBW was calculated to be 37 l. Monte Carlo simulation showed that the expected inaccuracy of determination of parameters due to unsystematic sources in the measurement data was around 5% for most parameters. Our data show that water extraction to tissue is somewhat higher than would be predicted from the tabulated values, probably because skeletal blood flow is sensitive to physiological status and environmental conditions. The study provides valuable reference data on the distribution and kinetics of water in man. Using the parameters and model from this study, reference input time-activity curves can be calculated, e.g. for the Monte Carlo study of error propagation in PET studies.

Adult↗
PubMed2003

Reward processing in the brain: a prerequisite for movement preparation?

In the last decade, expanding animal studies on the cerebral organization of reward processing toward human in vivo situations has become possible. In this review, we define some of the concepts associated with reward, summarize the crucial importance of the dopaminergic system, and discuss the currently available neuroimaging studies in man. We will show that abstract concepts of human behavior like emotions, drive, arousal, and reinforcement are now open for further exploration in man at the level of neuronal circuit organization. The cerebral dopaminergic neurotransmitter circuitry does play an important role in the organization of both the motor and motivational system.

Animals↗