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ABSTRACT: BACKGROUND: The objective of this study was to validate disease-related metabolic brain patterns for Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. METHODS: The study included 20 patients with Parkinson's disease, 21 with multiple system atrophy, and 17 with progressive supranuclear palsy, all of whom had undergone a clinically motivated [18F]-fluoro-deoxyglucose positron emission tomography scan at an early stage of their disease. At a follow-up time after the scan of 2-4 years, a clinical diagnosis was made according to established clinical research criteria. Patient groups were compared with 18 healthy controls using a multivariate covariance image analysis technique called scaled subprofile model/principal component analysis. RESULTS: Disease-related metabolic brain patterns for these parkinsonian disorders were identified. Validation showed that these patterns were highly discriminative of the 3 disorders. CONCLUSIONS: Early diagnosis of parkinsonian disorders is feasible when the expression of disease-related metabolic brain patterns is quantified at a single-subject level. © 2013 Movement Disorder Society.
Movement Disorders 03/2013; · 4.51 Impact Factor
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ABSTRACT: Clinically normal hand movement with altered cerebral activation patterns in cervical dystonia (CD) may imply cerebral adaptation. Since impaired sensorimotor integration appears to play a role in dystonia, left superior parietal cortex modulation with repetitive transcranial magnetic stimulation (TMS) was employed to further challenge adaptation mechanisms reflected by changes in cerebral activation.
Seven CD patients and ten healthy controls were scanned on a 3T magnetic resonance imaging (MRI) scanner with 1 Hz inhibitory interleaved TMS. They executed and imagined right wrist flexion/extension movements. Each task was preceded by a 10-s period with or without TMS.
The activations of both tasks after TMS in controls showed a similar pattern as found in CD without TMS, i.e. activation increases in bilateral prefrontal and posterior parietal regions during both tasks and decreases in right anterior parietal cortex during imagery (P<0.001). the activations of both tasks after TMS in CD were weaker but with a similar trend in activation changes. Only in the right angular gyrus, TMS significantly failed to induce an activation increase in CD as was seen in the controls (P<0.001).
The similarity between TMS effects on the distribution of cerebral activations in controls and the pattern seen in CD may support the concept that CD make use of compensatory circuitry enabling clinically normal hand movement. The fact that a similar but weaker TMS effect occurred in CD could suggest that the capacity of compensation is reduced. Particularly for the right angular gyrus, this reduction was statistically significant.
Clinical neurology and neurosurgery 03/2012; 114(7):914-21. · 1.30 Impact Factor
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ABSTRACT: Parkinson's disease (PD) characteristically presents with asymmetrical symptoms, contralateral to the side of the most extensive cerebral affection. This intriguing asymmetry, even included in the definition for diagnosing PD, however, is still part of a mystery. The relation with handedness as a common indicator of cerebral asymmetry might provide a clue in the search for causal factors of asymmetrical symptom onset in PD. This possible relationship, however, is still under debate. The objective of this study was to establish whether a relation between handedness and dominant PD side exists. We searched for cross-sectional or cohort studies that registered handedness and onset side in PD patients in PubMed, EMBASE, and Web of Science from their first record until 14 February 2011. Data about handedness and dominant PD side was extracted. Authors who registered both but not described their relation were contacted for further information. Odds ratios (ORs) were analyzed with a fixed effect Mantel-Haenszel model. Heterogeneity and indications of publication bias were limited. Our electronic search identified 10 studies involving 4405 asymmetric PD patients. Of the right-handed patients, 2413 (59.5%) had right-dominant and 1644 (40.5%) had left-dominant PD symptoms. For the left-handed patients this relation was reversed, with 142 (40.8%) right-dominant and 206 (59.2%) left-dominant PD symptoms. Overall OR was 2.13 (95% confidence interval [CI], 1.71-2.66). Handedness and symptom dominance in PD are firmly related with each other in such a way that the PD symptoms emerge more often on the dominant hand-side. Possible causal factors are discussed.
Movement Disorders 02/2012; 27(2):206-10. · 4.51 Impact Factor
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ABSTRACT: Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular.
PLoS ONE 01/2012; 7(7):e41042. · 4.09 Impact Factor
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Movement Disorders 12/2011; 27(4):580-1. · 4.51 Impact Factor
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ABSTRACT: In this study, we describe a 58-year-old male patient (FZ) with a right-amygdala lesion after temporal lobe infarction. FZ is unable to recognize fearful facial expressions. Instead, he consistently misinterprets expressions of fear for expressions of surprise. Employing EEG/ERP measures, we investigated whether presentation of fearful and surprised facial expressions would lead to different response patterns. We also measured ERPs to aversively conditioned and unconditioned fearful faces. We compared ERPs elicited by supraliminally and subliminally presented conditioned fearful faces (CS+), unconditioned fearful faces (CS-) and surprised faces. Despite FZ's inability to recognize fearful facial expressions in emotion recognition tasks, ERP components showed different response patterns to pictures of surprised and fearful facial expressions, indicating that covert or implicit recognition of fear is still intact. Differences between ERPs to CS+ and CS- were only found when these stimuli were presented subliminally. This indicates that intact right amygdala function is not necessary for aversive conditioning. Previous studies have stressed the importance of the right amygdala for discriminating facial emotional expressions and for classical conditioning. Our study suggests that the right amygdala is necessary for explicit recognition of fear, while implicit recognition of fear and classical conditioning may still occur following lesion of the right amygdala.
Neurocase 08/2011; 17(4):297-312. · 1.11 Impact Factor
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Bauke M de Jong
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ABSTRACT: Free will is classically attributed to the prefrontal cortex. In clinical neurology, prefrontal lesions have consistently been shown to cause impairment of internally driven action and increased reflex-like behaviour. Recently, parietal contributions to both free selection at early stages of sensorimotor transformations and perception of specifically self-intended movements were demonstrated in the healthy brain. Such findings generated the concept that 'free will' is not a function restricted to the prefrontal cortex but is more widely embedded in the brain, indeed including the parietal cortex. In this paper, a systematic re-interpretation of parietal symptoms, such as apraxia and reduced sense of agency, is given with reference to the consequences of reduced freedom of selection at early stages of sensorimotor transformation. Failed selection between possible movement options is argued to represent an intrinsic characteristic of apraxia. Paradoxical response facilitation supports this view. Perception of self-intended movement corresponds with a sense of agency. Impaired parietal distinction between predicted and perceived movement sensations may thus equal a restricted repertoire for selection between possible movement options of which intention is attributed to either oneself, others or an alien hand. Sense of agency, and thus perception of free will, logically fits a model of the parietal cortex as a neuronal interface between the internal drive to reach a goal and a body scheme required to select possible effectors for motor preparation.
Cortex 06/2011; 47(10):1160-5. · 6.08 Impact Factor
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ABSTRACT: The present study investigated how direction of hand movement, which is a well-described parameter in cerebral organization of motor control, is incorporated in the somatotopic representation of the manual effector system in the human primary motor cortex (M1). Using functional magnetic resonance imaging (fMRI) and a manual step-tracking task we found that activation patterns related to movement in different directions were spatially disjoint within the representation area of the hand on M1. Foci of activation related to specific movement directions were segregated within the M1 hand area; activation related to direction 0° (right) was located most laterally/superficially, whereas directions 180° (left) and 270° (down) elicited activation more medially within the hand area. Activation related to direction 90° was located between the other directions. Moreover, by investigating differences between activations related to movement along the horizontal (0°+180°) and vertical (90°+270°) axis, we found that activation related to the horizontal axis was located more anterolaterally/dorsally in M1 than for the vertical axis, supporting that activations related to individual movement directions are direction- and not muscle related. Our results of spatially segregated direction-related activations in M1 are in accordance with findings of recent fMRI studies on neural encoding of direction in human M1. Our results thus provide further evidence for a direct link between direction as an organizational principle in sensorimotor transformation and movement execution coded by effector representations in M1.
PLoS ONE 01/2011; 6(11):e27838. · 4.09 Impact Factor
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ABSTRACT: Purposeful movements are attained by gradually adjusted activity of opposite muscles, or synergists. This requires a motor system that adequately modulates initiation and inhibition of movement and selectively activates the appropriate muscles. In patients with Parkinson's disease (PD) initiation and inhibition of movements are impaired which may manifest itself in e.g. difficulty to start and stop walking. At single-joint level, impaired movement initiation is further accompanied by insufficient inhibition of antagonist muscle activity. As the motor symptoms in PD primarily result from cerebral dysfunction, quantitative investigation of gradually adjusted muscle activity during execution of purposeful movement is a first step to gain more insight in the link between impaired modulation of initiation and inhibition at the levels of (i) cerebrally coded task performance and (ii) final execution by the musculoskeletal system. To that end, the present study investigated changes in gradual adjustment of muscle synergists using a manipulandum that enabled standardized smooth movement by continuous wrist circumduction. Differences between PD patients (N = 15, off-medication) and healthy subjects (N = 16) concerning the relation between muscle activity and movement performance in these groups were assessed using kinematic and electromyographic (EMG) recordings. The variability in the extent to which a particular muscle was active during wrist circumduction--defined as muscle activity differentiation--was quantified by EMG. We demonstrated that more differentiated muscle activity indeed correlated positively with improved movement performance, i.e. higher movement speed and increased smoothness of movement. Additionally, patients employed a less differentiated muscle activity pattern than healthy subjects. These specific changes during wrist circumduction imply that patients have a decreased ability to gradually adjust muscles causing a decline in movement performance. We propose that less differentiated muscle use in PD patients reflects impaired control of modulated initiation and inhibition due to decreased ability to selectively and jointly activate muscles.
PLoS ONE 01/2011; 6(9):e24572. · 4.09 Impact Factor
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ABSTRACT: The etiology of medically unexplained symptoms such as conversion disorder is poorly understood. This is partly because the interpretation of neuroimaging results in conversion paresis has been complicated by the use of different control groups, tasks and statistical comparisons. The present study includes these different aspects in a single data set. In our study we included both normal controls and feigners to control for conversion paresis. We studied both movement execution and imagery, and we contrasted both within-group and between-group activation. Moreover, to reveal hemisphere-specific effects that have not been reported before, we performed these analyses using both flipped and unflipped data. This approach resulted in the identification of abnormal parietal activation which was specific for conversion paresis patients. Patients also showed reduced activity in the prefrontal cortex, supramarginal gyrus and precuneus, including hemisphere-specific activation that is lateralized in the same hemisphere, regardless of right- or left-sided paresis. We propose that these regions are candidates for an interface between psychological mechanisms and disturbed higher-order motor control. Our study presents an integrative neurophysiological view of the mechanisms that contribute to the etiology of this puzzling psychological disorder, which can be further investigated with other types of conversion symptoms.
PLoS ONE 01/2011; 6(10):e25918. · 4.09 Impact Factor
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ABSTRACT: In our previous functional magnetic resonance imaging study, Parkinson's disease (PD) patients with visual hallucinations (VH) showed reduced activations in ventral/lateral visual association cortices preceding image recognition, compared with both PD patients without VH and healthy controls. The primary aim of the current study was to investigate whether functional deficits are associated with grey matter volume changes. In addition, possible grey matter differences between all PD patients and healthy controls were assessed. By using 3-Tesla magnetic resonance imaging (MRI) and voxel-based morphometry (VBM), we found no differences between PD patients with (n = 11) and without VH (n = 13). However, grey matter decreases of the bilateral prefrontal and parietal cortex, left anterior superior temporal, and left middle occipital gyrus were found in the total group of PD patients, compared with controls (n = 14). This indicates that previously demonstrated functional deficits in PD patients with VH are not associated with grey matter loss. The strong left parietal reduction in both nondemented patient groups was hemisphere specific and independent of the side of PD symptoms. © 2010Movement Disorder Society.
Movement Disorders 12/2010; 26(1):142 - 147. · 4.51 Impact Factor
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Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):1295-6. · 4.87 Impact Factor
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ABSTRACT: The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.
Movement Disorders 10/2010; 25(14):2395-404. · 4.51 Impact Factor
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ABSTRACT: The aim of this retrospective study was to assess the presence of a possible association between handedness and the side of symptom dominance in 963 patients with Parkinson's disease (PD). In only 287 patients the hand dominance was registered. Out of 254 right-handed patients, 158 (62%) had a right-side dominance of PD symptoms, while 96 patients (38%) had left-lateralized symptom dominance (p < 0.001). For the 33 left-handed subjects, 18 (55%) had left- and 15 (45%) had right-sided symptom dominance (p = 0.602). Right-handedness thus appeared to be associated with right-sided dominance of PD symptoms, while the group of left-handed patients was too small to draw conclusions from. Possible explanations are discussed.
Parkinsonism & Related Disorders 10/2010; 17(1):58-60. · 3.80 Impact Factor
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ABSTRACT: In our previous functional magnetic resonance imaging study, Parkinson's disease (PD) patients with visual hallucinations (VH) showed reduced activations in ventral/lateral visual association cortices preceding image recognition, compared with both PD patients without VH and healthy controls. The primary aim of the current study was to investigate whether functional deficits are associated with grey matter volume changes. In addition, possible grey matter differences between all PD patients and healthy controls were assessed. By using 3-Tesla magnetic resonance imaging (MRI) and voxel-based morphometry (VBM), we found no differences between PD patients with (n = 11) and without VH (n = 13). However, grey matter decreases of the bilateral prefrontal and parietal cortex, left anterior superior temporal, and left middle occipital gyrus were found in the total group of PD patients, compared with controls (n = 14). This indicates that previously demonstrated functional deficits in PD patients with VH are not associated with grey matter loss. The strong left parietal reduction in both nondemented patient groups was hemisphere specific and independent of the side of PD symptoms.
Movement Disorders 10/2010; 26(1):142-7. · 4.51 Impact Factor
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ABSTRACT: One of the predictive factors of outcome in traumatic brain injury is high intracranial pressure (ICP). Recently, the time course of ICP has been described but few data are available on the relation of these ICP profiles and outcome. The aim of this study is to investigate the relation of the time course of ICP with CT-findings and outcome.
Retrospective analysis of prospectively collected data of 246 patients with traumatic brain injury admitted to the neurosurgical intensive care unit.
Early rise in ICP (within the first 2 days) was present in 32%, an intermediate rise (between days 3 and 5) in 34% and a late rise (after day 5) in 34% of patients. Half of the patients with a normal opening pressure (76%) developed intermediate or late ICP rise profiles. More mass lesions and sub/epidural hematomas were present in the late rise group. Patients with a late ICP rise required significant more intensive treatment (65% vs. 37 and 33%) when compared to the early and intermediate rise groups. In multiple regression analysis both ICP profiles and extracranial hematomas were related to outcome. With late ICP rise more unfavorable outcome (46 vs. 17%, P < 0.001) was seen although one in four patients showed a favorable outcome.
During ICP monitoring different ICP profiles are present over time. These profiles are related to CT-characteristics and outcome. The importance of early and late monitoring of ICP is underlined.
Neurocritical Care 06/2010; 12(3):362-8. · 2.47 Impact Factor
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ABSTRACT: Impaired visual processing may play a role in the pathophysiology of visual hallucinations in Parkinson's disease. In order to study involved neuronal circuitry, we assessed cerebral activation patterns both before and during recognition of gradually revealed images in Parkinson's disease patients with visual hallucinations (PDwithVHs), Parkinson's disease patients without visual hallucinations (PDnonVHs) and healthy controls. We hypothesized that, before image recognition, PDwithVHs would show reduced bottom-up visual activation in occipital-temporal areas and increased (pre)frontal activation, reflecting increased top-down demand. Overshoot of the latter has been proposed to play a role in generating visual hallucinations. Nine non-demented PDwithVHs, 14 PDnonVHs and 13 healthy controls were scanned on a 3 Tesla magnetic resonance imaging scanner. Static images of animals and objects gradually appearing out of random visual noise were used in an event-related design paradigm. Analyses were time-locked on the moment of image recognition, indicated by the subjects' button-press. Subjects were asked to press an additional button on a colour-changing fixation dot, to keep attention and motor action constant and to assess reaction times. Data pre-processing and statistical analysis were performed with statistical parametric mapping-5 software. Bilateral activation of the fusiform and lingual gyri was seen during image recognition in all groups (P < 0.001). Several seconds before image recognition, PDwithVHs showed reduced activation of the lateral occipital cortex, compared with both PDnonVHs and healthy controls. In addition, reduced activation of extrastriate temporal visual cortices was seen just before image recognition in PDwithVHs. The association between increased vulnerability for visual hallucinations in Parkinson's disease and impaired visual object processing in occipital and temporal extrastriate visual cortices supported the hypothesis of impaired bottom-up visual processing in PDwithVHs. Support for the hypothesized increased top-down frontal activation was not obtained. The finding of activation reductions in ventral/lateral visual association cortices in PDwithVHs before image recognition further helps to explain functional mechanisms underlying visual hallucinations in Parkinson's disease.
Brain 09/2009; 132(Pt 11):2980-93. · 9.46 Impact Factor
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ABSTRACT: The left parietal cortex contributes to goal-directed hand movement. In this study, we targeted this region with transcranial magnetic stimulation (TMS) to assess the effects on a wider distributed circuitry related to motor control. Ten healthy subjects underwent 3 Tesla functional magnetic resonance imaging (fMRI) with interleaved TMS. They either executed or imagined right wrist flexion/extension movements, which was preceded by a 10-second period either with or without TMS. This was applied to the left superior parietal cortex in 10 stimuli of 1 Hz at 115% motor threshold intensity. TMS preceding the movement execution condition resulted in significantly increased activation in the bilateral prefrontal, right temporo-parietal and left posterior parietal cortices, when compared to movement without such intervention (P<0.001 voxel-level; P<0.05, volume corrected). Movement imagery after TMS showed significantly increased activation in the left medial prefrontal cortex, right lateral prefrontal cortex, left supramarginal gyrus and right occipital cortex, while a decrease was present in bilateral anterior parietal cortex (P<0.01 voxel-level; P<0.05 volume corrected). Activation changes after TMS of left superior parietal cortex thus appears to increase prefrontal and posterior parietal cortex activation, associated with a reduced function of the anterior parietal cortex, including S2. These changes are thought to reflect an impaired ability to estimate the proprioceptive consequences of movement during its preparation, which is compensated by the increased contribution of more remote parietal and prefrontal cortical regions.
Brain research 07/2009; 1285:58-68. · 2.46 Impact Factor
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ABSTRACT: To determine whether motor imagery during the immobilization period after flexor tendon injury results in a faster recovery of central mechanisms of hand function.
Randomized controlled trial.
Tertiary referral hospital.
Patients (N=28) after surgical flexor tendon repair were assigned to either an intervention group or a control group.
Kinesthetic motor imagery of finger flexion movements during the postoperative dynamic splinting period.
The central aspects of hand function were measured with a preparation time test of finger flexion in which subjects pressed buttons as fast as possible following a visual stimulus. Additionally, the following hand function modalities were recorded: Michigan Hand Questionnaire, visual analog scale for hand function, kinematic analysis of drawing, active total motion, and strength.
After the immobilization period, the motor imagery group demonstrated significantly less increase of preparation time than the control group (P=.024). There was no significant influence of motor imagery on the other tested hand function (P>.05). All tests except kinematic analysis (P=.570) showed a significant improvement across time after the splinting period (P</=.001).
Motor imagery significantly improves central aspects of hand function, namely movement preparation time, while other modalities of hand function appear to be unaffected.
Archives of physical medicine and rehabilitation 04/2009; 90(4):553-9. · 2.18 Impact Factor
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ABSTRACT: Positive feedbacks reinforce goal-directed behavior and evoke pleasure. In Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary feedback and positive informative feedback), both compared to meaningless feedback, in PD patients and elderly healthy controls, using fMRI. In addition, positive informative feedback will be compared to monetary feedback to determine whether positive informative feedback is just as salient as monetary feedback. Healthy controls showed increased activation in the left putamen during the monetary feedback condition compared to both the positive informative and meaningless feedback condition, without an effect in the medial Prefrontal Cortex (mPFC). In contrast, PD patients showed increased activation in the left putamen during the meaningless feedback condition compared to both positive feedback conditions. In addition, PD patients showed increased activation of the mPFC during both positive feedback conditions. This suggests that when confronted with positive feedback, the mPFC compensates for the striatal deficit. In conclusion, striatal activation was seen in healthy controls specifically during the monetary feedback condition. PD patients did not differentiate between both types of positive feedback. If PD patients are provided with positive feedback, the mPFC compensates for the striatal dysfunction. If however, PD patients are provided with meaningless feedback, the mPFC is less stimulated and the striatum becomes prominent. This study thus demonstrates striatal involvement in positive feedback processing and altered positive feedback processing in PD.
Brain Research 09/2008; 1236:225-33. · 2.73 Impact Factor
