Functional networks in motor sequence learning: Abnormal topographies in Parkinson's disease

Nakamura, Tomoya; Ghilardi, M. F.; Mentis, Marc J.; Dhawan, Vijay; Fukuda, Masafumi; Hacking, Antony G.; Moeller, James R.; Ghez, Claude; Eidelberg, David

doi:10.1002/1097-0193(200101)12:1<42::aid-hbm40>3.0.co;2-d

Cited by 125 publications

(181 citation statements)

References 67 publications

(94 reference statements)

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“…5,6,9 Nonetheless, despite comparable task performance, the gene carriers displayed enhanced activation in premotor areas and in multimodal parietal association cortex. Overactivation of SMA has been reported in affected idiopathic dystonia patients performing freely chosen joystick movements.…”

Section: Brain Activationmentioning

confidence: 95%

“…Subjects were informed that a sequence was to be presented; they were instructed to learn the sequence order while reaching for the targets, to anticipate successive targets, and to reach each target in synchrony with the tone. 6,8 At the end of the block, they reported the order of the sequence verbally. This task was kinematically equivalent to CCW and was used to assess learning performance.…”

Section: Motor Tasksmentioning

confidence: 99%

“…The following measures were computed for each movement in each of the motor tasks 5,6 : (1) Spatial error: the shortest distance of the end point from the center of the target; (2) directional error at the peak velocity: the difference between the direction of the vector from the starting point to the target and that of the vector from the starting point to the movement peak velocity; (3) movement time: the time from movement onset to the reversal point; (4) onset time: the time from target and tone presentation to movement onset. Negative values indicate responses that initiated before the tone.…”

Section: Task Performancementioning

confidence: 99%

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Impaired sequence learning in carriers of the DYT1 dystonia mutation

Ghilardi

Carbon

Silvestri

et al. 2003

Annals of Neurology

187

147

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Previous positron emission tomography (PET) studies have shown that nonmanifesting carriers of the DYT1 dystonia mutation express an abnormal pattern of resting glucose metabolism. To determine whether motor behavior is impaired in these subjects, we compared movement and sequence learning in 12 clinically unaffected DYT1 carriers with 12 age-matched controls. Regional differences in brain function during task performance were assessed with simultaneous H 2 15 O/PET. We found that motor performance was similar in the DYT1 and control groups, with no significant differences in movement time and spatial accuracy measured during each of the tasks. In contrast, sequence learning was reduced in gene carriers relative to controls (p < 0.01). PET imaging during motor execution showed increased activation in gene carriers (p < 0.001, uncorrected) in the left premotor cortex and right supplementary motor area, with concomitant reduction in the posterior medial cerebellum. During sequence learning, activation responses in DYT1 carriers were increased in the left ventral prefrontal cortex, and lateral cerebellum. These findings suggest that abnormalities in motor behavior and brain function exist in clinically nonmanifesting DYT1 carriers. Although localized increases in neural activity may enable normal movement execution in these subjects, this mechanism may not compensate for their defect in sequence learning. Neurol 2003;54:102-109 Primary torsion dystonia is a hyperkinetic movement disorder associated with several genetic variants. Ann1 One genetic variant is the GAG deletion in the DYT1 gene at 9q34. This mutation commonly causes early limb onset primary torsion dystonia and is inherited as an autosomal dominant condition with incomplete (30 -40%) clinical penetrance.2 Using 18 F-fluorodeoxyglucose and positron emission tomography (PET), we had identified previously abnormalities in resting glucose utilization in the putamen/globus pallidus, supplementary motor area (SMA), and cerebellum of DYT1 mutation carriers, including clinically nonpenetrant subjects in whom signs and symptoms of dystonia are lacking. 3,4 Given the presence of metabolic abnormalities in key elements of motor control pathways, we sought to determine whether clinically unaffected mutation carriers also display abnormalities in the trajectory control of reaching movements and in learning motor sequences. To this end, we utilized a series of tasks with similar and welldefined kinematics to assess performance during motor execution and learning. 5,6 Simultaneous PET recordings were acquired during task performance to determine whether specific abnormalities in brain activation responses were present within corticostriatopallidothalamocortical loops and related pathways. Subjects and Methods SubjectsWe studied 12 right-handed nonmanifesting carriers of the DYT1 mutation (four men and eight women; aged 50.3 Ϯ 14.4 years, mean Ϯ standard deviation [SD]). These subjects were recruited through the Dystonia Clinical Research Center at Beth Israel Hosp...

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Section: Brain Activationmentioning

confidence: 95%

Section: Motor Tasksmentioning

confidence: 99%

Section: Task Performancementioning

confidence: 99%

See 1 more Smart Citation

Impaired sequence learning in carriers of the DYT1 dystonia mutation

Ghilardi

Carbon

Silvestri

et al. 2003

Annals of Neurology

187

147

View full text Add to dashboard Cite

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“…Derivation of AD-related pattern-To identify network-correlates of early dementia and age, we employed the Scaled Subprofile Model (SSM), a covariance-analysis method (Alexander et al, 1999;Moeller et al, 1987) that has been used previously in resting imaging studies of normal aging and a variety of neurological diseases (Alexander et al, 1999;Hutchinson et al, 2000;Moeller et al, 1996;Nakamura et al, 2001). This analysis was applied to the FDG-PET images acquired for AD and control subjects.…”

Section: Pca Approachmentioning

confidence: 99%

Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

et al. 2008

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We performed univariate and multivariate discriminant analysis of FDG-PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG-PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic ADmarkers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures.

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“…Functional imaging studies have generally focused upon activation experiments to detect abnormal patterns of neural activity in PD patients during task performance (e.g., Dagher et al, 1999;Nakamura et al, 2001;Owen, 2004). Relevant information has also been obtained through imaging studies conducted in the rest state.…”

Section: Introductionmentioning

confidence: 99%

Metabolic brain networks associated with cognitive function in Parkinson's disease

et al. 2007

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The motor manifestations of Parkinson's disease (PD) have been linked to an abnormal spatial covariance pattern involving basal ganglia thalamocortical pathways. By contrast, little is known about the functional networks that underlie cognitive dysfunction in this disorder. To identify such patterns, we studied 15 non-demented PD patients using FDG PET and a voxel-based network modeling approach. We detected a significant covariance pattern that correlated (p< 0.01) with performance on tests of memory and executive functioning. This PD-related cognitive pattern (PDCP) was characterized by metabolic reductions in frontal and parietal association areas and relative increases in the cerebellar vermis and dentate nuclei. To validate this pattern, we analyzed data from 32 subsequent PD patients of similar age, disease duration and severity. Prospective measurements of PDCP activity predicted memory performance (p<0.005), visuospatial function (p<0.01), and perceptual motor speed (p<0.005) in this validation sample. PDCP scores additionally exhibited an excellent degree of test-retest reliability (intraclass correlation coefficient, ICC=0.89) in patients undergoing repeat FDG PET at an 8-week interval. Unlike the PD-related motor pattern, PDCP expression was not significantly altered by antiparkinsonian treatment with either intravenous levodopa or deep brain stimulation (DBS). These findings substantiate the PDCP as a reproducible imaging marker of cognitive function in PD. Because PDCP expression is not altered by routine antiparkinsonian treatment, this measure of network activity may prove useful in clinical trials targeting the progression of non-motor manifestations of this disorder.

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Functional networks in motor sequence learning: Abnormal topographies in Parkinson's disease

Cited by 125 publications

References 67 publications

Impaired sequence learning in carriers of the DYT1 dystonia mutation

Impaired sequence learning in carriers of the DYT1 dystonia mutation

Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

Metabolic brain networks associated with cognitive function in Parkinson's disease

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