Morphometric fingerprint of asymptomatic
            <i>Parkin</i>
            and
            <i>PINK1</i>
            mutation carriers in the basal ganglia

Binkofski, Ferdinand; Reetz, Kathrin; Gaser, Christian; Hilker, Rüdiger; Hagenah, Johann; Hedrich, Katja; Eimeren, Thilo van; Thiel, Alexander; Büchel, Christian; Pramstaller, Peter P.; Siebner, Hartwig R.; Klein, Christine

doi:10.1212/01.wnl.0000267844.72421.6c

Cited by 68 publications

(58 citation statements)

References 53 publications

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“…Consistent with previous studies, the present study observed the increased GMV in the limbic/paralimbic system and globus pallidus internus/putamen in patients with PD compared with controls. 10,21,22 Although the present study provides no evidence regarding the mechanisms leading to increased brain volume in PD, as a chronically progressive neurodegenerative disorder, the effect may be due to a compensatory response to impaired cerebral function in early PD. 10,[21][22][23][24] In the present study, the findings of GMV changes (decrease and increase) in patients with PD were not wholly consistent with findings in any of the previous studies.…”

Section: Group Differences: Gmv Changes For Patients With Pd Comparedmentioning

confidence: 61%

Longitudinal Study of Gray Matter Changes in Parkinson Disease

Jia

Liang

et al. 2015

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:The pathology of Parkinson disease leads to morphological brain volume changes. So far, the progressive gray matter volume change across time specific to patients with Parkinson disease compared controls remains unclear. Our aim was to investigate the pattern of gray matter changes in patients with Parkinson disease and to explore the progressive gray matter volume change specific to patients with Parkinson disease with disease progression by using voxel-based morphometry analysis.

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Section: Group Differences: Gmv Changes For Patients With Pd Comparedmentioning

confidence: 61%

Longitudinal Study of Gray Matter Changes in Parkinson Disease

Jia

Liang

et al. 2015

AJNR Am J Neuroradiol

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“…This finding extends our recent morphometric MRI study showing an increase in gray matter volume in the basal ganglia in a comparable group of nonmanifesting carriers of a Parkin or PINK1 mutation. 25 Together, the functional and structural MRI data suggest that mutations in the Parkin and PINK1 gene produce a very similar functional and structural endophenotype. This implies that single heterozygous mutations in these two genes have a similar impact on the human motor system.…”

Section: Resultsmentioning

confidence: 93%

Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype

Nuenen¹,

Weiss²,

Bloem³

et al. 2009

Neurology

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Objective: To use a combined neurogenetic-neuroimaging approach to examine the functional consequences of preclinical dopaminergic nigrostriatal dysfunction in the human motor system. Specifically, we examined how a single heterozygous mutation in different genes associated with recessively inherited Parkinson disease alters the cortical control of sequential finger movements. Methods:Nonmanifesting individuals carrying a single heterozygous Parkin (n ϭ 13) or PINK1 (n ϭ 9) mutation and 23 healthy controls without these mutations were studied with functional MRI (fMRI). During fMRI, participants performed simple sequences of three thumb-to-finger opposition movements with their right dominant hand. Since heterozygous Parkin and PINK1 mutations cause a latent dopaminergic nigrostriatal dysfunction, we predicted a compensatory recruitment of those rostral premotor areas that are normally implicated in the control of complex motor sequences. We expected this overactivity to be independent of the underlying genotype.Results: Task performance was comparable for all groups. The performance of a simple motor sequence task consistently activated the rostral supplementary motor area and right rostral dorsal premotor cortex in mutation carriers but not in controls. Task-related activation of these premotor areas was similar in carriers of a Parkin or PINK1 mutation. Conclusion: Mutations in different genes linked to recessively inherited Parkinson disease areassociated with an additional recruitment of rostral supplementary motor area and rostral dorsal premotor cortex during a simple motor sequence task. These premotor areas were recruited independently of the underlying genotype. The observed activation most likely reflects a "generic" compensatory mechanism to maintain motor function in the context of a mild dopaminergic deficit. Neurology ® 2009;72:1041-1047 GLOSSARY BOLD ϭ blood oxygen level-dependent; CMA ϭ cingulate motor area; FDR ϭ false discovery rate; fMRI ϭ functional MRI; HRF ϭ hemodynamic response function; IPS ϭ intraparietal sulcus; M1 HAND ϭ primary motor hand area; PD ϭ Parkinson disease; PMd ϭ dorsal premotor cortex; SMA ϭ supplementary motor area; SPM ϭ statistical parametric mapping; SVC ϭ small volume correction; TE ϭ echo time; TMS ϭ transcranial magnetic stimulation; TR ϭ repetition time; VOI ϭ volumes of interest.Several genes have been identified that can lead to Parkinson disease (PD), including four recessively inherited forms caused by mutations in the Parkin (PARK2), DJ-1 (PARK7), PINK1 (PARK6), and ATP13A2 (PARK9) genes.1-3 These familial forms of PD show a substantial clinical overlap with sporadic PD. Nonmanifesting individuals who carry a single heterozygous mutation in the Parkin and PINK1 gene associated with recessively inherited PD

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“…Morphometric studies in children aged 7-16 have described a substantial loss of striatal and pallidal volume during normal development (Sowell et al, 1999;Thompson et al, 2000), likely because of pruning processes. Studies in genetically caused disorders found a relative size increase of these structures compared with controls (Binkofski et al, 2007;Gothelf et al, 2008). We hypothesize that the environmental challenge posed by forced right-handed writing enhances normal pruning in the territory of the putamen that integrates executive and cognitive aspects of motor control.…”

Section: Structural Changes In the Basal Gangliamentioning

confidence: 86%

Nurture versus Nature: Long-Term Impact of Forced Right-Handedness on Structure of Pericentral Cortex and Basal Ganglia

Klöppel¹,

Mangin²,

Vongerichten³

et al. 2010

J. Neurosci.

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Does a conflict between inborn motor preferences and educational standards during childhood impact the structure of the adult human brain? To examine this issue, we acquired high-resolution T1-weighted magnetic resonance scans of the whole brain in adult "converted" left-handers who had been forced as children to become dextral writers. Analysis of sulcal surfaces revealed that consistent right-and left-handers showed an interhemispheric asymmetry in the surface area of the central sulcus with a greater surface contralateral to the dominant hand. This pattern was reversed in the converted group who showed a larger surface of the central sulcus in their left, nondominant hemisphere, indicating plasticity of the primary sensorimotor cortex caused by forced use of the nondominant hand. Voxel-based morphometry showed a reduction of gray matter volume in the middle part of the left putamen in converted left-handers relative to both consistently handed groups. A similar trend was found in the right putamen. Converted subjects with at least one left-handed first-degree relative showed a correlation between the acquired right-hand advantage for writing and the structural changes in putamen and pericentral cortex. Our results show that a specific environmental challenge during childhood can shape the macroscopic structure of the human basal ganglia. The smaller than normal putaminal volume differs markedly from previously reported enlargement of cortical gray matter associated with skill acquisition. This indicates a differential response of the basal ganglia to early environmental challenges, possibly related to processes of pruning during motor development.

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Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal ganglia

Abstract: Background: Mutations in the Parkin and PINK1 genes can cause parkinsonism. Since asymptom-

Cited by 68 publications

References 53 publications

Longitudinal Study of Gray Matter Changes in Parkinson Disease

Longitudinal Study of Gray Matter Changes in Parkinson Disease

Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype

Nurture versus Nature: Long-Term Impact of Forced Right-Handedness on Structure of Pericentral Cortex and Basal Ganglia

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