Linked Life Data

21515903

Source:http://linkedlifedata.com/resource/pubmed/id/21515903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 5
pubmed:dateCreated
2011-5-20
pubmed:abstractText
Abnormalities in motor sequence learning have been observed in non-manifesting carriers of the DYT1 dystonia mutation. Indeed, motor sequence learning deficits in these subjects have been associated with increased cerebellar activation during task performance. In the current study, we determined whether similar changes are also present in clinically manifesting DYT1 carriers as well as in carriers of other primary dystonia mutations such as DYT6. Additionally, we determined whether sequence learning performance and associated brain activation in these subjects correlate with previously described genotype-related abnormalities of cerebellar pathway integrity and striatal D2 dopamine receptor binding. Nineteen DYT1 carriers (10 non-manifesting DYT1: 51.5±15.1 years; nine manifesting DYT1: 46.1±15.1 years) and 12 healthy control subjects (42.8±15.3 years) were scanned with H2(15)O positron emission tomography while performing controlled sequence learning and reference tasks. Eleven DYT6 carriers (four non-manifesting DYT6: 38.0±22.1; seven manifesting DYT6: 35.3±14.2 years) were evaluated during task performance without concurrent imaging. DYT1 and DYT6 carriers also underwent diffusion tensor magnetic resonance imaging for the assessment of tract integrity and 11C-raclopride positron emission tomography to measure caudate/putamen D2 receptor binding. These imaging measures were correlated with sequence learning performance and associated activation responses. Sequence learning deficits of similar magnitude were observed in manifesting and non-manifesting DYT1 carriers. In contrast, learning deficits were not detected in DYT6 carriers, irrespective of clinical penetrance. Affected DYT1 carriers exhibited significant increases in sequence learning-related activation in the left lateral cerebellar cortex and in the right premotor and inferior parietal regions. Increases in premotor cortical activation observed in the mutation carriers correlated with reductions in cerebellar pathway integrity measured using magnetic resonance diffusion tensor imaging and probabilistic tractography. Additionally, the cerebellar tract changes correlated with reductions in dentate nucleus activation recorded during task performance. Sequence learning performance and task-related activation responses did not correlate with striatal D2 receptor binding. In summary, we found that sequence learning deficits and concomitant increases in cerebellar activation are specific features of the DYT1 genotype. The close relationship between reduced cerebellar pathway integrity and increased learning-related activation of the premotor cortex is compatible with the view of DYT1 dystonia as a neurodevelopmental circuit disorder.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1460-2156
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1416-27
pubmed:meshHeading
pubmed-meshheading:21515903-Adult, pubmed-meshheading:21515903-Apoptosis Regulatory Proteins, pubmed-meshheading:21515903-Brain Mapping, pubmed-meshheading:21515903-Cerebellum, pubmed-meshheading:21515903-DNA-Binding Proteins, pubmed-meshheading:21515903-Dystonia, pubmed-meshheading:21515903-Female, pubmed-meshheading:21515903-Genotype, pubmed-meshheading:21515903-Humans, pubmed-meshheading:21515903-Learning Disorders, pubmed-meshheading:21515903-Magnetic Resonance Imaging, pubmed-meshheading:21515903-Male, pubmed-meshheading:21515903-Middle Aged, pubmed-meshheading:21515903-Molecular Chaperones, pubmed-meshheading:21515903-Motor Activity, pubmed-meshheading:21515903-Mutation, pubmed-meshheading:21515903-Neuropsychological Tests, pubmed-meshheading:21515903-Nuclear Proteins, pubmed-meshheading:21515903-Photic Stimulation, pubmed-meshheading:21515903-Positron-Emission Tomography, pubmed-meshheading:21515903-Serial Learning, pubmed-meshheading:21515903-Statistics as Topic
pubmed:year
2011
pubmed:articleTitle
Impaired sequence learning in dystonia mutation carriers: a genotypic effect.
pubmed:affiliation
Centre for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA. marencarbon@hotmail.com
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural