{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:59:58Z","timestamp":1790207998303,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T00:00:00Z","timestamp":1465257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Machado\u2010Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole\u2010brain functional biomarkers, based on parametric performance\u2010level\u2010dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral\/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel\u2010based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio\u2010paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance\u2010level\u2010based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency\u2010dependent cortico\/subcortical activation\/deactivation patterns. Cerebellar\/cortical rate\u2010dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger\u2010tapping task significantly often reached &gt;80% sensitivity and specificity in single regions\u2010of\u2010interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and\/or therapeutic targets in hereditary ataxia. <jats:italic>Hum Brain Mapp 37:3656\u20133668, 2016<\/jats:italic>. \u00a9 <jats:bold>2016 Wiley Periodicals, Inc<\/jats:bold>.<\/jats:p>","DOI":"10.1002\/hbm.23266","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T14:41:13Z","timestamp":1465310473000},"page":"3656-3668","source":"Crossref","is-referenced-by-count":23,"title":["Parametric fMRI of paced motor responses uncovers novel whole\u2010brain imaging biomarkers in spinocerebellar ataxia type 3"],"prefix":"10.1002","volume":"37","author":[{"given":"Jo\u00e3o 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