title: Affected functional networks associated with sentence production in classic galactosemia.
abstract: Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients.
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Timmers
authors.affiliation: Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Center (M-BIC), Maastricht, The Netherlands; Laboratory of Biological Psychology, University of Leuven, Leuven, Belgium.
authors.forename: Job
authors.initials: J
authors.lastname: van den Hurk
authors.affiliation: Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Paul Am
authors.initials: PA
authors.lastname: Hofman
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Luc Ji
authors.initials: LJ
authors.lastname: Zimmermann
authors.affiliation: Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Center (M-BIC), Maastricht, The Netherlands.
authors.forename: Kâmil
authors.initials: K
authors.lastname: Uludağ
authors.affiliation: Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Center (M-BIC), Maastricht, The Netherlands.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Jansma
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; Laboratory of Genetic Metabolic Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: estela.rubio@mumc.nl.
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
mesh_terms: D000293:Adolescent; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005693:Galactosemias / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007806:Language Disorders / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood
chemical_list: D010100:Oxygen
keywords: Classic galactosemia; Functional connectivity; Functional magnetic resonance imaging; Language production; Syntactic encoding