title: Functional Connectivity Changes and Executive and Social Problems in Neurofibromatosis Type I.
abstract: Neurofibromatosis type 1 (NF1) has regularly been associated with cognitive, social, and behavioral problems. The fact that many different cognitive and behavioral impairments have been observed in NF1 suggests that networks of brain regions are involved rather than specific brain regions. Here, we examined whether functional connectivity was different in NF1 and, if so, whether associations were present with cognitive, social, and behavioral outcomes. Fourteen NF1 patients (8 male, age: M=12.49, SD=2.65) and 30 healthy controls (HC; 23 male, age: M=12.30, SD=2.94; p=0.835) were included. Functional connectivity was assessed using functional resting-state scanning. We analyzed brain regions that have been associated with cognitive and social functions: the bilateral ventral anterior cingulate cortex (vACC), the bilateral amygdala, the bilateral orbitofrontal cortex (OFC), and the posterior cingulate cortex (PCC). For NF1 patients, connection strengths between brain regions showing HC-NF1 differences were correlated with parent reports of cognitive, social, and behavioral functioning. Compared to HC, patients showed differences in functional connectivity between the left vACC and the frontal cortex, insula, and subcortical areas (caudate, putamen), between the left amygdala and the frontal cortex, insula, supramarginal gyrus, and PCC/precuneus, and between the left OFC and frontal and subcortical areas (caudate, pallidum). In patients, indications were found for associations between increased frontofrontal and temporofrontal functional connectivity with cognitive, social, and behavioral deficits (r-range=0.536-0.851). NF1 patients showed differences in functional connectivity between areas associated with cognitive and social functioning when compared to controls. This, plus the fact that connectivity strengths in these networks were associated with worse cognitive, social, and behavioral outcomes, suggests a neuropathological basis for the widespread deficits observed in NF1.
authors.affiliation: 1 Leiden Institute for Brain and Cognition (LIBC), Leiden University , Leiden, The Netherlands .|2 Department of Clinical Child and Adolescent Studies, Leiden University , Leiden, The Netherlands .|3 Department of Neurology, Medical University of Graz , Graz, Austria .
authors.forename: Marisa
authors.initials: M
authors.lastname: Loitfelder
authors.affiliation: 1 Leiden Institute for Brain and Cognition (LIBC), Leiden University , Leiden, The Netherlands .|2 Department of Clinical Child and Adolescent Studies, Leiden University , Leiden, The Netherlands .
authors.forename: Stephan C J
authors.initials: SC
authors.lastname: Huijbregts
authors.affiliation: 1 Leiden Institute for Brain and Cognition (LIBC), Leiden University , Leiden, The Netherlands .|4 Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Ilya Milos
authors.initials: IM
authors.lastname: Veer
authors.affiliation: 1 Leiden Institute for Brain and Cognition (LIBC), Leiden University , Leiden, The Netherlands .|2 Department of Clinical Child and Adolescent Studies, Leiden University , Leiden, The Netherlands .
authors.forename: Hanna S
authors.initials: HS
authors.lastname: Swaab
authors.affiliation: 1 Leiden Institute for Brain and Cognition (LIBC), Leiden University , Leiden, The Netherlands .|5 Department of Radiology, Leiden University Medical Center , Leiden, The Netherlands .
authors.forename: Mark A
authors.initials: MA
authors.lastname: Van Buchem
authors.affiliation: 3 Department of Neurology, Medical University of Graz , Graz, Austria .
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: 1 Leiden Institute for Brain and Cognition (LIBC), Leiden University , Leiden, The Netherlands .|5 Department of Radiology, Leiden University Medical Center , Leiden, The Netherlands .|6 Institute of Psychology, Leiden University , Leiden, The Netherlands .
authors.forename: Serge A
authors.initials: SA
authors.lastname: Rombouts
mesh_terms: D000293:Adolescent; D001931:Brain Mapping; D002648:Child; D003072:Cognition Disorders / Q000209:etiology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology*; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000473:pathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012146:Rest; D012920:Social Behavior Disorders / Q000209:etiology*; D013223:Statistics as Topic; D011795:Surveys and Questionnaires
chemical_list: D010100:Oxygen
keywords: behavioral problems; executive dysfunction; functional connectivity; neurofibromatosis type 1; resting-state social problems