title: Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.
abstract: Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|ICNAS, University of Coimbra, Coimbra, Portugal.
authors.forename: João V
authors.initials: JV
authors.lastname: Duarte
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|ICNAS, University of Coimbra, Coimbra, Portugal.|Laboratory of Biostatistics and Medical Informatics, Institute for Biomedical Imaging in Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: João M S
authors.initials: JM
authors.lastname: Pereira
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|ICNAS, University of Coimbra, Coimbra, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Quendera
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Raimundo
authors.affiliation: Department of Endocrinology, University Hospital of Coimbra (CHUC), Coimbra, Portugal.
authors.forename: Carolina
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Department of Endocrinology, University Hospital of Coimbra (CHUC), Coimbra, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Gomes
authors.affiliation: Department of Endocrinology, University Hospital of Coimbra (CHUC), Coimbra, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Carrilho
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|ICNAS, University of Coimbra, Coimbra, Portugal.|Laboratory of Biostatistics and Medical Informatics, Institute for Biomedical Imaging in Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Castelo-Branco
mesh_terms: D002560:Cerebrovascular Circulation; D002755:Choice Behavior; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000523:psychology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000069336:Neurovascular Coupling; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011597:Psychomotor Performance; D011601:Psychophysics
chemical_list: D010100:Oxygen