title: Impaired and preserved aspects of feedback learning in aMCI: contributions of structural connectivity.
abstract: Distinct lines of research demonstrated that patients with amnestic mild cognitive impairment (aMCI), a potential precursor of Alzheimer disease (AD), are particularly impaired in remembering relations between items and that the use of emotional targets can facilitate memory in patients with AD. We link these findings by examining learning through positive and negative feedback in patients with aMCI, and explore its anatomic underpinnings with diffusion tensor imaging and tractography. Compared to healthy controls, patients with single-domain aMCI were impaired in learning from positive feedback, while learning from negative outcomes was preserved. Among pathways within the brain circuit involved in feedback learning, abnormal white matter microstructure was observed in tracts, which connect left-hemispheric amygdala with hippocampus and entorhinal cortex. In all participants, reduced white matter integrity in this left fiber tract was specifically associated with learning from positive outcomes. Microstructure of right-hemispheric tracts between amygdala and entorhinal cortex was related to learning from negative feedback, and was not compromised in aMCI patients. Our results provide new insight into how anatomical connections might contribute to impaired and preserved aspects of learning behaviors in the early AD process and indicate potential compensatory mechanisms.
authors.affiliation: Department of Clinical Psychology and Neuropsychology, Institute for Psychology, Johannes Gutenberg-University Mainz, Wallstraße 3, 55122, Mainz, Germany. wessa@uni-mainz.de.
authors.forename: Michèle
authors.initials: M
authors.lastname: Wessa
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Andrea V
authors.initials: AV
authors.lastname: King
authors.affiliation: Department of Clinical Psychology and Neuropsychology, Institute for Psychology, Johannes Gutenberg-University Mainz, Wallstraße 3, 55122, Mainz, Germany.
authors.forename: Patric
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Department of Gerontopsychiatry, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: NeuroSpin, I2BM, CEA Saclay & Paris-Saclay University, Gif-Sur-Yvette, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Poupon
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoppstädter
authors.affiliation: Department of Clinical Psychology and Neuropsychology, Institute for Psychology, Johannes Gutenberg-University Mainz, Wallstraße 3, 55122, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Linke
mesh_terms: D000368:Aged; D000647:Amnesia / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D000679:Amygdala / Q000473:pathology; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D056324:Diffusion Tensor Imaging; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D000068156:Formative Feedback; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology; D066127:White Matter / Q000473:pathology*
keywords: Amnestic mild cognitive impairment; Amygdala; Diffusion tensor imaging; Entorhinal cortex; Hippocampus; Tractography