title: Disruption of amygdala-entorhinal-hippocampal network in late-life depression.
abstract: Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California.|Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Leal
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Noche
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Murray
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.
authors.forename: Michael A
authors.identifier: 0000-0002-8635-1498
authors.initials: MA
authors.lastname: Yassa
mesh_terms: D000368:Aged; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D003863:Depression / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004192:Discrimination, Psychological / Q000502:physiology*; D004644:Emotions / Q000502:physiology*; D018728:Entorhinal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D021641:Recognition, Psychology / Q000502:physiology; D014796:Visual Perception / Q000502:physiology
keywords: aging; emotion; hippocampus; memory; pattern separation