title: Neural correlates of individual differences in fear learning.
abstract: Variability in fear conditionability is common, and clarity regarding the neural regions responsible for individual differences in fear conditionability could uncover brain-based biomarkers of resilience or vulnerability to trauma-based psychopathologies (e.g., post-traumatic stress disorder). In recent years, neuroimaging work has yielded a detailed understanding of the neural mechanisms underlying fear conditioning common across participants, however only a minority of studies have investigated the brain basis of inter-individual variation in fear learning. Moreover, the majority of these studies have employed small sample sizes (mean n=17; range n=5-27) and all have failed to meet the minimum recommended sample size for functional magnetic resonance imaging (fMRI) studies of individual differences. Here, using fMRI, we analyzed blood-oxygenation level dependent (BOLD) response recorded simultaneously with skin conductance response (SCR) and ratings of unconditioned stimulus (US) expectancy in 49 participants undergoing Pavlovian fear conditioning. On average, participants became conditioned to the conditioned stimulus (CS+; higher US expectancy ratings and SCR for the CS+ compared to the unpaired conditioned stimulus, CS-); the CS+ also robustly increased activation in the bilateral insula. Amygdala activation was revealed from a regression analysis that incorporated individual differences in fear conditionability (i.e., a between-subjects regressor of mean CS+>CS- SCR). By replicating results observed using much smaller sample sizes, the results confirm that variation in amygdala reactivity covaries with individual differences in fear conditionability. The link between behavior (SCR) and brain (amygdala reactivity) may be a putative endophenotype for the acquisition of fear memories.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA. Electronic address: annmarie.macnamara@gmail.com.
authors.forename: Annmarie
authors.initials: A
authors.lastname: MacNamara
authors.affiliation: Departments of Pharmacy Practice and Psychiatry & Behavioral Neurosciences and Translational Neuroscience Program, Wayne State University, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Rabinak
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA; Mental Health Service Line, Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL 60612, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fitzgerald
authors.affiliation: Department of Radiology and Center for Magnetic Resonance Research, University of Illinois at Chicago, Suite 103, 2242 West Harrison Street, Chicago, IL 60612, USA.
authors.forename: Xiaohong Joe
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA; Department of Psychology, University of Illinois at Chicago, 1007 West Harrison Street, Chicago, IL 60607, USA.
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Shankman
authors.affiliation: Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, Cny 2614, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA; Mental Health Service Line, Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL 60612, USA; Department of Psychology, University of Illinois at Chicago, 1007 West Harrison Street, Chicago, IL 60607, USA; Department of Anatomy and Cell Biology and the Graduate Program in Neuroscience, University of Illinois at Chicago, 808 South Wood Street, Room 578, MC 512, Chicago, IL 60612, USA.
authors.forename: K Luan
authors.initials: KL
authors.lastname: Phan
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response; D006801:Humans; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D055815:Young Adult
keywords: Amygdala; Fear conditioning; Individual differences; SCR; Skin conductance response; fMRI
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