AUTHOR=Nair Sangeeta , Nenert Rodolphe E. , Allendorfer Jane B. , Goodman Adam M. , Vannest Jennifer , Mirman Daniel , Szaflarski Jerzy P. TITLE=Sex, Age, and Handedness Modulate the Neural Correlates of Active Learning JOURNAL=Frontiers in Neuroscience VOLUME=Volume 13 - 2019 YEAR=2019 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.00961 DOI=10.3389/fnins.2019.00961 ISSN=1662-453X ABSTRACT=Background: Self-generation of material compared to passive learning results in mproved memory performance; this may be related to recruitment of a fronto-temporal encoding network. Using a verbal paired-associate learning fMRI task, we examined the effects of sex, age, and handedness on the neural correlates of self-generation. Methods: Data from 174 healthy English-speaking participants (78M, 56 atypically-handed; ages 19-76) were preprocessed using AFNI and FSL. Independent component analysis was conducted using GIFT (Group ICA fMRI Toolbox). Forty-one independent components were temporally sorted by task time series. Retaining correlations (r>0.25) resulted in three task-positive (“generate”) and three task-negative (“read”) components. Using participants’ back-projected components, we evaluated the effects of sex, handedness, and aging on activation lateralization and localization in task-relevant networks with two-sample t-tests. Further, we examined the linear relationship between sex and neuroimaging data with multiple regression, covarying for scanner, age, and handedness. Results: Task-positive components identified using ICA revealed a fronto-parietal network involved with self-generation, while task-negative components reflecting passive reading showed temporo-occipital involvement. Compared to older adults, younger adults exhibited greater task-positive involvement of the left inferior frontal gyrus and insula, whereas older adults exhibited reduced prefrontal lateralization. Greater involvement of the left angular gyrus in task-positive encoding networks among right-handed individuals suggests the reliance on left dominant semantic processing areas may be modulated by handedness. Sex effects on task-related encoding networks while controlling for age and handedness suggest increased right hemisphere recruitment among males compared to females, specifically in the paracentral lobe during self-generation and the suparmarginal gyrus during passive reading. Implications: Identified neuroimaging differences suggest that sex, age, and handedness are factors in the differential recruitment of encoding network regions for both passive and active learning.