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Front Syst Neurosci. 2016 Nov 16;10:93. eCollection 2016.

The Inverse Relationship between the Microstructural Variability of Amygdala-Prefrontal Pathways and Trait Anxiety Is Moderated by Sex.

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Department of Psychological and Brain Sciences, Dartmouth College Hanover, NH, USA.
Department of Psychological and Brain Sciences, Dartmouth CollegeHanover, NH, USA; Division of Epidemiology, The Ohio State University College of Public HealthColumbus, OH, USA.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA.


Anxiety impacts the quality of everyday life and may facilitate the development of affective disorders, possibly through concurrent alterations in neural circuitry. Findings from multimodal neuroimaging studies suggest that trait-anxious individuals may have a reduced capacity for efficient communication between the amygdala and the ventral prefrontal cortex (vPFC). A diffusion-weighted imaging protocol with 61 directions was used to identify lateral and medial amygdala-vPFC white matter pathways. The structural integrity of both pathways was inversely correlated with self-reported levels of trait anxiety. When this mask from our first dataset was then applied to an independent validation dataset, both pathways again showed a consistent inverse relationship with trait anxiety. Importantly, a moderating effect of sex was found, demonstrating that the observed brain-anxiety relationship was stronger in females. These data reveal a potential neuroanatomical mediator of previously documented functional alterations in amygdala-prefrontal connectivity that is associated with trait anxiety, which might prove informative for future studies of psychopathology.


amygdala; anxiety; connectivity; ventral prefrontal cortex; white matter

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