Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.

Garth Coombs Iii,Douglas N Greve,Marco L Loggia,Daphne J Holt,Carles Soriano-Mas

doi:10.1371/journal.pone.0097466

Abstract

BackgroundPrevious studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.MethodsHere we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.ResultsBLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.ConclusionsThese results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.

Highlights

One commonly cited model of mental illness is derived from the writings of the neurologist Hughlings Jackson, who observed that frontal lobe lesions were associated with ‘release behaviors’, i.e., disinhibition of suppressed, primitive reflexes that are generated subcortically [1,2]
Factor analyses have shown that the State and Trait Anxiety Inventory (STAI) measures symptoms typically associated with depression, as well as those associated with anxiety; it appears to index the broad construct of negative affect, rather than anxiety only [29,30,31,32,33,34]
arterial spin labeling (ASL) Analysis Perfusion of both the right and left basolateral nucleus of the amygdala (BLA) was significantly correlated with anxiety levels (Figure 1A and 1B)

Summary

Introduction

One commonly cited model of mental illness is derived from the writings of the neurologist Hughlings Jackson, who observed that frontal lobe lesions were associated with ‘release behaviors’, i.e., disinhibition of suppressed, primitive reflexes that are generated subcortically [1,2]. Neuroimaging research over the past several decades has generated support for this model [8,9,10,11], most consistently with demonstrations of associations between increases in negative affect (i.e., anxiety, depression, or subsyndromal expressions of those symptoms [12]) and 1) increased responses [13] or resting activity [14,15] of the amygdala, or 2) decreased strength of the connections between the prefrontal cortex and amygdala [16,17,18]. It is not known whether elevated amygdala activity is associated with decreased amygdalaprefrontal connectivity during negative affect states

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