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

Coombs G, Loggia ML, Greve DN, Holt DJ - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: The Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America; The MGH/HST/MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Center for Brain Science, Department of Psychology, Harvard University, Cambridge, Massachusetts, United States of America.

ABSTRACT

Background: Previous 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.

Methods: Here 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.

Results: BLA 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.

Conclusions: These 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.

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Related in: MedlinePlus

BLA perfusion mediates the relationship between BLA-mPFC connectivity and anxiety levels.Mediation analyses revealed that BLA perfusion levels mediate the relationship between BLA-mPFC connectivity and anxiety (A: Model #1). In contrast, BLA-mPFC connectivity did not mediate the relationship between BLA perfusion levels and anxiety (B: Model #2). Values are unstandardized regression coefficients reflecting the direct (paths a, b, and c’) and total (path c) effects of each relationship in the mediation model. BLA, basolateral amygdala; mPFC, medial prefrontal cortex; *p<.05, **p<.01, †p<.001, ††p<.0001.
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pone-0097466-g004: BLA perfusion mediates the relationship between BLA-mPFC connectivity and anxiety levels.Mediation analyses revealed that BLA perfusion levels mediate the relationship between BLA-mPFC connectivity and anxiety (A: Model #1). In contrast, BLA-mPFC connectivity did not mediate the relationship between BLA perfusion levels and anxiety (B: Model #2). Values are unstandardized regression coefficients reflecting the direct (paths a, b, and c’) and total (path c) effects of each relationship in the mediation model. BLA, basolateral amygdala; mPFC, medial prefrontal cortex; *p<.05, **p<.01, †p<.001, ††p<.0001.

Mentions: A follow-up, secondary mediation analysis was then conducted to assess the relationship among the findings of the regression analyses conducted above, to distinguish between the following two models (also see Figure 4): 1) BLA perfusion mediates the relationship between BLA-mPFC connectivity and anxiety (Model #1), or 2) BLA-mPFC connectivity mediates the relationship between BLA perfusion and anxiety (Model #2).


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

Coombs G, Loggia ML, Greve DN, Holt DJ - PLoS ONE (2014)

BLA perfusion mediates the relationship between BLA-mPFC connectivity and anxiety levels.Mediation analyses revealed that BLA perfusion levels mediate the relationship between BLA-mPFC connectivity and anxiety (A: Model #1). In contrast, BLA-mPFC connectivity did not mediate the relationship between BLA perfusion levels and anxiety (B: Model #2). Values are unstandardized regression coefficients reflecting the direct (paths a, b, and c’) and total (path c) effects of each relationship in the mediation model. BLA, basolateral amygdala; mPFC, medial prefrontal cortex; *p<.05, **p<.01, †p<.001, ††p<.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016310&req=5

pone-0097466-g004: BLA perfusion mediates the relationship between BLA-mPFC connectivity and anxiety levels.Mediation analyses revealed that BLA perfusion levels mediate the relationship between BLA-mPFC connectivity and anxiety (A: Model #1). In contrast, BLA-mPFC connectivity did not mediate the relationship between BLA perfusion levels and anxiety (B: Model #2). Values are unstandardized regression coefficients reflecting the direct (paths a, b, and c’) and total (path c) effects of each relationship in the mediation model. BLA, basolateral amygdala; mPFC, medial prefrontal cortex; *p<.05, **p<.01, †p<.001, ††p<.0001.
Mentions: A follow-up, secondary mediation analysis was then conducted to assess the relationship among the findings of the regression analyses conducted above, to distinguish between the following two models (also see Figure 4): 1) BLA perfusion mediates the relationship between BLA-mPFC connectivity and anxiety (Model #1), or 2) BLA-mPFC connectivity mediates the relationship between BLA perfusion and anxiety (Model #2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: The Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America; The MGH/HST/MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States of America; Center for Brain Science, Department of Psychology, Harvard University, Cambridge, Massachusetts, United States of America.

ABSTRACT

Background: Previous 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.

Methods: Here 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.

Results: BLA 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.

Conclusions: These 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.

Show MeSH
Related in: MedlinePlus