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Table 1.

Participant demographics.

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Table 2.

Regions showing a correlation between perfusion and anxiety levels.

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Figure 1.

Perfusion of the basolateral nucleus of the amygdala (BLA) is correlated with anxiety levels.

Significant correlations were found between anxiety levels and perfusion of the left (A) and right (B) basolateral amygdala (BLA), as defined using anatomical regions-of-interest. These findings were then confirmed in a voxel-wise, whole brain regression analysis (C). In C, the BLA regions-of-interest are outlined in blue; the voxel-level display threshold is p<.005 (showing only clusters surviving whole-brain correction, see Methods). Clusters that showed cluster-wise significance (p<.05, whole brain corrected) are reported in the text and in Table 2. R, right.

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Figure 2.

Perfusion of a distributed network of regions outside of the amygdala is also correlated with anxiety levels.

A voxel-wise whole brain regression analysis revealed that, in addition to the basolateral amygdala (BLA), perfusion of the superior frontal gyri and posterior cingulate cortex (A), and anterior putamen (B), among other regions (see Table 2), were significantly correlated with anxiety levels. Whole-brain corrected results (see Methods) are displayed here using a voxel-level threshold of p<.005. Clusters that showed cluster-wise significance (p<.05, whole brain corrected) are reported in the text and in Table 2. R, right; PCC, posterior cingulate cortex; SFG, superior frontal gyri.

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Figure 3.

Functional connectivity between the BLA and mPFC is inversely correlated with BLA perfusion and anxiety levels.

An average map of basolateral amygdala (BLA) functional connectivity is shown in A. A whole-brain voxel-wise regression revealed that the strength of connectivity between the BLA and mPFC was negatively correlated with both: anxiety levels (B, C) and BLA perfusion (D, E). In A, B, and D, voxels with positive connectivity with the BLA (A) or showing positive correlations between their connectivity with the BLA and anxiety levels (B) or BLA perfusion (D) are shown in warm colors; voxels with negative correlations are shown in cool colors. The scatter plots in C and E are derived from the accompanying voxel-wise regression maps shown in B and D and are presented for the purpose of illustrating the range of values only. Data are displayed at a threshold of p<.05. The clusters indicated with arrows in B and D met a cluster-wise correction (FWE, p<.05) within the ventral mPFC. The peaks of the clusters in B (4, 2, −7) and D (2, 4, −4) were localized to the posterior-most portion of the SGC (with both clusters extending into the hypothalamus) using two independent atlases (the Talairach and Tournoux Stereotaxic Atlas [46] and the Wake Forrest University (WFU) PickAtlas [47]; see Methods). Prior work further supports this localization; previously reported sites that have been localized to the SGC (BA25), as well as an architectonic mapping of BA25 [68], overlap with the two clusters reported here, with nearby peaks: 4, 2, −4 [69]; −2, 6, −6 [8]; −2, 8, −10 [70]; −3, 9, −6 [71]; −4, 9, −12 & 2, 11, −7 [72]; 0, 8, −16 [73]. BLA, basolateral amygdala; FC, functional connectivity; Hy, hypothalamus; SGC, subgenual cingulate gyrus; mPFC, medial prefrontal cortex.

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Table 3.

Basolateral amygdala functional connectivity.

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Table 3 Expand

Figure 4.

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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