Resting State Analyses (Fixation versus Shape-Matching)
In the fixation condition, relative to shape-matching, there was widespread activation throughout a network of areas (; ) that have been referred to as the default network (Gusnard and Raichle, 2001
). These included the four areas most commonly included in the default network (Buckner, Andrews-Hanna, & Schacter, 2008
): a large midline cluster with a peak in the precuneus/posterior cingulate (−2, −36,48; t=6.48, p <0.005), inferior parietal lobule, bilaterally (−36, −78,40; t=5.03, p < 0.005; and 36, −76,40, 4.49, p < 0.005), dorsomedial prefrontal cortex (BA 9: 0,46,34, t=3.44, p < 0.005), and medial prefrontal cortex (BA10: 2,50,10; t=3.75, p < 0.005). In addition, there was activation in medial and lateral temporal lobe areas associated with the default network (Buckner, et al., 2008
) including the left and right amygdala (−22, −6, −16, t =4.84; 22,0, −32, t = 4.42, p < 0.005), the left and right parahippocampal gyrus (−20, −28, −24, t = 5.84; 36, −8, −40, t = 6.29, p < 0.005), and the left (−64, −42, −10, t = 3.97, p < 0.005) and right (rostral: 58, −2, −24, t = 4.49; caudal: 64, −52, 6, t = 4.91, p < 0.005) middle temporal gyrus. The bilateral fusiform gyrus also showed greater activation (30, −92, −10, t=7.00; −32, −94,12, t = 6.33, p < 0.005), which is common when a passive sensory task rather than eyes-closed rest is used as the baseline (Gusnard and Raichle, 2001
). Additionally, the right dorsal anterior cingulate cortex (2,12,24, t = 4.15, p < 0.005) and the dorsal striatum (8,18,8, t = 6.26, p < 0.005) were activated.
Baseline neural activation during fixation relative to shape matching..
Activations in the Fixation relative to Shape Match contrast. Denoted areas are part of the default network. DMPFC = dorsomedial prefrontal cortex; VMPFC = ventromedial prefrontal cortex; IPL = Inferior Parietal Lobule; LTC = Lateral Temporal Cortex.
In this same resting-state contrast, the BDI was positively correlated with activation in the right amygdala (22, 0, −28; t = 3.28, p < 0.005, k = 40), medial prefrontal cortex (BA10/11: 4,56, −14; t = 3.37, p < 0.005), inferior frontal gyrus (−42,42,6; t = 3.46, p < 0.005), and several areas in the visual cortex (; ). As anxiety related constructs have been related to amygdala activity (Etkin & Wager, 2007
), the relationship of both trait anxiety and neuroticism with amygdala activity were examined. Neither variable exhibited a significant correlation with amygdala activity and when they were used as covariates in an assessment of the neural correlates of the BDI, the relationship between BDI score and right amygdala activity remained significant (26, 2, −24, t = 3.76, p < 0.005, k = 55). In terms of areas inversely correlated with BDI scores, only one cluster had a significant negative relationship and that was in the superior frontal gyrus (30,46,38; t=3.34, p < 0.005, k=47).
Areas positively correlated with Beck Depression Inventory Score
Figure 3 Correlations of depression and mindfulness with self-referential regions during rest (Fixation versus Shape-Match). Positive correlations with Beck Depression Inventory score in the ventromedial prefrontal cortex (A; 4,56, −14) and negative correlations (more ...)
In this same fixation versus shape-match contrast, dispositional mindfulness was negatively correlated with activity in multiple areas (). The global maximum was centered in the left amygdala/hippocampal transition area (−12, −12, −20; t = 5.22, p < 0.005, k = 301) and extended both rostrally and caudally from this peak. There was also a peak in the right anterior medial temporal lobe (34, 10, −26; t = 3.99, p < 0.005, k = 109) that extended caudally to encompass the rostral amygdala. In addition, the left ventrolateral prefrontal cortex (−44, 34, −10; t = 3.73, p < 0.005, k = 134) was negatively associated with dispositional mindfulness. With respect to areas considered part of the default network, dispositional mindfulness was also negatively related to precuneus activity (2, −48, 56; t = 3.68, p < 0.005, k = 101). As for the positive correlation with dispositional mindfulness, no areas exceeded the statistical threshold for significant activation.
Areas negatively correlated with dispositional mindfulness.
To examine the unique relationship of mindfulness to neural activity in the fixation versus shape match contrast, the residualized dispositional mindfulness measure (controlling for gender and public self-consciousness) was used as a regressor in a random effects whole-brain analysis. The residualized dispositional mindfulness variable was negatively correlated with activity in multiple subcortical areas, including both the right (24, 2, −20, t=4.09, p < 0.005, k=367) and left amygdala (−20, 2, −20, t=3.73, p<0.005, k=31), the hippocampus bilaterally (−28, −20, −10, t = 3.81; 42, −18, −22, t = 3.90, p < 0.005), and the thalamus bilaterally (−22, −20,14, t = 3.69; 14, −6,2, t = 4.64, p < 0.005). Cortically, there was a significant negative correlation of residualized dispositional mindfulness with midline clusters of activation in the medial prefrontal cortex (BA10: 16,68,12, t = 3.40, p < 0.005) and the posterior cingulate (8, −34,48, t = 3.42), as well as with several clusters in the temporal cortex and visual cortex (; ). In contrast to these negative correlations, the residualized dispositional mindfulness variable was positively related to a single cluster in the right orbitofrontal gyrus (18,40, −14, t=3.88, p < 0.005).
Areas negatively correlated with dispositional mindfulness residualized for gender and public self-consciousness.
To identify areas that correlated with dispositional mindfulness as well as depressive symptomatology and thus might be involved in both processes, clusters of activation from each respective correlation map were assessed for spatial overlap. Only one area, the right amygdala, had a cluster (22, 0, −26, k = 20) possessing a significant relationship with both variables. This 20 voxel cluster was positively correlated with BDI scores and negatively correlated with the residualized dispositional mindfulness variable (). To determine the degree to which shared variance accounted for the relationship of depressive symptomatology and dispositional mindfulness, each variable was entered into a multiple regression with this 20 voxel right amygdala cluster as the dependent variable. Both the residualized dispositional mindfulness variable (β = −0.47, t = −3.18, p < 0.005) and the BDI (β = 0.43, t = 2.87, p < 0.01) were significantly related to activity in this cluster. Thus, each variable was uniquely associated with amygdala activity. In addition, the mean activation for this ROI was not significantly different between males and females, according to an independent samples t-test (t(25)= 1.1, p = 0.29).
Figure 4 Left panel: coronal sections showing the activations in the Fixation relative to Shape Match contrast for the positive correlation with depressive symptomatology (A) and the negative correlation with the dispositional mindfulness variable (C). In the (more ...) Reactivity Analyses (Affect Matching relative to Shape Matching)
To examine the relationship of depressive symptomatology and dispositional mindfulness with amygdala reactivity, the right amygdala ROI (described above) was used to extract values from the affect matching relative to shape matching contrast (). Consistent with predictions, the dispositional mindfulness variable was negatively correlated with amygdala activation (r = −0.53, p < 0.005) when viewing threatening and fearful faces, relative to shape-matching. Similarly, BDI scores were positively correlated with amygdala activation in this contrast (r = 0.63, p < 0.001). Thus, the right amygdala showed the same pattern of relationship with both depressive symptomatology and the residualized dispositional mindfulness variable in the reactivity analysis as it did in the resting state analysis.
Figure 5 Amygdala Reactivity. Scatterplots of the relationship between activity in the right amygdala and either dispositional mindfulness (A; r = −0.53, p < 0.005) or depressive symptomatology (B; r = 0.63, p < 0.005) when viewing negative (more ...)
Critical for the interpretation of these results is to remember that the amygdala reactivity observed in this analysis stems from comparing affect matching with a neutral, goal-directed task, as is typically done in the field. However, according to the resting analyses, there is also greater amygdala activity when passive fixation is compared to shape matching. This gives rise to the question as to whether or not there is amygdala activation during affect matching that exists over and above that during resting activity. In other words, is the amygdala activity seen in the affect match versus shape match contrast more attributable to amygdala activation over and above passive fixation or is it more attributable to the deactivation from passive fixation during shape matching? To disentangle these alternative interpretations, amygdala response to the viewing of emotional faces was compared to the passive viewing of the fixation cross (as opposed to shape-matching). As in the previous contrast, the same right amygdala ROI defined in the fixation versus shape-matching contrast was used to extract parameter estimates. There was no significant relationship between the residualized dispositional mindfulness measure and amygdala activation (r = − 0.26, p = 0.18) in this affect match versus fixation contrast (). Thus, when amygdala reactivity is assessed relative to a passive rather than goal-directed task, the relationship with the dispositional mindfulness measure is no longer significant. This indicates that for those either high or low in dispositional mindfulness there were relatively similar degrees of amygdala activation when viewing emotional faces relative to passive viewing of a fixation cross. In other words, when the measure of resting activity is subtracted from the measure of reactivity, there is not a relationship between the residualized dispositional mindfulness variable and amygdala activity, indicating that the association between dispositional mindfulness and amygdala reactivity is largely attributable to the differences in resting activity. More specifically, because there were no mindfulness related differences in amygdala activation when affect matching was compared to passive fixation, but there were robust differences when affect matching was compared to shape matching, the relationship of mindfulness to amygdala activation in the affect matching versus shape matching contrast would appear to be explained by the difference in amygdala activity between fixation and shape matching.
Figure 6 Right amygdala activation (22,0, −26) to viewing affective faces, shapes, and fixation stimuli as a function of dispositional mindfulness (A) or depressive symptomatology (B). Denoted on the graphs are the mean parameter estimates (±SEM) (more ...)
With respect to depressive symptomatology, there was a positive correlation between BDI scores and amygdala activation (r = 0.44, p = 0.02) in the affect matching versus fixation contrast (). This suggests that the association of depressive symptomatology with amygdala activity in the affect matching versus shape-matching contrast was a reflection of both greater amygdala response to the viewing of emotional faces as well as greater deactivation during shape matching, relative to fixation. However, the effect in the latter condition was more robust.