The studies reviewed above delineate potential mechanisms of limbic-cortical interactions that may be crucial to understand how the human brain accomplishes the business of normal and abnormal emotion regulation. Emotional arousal accompanying the experience of intense subjective feelings in healthy subjects (Liotti et al., 2000a; Damasio et al., 2000) or active episodes of major depression (Mayberg et al., 1999) as well the emotional arousal in the presence of basic drives such as air hunger, thirst, or pain (Liotti et al., 2001) give rise to activation of subcortical, paleocerebel-lum, and limbic structures, as well as paralimbic cortex, and the concomitant, inverse sign, namely deactivation of neocortical regions known to subserve cognitive functions (Liotti and Mayberg, 2001). Conversely, cognitive processing and recovery from an acute episode of depression are accompanied by increased activation in neocortical networks subserving attentional processing, such as the DLPFC, inferior parietal cortex, and dorsal ACC, and a concomitant deactivation of paralimbic cortex (subgenual ACC 25) and limbic structures (e.g., amygdala), all of which are well-known substrates of emotion (Drevets and Raichle, 1998; Liotti et al., 2000b).
In their study of the neural correlates of sadness and depression recovery, Mayberg et al. (1999) also carried out regional rCBF and rGlu correlations and found that subgenual ACC 25 and right DLPFC showed the most significant correlation (a negative one) among all regions studied (also see Chapter 7). They concluded that, since animal connectivity studies show definite reciprocal projections between subgenual cingulate cortex BA25 and DLPFC (BA9 and 46), the rCBF and metabolic interactions they observed in these regions during sadness and recovery from depression may reflect functional changes in obligatory, hard-wired circuits (Mayberg et al., 1999). A number of other neuroimaging studies have reported negative correlations between blood flow in prefrontal cortex and amygdala in depression (reviewed in Drevets and Raichle, 1998; Drevets, 2000).
Another line of evidence in favor of inverse-sign interactions between limbic and neocortical regions comes from evidence of modulations in fMRI amygdala response to fearful faces as a function of: (1) implicit (activation) versus explicit (deactivation) processing of emotion (Hariri et al., 2000), which may be mediated by the amygdala's inhibition by frontal cortex, and (2) development, with greater activation in preadoles-cence followed by a postadolescent shift from amygdala-mediated processing to frontal lobe-mediated processing (Killgore et al., 2001), as well as a later general decline of amygdala activation with increasing age (cited in Adolphs, 2002).
A third line comes from recent studies looking at voluntary suppression of emotion. Male sexual arousal has been found to produce a significant activation of the right amygdala, right anterior temporal pole (BA38), and hypothalamus, but when subjects voluntarily inhibited their sexual arousal, no significant loci of activation were noted in these structures. Instead, significant activations were present in the right medial DLPFC (BA10) and the right ACC BA32 (Beauregard et al., 2001). Similarly, healthy females induced into a sad state while watching sad film clips showed activation of subgenual cingulate, insula, amygdala, and midbrain. When instructed to suppress their sad feelings, subjects showed significant loci of activation in the right DLPFC (BA9) and the right orbitofrontal cortex (OFC) (BA11). This is consistent with the role of right DLPFC in negative mood, as pinpointed by Liotti and Mayberg (2001) as well as TMS methodologies in treating depression (see Chapter 19).
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