Figure. 6.13. A visual representation of the results presented in section 6.4.2. (a) Shows the negative coupling observed in the three different emotion conditions from the psychophysiological interaction analysis. In the fear (red) condition negative coupling was observed between the anterior cingulate cortex (ACC) and the right amygdala and between the left amygdala, ventromedial prefrontal cortex (vmPFC) and precuneus. In the neutral (green) condition negative coupling between the right amygdala, vmPFC and precuneus. In the happy condition (blue) negative coupling was observed between the thalamus and right amygdala. (b) shows the results of the ROI analysis of the PPI results which found a valence by hemisphere interaction between the amygdala and dorsomedial prefrontal cortex (dmPFC) coupling. Although follow up results were not significant, this diagram shows that there appears to be a valence dependent shift in negative coupling between the left amygdala and dmPFC (in the happy condition) and the right amygdala and dmPFC (in the fear and neutral) conditions. In addition analysis revealed that regardless of valence (black), the right amygdala showed negative connectivity with the ACC, whilst the left amygdala showed no connectivity with the ACC.
6.6.1.1 Lateralisation
Observing both results from the typical PPI analysis and from the ROI analysis, it is evident that the two amygdalae are differentially connected during emotion processing. In particular, the right amygdala shows a distinct pattern of negative connectivity with frontal areas (specifically with the vmPFC and to some extent with the dmPFC), as well as with the ACC, during presentation of fearful and neutral stimuli (see Figure 6.13). As discussed previously, there is evidence that neutral stimuli can be interpreted as a potential threat to the individual requiring immediate response, as they are perceived as more emotionally ambiguous
164 (Michael Davis & Whalen, 2001), (for further discussion see section 5.7). In this way, fearful and neutral stimuli may activate common threat-related processing pathways. The reduction in connectivity between frontal areas and the ACC is suggestive of a decline in or absence of top down inhibition on right amygdala activity. As a result, increased amygdala activation would be expected in response to fearful and neutral stimuli. This pattern of frontal
decoupling with the right amygdala supports the evidence of laterality seen in other recent research on amygdala-frontal coupling which also observed weaker right amygdala-frontal coupling (Eden et al., 2015; Gold et al., 2015; Motzkin et al., 2014).
Conversely, negative coupling was observed between the right amygdala and the thalamus during presentation of happy face stimuli only. This is in line with the dual processing model of emotion processing discussed in detail in section 1.5.2 and Chapter 5, whereby there is a direct pathway to the basolateral nucleus of the amygdala from the thalamus and an indirect pathway to the amygdala via the sensory cortex. The direct pathway is involved in rapid detection of basic information and instinctual, cognition free responses to threat, and is associated with the right amygdala. The data here support this notion, with reduced top-down inhibition during fear or ambiguous threat (neutral) stimuli, and disconnectivity with the thalamus during non-threat stimuli that does not require rapid processing (happy). In contrast to the right amygdala’s role in immediate threat detection, the left amygdala appears to be more involved in some form of salience detection, as negative coupling between the left amygdala and frontal areas occurs only in fearful and tentatively in happy conditions. This result could suggest reduced top-down inhibition, and greater left amygdala activation in response to fearful and happy stimuli which may be part of a system of re- evaluation suggested by Cunningham, Dunfield, and Stillman (2013). The indirect processing pathway, discussed above, is associated with the left amygdala and is involved in deeper evaluation of stimuli using data from multiple sensory inputs. Indeed, while there is evidence that the amygdalae are involved in rapid orientation to a stimulus with a range of differently valenced stimuli (e.g. section 1.5.3.1. Yang et al., 2002), this immediate response bypasses any more in-depth evaluative processing. There is also a need to assess the social, and biological, value of the incoming stimulus using information from multiple sensory inputs. The data here suggests that the functional roles of the amygdalae are divided hemispherically with the right amygdala primarily responsible for rapid orienting of attention, whilst the left amygdala is involved in a more complex system of feedback with sensory cortices and frontal regions of the brain.
165 6.6.1.2 Valence
Reduction in top-down frontal and ACC inhibition with the right amygdala during fearful and neutral conditions and with the left amygdala during fear and tentatively happy conditions would suggest that there should be an apparent effect of valence on amygdala activation. Whilst there were lateralisation and lateralisation by valence effects as described above, there was no direct effect of valence on the PPI data reported here. The precuneus activation was seen to decouple with the left amygdala during the fear condition and with the right amygdala during neutral. This pattern of decoupling with the precuneus (a key node in the default mode network) suggests an interaction of valence related to attention to task with possible parallel processing of a stimulus. It is only by investigating the interaction between lateralisation and valence that subtle nuances in amygdala function are detected in relation to possible discrete functions.
6.6.1.3 Specificity within the frontal cortex
Looking into the fronto-amygdala connectivity in more detail to consider the dorsal and ventral medial prefrontal cortex (dmPFC, vmPFC), there emerges a pattern of decoupling which could be explained by the recent framework put forward by Etkin, Egner, and Kalisch (2011). As mentioned previously, the authors suggest that amygdala connectivity to the dmPFC is associated with appraisal and expression of negative emotion, whereas amygdala connectivity with the vmPFC is attributed to generating emotion responses through the limbic system after such appraisal. Furthermore, it has been suggested that the specific mechanism through which the vmPFC generates emotion responses is through resolving emotional ambiguity (Kim et al., 2003; Hye-young Kim et al., 2004; Kim, Loucks, et al., 2011), with greater vmPFC activity (and thus decreased amygdala activation) leading to positive
perception of ambiguous stimuli and reduced vmPFC activity leading to negative perception (Kim et al., 2011).
The current data reveals decoupling between right amygdala and vmPFC in neutral
conditions and a numerical pattern of decoupling with the dmPFC specific to fear and neutral conditions. If the decoupling is assumed to mean increased frontal activity, this could
suggest, from the Etkin et al. (2011) model, that dmPFC was involved in the appraisal of the negative emotion, and vmPFC in a positive response to the negative or ambiguous stimuli.
166 Alternatively, the decoupling could be due to a lack of frontal appraisal and response
mechanisms as an immediate response was necessary from the right amygdala. This supports the previous theories suggesting that right amygdala connectivity is arranged in a system conducive to rapid response to threat stimuli. The reduced right amygdala-precuneus
coupling in the neutral condition would suggest the latter may be the case as decoupling with the precuneus is associated with attentional shifts and the default mode network (Utevsky et al., 2014). Frontal connectivity with the left amygdala is more complex, with vmPFC
decoupling observed during the fear condition and a pattern of dmPFC decoupling during the happy condition. This suggests there is a bilateral amygdala-frontal decoupling during the potentially threatening fear stimuli, with the right amygdala involved in immediate response and the left in appraisal of the threat stimuli. In this case, the vmPFC decoupling may
represent positive perception and emotional response to these faces, as discussed above (Kim and colleagues (2011)). Indeed, the left amygdala is thought to be more involved in
evaluative processing (Cunningham, Dunfield, and Stillman (2013)), and as such the tentative dmPFC decoupling during the happy condition suggest either lower frontal involvement in the appraisal of happy stimuli, or, more likely, lower left amygdala (evaluative processing) of the non-ambiguous happy stimuli.
167