Lateralization of affective processing in the insula
Introduction
The insula is an essential brain region for the integration of interoceptive information (sense of the physiological state of the body) and emotional experience (Craig, 2002, Craig, 2009). These properties are afforded to the insula through extensive viscerosensory input from the periphery and reciprocal connections with limbic, somatosensory, prefrontal and temporal cortices (Augustine, 1996, Mesulam and Mufson, 1982a, Mesulam and Mufson, 1982b). The insula processes appetitive and aversive physiological sensations (i.e. thirst, hunger, pain) and the associated emotional arousal that results in the conscious perception of one's affective state (James, 1884, Lange, 1885, Russell, 2003, Schachter and Singer, 1962).
Evidence from electrophysiological studies and hemispheric inactivation procedures has indicated strong lateralization of affective processing within the insula based on autonomic input to this region (Hilz et al., 2001, Oppenheimer et al., 1992). However, inconsistent results have come from lesion studies in patients and findings from functional neuroimaging studies. Meta-analyses of functional imaging data permit the collation of findings across studies and can provide precise spatial localization of affective processing to develop a topographical model of emotional functions within the insula.
Historically, emotional processes were believed to be mediated by the right hemisphere (for review see (Harrington, 1995)). More recent reports with patients and functional neuroimaging studies have indicated that emotional processing is left- or right-lateralized based on stimulus valence (positive/negative emotions) (Davidson et al., 1979, Hellige, 1993, Silberman, 1986), behavior (approach/withdrawal) (Davidson et al., 1990) and/or phenomenal state (perception/experience) (Garrett and Maddock, 2006, Peelen et al., 2010, Zaki and Ochsner, 2011).
Lateralization of emotional processing in the insula has been supported by evidence suggesting differential autonomic inputs (parasympathetic/sympathetic) to this region (Craig, 2005). For example, direct stimulation of the left insula results in changes in parasympathetic functions (Oppenheimer et al., 1992) involving nourishment, safety, positive affect and approach behavior (Craig, 2005), whereas the right insula has been implicated in top-down control of sympathetic-nervous system functioning, which is involved in hunger, survival, negative affect and avoidance behavior.
Support for this stimulus-valence processing scheme has come from functional neuroimaging, but with some discrepancy among the findings (Caria et al., 2010, Phillips et al., 1997, Simmons et al., 2004, Simmons et al., 2012, Sprengelmeyer et al., 1998, Wager et al., 2003). For example, functional imaging studies of passionate, maternal and unconditional love showed that these positive stimuli activated the left more than the right insula (for review, see (Ortigue et al., 2010)); however, these results may be influenced by sex as 83% of the studies reviewed tested female participants. In line with the valence hypothesis, the right anterior and mid-insula were activated during negative experiences including motion-induced nausea (Napadow et al., 2012) and viewing intense facial expressions of disgust (Phillips et al., 1997). In contrast, other imaging studies have indicated that the left anterior insula mediates negative stimuli, such as viewing unpleasant visual stimuli (Caria et al., 2010). To determine the effect of valence (positive and negative stimuli) on insular activation was one of the main aims of the current work, with a focus on the hemispheric contributions of anterior, middle and posterior regions.
Previous reports concerning the lateralization of emotional processing in the insula were based largely on results obtained from participants viewing emotional stimuli. Further distinctions can be made in the viewing of emotional stimuli in terms of perceiving or actually experiencing an emotion (Garrett and Maddock, 2006, Kober et al., 2008, Lindquist et al., 2012, Peelen et al., 2010, Zaki and Ochsner, 2011). Individual neuroimaging studies have tested this hypothesis and have suggested some lateralization of processing (Modinos et al., 2011, Wicker et al., 2003). For example, bilateral insular cortex was activated in individuals who smelled disgusting odors (experience), but only the left side was activated when viewing others performing the same act (perception) (Wicker et al., 2003). Few individual neuroimaging studies have contrasted self versus another's emotional experience within the same experimental protocol and therefore the laterality of these processes remains uncertain. In the present work, hemispheric and region-specific (anterior/middle/posterior insula) preferential emotional processing related to self and others was assessed.
Subtle differentiations in self/other emotional processing could have strong clinical relevance. For example, in individuals with autism spectrum disorder (ASD) atypical activity in the insula may underlie deficits in understanding the thoughts and emotions of others (Allman et al., 2005, Silani et al., 2008). Children with ASD were found to activate the right insula when viewing neutral images of themselves as seen in typically-developing children, but they did not activate the right insula when viewing images of others (Uddin et al., 2008). Improved understanding of the localizations of these subtleties of functions in a normative population will greatly facilitate the understanding of findings in clinical populations.
Lastly, further distinctions in emotional processing in the insular cortices may be influenced by the sex of the participants. This line of reasoning comes from several sources such as behavioral evidence suggesting that females are better than males at understanding the emotions of themselves and others (Baron-Cohen and Wheelwright, 2004, Eisenberg and Lennon, 1983). Females demonstrate increased affective arousal or expression of emotion during social interactions (Brody and Hall, 2000), although this may depend on contextual factors (Barrett et al., 1998). Key to emotional competence is the ability to recognize facial expressions; females compared to males have a greater ability to recognize facially expressed emotions, even in instances where stimuli are presented for brief periods (Donges et al., 2012, Hall, 1978, Hall and Matsumoto, 2004, Hoffmann et al., 2010). Several brain-imaging studies have demonstrated differential neural processing in females and males during emotional processing tasks (Cahill, 2006, Derntl et al., 2009, Hofer et al., 2006, Hofer et al., 2007). For example, in an fMRI experiment that tested both sexes, only females recruited bilateral insular cortices in conjunction with the amygdalae during the perception of humorous stimuli (Kohn et al., 2011), a finding that the authors attributed to potentially greater emotional-regulation abilities in females. Some evidence also suggests sex-differences in the lateralization of stimulus-valence processing within the insula. An fMRI study examining cognitive modulation of emotion reported activation in the left insula only in females during the perception of aversive stimuli (Koch et al., 2007). Additionally, a recent meta-analysis of 88 studies examining brain activation associated with emotional stimuli reported that females activated the left insula in response to negative emotional stimuli whereas males showed bilateral activation in this region (Stevens and Hamann, 2012). Given these previous findings, we investigated activation in the insula in response to emotional stimuli in males and females separately.
Lateralization of emotional processing in the insular cortices is a fundamental aspect of interpreting the functions of this region; however, no clear consensus on the roles of the left and right insula in emotional processing has been established. Here, using affect-related data from fMRI studies, we explored topographical distinctions of the various aspects of emotional processing (i.e., positive, negative, perception, experience) within the insula and provide normative atlases for these processes in stereotaxic space. The meta-analyses tested: (1) right-insular cortex dominance for global emotional processing, (2) lateralization of stimulus valence (positive vs. negative), (3) perceiving vs. experiencing emotional stimuli and (4) sex differences.
Section snippets
Article selection and literature search
An initial broad search of the literature was conducted to determine the range of affective-, cognitive-, motor- and sensory-evoked activation in the insula measured using fMRI. The Web of Science (http://www.isiknowledge.com) was searched for articles published between January 1990 and October 2010 using the keywords fMRI and insula. The initial search yielded a total of 1263 articles. The studies were screened for the following inclusion criteria: (1) written in English; (2) fMRI experiment;
Demographic information
The 143 studies of emotion included 2721 participants (51.6% female), the median of the mean age of the participants was 24.7; 78% of studies reported handedness and tested mainly right-handed individuals (eight of these studies included 1–10 left-handed individuals). For more details on the studies included in the meta-analyses see Table 1.
All emotion
A total of 565 foci were extracted from the 143 experiments reporting activation in the insula in response to emotional stimuli. The stimuli used in the
Discussion
Through meta-analyses of existing functional neuroimaging data, the spatial location and extent of activation in the insula associated with affective processing were assessed. Four key results were found:
- (a)
Activation in response to all emotional stimuli occurred bilaterally in the anterior and mid-insula extending to the posterior insula. Laterality indices revealed that within the posterior insula the left side was activated more than the right.
- (b)
Positive emotional stimuli showed left-hemisphere
Summary and conclusions
By performing meta-analyses of activation in the insula in response to emotional stimuli, we showed that this complex brain structure has a strong role in global-emotional processing and awareness. All emotional stimuli, and the subcategories, activated the anterior and mid-insula more than the posterior insula and exhibited hemispheric asymmetries as a function of the three insular sections (anterior, mid and posterior). Our results suggest a posterior-to-anterior processing scheme whereby
Acknowledgments
The authors would like to thank Alexandra Trelle, Jessica Chan and Anna Oh for their excellent work in searching and retrieving articles and for entering the information from the studies into a database. This work was supported by a Research Training Competition Fellowship from The Hospital for Sick Children (EGD), and a Reva Gerstein Fellowship in Paediatric Psychology (EGD).
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