An Integrative Neuroscience Approach to Understanding Emotion Face Perception: Impact of frontal asymmetry and the serotonin transporter gene (5-HTT)

Proposal details

Title: An Integrative Neuroscience Approach to Understanding Emotion Face Perception: Impact of frontal asymmetry and the serotonin transporter gene (5-HTT)
Research Area(s): Emotion and Self Regulation
Background: This study will extend on initial findings relating to a number of previously approved BrainNet projects titled: “Using neurophsysiological methods to differentiate between anxiety and depression in the normal population” and “Frontal Laterality, Personality and Social Cognition”, as well as a related publication in the peer reviewed journal Emotion titled: “Investigating models of affect: Relationships among EEG alpha asymmetry, depression and anxiety” (Mathersul, Williams, Hopkinson, Kemp, in press). Findings from this research indicate that while groupings on the basis of a self-report measure of depression and anxiety (DASS) distinguish frontal alpha asymmetry, groupings on the basis of left and right frontal asymmetry (associated with approach and withdrawal emotions, respectively) did not differentiate levels of depression (associated with reduced approach) or anxiety (associated with increased withdrawal). These findings were interpreted in line with theories that suggest frontal asymmetries may reflect a “diathesis” that may predispose an individual towards a particular affective style. In otherwords, frontal asymmetry (particularly in the alpha bandwidth) may represent a risk factor for developing clinical disorders, such as depression and anxiety. However, research conducted by Kemp and colleagues (2004, Neuroimage, 22, 1084-1096) highlight that self-report measures may not be a good source for making inferences about underlying processes relating to emotion. It is unclear therefore, whether or not participants categorized as left or right-frontal activators will display impairments on brain measures associated with the processing of emotional stimuli. Other lines of research highlight that integration of genetic information with measures of brain function provides a powerful approach to explore the functional impact of genetic variation in the absence of observable behavior (Hariri and Lewis, 2006; Hariri and Weinberger, 2003b). For example, non-depressed participants with the 5-HTT S-allele are reported to display heightened amygdala activity, reduced gray matter volume in the perigenual cingulate and amygdala, and an uncoupling of the feedback circuit in these regions which may be associated with less effective extinction of negative affect (Hariri et al., 2005, Arch Gen Psychiatry, 62, 146-152; Hariri et al., 2002, Science, 297, 400-403; Pezawas et al., 2005, Nat Neurosci, 8, 828-834). Moreover, these brain findings need not be apparent on measures of mood or temperament, concluding that the 5-HTT S-allele may represent a susceptibility factor for affective disorders by biasing amygdala activity to hyper-respond during stressful life events or ineffective cortical input. Although frontal laterality and 5-HTT have been implicated as risk factors for depression and anxiety, the relationship between these two variables is not well understood. The Brain Resource International Database (BRID) provides a unique opportunity to explore associations between resting state frontal laterality and genetics, and to examine the differences between individuals classed as left- and right-lateralised activators and their response to emotional facial expressions.
Aims: The aim of the current study is to examine the impact of left and right frontal laterality and genetic polymorphisms in the serotonin transporter gene (5-HTT). It is hypothesised that participants classified as left-lateralised will possess either the s/l or l/l genotype, whilst participants classified as right-lateralised will possess the s/s genotype. It is also hypothesised that right-lateralised individuals will show greater activation to negative facial expressions whilst left-lateralised individuals will show greater activation to positive facial expression. Finally, it is hypothesised that the an interaction between frontal asymmetry and 5-HTT polymorphisms will be observed such that left-lateralised individuals with the l/l genotype will display the most sensitivity to positive stimuli while right-lateralised individuals with the s/s genotype will display the most sensitivity to negative stimuli.
Method: Healthy control subjects in the BRID will be selected for analysis. Subjects will then be categorised on baseline frontal asymmetry and on 5-HTT polymorphisms. Differences in ERP responses to emotional facial expressions will be examined in these groups using a 6 Group (2 asymmetries x 3 polymorphisms) X 4 Emotion (Fear, Sad, Neutral, Happy) x 2 Condition (conscious, unconscious) repeated measures ANOVA.