Depression or anxiety: which is best able to predict patterns of lateralisation for the processing of emotional faces?

Previous research has shown that both anxiety and depression are associated with strength of lateralisation for the processing of emotive faces, although these clinical measures have always been considered in separate studies. In the present study, we measure depression and anxiety, within the same non-clinical sample, and consider whether these variables can predict strength of lateralisation, measured using the chimeric faces test. There are two key findings from this study. First, for females only, anxiety is negatively associated with right hemispheric superiority for processing of negative emotional expressions. Second, there was only one finding for depression, showing a relationship with strength of lateralisation for the processing of fearful faces that differed according to sex.

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called "beneficial" regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control.

Individual differences in emotion lateralisation and the processing of emotional information arising from social interactions.

Previous research examining the possible association between emotion lateralisation and social anxiety has found conflicting results. In this paper two studies are presented to assess two aspects related to different features of social anxiety: fear of negative evaluation (FNE) and emotion regulation. Lateralisation for the processing of facial emotion was measured using the chimeric faces test. Individuals with greater FNE were more strongly lateralised to the right hemisphere for the processing of anger, happiness and sadness; and, for the processing of fearful faces the relationship was found for females only. Emotion regulation strategies were reduced to two factors: positive strategies and negative strategies. For males, but not females, greater reported use of negative emotion strategies is associated with stronger right hemisphere lateralisation for processing negative emotions. The implications for further understanding the neuropsychological processing of emotion in individuals with social anxiety are discussed.

Prenatal sex hormone exposure and risk of Alzheimer disease: a pilot study using the 2D:4D digit length ratio.

OBJECTIVE: Our aim was to investigate an association between prenatal sex hormone exposure and dementia diagnosis. BACKGROUND: Some evidence indicates that relatively low testosterone levels are a risk factor for men to develop Alzheimer disease (AD). Most research has examined current rather than premorbid testosterone levels, and little research has addressed testosterone and AD in women. METHODS: In 20 men and women diagnosed with AD and 20 controls, we estimated prenatal exposure to testosterone and estrogen using the ratio of the length of the second to the fourth digit (2D:4D). We analyzed the data using a 2 (men versus women)×2 (controls versus AD participants) analysis of variance. RESULTS: The men with AD had significantly higher 2D:4D ratios than the male controls, indicating lower levels of prenatal testosterone and higher levels of prenatal estrogen exposure. The women with AD had significantly lower 2D:4D ratios than the female controls, indicating higher levels of prenatal testosterone and lower levels of prenatal estrogen exposure. CONCLUSIONS: These findings suggest that lower levels of prenatal testosterone and higher levels of estrogen exposure are a risk factor for AD in men, and that higher levels of prenatal testosterone and lower levels of prenatal estrogen exposure are a risk factor for women. Risk for AD may be related to prenatal exposure to a sex hormone different from an individual's chromosomal sex.

Paranoid males have reduced lateralisation for processing of negative emotions: an investigation using the chimeric faces test.

Reduced strength of lateralisation in patients with schizophrenia has been reported in a number of studies. However the exact nature of this relationship remains unclear. In this study, lateralisation for processing emotional faces was measured using the chimeric faces test and examined in relation to paranoia in a non-clinical sample. For males only, those with higher scores on a paranoia questionnaire had reduced lateralisation for processing negative facial emotion. For females there were no significant relationships. These findings suggest that atypical patterns of lateralisation for processing emotional stimuli may be implicated in, or associated with, increased levels of paranoia.

Sex differences in the relationship between children's emotional expression discrimination and their developing hemispheric lateralization.

Strength of lateralization for processing facial emotion becomes more right hemisphere lateralized throughout childhood, but sex differences in this development are not currently understood. This study examines patterns of lateralization for emotion discrimination in 185 6-10-year-olds. Strength of right hemisphere lateralization was stronger in the older children, and right hemisphere dominance emerged at around age 8. Children who were more strongly lateralized performed with greater accuracy on a behavioral test of emotion discrimination and this relationship was significant for boys but not girls, demonstrating that there is a relationship between lateralization and performance (particularly, the discrimination of emotions).

Examining the relationship between lateralisation for processing emotional faces, depression, and sex.

It is now relatively well established that the right hemisphere is specialised for processing facial emotion; however, there is variability in this pattern of lateralisation. One factor that has been examined is atypical lateralisation in individuals diagnosed with clinical psychological conditions. To date the evidence regarding the neuropsychological processing of emotional stimuli in individuals with depression is contradictory. In this study 160 participants completed the Beck Depression Inventory and the chimeric faces test, a test of lateralisation for the processing of facial expressions of each of the six basic emotions. A negative relationship between depression and lateralisation was found for females only, showing that women with higher depression scores tend to be less strongly lateralised to the right hemisphere, or even lateralised to the left hemisphere, for processing facial emotion. The strength of this relationship also varied across the different emotions with the clearest results for the processing of anger, disgust, and fear. There were no significant findings for males. The possible reasons for there being a sex difference in our findings and an attempt to reconcile the disparate findings within this area of research are discussed.

Emotion lateralisation: developments throughout the lifespan.

There is a great amount of research on hemispheric lateralisation for processing emotions and on the recognition of emotions across the lifespan. However, few researchers have explored the links between these two measures. This paper highlights how trends in these two research areas inform our understanding of how lateralisation for emotion processing may influence emotion recognition performance throughout the lifespan, including if the development of emotion lateralisation is a response to our environmental experiences of learning (experience dependent) or a result of having specific experiences at a particular time (experience expectant). The development of emotion lateralisation across the lifespan (infancy through to late adulthood) is explored with reference to past research and through the integration of the novel research offered within this special issue of Laterality. We also explore what we can learn from atypical populations. We propose that researchers need to focus on three key avenues of future research (longitudinal research, investigating the role of hormones, and research that explores the evolution of laterality) all which will provide greater insight into the development of laterality and how this may be associated with emotion processing.

Strength of lateralisation for processing facial emotion in relation to autistic traits in individuals without autism.

A great number of studies have shown that non-clinical individuals rely predominantly on the right hemisphere to process facial emotion. Previous studies have shown that males suffering from Asperger's syndrome show a typical right hemisphere bias for processing facial emotion (happiness and sadness) but a reduced right hemisphere bias for processing facial identity. This study looks at the lateralisation of all six basic emotions using the chimeric faces test in 64 non-clinical participants (32 males, 32 females) and correlates it with their autistic traits measured using the Broad Autistic Phenotype Questionnaire. For males only, regression analyses showed a relationship between the aloof personality trait and lateralisation for fear, happiness, and surprise. Males with high autistic scores on the aloof personality subscale (showing a lack of interest in social interaction) were more strongly lateralised to the right hemisphere for processing fear, happiness, and surprise. For males there was no relationship with anger, disgust, sadness, or non-facial stimuli, and for females there were no significant relationships at all. The autistic traits of rigidity and pragmatic language were not significant predictors of emotion lateralisation. The over-reliance on the right hemisphere for processing facial emotion in males seems to support the idea that the autistic brain could be seen as hyper-masculinised, possibly due to prenatal testosterone exposure.

Lateralisation for processing facial emotion and anxiety: contrasting state, trait and social anxiety.

Recent neuropsychological studies have attempted to distinguish between different types of anxiety by contrasting patterns of brain organisation or activation; however, lateralisation for processing emotional stimuli has received relatively little attention. This study examines the relationship between strength of lateralisation for the processing of facial expressions of emotion and three measures of anxiety: state anxiety, trait anxiety and social anxiety. Across all six of the basic emotions (anger, disgust, fear, happiness, sadness, surprise) the same patterns of association were found. Participants with high levels of trait anxiety were more strongly lateralised to the right hemisphere for processing facial emotion. In contrast, participants with high levels of self-reported physiological arousal in response to social anxiety were more weakly lateralised to the right hemisphere, or even lateralised to the left hemisphere, for the processing of facial emotion. There were also sex differences in these associations: the relationships were evident for males only. The finding of distinct patterns of lateralisation for trait anxiety and self-reported physiological arousal suggests different neural circuitry for trait and social anxiety.

One face or two? Contrasting different versions of the chimeric faces test.

The chimeric faces test is a frequently used behavioural test of lateralisation; however the methodologies used vary considerably. In this experiment the one- and two-face versions of the test, using neutral/happy chimeras, were compared to see whether the laterality biases found are correlated. Both versions showed a significant left visual field (or half face) bias, indicating that both reflect the underlying right hemisphere superiority for processing positive facial emotion. Furthermore, the laterality bias was significantly correlated in both versions although reliability was higher for the two-face version.

Examining the effects of inversion on lateralisation for processing facial emotion.

There is an increasing amount of evidence which suggests that each hemisphere is differently specialised for processing facial stimuli, with the right hemisphere specialised for the processing of configural information and the left hemisphere specialised for the processing of featural information. While there is evidence for this distinction from studies of face recognition, it has not been shown in studies of lateralisation for processing facial emotion. In this study the chimeric faces test was used with faces expressing anger, disgust, fear, happiness, sadness or surprise, presented in either an upright or an inverted orientation. When presented upright, a significant right hemisphere bias was found for all six emotions. However, when inverted, a significant left hemisphere bias was found for the processing of happiness and surprise, but not for the processing of negative emotions (although the analysis was approaching significance for anger). These findings support the hypothesis that each hemisphere is differently specialised for processing facial emotion, but contradicts previous work that examined the effects of inversion on chimeric face stimuli.

Solvent exposure and cognitive ability at age 67: a follow-up study of the 1947 Scottish Mental Survey.

OBJECTIVES: Organic solvent exposure may be associated with cognitive impairment in later life although the evidence for this association is inconsistent. This study sought to examine the association between organic solvent exposure and cognitive function in later life. METHODS: A prospective longitudinal study set in Aberdeen, Scotland examined 336 men and women born in 1936 who participated in the 1947 Scottish Mental Survey. Cognitive function at age 67 years was measured using the Trail Making Test B (TMT B), the Digit Symbol (DS) test, and the Auditory Verbal Learning Test (AVLT). Occupational hygienists reviewed occupational histories, blind to cognitive function, and estimated lifetime solvent exposures. Multiple regression analyses were employed to explore the association between solvent exposure and cognitive performance after adjustment for confounders. RESULTS: After adjusting for childhood IQ, smoking, alcohol and sex, the solvent exposed group took on average almost 10 s longer than the unexposed group to complete the TMT B, a highly significant difference. For the DS test, after adjusting for childhood IQ, smoking and gender, the exposed group scored on average two points lower than the unexposed group, which was again highly significant. There was no evidence of an effect for cumulative solvent exposure on the TMT B or DS test. For the AVLT there were no significant differences associated with exposure. CONCLUSIONS: This study of subjects with generally low exposures, found no clear evidence of an association between solvent exposure and cognitive function.

Examining the sex difference in lateralisation for processing facial emotion: does biological sex or psychological gender identity matter?

The research examining sex differences in functional lateralisation has shown varying results. While some provide evidence for males being more strongly lateralised than females, a number have shown either no relationship or the opposite pattern of findings. In this study we consider whether psychological gender identity might clarify some of the conflicting results in this area of research. Eight five participants (39 males) aged from 18 to 49 years old were tested. We found that psychological masculinity was associated with stronger patterns of lateralisation for the processing of a range of emotional expressions. We also found an interaction between biological sex and psychological gender identity, with a positive relationship between psychological masculinity and lateralisation found for males, but a negative relationship found for females. The possible role of hormonal exposure in this relationship is discussed.

Hormone exposure and functional lateralisation: examining the contributions of prenatal and later life hormonal exposure.

An increasing amount of research has shown a relationship between hormonal exposure and functional lateralisation. In this study different sources of hormonal exposure were examined: prenatal exposure, estimated using the 2D:4D ratio, and later life exposure through examining the effects of hormone replacement therapy. In addition to considering multiple sources of hormonal exposure, three tests of functional lateralisation were used: two versions of the chimeric faces test, one using positive emotion and the other using negative emotion, and the landmark task. The same effects were found across all three measures of lateralisation. Lower 2D:4D ratios, which indicate high levels of prenatal testosterone exposure, were associated with stronger right hemisphere dominance. Later life hormonal exposure was not found to be associated with any of the lateralisation measures. This finding suggests a relationship between prenatal hormonal exposure and brain organisation.

Examining the hemispheric distribution of semantic information using lateralised priming of familiar faces.

The way in which the semantic information associated with people is organised in the brain is still unclear. Most evidence suggests either bilateral or left hemisphere lateralisation. In this paper we use a lateralised semantic priming paradigm to further examine this neuropsychological organisation. A clear semantic priming effect was found with greater priming occurring when semantically related prime faces were presented to the left visual field than when presented to the right visual field. Possible explanations for this finding are discussed in terms of the bilateral distribution of different classes of semantic information, a possible role of associative processes within semantic priming and interhemispheric transfer.

Lateralised repetition priming for featurally and configurally manipulated familiar faces: evidence for differentially lateralised processing mechanisms.

Although early research suggested that the right hemisphere was dominant for processing faces, more recent studies have provided evidence for both hemispheres being involved, at least to some extent. In this experiment we examined hemispheric specialisations by using a lateralised repetition-priming paradigm with selectively degraded faces. Configurally degraded prime faces produced negative priming when presented to the left visual field (right hemisphere) and positive priming (facilitation) when presented to the right visual field (left hemisphere). Featurally degraded prime faces produced the opposite pattern of effects: positive priming when presented to the left visual field (right hemisphere) and negative priming when presented to the right visual field (left hemisphere). These results support the proposal that each hemisphere is differentially specialised for processing distinct forms of facial information: the right hemisphere for configural information and the left hemisphere for featural information.

Examining the relationship between degree of handedness and degree of cerebral lateralization for processing facial emotion.

This paper examines the relationship between degree of handedness and degree of cerebral lateralization on a task of processing positive facial emotion in right-handed individuals. Three hundred and thirteen right-handed participants (157 women) were given two behavioral tests of lateralization: a handedness questionnaire and a chimeric faces test. Two further handedness measures were taken: familial left-handedness and writing posture. Regression analysis showed that both degree of handedness and sex were predictive of degree of lateralization. Individuals who were strongly right-handed were also more strongly lateralized to the right hemisphere for the task. Men were more strongly lateralized than women. Data were reanalyzed for men and women separately. The relationship between handedness and lateralization remained for men only. Neither familial left-handedness nor writing posture were associated with cerebral lateralization for men or women. The results suggest a positive relationship between degree of handedness and degree of cerebral lateralization, and further that there is a sex difference in this relationship.

Is retaining the youthful functional anatomy underlying speed of information processing a signature of successful cognitive ageing? An event-related fMRI study of inspection time performance.

It has been hypothesized that individual differences in cognitive ageing might in part be based on the relative preservation of speed of information processing. However, the biological foundations of processing speed are not understood. Here we compared two groups of non-demented older people who had relatively similar IQs at age 11 but differed markedly in non-verbal reasoning ability at age 70: 'cognitive sustainers' (n=25), and 'cognitive decliners' (n=15). Using an event-related fMRI design, we studied the BOLD response while they performed an inspection time task. Inspection time is a two-alternative forced choice, backward masking test of the speed of the early stages of visual information processing. Inspection time has a well-established, significant association with higher cognitive abilities. The group of cognitive sustainers showed a pattern of BOLD activation-deactivation in response to inspection time stimulus duration differences that was similar to a healthy young sample [Deary, I.J., Simonotto, E., Meyer, M., Marshall, A., Marshall, I., Goddard, N., Watdlaw, J.M., 2004a. The functional anatomy of inspection time: an event-related fMRI study. NeuroImage 22, 1466-1479]. The group of cognitive decliners lacked these clear neural networks. The relative preservation of complex reasoning skills in old age may be associated with the preservation of the neural networks that underpin fundamental information processing in youth.

n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood.

BACKGROUND: Evidence for an inverse relation between dietary intake of n-3 polyunsaturated fatty acids (PUFAs) and age-related cognitive decline is inconsistent. This inconsistency may arise because the relation is present only in the absence of the apolipoprotein E epsilon4 (APOE epsilon4) allele. OBJECTIVE: We aimed to determine the contribution of erythrocyte n-3 PUFA content to cognitive aging in the presence or absence of the APOE epsilon4 allele. DESIGN: We followed up 120 volunteers, born in 1936, at approximate ages of 64, 66, and 68 y. Their intelligence quotient at 11 y old was available. At first follow-up, we determined APOE genotype and measured the PUFA composition of erythrocyte membranes. Six cognitive tests were administered at all follow-ups. We related cognitive performance at approximately 64 y old and cognitive changes from approximately 64 to approximately 68 y old to erythrocyte n-3 PUFA composition on recruitment and to APOE epsilon4 allele status. RESULTS: Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at approximately 64 y old and from approximately 64 to approximately 68 y old. After adjustment for sex, APOE epsilon4 status, and intelligence quotient at 11 y old, the effects associated with total n-3 PUFA remained significant. Cognitive benefits were associated with higher erythrocyte n-3 PUFA content but were significant only in the absence of the APOE epsilon4 allele. CONCLUSIONS: These data are evidence of a gene x environment interaction for cognitive aging. They are relevant to the analysis of trials of n-3 PUFA supplements in cognitive aging and dementia prevention, and they support heterogeneity in cognitive aging and, possibly, in Alzheimer disease.