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Klára Marečková,
M Mallar Chakravarty,
Mei Huang,
Claire Lawrence, Gabriel Leonard,
Michel Perron,
Bruce G Pike,
Louis Richer,
Suzanne Veillette,
Zdenka Pausova,
Tomáš Paus
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ABSTRACT: In our previous work, we described facial features associated with a successful recognition of the sex of the face (Mareckova et al. 2011). These features were based on landmarks placed on the surface of faces reconstructed from magnetic resonance (MR) images; their position was therefore influenced by both soft tissue (fat and muscle) and bone structure of the skull. Here, we ask whether bone structure has dissociable influences on observers' identification of the sex of the face. To answer this question, we used a novel method of studying skull morphology using MR images and explored the relationship between skull features, facial features, and sex recognition in a large sample of adolescents (n=876; including 475 adolescents from our original report). To determine whether skull features mediate the relationship between facial features and identification accuracy, we performed mediation analysis using bootstrapping. In males, skull features mediated fully the relationship between facial features and sex judgments. In females, the skull mediated this relationship only after adjusting facial features for the amount of body fat (estimated with bioimpedance). While body fat had a very slight positive influence on correct sex judgments about male faces, there was a robust negative influence of body fat on the correct sex judgments about female faces. Overall, these results suggest that craniofacial bone structure is essential for correct sex judgments about a male face. In females, body fat influences negatively the accuracy of sex judgments, and craniofacial bone structure alone cannot explain the relationship between facial features and identification of a face as female.
NeuroImage 05/2013; · 5.89 Impact Factor
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ABSTRACT: BACKGROUND: The purpose of this investigation was to evaluate an association between duration of exclusive breastfeeding and structure of cortical regions implicated in general intelligence. METHODS: We studied adolescents (n = 571; aged 12-18 years) participating in the Saguenay Youth Study; half of the participants were exposed to maternal cigarette smoking during pregnancy. Hierarchical linear modelling was used to assess whether breastfeeding is an important predictor of cortical thickness when other predictors, such as age, sex, parental education and exposure to maternal smoking during pregnancy, are also considered. Target cortical regions were identified using a meta-analysis of functional neuroimaging studies of cognitive abilities relevant for general intelligence. RESULTS: We found that duration of exclusive breastfeeding was associated with cortical thickness in the superior and inferior parietal lobules (t = 2.31, P = 0.02). We also replicated the association between breastfeeding and general intelligence (t = 2.69, P = 0.008). CONCLUSION: In this study, we showed that breastfeeding is associated with variations in the thickness of the parietal cortex in a community-based sample of adolescents. We also found association of breastfeeding duration with full scale and performance IQ, as observed previously.
International Journal of Epidemiology 11/2012; · 6.41 Impact Factor
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ABSTRACT: Adults show great variation in their auditory skills, such as being able to discriminate between foreign speech-sounds. Previous research has demonstrated that structural features of auditory cortex can predict auditory abilities; here we are interested in the maturation of 2-Hz frequency-modulation (FM) detection, a task thought to tap into mechanisms underlying language abilities. We hypothesized that an individual's FM threshold will correlate with gray-matter density in left Heschl's gyrus, and that this function-structure relationship will change through adolescence. To test this hypothesis, we collected anatomical magnetic resonance imaging data from participants who were tested and scanned at three time points: at 10, 11.5 and 13 years of age. Participants judged which of two tones contained FM; the modulation depth was adjusted using an adaptive staircase procedure and their threshold was calculated based on the geometric mean of the last eight reversals. Using voxel-based morphometry, we found that FM threshold was significantly correlated with gray-matter density in left Heschl's gyrus at the age of 10 years, but that this correlation weakened with age. While there were no differences between girls and boys at Times 1 and 2, at Time 3 there was a relationship between gray-matter density in left Heschl's gyrus in boys but not in girls. Taken together, our results confirm that the structure of the auditory cortex can predict temporal processing abilities, namely that gray-matter density in left Heschl's gyrus can predict 2-Hz FM detection threshold. This ability is dependent on the processing of sounds changing over time, a skill believed necessary for speech processing. We tested this assumption and found that FM threshold significantly correlated with spelling abilities at Time 1, but that this correlation was found only in boys. This correlation decreased at Time 2, and at Time 3 we found a significant correlation between reading and FM threshold, but again, only in boys. We examined the sex differences in both the imaging and behavioral data taking into account pubertal stages, and found that the correlation between FM threshold and spelling was strongest pre-pubertally, and the correlation between FM threshold and gray-matter density in left Heschl's gyrus was strongest mid-pubertally.
NeuroImage 01/2012; 60(2):1287-95. · 5.89 Impact Factor
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Tomás Paus,
Manon Bernard,
M Mallar Chakravarty,
George Davey Smith,
Jesse Gillis,
Anbarasu Lourdusamy,
Melkaye G Melka, Gabriel Leonard,
Paul Pavlidis,
Michel Perron,
G Bruce Pike,
Louis Richer,
Gunter Schumann,
Nicholas Timpson,
Roberto Toro,
Suzanne Veillette,
Zdenka Pausova
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ABSTRACT: The most dramatic growth of the human brain occurs in utero and during the first 2 years of postnatal life. Genesis of the cerebral cortex involves cell proliferation, migration, and apoptosis, all of which may be influenced by prenatal environment. Here, we show that variation in KCTD8 (potassium channel tetramerization domain 8) is associated with brain size in female adolescents (rs716890, P = 5.40 × 10(-09)). Furthermore, we found that the KCTD8 locus interacts with prenatal exposure to maternal cigarette smoking vis-à-vis cortical area and cortical folding: In exposed girls only, the KCTD8 locus explains up to 21% of variance. Using head circumference as a proxy of brain size at 7 years of age, we have replicated this gene-environment interaction in an independent sample. We speculate that KCTD8 might modulate adverse effects of smoking during pregnancy on brain development via apoptosis triggered by low intracellular levels of potassium, possibly reducing the number of progenitor cells.
Cerebral Cortex 12/2011; 22(11):2634-42. · 6.54 Impact Factor
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Klára Marečková,
Zohar Weinbrand,
M Mallar Chakravarty,
Claire Lawrence,
Rosanne Aleong, Gabriel Leonard,
Michel Perron,
G Bruce Pike,
Louis Richer,
Suzanne Veillette,
Zdenka Pausova,
Tomáš Paus
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ABSTRACT: Sex identification of a face is essential for social cognition. Still, perceptual cues indicating the sex of a face, and mechanisms underlying their development, remain poorly understood. Previously, our group described objective age- and sex-related differences in faces of healthy male and female adolescents (12-18 years of age), as derived from magnetic resonance images (MRIs) of the adolescents' heads. In this study, we presented these adolescent faces to 60 female raters to determine which facial features most reliably predicted subjective sex identification. Identification accuracy correlated highly with specific MRI-derived facial features (e.g. broader forehead, chin, jaw, and nose). Facial features that most reliably cued male identity were associated with plasma levels of testosterone (above and beyond age). Perceptible sex differences in face shape are thus associated with specific facial features whose emergence may be, in part, driven by testosterone.
Hormones and Behavior 11/2011; 60(5):681-90. · 3.87 Impact Factor
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ABSTRACT: This study investigated the fine-grained development of the EEG power spectra in early adolescence, and the extent to which it is reflected in changes in peak frequency. It also sought to determine whether sex differences in the EEG power spectra reflect differential patterns of maturation. A group of 56 adolescents were tested at age 10 years and then at two further time-points approximately 18 months apart. The EEG was recorded during both eyes-closed and eyes-open conditions and Fourier transformed to provide estimates of absolute and relative spectral power at 0.5 Hz intervals from 0.5 to 40 Hz. The peak alpha frequency for each individual at each time-point was also determined for relative spectral power. Partial Least Squares (PLS) analysis was used to determine the combination of electrodes and frequencies that showed developmental change, or differed between the sexes. As a function of age, absolute delta and theta frequencies power decreased, and relative alpha2 and beta frequencies increased, replicating the standard findings of a decrease in lower, and increase in higher, frequencies with age. A small but significant increase in peak alpha frequency with age was detected. Moreover PLS analysis performed with individual alpha frequencies aligned to 10 Hz suggested that the age-related increase seen in alpha2 relative power was driven by changes in the peak frequency. Although males demonstrated higher alpha power than females, there were no sex differences in peak frequency, suggesting that there may be more to sex differences in EEG power than simply different rates of maturation between the two sexes.
Developmental Science 09/2011; 14(5):935-43. · 3.89 Impact Factor
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ABSTRACT: Successful interpersonal interactions rely on an ability to read the emotional states of others and to modulate one's own behavior in response. The actions of others serve as valuable social stimuli in this respect, offering the observer an insight into the actor's emotional state. Social cognition continues to mature throughout adolescence. Here we assess longitudinally the development of functional connectivity during early adolescence within two neural networks implicated in social cognition: one network of brain regions consistently engaged during action observation and another one associated with mentalizing. Using fMRI, we reveal a greater recruitment of the social-emotional network during the observation of angry hand actions in male relative to female adolescents. These findings are discussed in terms of known sex differences in adolescent social behavior.
Journal of Cognitive Neuroscience 08/2011; 23(12):3713-24. · 5.18 Impact Factor
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J. Cognitive Neuroscience. 01/2011; 23:3713-3724.
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ABSTRACT: Adolescence places high demands on inter-personal interactions and, hence, on the extraction and processing of social cues. Here we assess longitudinally the development of brain activity within a network implicated in social cognition--the action observation network. We performed activation likelihood estimation meta-analyses to define regions of interest based upon the mature action observation network of adults. Using functional magnetic resonance imaging, we then examined developmental trajectories of functional brain activity within these brain regions. Using this approach, we reveal quadratic trajectories within a fronto-parietal network previously shown to demonstrate correlated morphological development.
Social Cognitive and Affective Neuroscience 01/2011; 7(1):64-80. · 6.13 Impact Factor
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ABSTRACT: Quantitative analysis of craniofacial morphology is of interest to scholars working in a wide variety of disciplines, such as anthropology, developmental biology, and medicine. T1-weighted (anatomical) magnetic resonance images (MRI) provide excellent contrast between soft tissues. Given its three-dimensional nature, MRI represents an ideal imaging modality for the analysis of craniofacial structure in living individuals. Here we describe how T1-weighted MR images, acquired to examine brain anatomy, can also be used to analyze facial features. Using a sample of typically developing adolescents from the Saguenay Youth Study (N = 597; 292 male, 305 female, ages: 12 to 18 years), we quantified inter-individual variations in craniofacial structure in two ways. First, we adapted existing nonlinear registration-based morphological techniques to generate iteratively a group-wise population average of craniofacial features. The nonlinear transformations were used to map the craniofacial structure of each individual to the population average. Using voxel-wise measures of expansion and contraction, we then examined the effects of sex and age on inter-individual variations in facial features. Second, we employed a landmark-based approach to quantify variations in face surfaces. This approach involves: (a) placing 56 landmarks (forehead, nose, lips, jaw-line, cheekbones, and eyes) on a surface representation of the MRI-based group average; (b) warping the landmarks to the individual faces using the inverse nonlinear transformation estimated for each person; and (3) using a principal components analysis (PCA) of the warped landmarks to identify facial features (i.e. clusters of landmarks) that vary in our sample in a correlated fashion. As with the voxel-wise analysis of the deformation fields, we examined the effects of sex and age on the PCA-derived spatial relationships between facial features. Both methods demonstrated significant sexual dimorphism in craniofacial structure in areas such as the chin, mandible, lips, and nose.
PLoS ONE 01/2011; 6(5):e20241. · 4.09 Impact Factor
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ABSTRACT: Prenatal exposure to maternal cigarette smoking (PEMCS) is associated with variations in brain and behavior in adolescence. Epigenetic mechanisms may mediate some of the consequences of PEMCS through methylation of deoxyribonucleic acid (DNA) in genes important for brain development, such as the brain-derived neurotrophic factor (BDNF). In the current study, we used bisulfite sequencing to assess DNA methylation of the BDNF promoter in the blood of adolescents whose mothers smoked during pregnancy. We demonstrate that PEMCS is associated with higher rates of DNA methylation in the BDNF-6 exon. These results suggest that PEMCS may lead to long-term down-regulation of BDNF expression via the increase of DNA methylation in its promoter region. Such mechanisms could, in turn, lead to modifications in both development and plasticity of the brain exposed in utero to maternal cigarette smoking.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2010; 153B(7):1350-4. · 3.70 Impact Factor
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Shahrdad Lotfipour,
Eamonn Ferguson, Gabriel Leonard,
Michel Perron,
Bruce Pike,
Louis Richer,
Jean R Séguin,
Roberto Toro,
Suzanne Veillette,
Zdenka Pausova,
Tomás Paus
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ABSTRACT: Prenatal exposure to maternal cigarette smoking (PEMCS) may affect brain development and behavior in adolescent offspring.
To evaluate the involvement of the orbitofrontal cortex (OFC) in mediating the relationship between PEMCS and substance use.
Cross-sectional analyses from the Saguenay Youth Study aimed at evaluating the effects of PEMCS on brain development and behavior among adolescents. Nonexposed adolescents were matched with adolescents exposed prenatally to cigarette smoking by maternal educational level.
A French Canadian founder population of the Saguenay-Lac-Saint-Jean region of Quebec, Canada. The behavioral data set included 597 adolescents (275 sibships; 12-18 years of age), half of whom were exposed in utero to maternal cigarette smoking. Analysis of cortical thickness and genotyping were performed using available data from 314 adolescents.
The likelihood of substance use was assessed with the Diagnostic Interview Schedule for Children Predictive Scales. The number of different drugs tried by each adolescent was assessed using another questionnaire. Thickness of the OFC was estimated from T1-weighted magnetic resonance images using FreeSurfer software.
Prenatal exposure to maternal cigarette smoking is associated with an increased likelihood of substance use. Among exposed adolescents, the likelihood of drug experimentation correlates with the degree of OFC thinning. In nonexposed adolescents, the thickness of the OFC increases as a function of the number of drugs tried. The latter effect is moderated by a brain-derived neurotrophic factor (BDNF) genotype (Val66Met).
We speculate that PEMCS interferes with the development of the OFC and, in turn, increases the likelihood of drug use among adolescents. In contrast, we suggest that, among nonexposed adolescents, drug experimentation influences the OFC thickness via processes akin to experience-induced plasticity.
Archives of general psychiatry 11/2009; 66(11):1244-52. · 12.26 Impact Factor
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Roberto Toro,
Marie Chupin,
Line Garnero, Gabriel Leonard,
Michel Perron,
Bruce Pike,
Alain Pitiot,
Louis Richer,
Suzanne Veillette,
Zdenka Pausova,
Tomáš Paus
Brain Structure and Function 10/2009; · 5.63 Impact Factor
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Roberto Toro,
Marie Chupin,
Line Garnero, Gabriel Leonard,
Michel Perron,
Bruce Pike,
Alain Pitiot,
Louis Richer,
Suzanne Veillette,
Zdenka Pausova,
Tomás Paus
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ABSTRACT: A common Single-Nucleotide Polymorphism in the Brain-Derived Neurotrophic Factor (BDNF) gene coding the Val66Met substitution in the pro-BDNF protein has been associated with a number of behavioural and neuroanatomical phenotypes; the latter include, for example, regional differences in volumes of the hippocampus and prefrontal grey matter. Here, we show that the observed regional differences may not stem from a localised effect of this gene. Our analysis of regional brain volume in a cohort of 331 adolescents indicates that the Val66Met substitution has a global effect on brain volume, and that the observed local differences are to be expected if brain allometry-the covariance pattern of regional brain volumes-is taken into account.
Brain Structure and Function 03/2009; 213(6):501-9. · 5.63 Impact Factor
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ABSTRACT: With anatomical magnetic resonance imaging, the signal intensity of the corticospinal tract (CST) at the level of the internal capsule is often paradoxically similar to that of grey matter. As shown previously in histological studies, this is likely due to the presence of very large axons. We measured the apparent grey-matter density (aGMd) of the putative CST (pCST) in a large cohort of adolescents (n = 409, aged 12-18 years). We tested the following hypotheses: (1) The aGMd in the pCST shows a hemispheric asymmetry that is, in turn, related to hand preference; (2) the maturation of the CST during adolescence differs between both sexes, due to the influence of testosterone; (3) variations in aGMd in the pCST reflect inter-individual differences in manual skills. We confirmed the first two predictions. Thus, we found a strong left > right hemispheric asymmetry in aGMd that was, on average, less marked in the 40 left-handed subjects. Apparent GMd in the pCST increased with age in adolescent males but not females, and this was particularly related to rising plasma levels of testosterone in male adolescents. This finding is compatible with the idea that testosterone influences axonal calibre rather than myelination. The third prediction, namely that of a relationship between age-related changes in manual skills and maturation of the pCST, was not confirmed. We conclude that the leftward asymmetry of the pCST may reflect an early established asymmetry in the number of large corticomotoneuronal fibres in the pCST.
Human Brain Mapping 03/2009; 30(10):3151-62. · 5.88 Impact Factor
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ABSTRACT: The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.
Journal of Neuroscience 10/2008; 28(38):9519-24. · 7.11 Impact Factor
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ABSTRACT: Smoking during pregnancy is associated with long-term consequences on offspring behavior. We measured thickness of the cerebral cortex using magnetic resonance images obtained in 155 adolescents exposed in utero to maternal smoking and compared them with 159 non-exposed subjects matched by maternal education. Orbitofrontal, middle frontal, and parahippocampal cortices were thinner in exposed, as compared with non-exposed, individuals; these differences were more pronounced in female adolescents. In exposed females, the thickness of the orbitofrontal cortex correlated negatively with a self-rated assessment of caring, one of the components of a model of positive youth development. These findings provide evidence of the long-term impact of prenatal environment on a neural substrate of cognition and social behavior.
Neuropsychopharmacology 05/2008; 33(5):1019-27. · 7.99 Impact Factor
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ABSTRACT: Children with high resistance to peer influences differ from their low-resistance counterparts in the degree of functional connectivity in fronto-parietal and prefrontal cortical networks. Here we explored the possibility that the degree of morphological similarities across the same cortical regions also varies as a function of this behavioral trait. Using structural magnetic-resonance (MR) images, we measured cortical thickness in a total of 295 adolescents (12 to 18 years of age). We found that inter-regional correlations in cortical thickness increased with the resistance to peer influence (RPI); this was especially the case, in female adolescents, in the premotor and prefrontal networks. We also observed significant differences between the adolescents with high and low RPI scores in their general intelligence and the scores of positive youth development. We suggest that these morphological findings might reflect differences, between adolescents with high vs. low resistance to peer influences, in a repeated and concurrent engagement of these networks in social context.
Social neuroscience 02/2008; 3(3-4):303-16. · 3.17 Impact Factor
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An C M Jansen,
Henian Cao,
Paige Kaplan,
Kenneth Silver, Gabriel Leonard,
Linda De Meirleir,
Willy Lissens,
Inge Liebaers,
Martin Veilleux,
Frederick Andermann,
Robert A Hegele,
Eva Andermann
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ABSTRACT: Mucopolysaccharidosis type IIID (MPS-IIID), or Sanfilippo syndrome type D, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylglucosamine-6-sulfatase (GNS) gene, leading to impaired degradation of heparan sulfate.
To report the natural history of MPS-IIID in 2 siblings described by Kaplan and Wolfe in 1987 and to study the phenotype in 2 other unrelated families with MPS-IIID. Design, Setting, and Patients Case series of 4 patients with MPS-IIID: 2 siblings followed up at the Montreal Neurological Hospital and Institute, 1 patient followed up at the UZ Brussel, and 1 patient recruited through the prenatal counseling program at the UZ Brussel.
Clinical and molecular data collected from 3 families with enzyme-based diagnosis of MPS-IIID.
The course of the disease was characteristic of MPS-IIID in all patients, although survival may be longer than was previously reported. In family 1, both siblings were homozygous for a novel nonsense mutation in the GNS gene (c.1168C>T). In family 2, the proband carried a heterozygous mutation occurring in a splice recognition site in the intron 7 boundary (c.876-2A>G). The second mutation in this patient remains to be identified. In family 3, the proband was homozygous for a novel frameshift mutation in GNS due to the insertion of 5 nucleotides (c.1138_1139insGTCCT).
Major issues in the care of patients with MPS-IIID include behavioral problems, sleep problems, recurrent infections, dysphagia, and pain from orthopedic complications. To date, all mutations in GNS predict protein truncation, and there is no obvious genotype-phenotype correlation.
Archives of Neurology 11/2007; 64(11):1629-34. · 7.58 Impact Factor
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ABSTRACT: The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. The neuropsychological assessment protocol for children aged 6 to 18 years is described and normative data are presented for participants in that age range (N = 385). For many measures, raw score performance improved steeply from 6 to 10 years, decelerating during adolescence. Sex differences were documented for Block Design (male advantage), CVLT, Pegboard and Coding (female advantage). Household income predicted IQ and achievement, as well as externalizing problems and social competence, but not the other cognitive or behavioral measures. Performance of this healthy sample was generally better than published norms. This linked imaging-clinical/behavioral database will be an invaluable public resource for researchers for many years to come.
Journal of the International Neuropsychological Society 10/2007; 13(5):729-46. · 2.76 Impact Factor
