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Showing papers in "Behavioral and Brain Functions in 2007"


Journal ArticleDOI
TL;DR: The face N170 response can be influenced by emotional expressions contained within facial stimuli, and the topography of this effect is consistent with the notion that fear stimuli exaggerates the N 170 response itself.
Abstract: According to the traditional two-stage model of face processing, the face-specific N170 event-related potential (ERP) is linked to structural encoding of face stimuli, whereas later ERP components are thought to reflect processing of facial affect. This view has recently been challenged by reports of N170 modulations by emotional facial expression. This study examines the time-course and topography of the influence of emotional expression on the N170 response to faces. Dense-array ERPs were recorded in response to a set (n = 16) of fear and neutral faces. Stimuli were normalized on dimensions of shape, size and luminance contrast distribution. To minimize task effects related to facial or emotional processing, facial stimuli were irrelevant to a primary task of learning associative pairings between a subsequently presented visual character and a spoken word. N170 to faces showed a strong modulation by emotional facial expression. A split half analysis demonstrates that this effect was significant both early and late in the experiment and was therefore not associated with only the initial exposures of these stimuli, demonstrating a form of robustness against habituation. The effect of emotional modulation of the N170 to faces did not show significant interaction with the gender of the face stimulus, or hemisphere of recording sites. Subtracting the fear versus neutral topography provided a topography that itself was highly similar to the face N170. The face N170 response can be influenced by emotional expressions contained within facial stimuli. The topography of this effect is consistent with the notion that fear stimuli exaggerates the N170 response itself. This finding stands in contrast to previous models suggesting that N170 processes linked to structural analysis of faces precede analysis of emotional expression, and instead may reflect early top-down modulation from neural systems involved in rapid emotional processing.

388 citations


Journal ArticleDOI
TL;DR: The results support the claim of an abstract semantic processing stage for numerical comparisons that is independent of input notation.
Abstract: A dominant view in numerical cognition is that numerical comparisons operate on a notation independent representation (Dehaene, 1992). Although previous human neurophysiological studies using scalp-recorded event-related potentials (ERPs) on the numerical distance effect have been interpreted as supporting this idea, differences in the electrophysiological correlates of the numerical distance effect in symbolic notations (e.g. Arabic numerals) and non-symbolic notations (e.g. a set of visually presented dots of a certain number) are not entirely consistent with this view. Two experiments were conducted to resolve these discrepancies. In Experiment 1, participants performed a symbolic and a non-symbolic numerical comparison task ("smaller or larger than 5?") with numerical values 1–4 and 6–9 while ERPs were recorded. Consistent with a previous report (Temple & Posner, 1998), in the symbolic condition the amplitude of the P2p ERP component (210–250 ms post-stimulus) was larger for values near to the standard than for values far from the standard whereas this pattern was reversed in the non-symbolic condition. However, closer analysis indicated that the reversal in polarity was likely due to the presence of a confounding stimulus effect on the early sensory ERP components for small versus larger numerical values in the non-symbolic condition. In Experiment 2 exclusively large numerosities (8–30) were used, thereby rendering sensory differences negligible, and with this control in place the numerical distance effect in the non-symbolic condition mirrored the symbolic condition of Experiment 1. Collectively, the results support the claim of an abstract semantic processing stage for numerical comparisons that is independent of input notation.

285 citations


Journal ArticleDOI
TL;DR: These findings suggest a meaningful interaction between the DRD2 TaqI A and DRD4 VNTR polymorphisms in the expression of impulsivity and provide initial support for the utility of using behavioral measures for clarifying genetic influences on impulsivity.
Abstract: Background Research on the genetic basis for impulsivity has revealed an array of ambiguous findings. This may be a result of limitations to self-report assessments of impulsivity. Behavioral measures that assess more narrowly defined aspects of impulsivity may clarify genetic influences. This study examined the relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic polymorphisms and performance on a behavioral measure of impulsivity, the delay discounting task (DDT), and three traditional self-report measures.

257 citations


Journal ArticleDOI
TL;DR: In the modified version of IGT, deck C was no longer preferred by normal decision makers, despite having a better long-term outcome than deck A, and the covered phenomenon leads to most IGT related studies misinterpreting the effect of gain-loss frequency in situations involving long- term outcomes.
Abstract: Dunn et al. performed a critical review identifying some problems in the Somatic Marker Hypothesis (SMH). Most of the arguments presented by Dunn focused on the insufficiencies for replication of skin conductance responses and somatic brain loops, but the study did not carefully reassess the core-task of SMH. In a related study, Lin and Chiu et al. identified a serious problem, namely the "prominent deck B phenomenon" in the original IGT. Building on this observation, Lin and Chiu also posited that deck C rather than deck A was preferred by normal decision makers due to good gain-loss frequency rather than good final-outcome. To verify this hypothesis, a modified IGT was designed that possessed high contrast of gain-loss value in each trial, with the aim of achieving a balance between decks A and C in terms of gain-loss frequency. Based on the basic assumption of IGT, participants should prefer deck C to deck A based on consideration of final-outcome. In contrast, based on the prediction of gain-loss frequency, participants should have roughly equal preferences for decks A and C. This investigation recruited 48 college students (24 males and 24 females) as participants. Two-stage IGT with high-contrast gain-loss value was launched to examine the deck C argument. Each participant completed the modified IGT twice and immediately afterwards was administered a questionnaire to assess their consciousness and final preferences following the game. The experimental results supported the predictions regarding gain-loss frequency participants choose the deck C with nearly identical frequency to deck A, despite deck C having a better final outcome than deck A. The "sunken deck C" phenomenon is clearly identified in this version of IGT which achieves a balance in gain-loss frequency. Moreover, the "sunken deck C" phenomenon not only appears during the first stage, but also during the second stage of IGT. In addition, questionnaires indicated that normal decision makers disliked deck C at the consciousness (explicit) levels. In the modified version of IGT, deck C was no longer preferred by normal decision makers, despite having a better long-term outcome than deck A. This study identified two problems in the original IGT. First, the gain-loss frequency between decks A and C is pseudo-balanced. Second, the covered phenomenon leads to most IGT related studies misinterpreting the effect of gain-loss frequency in situations involving long-term outcomes, and even leads to overstatement of the foresight of normal decision makers.

173 citations


Journal ArticleDOI
TL;DR: There is a specific training effect of neurofeedback of slow cortical potentials due to enhanced cortical control in Attention Deficit/Hyperactivity Disorder, however, non-specific factors, such as parental support, may also contribute to the positive behavioural effects induced by the Neurofeedback training.
Abstract: Although several promising studies on neurofeedback training in Attention Deficit/Hyperactivity Disorder (ADHD) have been performed in recent years, the specificity of positive treatment effects continues to be challenged. To evaluate the specificity of a neurofeedback training of slow cortical potentials, a twofold strategy was pursued: First, the efficacy of neurofeedback training was compared to a group training program for children with ADHD. Secondly, the extent of improvements observed in the neurofeedback group in relation to successful regulation of cortical activation was examined. Parents and teachers rated children's behaviour and executive functions before and after treatment. In addition, children underwent neuropsychological testing before and after training. According to parents' and teachers' ratings, children of the neurofeedback training group improved more than children who had participated in a group therapy program, particularly in attention and cognition related domains. On neuropsychological measures children of both groups showed similar improvements. However, only about half of the neurofeedback group learned to regulate cortical activation during a transfer condition without direct feedback. Behavioural improvements of this subgroup were moderately related to neurofeedback training performance, whereas effective parental support accounted better for some advantages of neurofeedback training compared to group therapy according to parents' and teachers' ratings. There is a specific training effect of neurofeedback of slow cortical potentials due to enhanced cortical control. However, non-specific factors, such as parental support, may also contribute to the positive behavioural effects induced by the neurofeedback training.

141 citations


Journal ArticleDOI
TL;DR: Investigating the involvement of all eight genes from the ERBB and NRG families for association with schizophrenia suggests that observed associations between NRG1 and schizophrenia may be mediated through functional interaction not just with ERBB4, but with other members of the NRG and ERBB families.
Abstract: Background: Evidence of genetic association between the NRG1 (Neuregulin-1) gene and schizophrenia is now well-documented. Furthermore, several recent reports suggest association between schizophrenia and singlenucleotide polymorphisms (SNPs) in ERBB4, one of the receptors for Neuregulin-1. In this study, we have extended the previously published associations by investigating the involvement of all eight genes from the ERBB and NRG families for association with schizophrenia. Methods: Eight genes from the ERBB and NRG families were tested for association to schizophrenia using a collection of 396 cases and 1,342 blood bank controls ascertained from Aberdeen, UK. A total of 365 SNPs were tested. Association testing of both alleles and genotypes was carried out using the fast Fisher's Exact Test (FET). To understand better the nature of the associations, all pairs of SNPs separated by ≥ 0.5 cM with at least nominal evidence of association (P < 0.10) were tested for evidence of pairwise interaction by logistic regression analysis. Results: 42 out of 365 tested SNPs in the eight genes from the ERBB and NRG gene families were significantly associated with schizophrenia (P < 0.05). Associated SNPs were located in ERBB4 and NRG1, confirming earlier reports. However, novel associations were also seen in NRG2, NRG3 and EGFR. In pairwise interaction tests, clear evidence of gene-gene interaction was detected for NRG1-NRG2, NRG1-NRG3 and EGFR-NRG2, and suggestive evidence was also seen for ERBB4-NRG1, ERBB4-NRG2, ERBB4-NRG3 and ERBB4-ERBB2. Evidence of intragenic interaction was seen for SNPs in ERBB4. Conclusion: These new findings suggest that observed associations between NRG1 and schizophrenia may be mediated through functional interaction not just with ERBB4, but with other members of the NRG and ERBB families. There is evidence that genetic interaction among these loci may increase susceptibility to schizophrenia.

134 citations


Journal ArticleDOI
TL;DR: The results suggest that a gene × gene interaction between DRD2 and DRD4 is associated with the development of conduct disorder and adult antisocial behavior in males.
Abstract: Antisocial behaviors are complex polygenic phenotypes that are due to a multifactorial arrangement of genetic polymorphisms. Little empirical research, however, has been undertaken that examines gene × gene interactions in the etiology of conduct disorder and antisocial behavior. This study examined whether adolescent conduct disorder and adult antisocial behavior were related to the dopamine D2 receptor polymorphism (DRD2) and the dopamine D4 receptor polymorphism (DRD4). A sample of 872 male participants from the National Longitudinal Study of Adolescent Health (Add Health) completed self-report questionnaires that tapped adolescent conduct disorder and adult antisocial behavior. DNA was genotyped for DRD2 and DRD4. Multivariate regression analysis revealed that neither DRD2 nor DRD4 had significant independent effects on conduct disorder or antisocial behavior. However, DRD2 interacted with DRD4 to predict variation in adolescent conduct disorder and in adult antisocial behavior. The results suggest that a gene × gene interaction between DRD2 and DRD4 is associated with the development of conduct disorder and adult antisocial behavior in males.

129 citations


Journal ArticleDOI
TL;DR: This study addressed the possibility that there might be important species differences by systematically examining and directly comparing the distribution of orexinergic neurons and fibers within the forebrains of species with very different patterns of sleep-wake behavior.
Abstract: The orexins (hypocretins) are a family of peptides found primarily in neurons in the lateral hypothalamus. Although the orexinergic system is generally thought to be the same across species, the orexins are involved in behaviors which show considerable interspecific variability. There are few direct cross-species comparisons of the distributions of cells and fibers containing these peptides. Here, we addressed the possibility that there might be important species differences by systematically examining and directly comparing the distribution of orexinergic neurons and fibers within the forebrains of species with very different patterns of sleep-wake behavior. We compared the distribution of orexin-immunoreactive cell bodies and fibers in two nocturnal species (the lab rat, Rattus norvegicus and the golden hamster, Mesocricetus auratus) and two diurnal species (the Nile grass rat, Arvicanthis niloticus and the degu, Octodon degus). For each species, tissue from the olfactory bulbs through the brainstem was processed for immunoreactivity for orexin A and orexin B (hypocretin-1 and -2). The distribution of orexin-positive cells was noted for each species. Orexin fiber distribution and density was recorded and analyzed using a principal components factor analysis to aid in evaluating potential species differences. Orexin-positive cells were observed in the lateral hypothalamic area of each species, though there were differences with respect to distribution within this region. In addition, cells positive for orexin A but not orexin B were observed in the paraventricular nucleus of the lab rat and grass rat, and in the supraoptic nucleus of the lab rat, grass rat and hamster. Although the overall distributions of orexin A and B fibers were similar in the four species, some striking differences were noted, especially in the lateral mammillary nucleus, ventromedial hypothalamic nucleus and flocculus. The orexin cell and fiber distributions observed in this study were largely consistent with those described in previous studies. However, the present study shows significant species differences in the distribution of orexin cell bodies and in the density of orexin-IR fibers in some regions. Finally, we note previously undescribed populations of orexin-positive neurons outside the lateral hypothalamus in three of the four species examined.

115 citations


Journal ArticleDOI
TL;DR: Findings indicated that poorer performance on WM tasks predicted inattentive behaviour, consistent with previous research linking WM deficits and poor attention in ADHD and normal populations.
Abstract: Existing literature to date suggests a relationship between cognitive attention and working memory (WM), but the relationship between overt inattentive behaviour and WM is less clear. This study examined the relationship between WM and parent-rated inattentive behaviour in a community sample of 140 children aged 7–12 years. Children completed 2 clinical (laboratory-based) measures of WM (auditory-verbal and visual-spatial) and a measure of real-life WM, designed specifically for this study, while their parents completed questionnaires about their child's inattentive behaviour and other areas of functioning. Findings indicated that poorer performance on WM tasks predicted inattentive behaviour. These results are consistent with previous research linking WM deficits and poor attention in ADHD and normal populations. The present findings support a controlled attention model of WM.

90 citations


Journal ArticleDOI
TL;DR: It remains inconclusive as to whether ineffecient cognitive control in the clinical sample was due to top-down failure or bottom-up engagement thereof, but novel evidence of inefficient interference control and task-set coordination in adults with persistent ADHD is delivered.
Abstract: Contemporary neuropsychological models of ADHD implicate impaired cognitive control as contributing to disorder characteristic behavioral deficiencies and excesses; albeit to varying degrees. While the traditional view of ADHD postulates a core deficiency in cognitive control processes, alternative dual-process models emphasize the dynamic interplay of bottom-up driven factors such as activation, arousal, alerting, motivation, reward and temporal processing with top-down cognitive control. However, neuropsychological models of ADHD are child-based and have yet to undergo extensive empirical scrutiny with respect to their application to individuals with persistent symptoms in adulthood. Furthermore, few studies of adult ADHD samples have investigated two central cognitive control processes: interference control and task-set coordination. The current study employed experimental chronometric Stroop and task switching paradigms to investigate the efficiency of processes involved in interference control and task-set coordination in ADHD adults. 22 adults diagnosed with persistent ADHD (17 males) and 22 matched healthy control subjects performed a manual trial-by-trial Stroop color-word test and a blocked explicitly cued task switching paradigm. Performance differences between neutral and incongruent trials of the Stroop task measured interference control. Task switching paradigm manipulations allowed for measurement of transient task-set updating, sustained task-set maintenance, preparatory mechanisms and interference control. Control analyses tested for the specificity of group × condition interactions. Abnormal processing of task-irrelevant stimulus features was evident in ADHD group performance on both tasks. ADHD group interference effects on the task switching paradigm were found to be dependent on the time allotted to prepare for an upcoming task. Group differences in sustained task-set maintenance and transient task-set updating were also found to be dependent on experimental manipulation of task preparation processes. With the exception of Stroop task error rates, all analyses revealed generally slower and less accurate ADHD group response patterns. The current data obtained with experimental paradigms deliver novel evidence of inefficient interference control and task-set coordination in adults with persistent ADHD. However, all group differences observed in these central cognitive control processes were found to be partially dependent on atypical ADHD group task preparation mechanisms and/or response inconsistency. These deficiences may have contributed not only to inefficient cognitive control, but also generally slower and less accurate ADHD group performance. Given the inability to dissociate these impairments with the current data, it remains inconclusive as to whether ineffecient cognitive control in the clinical sample was due to top-down failure or bottom-up engagement thereof. To clarify this issue, future neuropsychological investigations are encouraged to employ tasks with significantly more trials and direct manipulations of bottom-up mechanisms with larger samples.

86 citations


Journal ArticleDOI
TL;DR: The timing of the EEG distance effect suggests that a refined evaluation of numerical magnitude happened at a similar speed in each age group during both controlled and automatic magnitude processing.
Abstract: Background In the numerical Stroop paradigm (NSP) participants decide whether a digit is numerically or physically larger than another simultaneously presented digit This paradigm is frequently used to assess the automatic number processing abilities of children Currently it is unclear whether an equally refined evaluation of numerical magnitude occurs in both controlled (the numerical comparison task of the NSP) and automatic (the physical comparison task of the NSP) numerical comparison in both children and adults One of our objectives was to respond this question by measuring the speed of controlled and automatic magnitude processing in children and adults in the NSP Another objective was to determine how the immature executive functions of children affect their cognitive functions relative to adults in numerical comparison

Journal ArticleDOI
TL;DR: Findings suggest that the proposed filter is a useful tool for the analysis of physiological data especially in revealing very low frequency peaks which may otherwise be obscured by the 1/f spectral activity inherent in EEG/MEG recordings.
Abstract: Background It has been acknowledged that the frequency spectrum of measured electromagnetic (EM) brain signals shows a decrease in power with increasing frequency. This spectral behaviour may lead to difficulty in distinguishing event-related peaks from ongoing brain activity in the electro- and magnetoencephalographic (EEG and MEG) signal spectra. This can become an issue especially in the analysis of low frequency oscillations (LFOs) – below 0.5 Hz – which are currently being observed in signal recordings linked with specific pathologies such as epileptic seizures or attention deficit hyperactivity disorder (ADHD), in sleep studies, etc.

Journal ArticleDOI
TL;DR: Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases of the X chromosome, is responsible for a TS neurocognitive phenotype, described by the TSCS score.
Abstract: Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47) of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS) score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject's age, were unrelated to the TSCS score. Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb) of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1). Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are attractive candidates for this neurocognitive phenotype.

Journal ArticleDOI
TL;DR: Evidence is provided for association between the DTNBP1 gene and intelligence in patients with FEP and their unaffected siblings and several single SNPs were significantly associated with IQ scores in patients, siblings, and controls.
Abstract: Background The dystrobrevin-binding protein 1 (DTNBP1) gene is a susceptibility gene for schizophrenia There is growing evidence that DTNPB1 contributes to intelligence and cognition In this study, we investigated association between single nucleotide polymorphisms (SNPs) in the DTNBP1 gene and intellectual functioning in patients with a first episode of schizophrenia or related psychotic disorder (first-episode psychosis, FEP), their healthy siblings, and unrelated controls

Journal ArticleDOI
TL;DR: Evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol is interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of an influence on reactivity to the craving induction.
Abstract: Craving for alcohol is a highly controversial subjective construct and may be clarified by Loewenstein's visceral theory, which emphasizes craving's behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined. Thirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols. Factorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001). These results are interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed.

Journal ArticleDOI
TL;DR: The results demonstrated hyperbolic decay of SP is related todelay discounting, and delay discounting is, however, not attributable to precautious foresight in intertemporal choice, and a novel parameter of pure time preference is proposed.
Abstract: Background Hyperbolic discounting of delayed and probabilistic outcomes has drawn attention in psychopharmacology and neuroeconomics. Sozou's evolutionary theory proposed that hyperbolic delay discounting may be totally attributable to aversion to a decrease in subjective probability of obtaining delayed rewards (SP) which follows a hyperbolic decay function. However, to date, no empirical study examined the hypothesis, although this investigation is important for elucidating the roles of impatience, precaution, and uncertainty aversion in delay discounting processes.

Journal ArticleDOI
TL;DR: Findings suggest that ANX + ADHD relates to greater cognitive and academic vulnerability than ANX, but may relate to reduced perception of anger.
Abstract: Background Cognition in children with anxiety disorders (ANX) and comorbid Attention Deficit Disorder (ADHD) has received little attention, potentially impacting clinical and academic interventions in this highly disabled group. This study examined several cognitive features relative to children with either pure condition and to normal controls.

Journal ArticleDOI
TL;DR: It is reported that decreases in hippocampal volume may serve as an index of severity for cognitive impairments in children with DS22q11.2.
Abstract: Previous investigations of individuals with chromosome 22q11.2 deletion syndrome (DS22q11.2) have reported alterations in both brain anatomy and cognitive function. Neuroanatomical studies have reported multiple abnormalities including changes in both gray and white matter in the temporal lobe, including the amygdala and hippocampus. Separate investigations of cognitive abilities have established the prevalence of general intellectual impairment, although the actual extent to which a single individual is affected varies greatly within the population. The present study was designed to examine structures within the temporal lobe and assess their functional significance in terms of cognition in children with DS22q11.2. A total of 72 children (ages 7–14 years) participated in the investigation: 36 children (19 female, 17 male) tested FISH positive for chromosome 22q11.2 deletion (Mean age = 10 years 9 months, ± 2 yr 4 mo) and 36 were age-matched typically developing controls (13 female, 23 male; Mean age = 10 years 6 months, ± 1 yr 11 mo). For each subject, a three-dimensional high-resolution (1 mm isotropic) T1-weighted structural MRI was acquired. Neuroanatomical guidelines were used to define borders of the amygdala and hippocampus bilaterally and volumes were calculated based on manual tracings of the regions. The Wechsler Intelligence Scale for Children (WISC) was also administered. Volumetric reductions in total gray matter, white matter, and both the amygdala and hippocampus bilaterally were observed in children with DS22q11.2. Reductions in the left hippocampus were disproportionate to decreases in gray matter after statistically controlling for group differences in total gray matter, age, and data collection site. This specific reduction in hippocampal volume was significantly correlated with performance on standardized measures of intelligence, whereas the other neuroanatomical measures were not (gray/white matter, CSF, and amygdala). Results from this study not only contribute to the understanding of the neuroanatomical variation in DS22q11.2, but also provide insight into the nature and source of the cognitive impairments associated with the syndrome. Specifically, we report that decreases in hippocampal volume may serve as an index of severity for cognitive impairments in children with DS22q11.2.

Journal ArticleDOI
TL;DR: Results from this systematic review do not provide evidence to support an association between 5-HTTLPR and PD, and more studies are needed in different ethnic populations in order to evaluate a possible minor effect.
Abstract: The aim of this study is to assess the association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder (PD). This is a systematic review and meta-analysis of case-control studies with unrelated individuals of any ethnic origin examining the role of the 5-HTTLPR in PD according to standard diagnostic criteria (DSM or ICD). Articles published in any language between January 1996 and April 2007 were eligible. The electronic databases searched included PubMed, PsychInfo, Lilacs and ISI. Two separate analyses were performed: an analysis by alleles and a stratified analysis separating studies by the quality of control groups. Asymptotic DerSimonian and Laird's Q test were used to assess heterogeneity. Results of individual studies were combined using the fixed effect model with respective 95% confidence intervals. Nineteen potential articles were identified, and 10 studies were included in this meta-analysis. No statistically significant association between 5-HTTLPR and PD was found, OR = 0.91 (CI95% 0.80 to 1.03, p = 0.14). Three sub-analyses divided by ethnicity, control group quality and Agoraphobia comorbidity also failed to find any significant association. No evidence of heterogeneity was found between studies in the analyses. Results from this systematic review do not provide evidence to support an association between 5-HTTLPR and PD. However, more studies are needed in different ethnic populations in order to evaluate a possible minor effect.

Journal ArticleDOI
TL;DR: N170 represents an important step in visual word recognition, consisting probably in a prelexical orthographic processing, but during the reading of very frequent words or after a massive repetition of a word, it could represent a more holistic process where words are processed as a global visual pattern.
Abstract: Occipito-temporal N170 component represents the first step where face, object and word processing are discriminated along the ventral stream of the brain. N170 leftward asymmetry observed during reading has been often associated to prelexical orthographic visual word form activation. However, some studies reported a lexical frequency effect for this component particularly during word repetition that appears in contradiction with this prelexical orthographic step. Here, we tested the hypothesis that under word repetition condition, discrimination between words would be operated on visual rather than orthographic basis. In this case, N170 activity may correspond to a logographic processing where a word is processed as a whole. To test such an assumption, frequent words, infrequent words and pseudowords were presented to the subjects that had to complete a visual lexical decision task. Different repetition conditions were defined 1 – weak repetition, 2 – massive repetition and 3 – massive repetition with font alternation. This last condition was designed to change visual word shape during repetition and therefore to interfere with a possible visual strategy during word recognition. Behavioral data showed an important frequency effect for the weak repetition condition, a lower but significant frequency effect for massive repetition, and no frequency effect for the changing font repetition. Moreover alternating font repetitions slowed subject's responses in comparison to "simple" massive repetition. ERPs results evidenced larger N170 amplitude in the left hemisphere for frequent than both infrequent words and pseudowords during massive repetition. Moreover, when words were repeated with different fonts this N170 effect was not present, suggesting a visual locus for such a N170 frequency effect. N170 represents an important step in visual word recognition, consisting probably in a prelexical orthographic processing. But during the reading of very frequent words or after a massive repetition of a word, it could represent a more holistic process where words are processed as a global visual pattern.

Journal ArticleDOI
TL;DR: It is suggested that similar mechanisms underlie the perception of linguistically different but acoustically equivalent auditory events on the level of basic auditory analysis as well as overlapping spatio-temporal brain responses during the Perception of temporal acoustic cues in both speech and non-speech sounds.
Abstract: Speech perception is based on a variety of spectral and temporal acoustic features available in the acoustic signal. Voice-onset time (VOT) is considered an important cue that is cardinal for phonetic perception. In the present study, we recorded and compared scalp auditory evoked potentials (AEP) in response to consonant-vowel-syllables (CV) with varying voice-onset-times (VOT) and non-speech analogues with varying noise-onset-time (NOT). In particular, we aimed to investigate the spatio-temporal pattern of acoustic feature processing underlying elemental speech perception and relate this temporal processing mechanism to specific activations of the auditory cortex. Results show that the characteristic AEP waveform in response to consonant-vowel-syllables is on a par with those of non-speech sounds with analogue temporal characteristics. The amplitude of the N1a and N1b component of the auditory evoked potentials significantly correlated with the duration of the VOT in CV and likewise, with the duration of the NOT in non-speech sounds. Furthermore, current density maps indicate overlapping supratemporal networks involved in the perception of both speech and non-speech sounds with a bilateral activation pattern during the N1a time window and leftward asymmetry during the N1b time window. Elaborate regional statistical analysis of the activation over the middle and posterior portion of the supratemporal plane (STP) revealed strong left lateralized responses over the middle STP for both the N1a and N1b component, and a functional leftward asymmetry over the posterior STP for the N1b component. The present data demonstrate overlapping spatio-temporal brain responses during the perception of temporal acoustic cues in both speech and non-speech sounds. Source estimation evidences a preponderant role of the left middle and posterior auditory cortex in speech and non-speech discrimination based on temporal features. Therefore, in congruency with recent fMRI studies, we suggest that similar mechanisms underlie the perception of linguistically different but acoustically equivalent auditory events on the level of basic auditory analysis.

Journal ArticleDOI
TL;DR: Neighborhood consistency effects in this paradigm resemble lexico-semantic effects earlier found in simple arithmetic and in orthographic input processing and are compatible with current models on the representation of simple multiplication facts – in particular with the Interacting Neighbors Model – and with the notion of decomposed representations of two-digit numbers in general.
Abstract: Recent cognitive and computational models (e.g. the Interacting Neighbors Model) state that in simple multiplication decade and unit digits of the candidate answers (including the correct result) are represented separately. Thus, these models challenge holistic views of number representation as well as traditional accounts of the classical problem size effect in simple arithmetic (i.e. the finding that large problems are answered slower and less accurate than small problems). Empirical data supporting this view are still scarce. Data of 24 participants who performed a multiplication verification task with Arabic digits (e.g. 8 × 4 = 36 - true or false?) are reported. Behavioral (i.e. RT and errors) and EEG (i.e. ERP) measures were recorded in parallel. We provide evidence for neighborhood-consistency effects in the verification of simple multiplication problems (e.g. 8 × 4). Behaviorally, we find that decade-consistent lures, which share their decade digit with the correct result (e.g. 3 6), are harder to reject than matched inconsistent lures, which differ in both digits from the correct result (e.g. 28). This neighborhood consistency effect in product verification is similar to recent observations in the production of multiplication results. With respect to event-related potentials we find significant differences for consistent compared to inconsistent lures in the N400 (increased negativity) and Late Positive Component (reduced positivity). In this respect consistency effects in our paradigm resemble lexico-semantic effects earlier found in simple arithmetic and in orthographic input processing. Our data suggest that neighborhood consistency effects in simple multiplication stem at least partly from central (lexico-semantic') stages of processing. These results are compatible with current models on the representation of simple multiplication facts – in particular with the Interacting Neighbors Model – and with the notion of decomposed representations of two-digit numbers in general.

Journal ArticleDOI
TL;DR: The present study suggests that in addition to ethnic bias, socio-cultural factors should be considered while evaluating genotype phenotype correlations, in association and treatment response to complex disorders like schizophrenia.
Abstract: Alterations in the dopamine transmission and receptor density are hypothesized in the pathophysiology of schizophrenia but ethnic disparities are reported to exist in disease association and therapeutic response to psychotropic medication. Antipsychotics have higher binding affinity to D2 subtype of dopamine receptor. DRD2 Cys311, TaqIB1 and TaqIA1 variants are considered to have either reduced affinity for dopamine and hypo-dopaminergic activity. We examined the role of Taq1B, Taq1D, S311C, H313H and Taq1A polymorphisms of DRD2 gene in schizophrenia and antipsychotic treatment response in 213 patients and 196 controls from a homogenous South Indian population. A more detailed genotype phenotype association analysis was carried out to understand the disease in terms of its socio-cultural factors. H313HTT genotype was found to be associated with schizophrenia (P = 0.004) while TaqIB1B1 genotype was significantly associated with higher psychopathology score. When treatment response was considered H313HCC, TaqIA2A2 and Taq1D1D1 had higher mean improvement scores. TaqID1D1 and H313HTT genotype were found to be significantly higher in responders than in nonresponder group. Distinct shift in the LD patterns of responder and non-responder group was observed. Certain symptoms were characteristic of our patient population. Following medication the scores and presentation of these symptoms tend to vary in the responder and non-responder groups. Based on genotype phenotype correlations it can be suggested that certain polymorphisms can be defined for their critical functions in disease and their role in treatment response in South Indian population. The present study suggests that in addition to ethnic bias, socio-cultural factors should also be considered while evaluating genotype phenotype correlations, in association and treatment response to complex disorders like schizophrenia.

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TL;DR: A link is established between the on-line structuring of context-free (single sentences) and context-embedded utterances (dialogs) as measured by ERPs and the impact of prosodic phrasing and accentuation on the perception of spoken utterances on and beyond sentence level.
Abstract: Background The online segmentation of spoken single sentences has repeatedly been associated with a particular event-related brain potential. The brain response could be attributed to the perception of major prosodic boundaries, and was termed Closure Positive Shift (CPS). However, verbal exchange between humans is mostly realized in the form of cooperative dialogs instead of loose strings of single sentences. The present study investigated whether listeners use prosodic cues for structuring larger contextually embedded utterances (i.e. dialogs) like in single sentence processing.

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TL;DR: The results give support to the theory that synchronization of cortical ensembles in SI could significantly impact the topography of temporal perception, and these findings are speculated to be linked mechanistically to previously reported co-activation plasticity studies.
Abstract: Background: A subject's ability to differentiate the loci of two points on the skin depends on the stimulus-evoked pericolumnar lateral inhibitory interactions which increase the spatial contrast between regions of SI cortex that are activated by stimulus-evoked afferent drive. Nevertheless, there is very little known about the impact that neuronal interactions – such as those evoked by mechanical skin stimuli that project to and coordinate synchronized activity in adjacent and/or near-adjacent cortical columns – could have on sensory information processing. Methods: The temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 20 healthy adult subjects were assessed both in the absence and presence of concurrent conditions of tactile stimulation. These measures were obtained across a number of paired sites – two unilateral and one bilateral – and several conditions of adapting stimuli were delivered both prior to and concurrently with the TOJ and TDT tasks. The pairs of conditioning stimuli were synchronized and periodic, synchronized and non-periodic, or asynchronous and non-periodic. Results: In the absence of any additional stimuli, TOJ and TDT results obtained from the study were comparable across a number of pairs of stimulus sites – unilateral as well as bilateral. In the presence of a 25 Hz conditioning sinusoidal stimulus which was delivered both before, concurrently and after the TOJ task, there was a significant change in the TOJ measured when the two stimuli were located unilaterally on digits 2 and 3. However, in the presence of the same 25 Hz conditioning stimulus, the TOJ obtained when the two stimuli were delivered bilaterally was not impacted. TDT measures were not impacted to the same degree by the concurrent stimuli that were delivered to the unilateral or bilateral stimulus sites. This led to the speculation that the impact that the conditioning stimuli – which were sinusoidal, periodic and synchronous – had on TOJ measures was due to the synchronization of adjacent cortical ensembles in somatosensory cortex, and that the synchronization of these cortical ensembles could have been responsible for the degradation in temporal order judgment. In order to more directly test this hypothesis, the synchronized 25 Hz conditioning stimuli that were delivered during the initial TOJ test were replaced with asynchronous non-periodic 25 Hz conditioning stimuli, and these asynchronous conditioning stimuli did not impact the TOJ measures. Conclusion: The results give support to the theory that synchronization of cortical ensembles in SI could significantly impact the topography of temporal perception, and these findings are speculated to be linked mechanistically to previously reported co-activation plasticity studies. Additionally, the impact that such synchronizing conditioning stimuli have on TOJ – which can be measured relatively quickly – could provide an effective means to assess the functional connectivity of neurologically compromised subject populations.

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TL;DR: The present findings support previous studies showing increased behavioral variability in SHR relative to WKY controls and provide support for a steepened delay-of-reinforcement gradient as suggested in the dynamic developmental theory of ADHD.
Abstract: Background Attention-deficit/hyperactivity disorder (ADHD) is characterized by a pattern of inattention, hyperactivity, and impulsivity that is cross-situational, persistent, and produces social and academic impairment. Research has shown that reinforcement processes are altered in ADHD. The dynamic developmental theory has suggested that a steepened delay-of-reinforcement gradient and deficient extinction of behavior produce behavioral symptoms of ADHD and increased behavioral variability.

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TL;DR: An interpretive bias and generalization of phobia-specific responses in specific phobia is suggested, which has been observed in other anxiety disorders, such as social phobia and posttraumatic stress disorder.
Abstract: Background: Individuals with social phobia are more likely to misinterpret ambiguous social situations as more threatening, i.e. they show an interpretive bias. This study investigated whether such a bias also exists in specific phobia. Methods: Individuals with spider phobia or social phobia, spider aficionados and non-phobic controls saw morphed stimuli that gradually transformed from a schematic picture of a flower into a schematic picture of a spider by shifting the outlines of the petals until they turned into spider legs. Participants' task was to decide whether each stimulus was more similar to a spider, a flower or to neither object while EEG was recorded. Results: An interpretive bias was found in spider phobia on a behavioral level: with the first opening of the petals of the flower anchor, spider phobics rated the stimuli as more unpleasant and arousing than the control groups and showed an elevated latent trait to classify a stimulus as a spider and a response-time advantage for spider-like stimuli. No cortical correlates on the level of ERPs of this interpretive bias could be identified. However, consistent with previous studies, social and spider phobic persons exhibited generally enhanced visual P1 amplitudes indicative of hypervigilance in phobia. Conclusion: Results suggest an interpretive bias and generalization of phobia-specific responses in specific phobia. Similar effects have been observed in other anxiety disorders, such as social phobia and posttraumatic stress disorder.

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TL;DR: The findings suggest that HEV-laterality, like handedness or gender, is an important individual difference with significant implications for brain and behavioral research, and for guiding lateralized treatments such as rTMS.
Abstract: Background: Much has been theorized about the emotional properties of the hemispheres. Our review of the dominant hypotheses put forth by Schore, Joseph, Davidson, and Harmon-Jones on hemispheric emotional valences (HEV) shows that none are supported by robust data. Instead, we propose that individual's hemispheres are organized to have differing HEVs that can be lateralized in either direction. Methods: Probe auditory evoked potentials (AEP) recorded during a neutral and an upsetting memory were used to assess HEV in 28 (20 F) right-handed subjects who were either victims of childhood maltreatment (N = 12) or healthy controls. In a sub-population, we determined HEV by emotional response to lateral visual field stimulation (LVFS), in which vision is limited to one, then the other hemifield. We compare a number of morphometric and functional brain measures between individuals who have right-negative versus left-negative HEV. Results: Using AEPs to determine HEV, we found 62% of controls and 67% of maltreated subjects had right negative HEV. There was a strong interaction between HEV-laterality and gender, which together accounted for 60% of individual variability in total grey matter volume (GMV). HEVlaterality was associated with differences in hippocampal volume, amygdala/hippocampal ratios, and measures of verbal, visual and global memory. HEV-laterality was associated also with different constellations of symptoms comparing maltreated subjects to controls. Emotional response to LVFS provided a convenient and complementary measure of HEV-laterality that correlated significantly with the HEVs determined by AEPs. Conclusion: Our findings suggest that HEV-laterality, like handedness or gender, is an important individual difference with significant implications for brain and behavioral research, and for guiding lateralized treatments such as rTMS.

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TL;DR: Results fail to support prior findings of independent associations of these polymorphisms with smoking status, but exploratory findings suggestive of gene-gene and gene-treatment interactions warrants further investigation.
Abstract: Background Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.

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TL;DR: The results indicate that, in Spanish individuals, genotypes of the DRD2 Taq I A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males.
Abstract: Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) Taq I A polymorphism. We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females). The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70). Our results indicate that, in Spanish individuals, genotypes of the DRD2 Taq I A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males.