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Evidence of alterations in emotion processing in maltreated youth has been hypothesized to reflect latent vulnerability for psychopathology. However, previous studies have not systematically examined the influence of psychopathology on the results. Here, we examined emotion recognition and learning in youth who differed in terms of presence vs. absence of maltreatment and psychopathology and tested for potential sex effects. Maltreatment and psychopathology were assessed in 828 youth (514 females) aged 9–18 years using diagnostic interviews and self- and parent-report questionnaires. Emotion recognition was assessed via identification of morphed facial expressions of six universal emotions. For emotion learning, reward and punishment values were assigned to novel stimuli and participants had to learn to correctly respond/withhold response to stimuli to maximize points. A three-way interaction of maltreatment by psychopathology by emotion indicated that when psychopathology was low, maltreated youth were less accurate than non-maltreated youth for happy, fear and disgust. A three-way interaction of sex, maltreatment and emotion indicated that maltreated girls and boys were impaired for fear, but girls showed an impairment for happy, while boys for disgust. There were no effects of maltreatment, psychopathology, or sex on reward learning. However, a two-way interaction between sex and maltreatment showed that maltreated girls were worse at learning from punishment relative to non-maltreated girls, while maltreated boys were better than non-maltreated boys. The study provides the first clear evidence of latent-vulnerability in emotion recognition in maltreated youth and suggests that girls and boys might be characterized by distinct profiles of emotion recognition and learning following maltreatment.

Among youths with conduct disorder, those with callous-unemotional traits are at increased risk for persistent antisocial behaviour. Although callous-unemotional traits have been found to be associated with white-matter brain abnormalities, previous diffusion imaging studies were conducted in small samples, preventing examination of potential sex by callous-unemotional traits interaction effects on white matter. Here, we used tract-based spatial statistics at a whole-brain level and within regions of interest to compare the white matter correlates of callous-unemotional traits in female vs. male youths with conduct disorder, in a sample (n = 124) recruited through a multi-site protocol. A sex-specific association between callous-unemotional traits and white matter was found in the left uncinate fasciculus, where callous-unemotional traits were positively associated with axial diffusivity in males, while an opposite pattern was found in females. These findings are in line with previous studies suggesting that the uncinate fasciculus is a key tract implicated in the development of psychopathy, but also add to recent evidence showing that sexual dimorphism needs to be taken into account when examining the structural correlates of mental disorders in general, and callous-unemotional traits in conduct disorder in particular.

Voxel-based morphometry (VBM) studies of gray matter volume (GMV) in psychopathy have produced inconsistent results and few have been replicated. Therefore, to clarify GMV abnormalities associated with psychopathy as operationalized by Hare (2003), we conducted a meta-analysis of VBM studies using both categorical and dimensional analyses. We identified seven studies eligible for the categorical meta-analysis (136 men with psychopathy vs 150 male controls) and 11 studies (N = 519) eligible for dimensional metaregressions. First, we used seed-based d mapping with permutation of subject images for voxel-based meta-analyses. Statistical parametric maps of GMV were available for four (57%) of the studies included in the categorical meta-analysis and for five (45%) of the studies included in the dimensional metaregression analyses, with peak coordinates available for the remaining studies. Second, we used metadata of a large-scale neuroimaging database to provide an objective and quantitative account of psychological processes attributed to the brain regions we identified in our group meta-analysis and metaregressions. Men with psychopathy exhibited reliable GMV abnormalities circumscribed to the left hemisphere in the dorsolateral prefrontal cortex and the medial orbitofrontal cortex. Total psychopathy scores and Factors 1 and 2 scores were all related to decreased GMV within those two prefrontal regions, as well as decreased GMV in a wider set of regions encompassing midline, temporal, parietal, occipital, and subcortical structures. We discuss how decreased GMV in those regions likely account for the impairments in the emotion, cognition, action, and perception domains seen in the disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Theoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has tested small samples. Here, using computational modelling of a learning task collected from a large sample (N=742, 9-18 years, 11 countries), we tested differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling revealed that whilst punishment learning rates increased with age, reward learning remained stable. In parallel, action initiation biases decreased with age. Results were similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.

Theory of mind (ToM), or the ability to infer and predict the intentions, thoughts and beliefs of others, involves cognitive perspective taking (cognitive ToM/cToM) and understanding emotions (affective ToM/aToM). While behavioral evidence indicates that ToM is influenced by sex and age, no study has examined the influence of these variables on the neural correlates of cToM and aToM in late childhood/adolescence. Using fMRI with 35 typically-developing youths (aged 9–18 years, 12 males), we investigated the influence of sex and age on the neural correlates of cToM and aToM. We also examined how callous-unemotional traits, indexing a lack of empathy, were related to brain responses during aToM. Across both conditions, we found convergent activity in ToM network regions, such as superior temporal sulcus/temporoparietal junction (TPJ) and precuneus across males and females, but males recruited the left TPJ significantly more than females during cToM. During aToM, age was negatively correlated with brain responses in frontal, temporal and posterior midline regions, while callous-unemotional traits were positively correlated with right anterior insula responses. These results provide the first evidence in youth that sex influences the neural correlates of cToM, while age and callous-unemotional traits are specifically related to brain responses during aToM.

As most research on conduct disorder (CD) has been conducted on male participants, it has been suggested that female-specific symptoms may be underestimated based on current DSM-5 criteria. In particular, relational aggression, i.e. the hurtful, often indirect, manipulation of relationships with the intention of damaging the other's social position, has been proposed as a characteristic of CD that is more common in females. In addition, sex-specific studies on correlates of relational aggressive behavior are lacking. Relational aggression may be strongly related to the correlates of proactive aggression, namely low affective empathy, and high levels of callous-unemotional (CU) traits and relational victimization. Thus, the present study investigated sex differences in relational aggression, and associations between relational aggression and correlates of proactive aggression in 662 adolescents with CD (403 females) and 849 typically-developing controls (568 females) aged 9-18 years (M = 14.74, SD = 2.34) from the European multi-site FemNAT-CD study. Females with CD showed significantly higher levels of relational aggression compared to males with CD, whereas no sex differences were seen in controls. Relational aggression was only partly related to correlates of proactive aggression in CD: Independent of sex, CU traits showed a positive association with relational aggression. In females only, cognitive, but not affective empathy, was negatively associated with relational aggression. Relational victimization was more strongly associated with relational aggression in males compared to females. Despite interesting sex specific correlates of relational aggression, effects are small and the potential clinical implications should be investigated in future studies.

Less is known about the relationship between conduct disorder (CD), callous–unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9–18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence.

Among youths with conduct disorder, those with callous-unemotional traits are at increased risk for persistent antisocial behaviour. Although callous-unemotional traits have been found to be associated with white-matter brain abnormalities, previous diffusion imaging studies were conducted in small samples, preventing examination of potential sex by callous-unemotional traits interaction effects on white matter. Here, we used tract-based spatial statistics at a whole-brain level and within regions of interest to compare the white matter correlates of callous-unemotional traits in female vs. male youths with conduct disorder, in a sample (n = 124) recruited through a multi-site protocol. A sex-specific association between callous-unemotional traits and white matter was found in the left uncinate fasciculus, where callous-unemotional traits were positively associated with axial diffusivity in males, while an opposite pattern was found in females. These findings are in line with previous studies suggesting that the uncinate fasciculus is a key tract implicated in the development of psychopathy, but also add to recent evidence showing that sexual dimorphism needs to be taken into account when examining the structural correlates of mental disorders in general, and callous-unemotional traits in conduct disorder in particular.

The journal of child psychology and psychiatry 63(2), 218-228 (2022). doi:10.1111/jcpp.13428, Published by Wiley-Blackwell, Oxford

The catalytic reductive transformation of carboxylic esters into α-branched ethers is described. The procedure pivots on the chemoselective iridium-catalyzed hydrosilylation of ester and lactone functionality to afford a silyl acetal intermediate. Upon treatment with a Lewis acid, these hemilabile intermediates dissociate to form reactive oxocarbenium ions, which can be intercepted by allyltributyltin nucleophiles, resulting in the formation of valuable α-branched alkyl-alkyl ether derivatives. This reductive allylation procedure was found to be amenable to a range of carboxylic ester starting materials, and good chemoselectivity for ethyl over tert-butyl esters was demonstrated. Furthermore, downstream synthetic manipulation of α-amino acid-derived products led to the efficient formation of pyrrolidine, piperidine, and azepane frameworks.

Journal of the American Heart Association 10(4), e017405 (2021). doi:10.1161/JAHA.120.017405, Published by American Heart Association, New York, NY

Translational Psychiatry 11(1), 492 (2021). doi:10.1038/s41398-021-01609-y, Published by Nature Publishing Group, London

Conduct disorder (CD) with high levels of callous-unemotional traits (CD/HCU) has been theoretically linked to specific difficulties with fear and sadness recognition, in contrast to CD with low levels of callous-unemotional traits (CD/LCU). However, experimental evidence for this distinction is mixed, and it is unclear whether these difficulties are a reliable marker of CD/HCU compared to CD/LCU. In a large sample (N = 1263, 9–18 years), we combined univariate analyses and machine learning classifiers to investigate whether CD/HCU is associated with disproportionate difficulties with fear and sadness recognition over other emotions, and whether such difficulties are a reliable individual-level marker of CD/HCU. We observed similar emotion recognition abilities in CD/HCU and CD/LCU. The CD/HCU group underperformed relative to typically developing (TD) youths, but difficulties were not specific to fear or sadness. Classifiers did not distinguish between youths with CD/HCU versus CD/LCU (52% accuracy), although youths with CD/HCU and CD/LCU were reliably distinguished from TD youths (64% and 60%, respectively). In the subset of classifiers that performed well for youths with CD/HCU, fear and sadness were the most relevant emotions for distinguishing them from youths with CD/LCU and TD youths, respectively. We conclude that non-specific emotion recognition difficulties are common in CD/HCU, but are not reliable individual-level markers of CD/HCU versus CD/LCU. These findings highlight that a reduced ability to recognise facial expressions of distress should not be assumed to be a core feature of CD/HCU.

Background: At the group level, youths with conduct disorder (CD) show deficient emotion processing across various tasks compared to typically developing controls (TDC). But little is known about neuropsychological subgroups within the CD population, the clinical correlates of emotion processing deficits [for instance, with regard to the presence or absence of the DSM-5 Limited Prosocial Emotions (LPE) specifier], and associated risk factors.Methods: 542 children and adolescents with CD (317 girls) and 710 TDCs (479 girls), aged 9–18 years, were included from the FemNAT-CD multisite study. All participants completed three neuropsychological tasks assessing emotion recognition, emotion learning, and emotion regulation. We used a self-report measure of callous-unemotional traits to create a proxy for the LPE specifier.Results: Relative to TDCs, youths with CD as a group performed worse in all three emotion domains. But using clinically based cut-off scores, we found poor emotion recognition skills in only 23% of the participants with CD, followed by emotion regulation deficits in 18%, and emotion learning deficits in 13% of the CD group. Critically, the majority of youths with CD (~56%) did not demonstrate any meaningful neuropsychological deficit, and only a very small proportion showed pervasive deficits across all three domains (~1%). Further analyses indicate that established DSM-5 subtypes of CD are not tightly linked to neurocognitive deficits in one particular emotion domain over another (i.e., emotion recognition deficits in CD+LPE vs. emotion regulation deficits in CD–LPE).Conclusions: Findings from this large-scale data set suggest substantial neuropsychological diversity in emotion processing in the CD population and, consequently, only a subgroup of youths with CD are likely to benefit from additional behavioral interventions specifically targeting emotion processing mechanisms.

Background There is evidence that repetitive transcranial magnetic stimulation (rTMS) is effective for treating adult depression. However, it remains unclear whether rTMS is an effective treatment for adolescent depression. This systematic review examines the existing literature on the effectiveness and acceptability of rTMS in the treatment of adolescent depression. Methods After protocol registration (PROSPERO), we searched PubMed, Embase, PsycINFO, WoS and CENTRAL databases and the grey literature. We included studies that used rTMS in adolescents aged 12–25 years old who had a clinical diagnosis of depression. Study quality was assessed using the Newcastle-Ottawa Scale. Results Fourteen studies were identified, which included 8 open-trial studies (N = 142 participants) and six studies which performed further post-hoc/follow-up analyses on these open-trial datasets. All studies suffered from multiple biases but reported that rTMS treatment reduced depression scores in adolescents. A single study on theta burst stimulation also found a positive effect. No study to date includes a sham control. Reported side effects of rTMS included scalp pain, headache and dizziness. Limitations Study methodologies precluded a meta-analysis. Conclusions The current literature signals that rTMS could reduce adolescent depressive symptoms. However, sham controlled randomized trials are needed. These findings suggest that rTMS may be a promising treatment option for adolescents with depression.

Objective Conduct disorder (CD) is a serious neurodevelopmental disorder marked by notably higher prevalence rates for boys than girls. Converging evidence suggests that CD is associated with impairments in emotion recognition, learning, and regulation. However, it is not known whether there are sex differences in the relationship between CD and emotion dysfunction. Prior studies on emotion functioning in CD have so far been underpowered for investigating sex differences. Therefore, our primary aim was to characterize emotion processing skills in a large sample of girls and boys with CD compared to typically developing controls (TDCs) using a comprehensive neuropsychological test battery. Method We included 542 youths with CD (317 girls) and 710 TDCs (479 girls), 9 to 18 years of age, from a European multisite study (FemNAT-CD). Participants completed three experimental tasks assessing emotion recognition, learning, and regulation, respectively. Data were analyzed to test for effects of group and sex, and group-by-sex interactions, while controlling for potentially confounding factors. Results Relative to TDCs, youths with CD showed impaired emotion recognition (that was related to more physical and proactive aggression, and higher CU traits), emotional learning (specifically from punishment), and emotion regulation. Boys and girls with CD, however, displayed similar impairments in emotion processing. Conclusion This study provides compelling evidence for a relationship between CD and deficient neurocognitive functioning across three emotional domains that have previously been linked to CD etiology. However, there was no support for sex-specific profiles of emotion dysfunction, suggesting that current neurocognitive models of CD apply equally to both sexes.

Reduced responsiveness to emotions is hypothesized to contribute to the development of conduct disorder (CD) in children and adolescents. Accordingly, blunted psychophysiological responses to emotions have been observed in boys with CD, but this has never been tested in girls. Therefore, this study compared psychophysiological responses to sadness in girls and boys with and without CD, and different clinical phenotypes of CD: with versus without limited prosocial emotions (LPE), and with versus without comorbid internalizing disorders (INT). Nine-hundred and 27 girls (427 CD, 500 controls) and 519 boys (266 CD, 253 controls) aged 9-18 years participated. Psychophysiological responses were measured while participants watched two validated sad film clips, specifically: heart rate (HR), respiratory sinus arrhythmia (RSA; indexing parasympathetic activity), preejection period (PEP; indexing sympathetic activity). Girls and boys with CD showed larger HR responses to sadness than controls. This effect was rendered nonsignificant, however, after controlling for covariates. We observed aberrant RSA responses to sadness in CD compared with controls. Similarly, we found a significant positive association between RSA responsivity and antisocial behavior when assessed dimensionally. The effects were very small, though. Results were similar for boys and girls. We found no evidence for emotional underresponsiveness in CD in the largest psychophysiological study to date in this field. More research is needed to explore whether this is specific to sadness or generalizes to other emotions. Furthermore, we recommend that studies on emotion processing in CD assess different physiological measures to help disentangle CD-related effects on sympathetic and parasympathetic activity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

BackgroundPrevious studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared with typically developing controls.MethodsWe acquired diffusion-weighted magnetic resonance imaging data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum [retrosplenial cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed.ResultsThe CD group had lower FA and HMOA in the right RSC tract relative to controls. Importantly, these effects were moderated by sex – males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ.ConclusionsOur results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD.

Purpose: Autonomic nervous system (ANS) functioning has been widely studied in relation to antisocial behavior, such as Conduct Disorder (CD). However, research in females is scarce and findings are inconsistent. This study investigated baseline ANS activity in CD children and adolescents and tested for sex differences. Furthermore, subgroups of CD were investigated: +/‐ Limited Prosocial Emotions (LPE), +/‐ comorbid internalizing disorders (INT). Methods: Baseline ANS activity was measured by Heart Rate (HR), Heart Rate Variability (HRV; parasympathetic activity), Pre-Ejection Period (PEP; sympathetic activity), and Respiration Rate (RR). 659 females (296 CD, 363 controls) and 351 males (187 CD, 164 controls), aged 9–18 years participated. Results: Baseline HR, HRV and PEP did not differ between CD subjects and controls in both sexes. RR was higher in CD participants than controls amongst females, but not males. LPE was unrelated to ANS activity, whereas females with CD + INT presented lower HRV. Conclusions: These results suggest that baseline ANS activity is not a robust indicator for CD. However, deviant ANS activity – especially parasympathetic activity - was observed in CD females with internalizing comorbidity. The psychophysiological abnormalities observed in this subgroup are indicative of emotion regulation problems. Accordingly, this subgroup may require specific interventions.

Journal of the American Academy of Child and Adolescent Psychiatry : JAACAP 58(12), 1184-1196 (2019). doi:10.1016/j.jaac.2019.02.019, Published by Elsevier, Kidlington [u.a.]

Journal of criminal justice 65, 101536 (2019). doi:10.1016/j.jcrimjus.2018.01.004 special issue: "Practical implications of neuroscience in the field of criminal justice / Edited by Liza Cornet, Katy de Kogel, Florian Bootsman", Published by Pergamon Press, New York, NY [u.a.]

Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls (N = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability. General scientific summary This study suggests that callous-unemotional traits have a neuroanatomical correlate within typically developing boys, but not girls. Bilateral anterior insula volume explains up to 19% of the variance in callous-unemotional traits in boys., Highlights • Sex-specific correlations between callous-unemotional (CU) traits and insula volume. • CU-traits are positively linked to anterior insula in typically-developing boys. • Variations in insula volume explained 19% of the variance in CU-traits in boys. • Accounting for sex in neuroanatomical studies of individual differences is important.

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD.

Recent studies using repetitive transcranial magnetic stimulation (TMS) have demonstrated that disruptions of the articulatory motor cortex impair performance in demanding speech perception tasks. These findings have been interpreted as support for the idea that the motor cortex is critically involved in speech perception. However, the validity of this interpretation has been called into question, because it is unknown whether the TMS-induced disruptions in the motor cortex affect speech perception or rather response bias. In the present TMS study, we addressed this question by using signal detection theory to calculate sensitivity (i.e., d′) and response bias (i.e., criterion c). We used repetitive TMS to temporarily disrupt the lip or hand representation in the left motor cortex. Participants discriminated pairs of sounds from a “ba”–“da” continuum before TMS, immediately after TMS (i.e., during the period of motor disruption), and after a 30-min break. We found that the sensitivity for between-category pairs was reduced during the disruption of the lip representation. In contrast, disruption of the hand representation temporarily reduced response bias. This double dissociation indicates that the hand motor cortex contributes to response bias during demanding discrimination tasks, whereas the articulatory motor cortex contributes to perception of speech sounds.

Speech perception and comprehension are often challenged by the need to recognize speech sounds that are degraded or ambiguous. Here, we explore the cognitive and neural mechanisms involved in resolving ambiguity in the identity of speech sounds using syllables that contain ambiguous phonetic segments (e.g., intermediate sounds between /b/ and /g/ as in “blade” and “glade”). We used an audio-morphing procedure to create a large set of natural sounding minimal pairs that contain phonetically ambiguous onset or offset consonants (differing in place, manner, or voicing). These ambiguous segments occurred in different lexical contexts (i.e., in words or pseudowords, such as blade–glade or blem–glem) and in different phonological environments (i.e., with neighboring syllables that differed in lexical status, such as blouse–glouse). These stimuli allowed us to explore the impact of phonetic ambiguity on the speed and accuracy of lexical decision responses (Experiment 1), semantic categorization responses (Experiment 2), and the magnitude of BOLD fMRI responses during attentive comprehension (Experiment 3). For both behavioral and neural measures, observed effects of phonetic ambiguity were influenced by lexical context leading to slower responses and increased activity in the left inferior frontal gyrus for high-ambiguity syllables that distinguish pairs of words, but not for equivalent pseudowords. These findings suggest lexical involvement in the resolution of phonetic ambiguity. Implications for speech perception and the role of inferior frontal regions are discussed.

Journal of the American Academy of Child and Adolescent Psychiatry 56(8), 703-712 (2017). doi:10.1016/j.jaac.2017.05.015, Published by Elsevier, Kidlington [u.a.]

How do we achieve unitary perception of an object when it touches two parts of the sensory epithelium that are not contiguous? We investigated this problem with a simple psychophysical task, which we then used in an fMRI experiment. Two wooden rods were moved over two digits positioned to be spatially adjacent. The digits were either from one foot (or hand) or one digit was from either foot (or hand). When the rods were moving in phase, one object was reliably perceived. By contrast, when the rods were moving out of phase, two objects were reliably perceived. fMRI revealed four cortical areas where activity was higher when the moving rods were perceived as one object relative to when they were perceived as two separate objects. Areas in the right inferior parietal lobule, the left inferior temporal sulcus and the left middle frontal gyrus were activated for this contrast regardless of the anatomical configuration of the stimulated sensory epithelia. By contrast, the left intraparietal sulcus was activated specifically when integration across the midline was required, irrespective of whether the stimulation was applied to the hands or feet. These results reveal a network of brain areas involved in generating a unified percept of the presence of an object that comes into contact with different parts of the body surface.

Decades of research have shown that youths with disruptive behavior disorders (DBD) are a heterogeneous population. Over the past 20 years, researchers have distinguished youths with DBD as those displaying high (DBD/HCU) versus low (DBD/LCU) callous-unemotional (CU) traits. These traits include flat affect and reduced empathy and remorse, and are associated with more severe, varied, and persistent patterns of antisocial behavior and aggression. Conduct problems in youths with HCU and LCU are thought to reflect distinct causal vulnerabilities, with antisocial behavior in youths with DBD/HCU reflecting a predominantly genetic etiology, while antisocial behavior in youths with DBD/LCU is associated primarily with environmental influences. Here we selectively review recent functional (fMRI) and structural (sMRI) magnetic resonance imaging research on DBD, focusing particularly on the role of CU traits. First, fMRI studies examining the neural correlates of affective stimuli, emotional face processing, empathy, theory of mind, morality, and decision-making in DBD are discussed. This is followed by a review of the studies investigating brain structure and structural connectivity in DBD. Next, we highlight the need to further investigate females and the role of sex differences in this population. We conclude the review by identifying potential clinical implications of this research.

Perceiving speech engages parts of the motor system involved in speech production. The role of the motor cortex in speech perception has been demonstrated using low-frequency repetitive transcranial magnetic stimulation (rTMS) to suppress motor excitability in the lip representation and disrupt discrimination of lip-articulated speech sounds (Möttönen & Watkins, 2009). Another form of rTMS, continuous theta-burst stimulation (cTBS), can produce longer-lasting disruptive effects following a brief train of stimulation. We investigated the effects of cTBS on motor excitability and discrimination of speech and non-speech sounds. cTBS was applied for 40 seconds over either the hand or the lip representation of motor cortex. Motor-evoked potentials recorded from the lip and hand muscles in response to single pulses of TMS revealed no measurable change in motor excitability due to cTBS. This failure to replicate previous findings may reflect the unreliability of measurements of motor excitability related to inter-individual variability. We also measured the effects of cTBS on a listener’s ability to discriminate:(1) lip-articulated speech sounds from sounds not articulated by the lips (‘ba’vs.‘da’); (2) two speech sounds not articulated by the lips (‘ga’vs.‘da’); and (3) non-speech sounds produced by the hands (‘claps’vs.‘clicks’). Discrimination of lip-articulated speech sounds was impaired between 20 and 35 minutes after cTBS over the lip motor representation. Specifically, discrimination of across-category ba–da sounds presented with an 800-ms inter-stimulus interval was reduced to chance level performance. This effect was absent for speech sounds that do not require the lips for articulation and non-speech sounds. Stimulation over the hand motor representation did not affect discrimination of speech or non-speech sounds. These findings show that stimulation of the lip motor representation disrupts discrimination of speech sounds in an articulatory feature-specific way.

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. Researchers have used single-pulse and repetitive TMS to stimulate the lip representation in the motor cortex. The excitability of the lip motor representation can be investigated by applying single TMS pulses over this cortical area and recording TMS-induced motor evoked potentials (MEPs) via electrodes attached to the lip muscles (electromyography; EMG). Larger MEPs reflect increased cortical excitability. Studies have shown that excitability increases during listening to speech as well as during viewing speech-related movements. TMS can be used also to disrupt the lip motor representation. A 15-min train of low-frequency sub-threshold repetitive stimulation has been shown to suppress motor excitability for a further 15-20 min. This TMS-induced disruption of the motor lip representation impairs subsequent performance in demanding speech perception tasks and modulates auditory-cortex responses to speech sounds. These findings are consistent with the suggestion that the motor cortex contributes to speech perception. This article describes how to localize the lip representation in the motor cortex and how to define the appropriate stimulation intensity for carrying out both single-pulse and repetitive TMS experiments.

A large number of structural neuroimaging studies have used voxel-based morphometry (VBM) to identify gray matter abnormalities in youths with conduct problems (CP), but the findings have been disparate and few have been replicated.To conduct a meta-analysis of published whole-brain structural neuroimaging studies on youths with CP that used VBM methods to facilitate replication and aid further analyses by researchers.The PubMed, ScienceDirect, Scopus, Google Scholar, and Web of Science databases were searched for VBM studies published from January 1, 2007, through March 31, 2015. Manual searches were conducted using title and citation information. Authors were contacted for additional data.A literature search identified 28 studies. Studies were excluded if they (1) failed to use VBM, (2) failed to report a voxelwise comparison between youths with CP and typically developing (TD) youths, (3) used different significance or extent thresholds throughout the brain, (4) included duplicated datasets, and (5) did not provide peak coordinates or parametric maps after contact with the authors. Thirteen studies were deemed eligible for inclusion (394 youths with CP and 350 TD youths).Anisotropic effect-size signed differential mapping (SDM) was used for voxel-based meta-analyses. Statistical parametric maps comparing gray matter differences between youths with CP and TD youths were available for 11 of the studies, with peak coordinates available for the remaining studies.Regional gray matter volume (GMV) differences in youths with CP compared with TD youths.Youths with CP had decreased GMV in the left amygdala (SDM estimate = -0.218; P .001) (extending into anterior insula), right insula (SDM estimate = -0.174; P .001) (extending ventrolaterally into the prefrontal cortex and inferiorly into the superior temporal gyrus), left medial superior frontal gyrus (SDM estimate = -0.163; P = .001) (extending into the right anterior cingulate cortex), and left fusiform gyrus (SDM estimate = -0.146; P = .003). Subgroup meta-analysis assessing age-at-onset effects identified reduced GMV in the left anterior insula (SDM estimate = -0.232; P .001) (extending into amygdala). Meta-regression analyses revealed that greater scores on measures of callous-unemotional traits were associated with a lower reduction in GMV in the left putamen (SDM estimate = -0.911; P .001). The proportion of male and female youths in the sample was associated with decreased GMV in the left amygdala (SDM estimate = -0.31; P .001) and increased GMV in the right inferior temporal cortex (SDM estimate = 0.755; P .001). While there was no association with comorbid attention-deficit/hyperactivity disorder or IQ, age range was associated with gray matter differences in the left amygdala.We identified gray matter reductions within the insula, amygdala, frontal and temporal regions in youths with CP as well as inconsistencies in sample characteristics across studies that should be addressed in future research.

Functional neuroimaging research has shown that certain classes of visual stimulus selectively activate focal regions of visual cortex. Specifically, cortical areas that generally and selectively respond to faces (Kanwisher, N., McDermott, J., & Chun, M. M. (1997). The fusiform face area: a module in human extrastriate cortex specialized for face perception. Journal of Neuroscience, 17(11), 4302-4311; Puce, A., Allison, T., Asgari, M., Gore, J. C., & McCarthy, G. (1996). Differential sensitivity of human visual cortex to faces, letterstrings, and textures: a functional magnetic resonance imaging study. Journal of Neuroscience, 16(16), 5205-5215.) and to the human body (Downing, P. E., Jiang, Y., Shuman, M., & Kanwisher, N. (2001). A cortical area selective for visual processing of the human body. Science, 293(5539), 2470-2473.) have recently been described using fMRI. A parallel body of research has focused on the ability of faces to "capture" the focus of attention, compared to other kinds of objects (Lavie, N., Ro, T., & Russell, C. (2003). The role of perceptual load in processing distractor faces. Psychological Science, 14(5), 510-515; Ro, T., Russell, C., & Lavie, N. (2001). Changing faces: a detection advantage in the flicker paradigm. Psychological Science, 12(1), 94-99; Vuilleumier, P. (2000). Faces call for attention: evidence from patients with visual extinction. Neuropsychologia, 38(5), 693-700.). The present study uses Mack and Rock's "inattentional blindness" paradigm to investigate whether unexpected, task-irrelevant human body stimuli capture awareness when attention is occupied by a primary task (Mack, A., & Rock, I. (1998). Inattentional blindness. London: MIT Press). Silhouettes and stick figures of human bodies, and silhouettes of hands, were compared to control stimuli including object silhouettes, object stick figures, and scrambled silhouettes of bodies, body parts, and objects. Participants were significantly better able to detect a human figure relative to the control stimuli. These results suggest that the human body, like the face, may be prioritized for attentional selection. More generally, they are consistent with the proposal that the visual system assigns attentional priority to types of stimuli that are also represented in strongly selective cortical regions.

Functional imaging and TMS studies show that motor and premotor cortex responds to heard speech though the functional significance of this response is unclear. Three recent fMRI studies, showing modulation of motor responses to heard speech in the absence of overt spoken or manual responses, may shed light on how regions typically associated with speech production contribute to perception. (1) Motor activity remains robust during light anaesthetic sedation, but is obliterated for deeply sedated participants who are no longer aware of speech. (2) Motor cortex responds more to distorted yet intelligible noise‐vocoded words than to clear speech or unintelligible noise. This neural correlate of listening effort is also observed for "clear‐then‐vocoded" presentations that enhance perceptual adaptation compared to a matched "vocoded‐then‐clear" condition that doesn't enhance adaptation. (3) During paired priming of audio‐morphed syllables we see a greater response to acoustic changes that cross phonological category boundaries compared to acoustically‐equivalent within‐category changes. Additional responses to between‐category pairs extend to motor regions, suggesting that neural correlates of categorical perception include regions involved in speech production. These findings illustrate how perceptual awareness, adaptation and categorisation of speech all engage motor regions. Implications for neurobiological accounts of speech perception will be discussed.

What effects do within‐ and between‐category variations have on the perception of speech? Using audio‐morphing and the "Straight" channel vocoder (Kawahara, 2004), we produced 320 high‐quality phonetic continua varying in place, manner and voicing including word/word (blade/glade), word/pseudo (blouse/glouse), pseudo/word (bown/gown) and pseudo/pseudo (blem/glem) pairs. A 2AFC task confirmed the category boundary shift for word/pseudo and pseudo/word pairs (Ganong, 1980), equivalent for onset (bench/gench) and offset (flad/flag) pairs. This suggests that lexical influences on categorical perception are not produced on‐line but rather occur post‐perceptually, consistent with top‐down effects. Sensitivity to within‐ and between‐category phonological variation was investigated using sparse fMRI in a paired auditory repetition priming paradigm. Minimal pairs (48 across the 4 stimulus groups) were presented to participants who listened in the context of a semantic monitoring task. Between‐category pairs with a phonological change produced a greater neural response compared to within‐category same pairs with the same magnitude of acoustic difference. This response to phonologically different pairs provides a neural correlate of categorical perception in left middle temporal, inferior frontal and pre‐central regions. These responses in inferior frontal regions may contribute towards top‐down influences on categorical perception of speech (cf Ganong Effect).

The present invention relates generally to a stringed musical instrument with a modified bridge and acoustic damper. In a preferred embodiment of the invention, the modified stringed instrument is a guitar. The guitar has a face and an interior compartment. The guitar comprises a bridge, two acoustic dampers, and a pivot rod. The bridge is attached to the face of the guitar and comprises a mounting plate and a riser. The riser is attached to the mounting plate by at least one sound post and comprises a width and at least one pair of opposing angled string recesses across the width of the riser. The string recesses are rounded. The bridge has a plurality of string pegs attached to the mounting plate. Each string peg corresponds to a string recess and is attached to the mounting plate at an angle offset from a line extended from its corresponding string recess. The acoustic dampers comprise a first acoustic damping side attached to a second acoustic reflective side. The acoustic dampers are pivotally mounted within the interior compartment of the guitar. The acoustic dampers have a first operative position for damping sound and a second operative position for reflecting sound. The pivot rod is attached to the acoustic dampers such that the pivot rod can manipulate the acoustic dampers to the first and second operative positions. The pivot rod is accessible from an exterior location on the guitar.