Yidian Gao

Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder.

Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum.

Dysfunctional feedback processing in adolescent males with conduct disorder.

Abnormalities in neural feedback-processing systems may play a role in the development of dysfunctional behavior in individuals diagnosed with conduct disorder (CD). The present study investigated the relation between CD adolescents and feedback processing by measuring event-related potentials (ERPs) in a single outcome gambling task, which included reward valence (loss and gain) and reward magnitude (10 and 50cents) as outcomes. N2 and P3 components have been established as effective indicators in studies of behavioral disinhibition, reward processing, and decision-making. Eighteen adolescent males (age: 13-17years) diagnosed with CD and 19 healthy age-matched male controls were recruited. Compared to healthy controls, CD individuals exhibited reduced N2 amplitudes in response to loss condition. There was also a significant decreased P3 amplitude in all conditions. The amplitudes of P3 were negatively correlated with impulsivity scores across both groups, and the amplitudes of N2 were positively correlated with impulsivity scores across both groups. Our findings suggest that adolescents with CD may be impaired in neural sensitivity feedback and the processing of environmental cues compared to healthy controls. Moreover, N2 and P3 may be reliable indices to detect different sensitivity in reward and punishment feedback processing.

A Functional Polymorphism of the MAOA Gene Modulates Spontaneous Brain Activity in Pons

Objective. To investigate the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents. Methods. Thirty-one healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H) completed the 11-item Barratt Impulsiveness Scale (BIS-11) questionnaire and were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software. ALFF data were related to BIS scores and compared between genotype groups. Results. Compared with the MAOA-H group, the MAOA-L group showed significantly lower ALFFs in the pons. There was a significant correlation between the BIS scores and the ALFF values in the pons for MAOA-L group, but not for the MAOA-H group. Further regression analysis showed a significant genotype by ALFF values interaction effect on BIS scores. Conclusions. Lower spontaneous brain activity in the pons of the MAOA-L male adolescents may provide a neural mechanism by which boys with the MAOA-L genotype confers risk for impulsivity and aggression.

Distinguishing Adolescents With Conduct Disorder From Typically Developing Youngsters Based on Pattern Classification of Brain Structural MRI

Background: Conduct disorder (CD) is a mental disorder diagnosed in childhood or adolescence that presents antisocial behaviors, and is associated with structural alterations in brain. However, whether these structural alterations can distinguish CD from healthy controls (HCs) remains unknown. Here, we quantified these structural differences and explored the classification ability of these quantitative features based on machine learning (ML). Materials and Methods: High-resolution 3D structural magnetic resonance imaging (sMRI) was acquired from 60 CD subjects and 60 age-matched HCs. Voxel-based morphometry (VBM) was used to assess the regional gray matter (GM) volume difference. The significantly different regional GM volumes were then extracted as features, and input into three ML classifiers: logistic regression, random forest and support vector machine (SVM). We trained and tested these ML models for classifying CD from HCs by using fivefold cross-validation (CV). Results: Eight brain regions with abnormal GM volumes were detected, which mainly distributed in the frontal lobe, parietal lobe, anterior cingulate, cerebellum posterior lobe, lingual gyrus, and insula areas. We found that these ML models achieved comparable classification performance, with accuracy of 77.9 ∼ 80.4%, specificity of 73.3 ∼ 80.4%, sensitivity of 75.4 ∼ 87.5%, and area under the receiver operating characteristic curve (AUC) of 0.76 ∼ 0.80. Conclusion: Based on sMRI and ML, the regional GM volumes may be used as potential imaging biomarkers for stable and accurate classification of CD.

State-Independent and Dependent Neural Responses to Psychosocial Stress in Current and Remitted Depression

OBJECTIVE Stress is a strong risk factor for major depressive disorder, while sensitization to stress in remitted individuals plays a key role in depression recurrence. The present study explored the state-independent (trait) and dependent (state) neural responses to psychosocial stress in major depressive disorder. METHOD Thirty-six patients with medication-naive first-episode current depression, 33 patients with remitted depression, and 36 demographically matched healthy control participants were administered the Montreal Imaging Stress Task during functional MRI. One-way analyses of variance were used to assess differences in stress responses in the three groups. RESULTS Both currently depressed and remitted patients exhibited higher stress levels and cortisol responses than control subjects. Compared with control subjects, both depressed and remitted patients exhibited reduced activation in the ventromedial prefrontal cortex and increased activation in the precuneus. The stress-induced ventromedial prefrontal cortex activation changes negatively correlated with cortisol increases in all three groups. Additional increased activations were found in the dorsolateral prefrontal cortex and bilateral striatum in remitted patients compared with control subjects, and activation in these regions correlated inversely with depressive symptoms in the remitted group. CONCLUSIONS These findings provide novel evidence regarding the trait and state markers of depression on neural responses to psychosocial stress. Regional activation changes in the ventromedial prefrontal cortex and precuneus may reflect the trait markers of depression. Hyperactivation in the dorsolateral prefrontal cortex and striatum may represent a state-dependent compensatory mechanism during depression remission.

Disrupted Topological Patterns of Large-Scale Network in Conduct Disorder.

Regional abnormalities in brain structure and function, as well as disrupted connectivity, have been found repeatedly in adolescents with conduct disorder (CD). Yet, the large-scale brain topology associated with CD is not well characterized, and little is known about the systematic neural mechanisms of CD. We employed graphic theory to investigate systematically the structural connectivity derived from cortical thickness correlation in a group of patients with CD (N = 43) and healthy controls (HCs, N = 73). Nonparametric permutation tests were applied for between-group comparisons of graphical metrics. Compared with HCs, network measures including global/local efficiency and modularity all pointed to hypo-functioning in CD, despite of preserved small-world organization in both groups. The hubs distribution is only partially overlapped with each other. These results indicate that CD is accompanied by both impaired integration and segregation patterns of brain networks, and the distribution of highly connected neural network ‘hubs’ is also distinct between groups. Such misconfiguration extends our understanding regarding how structural neural network disruptions may underlie behavioral disturbances in adolescents with CD, and potentially, implicates an aberrant cytoarchitectonic profiles in the brain of CD patients.

Electrophysiological responses of feedback processing are modulated by MAOA genotype in healthy male adolescents.

A functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene is closely related to aggression. Although previous studies suggested that impaired ability of feedback processing might be associated with aggressive behaviour, studies concerning the MAOA gene-related aggression rarely focused on the link between MAOA gene and feedback processing. We therefore sought to investigate the effect of MAOA genotype on electrophysiological responses of feedback processing in 72 healthy male adolescents during a simple monetary gambling task. Feedback processing was investigated by measuring the feedback-related negativity (FRN) and the P300 as electrophysiological markers. We observed a decreased electrophysiological response of the loss-gain difference waves from 250 to 350 ms (dFRN) in individuals with the lower activity alleles (MAOA-L) during the task, an effect that was driven primarily by the considerably altered response to monetary gains. The reduced dFRN in MAOA-L group might indicate poor ability to learn from feedback, which is followed by adjusting future behaviour. And MAOA-L carriers exhibited lower P300 compared with subjects with higher activity alleles (MAOA-H), which suggested fewer attentional resources were allocated to feedback processing. In addition, MAOA-L carriers demonstrated higher aggression and the aggression were inversely correlated with dFRN across two groups; further analyses suggested that dFRN mediated the MAOA genotype-aggression relationship. Consequently, we concluded that it might be the altered feedback processing that makes MAOA-L carriers more vulnerable to aggressive behaviour.

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic–basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

Temporoparietal Junction Hypoactivity during Pain-Related Empathy Processing in Adolescents with Conduct Disorder

Background: Lack of empathy has been proposed to account for the characteristic behavioral problems exhibited by adolescents with conduct disorder (CD). Hence, the aim of this study was to determine whether adolescents with CD exhibit atypical affective and cognitive neural empathic responses during pain-related empathy processing. Methods: A total of 30 adolescents with a CD diagnosis and 36 without CD symptoms were recruited from out-patient clinics and local middle schools in the same region, respectively. All 66 participants were subjected to functional magnetic resonance imaging (fMRI) while viewing video clips depicting a face with a neutral expression receiving non-painful stimulation (Q-tip touch) or a face with a painful expression receiving painful stimulation (needle penetration) applied to the left or right cheek. Results: The regions associated with affective and cognitive empathy were activated in the HC group during pain-related empathy processing. Compared to HCs, adolescents with CD showed significantly reduced activation in the bilateral temporoparietal junction (TPJ). Conclusions: Adolescents with CD exhibited dampened hemodynamic responses during pain-related empathy processing in the bilateral TPJ, a region associated with cognitive empathy. These findings are consistent with the hypothesis that adolescents with CD may have a cognitive empathy deficiency.

State-independent alterations of intrinsic brain network in current and remitted depression

Background: It has been proposed that state‐independent, or trait, neurobiological alterations across illness phases may contribute to the high recurrence of major depressive disorder (MDD). Although intrinsic brain network abnormalities have been implicated consistently in MDD neuropathology, MDD state‐independent and ‐dependent resting‐state network alterations have not been clearly studied. Methods: Resting‐state functional magnetic resonance imaging (fMRI) data were collected from 57 medication‐naive first‐episode current MDD patients, 35 remitted MDD patients, and 66 healthy controls (HCs). Independent component analysis (ICA) was used to extract subnetworks of the default mode network (DMN), central executive network (CEN), and salience network (SN). Results: Relative to HCs, the current MDD and remitted MDD groups had decreased intra‐intrinsic functional connectivity (iFC) in the dorsal lateral prefrontal cortex (dlPFC) of the left CEN, increased inter‐FC between the SN and right CEN (rCEN), and decreased inter‐FC between the anterior DMN (aDMN) and rCEN. The altered intra‐iFC in the left CEN were correlated negatively with the depressive level in the remitted MDD. Conclusions: Hypoactivity of the dlPFC in the left CEN, increased inter‐FC between the SN and rCEN, and decreased inter‐FC between the aDMN and rCEN may reflect state‐independent biomarkers of MDD. HIGHLIGHTSTo identify state‐independent and state‐dependent network biomarkers of MDD employing fMRI with ICA.Intra‐iFC in the dlPFC of the CEN emerged as putative state‐independent biomarkers of MDD.Atypical inter‐FC between the rCEN and SN as well as the aDMN emerged as putative state‐independent biomarkers of MDD.