Disrupted cognitive and affective empathy network interactions in autistic children viewing social animation.

Empathy can be divided into two core components, cognitive empathy (CE) and affective empathy (AE), mediated by distinct neural networks. Deficient empathy is a central feature of autism spectrum conditions (ASCs), but it is unclear if this deficit results from disruption solely within empathy networks or from disrupted functional integration between CE and AE networks. To address this issue, we measured functional connectivity (FC) patterns both within and between empathy networks in autistic children (4-8 years, n = 31) and matched typically developing (TD) children (n = 26) using near-infrared spectroscopy during the presentation of an animated story evoking CE and AE. Empathy and social communication ability were also assessed using the Empathy Quotient/Systemizing Quotient (EQ/SQ) and Social Responsiveness Scale, respectively. The results showed that the FC in the AE network of autistic children did not differ from the TD group across conditions; however, the ASC group showed weaker FC in the CE network under the CE condition and weaker FC between networks when processing AE information, the latter of which was negatively correlated with EQ scores in ASC. The empathy defect in ASC may involve abnormal integration of CE and AE network activities under AE conditions.

Local structural and functional MRI markers of compulsive behaviors and obsessive-compulsive disorder diagnosis within striatum-based circuits.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a classic disorder on the compulsivity spectrum, with diverse comorbidities. In the current study, we sought to understand OCD from a dimensional perspective by identifying multimodal neuroimaging patterns correlated with multiple phenotypic characteristics within the striatum-based circuits known to be affected by OCD. METHODS: Neuroimaging measurements of local functional and structural features and clinical information were collected from 110 subjects, including 51 patients with OCD and 59 healthy control subjects. Linked independent component analysis (LICA) and correlation analysis were applied to identify associations between local neuroimaging patterns across modalities (including gray matter volume, white matter integrity, and spontaneous functional activity) and clinical factors. RESULTS: LICA identified eight multimodal neuroimaging patterns related to phenotypic variations, including three related to symptoms and diagnosis. One imaging pattern (IC9) that included both the amplitude of low-frequency fluctuation measure of spontaneous functional activity and white matter integrity measures correlated negatively with OCD diagnosis and diagnostic scales. Two imaging patterns (IC10 and IC27) correlated with compulsion symptoms: IC10 included primarily anatomical measures and IC27 included primarily functional measures. In addition, we identified imaging patterns associated with age, gender, and emotional expression across subjects. CONCLUSIONS: We established that data fusion techniques can identify local multimodal neuroimaging patterns associated with OCD phenotypes. The results inform our understanding of the neurobiological underpinnings of compulsive behaviors and OCD diagnosis.

A network perspective on cognitive function and obsessive-compulsive related symptoms.

BACKGROUND: The relationship between cognitive function and psychopathological symptoms has been an important research field in recent years. Previous studies have typically applied case-control designs to explore differences in certain cognitive variables. Multivariate analyses are needed to deepen our understanding of the intercorrelations among cognitive and symptom phenotypes in OCD. METHODS: The present study used network analysis to construct networks of cognitive variables and OCD-related symptoms in patients with OCD and healthy controls (N = 226), aiming to explore the relationship among numerous cognitive function variables and OCD-related symptoms in detail and compare the network features between the two groups. RESULTS: In the network of cognitive function and OCD-related symptoms, nodes representing IQ, letter/number span test, accuracy of task switching test and obsession were much important in the network in terms of their larger strengths and edges. By constructing the networks of these two groups respectively, there was a strong similarity except that the symptom's network in healthy group had a higher degree of overall connectivity. LIMITATIONS: Due to the small sample size, the stability of the network cannot be guaranteed. Due to the cross-sectional nature of the data, we were unable to determine how the cognitive-symptom network would change with disease deterioration or treatment. CONCLUSIONS: The present study highlights the important role of variables such as obsession and IQ from a network perspective. These results deepen our understanding of the multivariate relationship between cognitive dysfunction and OCD symptoms, and may promote the prediction and diagnosis of OCD.

Connectome-based predictive modeling of compulsion in obsessive-compulsive disorder.

Compulsion is one of core symptoms of obsessive-compulsive disorder (OCD). Although many studies have investigated the neural mechanism of compulsion, no study has used brain-based measures to predict compulsion. Here, we used connectome-based predictive modeling (CPM) to identify networks that could predict the levels of compulsion based on whole-brain functional connectivity in 57 OCD patients. We then applied a computational lesion version of CPM to examine the importance of specific brain areas. We also compared the predictive network strength in OCD with unaffected first-degree relatives (UFDR) of patients and healthy controls. CPM successfully predicted individual level of compulsion and identified networks positively (primarily subcortical areas of the striatum and limbic regions of the hippocampus) and negatively (primarily frontoparietal regions) correlated with compulsion. The prediction power of the negative model significantly decreased when simulating lesions to the prefrontal cortex and cerebellum, supporting the importance of these regions for compulsion prediction. We found a similar pattern of network strength in the negative predictive network for OCD patients and their UFDR, demonstrating the potential of CPM to identify vulnerability markers for psychopathology.

Imbalance between the caudate and putamen connectivity in obsessive-compulsive disorder.

BACKGROUND: Compulsive behaviors in obsessive-compulsive disorder (OCD) have been suggested to result from an imbalance in cortico-striatal connectivity. However, the nature of this impairment, the relative involvement of different striatal areas, their imbalance in genetically related but unimpaired individuals, and their relationship with cognitive dysfunction in OCD patients, remain unknown. METHODS: In the current study, striatal (i.e., caudate and putamen) whole-brain connectivity was computed in a sample of OCD patients (OCD, n = 62), unaffected first-degree relatives (UFDR, n = 53) and healthy controls (HC, n = 73) by ROI-based resting-state functional magnetic resonance imaging (rs-fMRI). A behavioral task switch paradigm outside of the scanner was also performed to measure cognitive flexibility in OCD patients. RESULTS: There were significantly increased strengths (Z-transformed Pearson correlation coefficient) in caudate connectivity in OCD patients. A significant correlation between the two types of connectivity strengths in the relevant regions was observed only in the OCD patient group. Furthermore, the caudate connectivity of patients was negatively associated with their task-switch performance. CONCLUSIONS: The imbalance between the caudate and putamen connectivity, arising from the abnormal increase of caudate activity, may serve as a clinical characteristic for obsessive-compulsive disorder.

Dysfunction of goal-directed control in patients with depression and nonsuicidal self-injury.

BACKGROUND: Non-suicidal self-injury (NSSI) is a common problem associated with dangerous outcomes. Dysfunction of goal-directed behavioral control may contribute to NSSI. To test this, we used a novel experimental paradigm (Pavlovian-to-Instrumental Transfer, PIT) to test whether patients with NSSI utilize Pavlovian conditioned stimuli (CSs) during goal-directed control of ongoing behavior. METHODS: Thirty-five depressed patients with NSSI (D-NSSI) and thirty-four healthy controls performed a PIT task. We measured the influence of positive and negative background CSs on instrumental responses for rewards. RESULTS: The results showed that D-NSSI performed significantly lower PIT than controls, and PIT measures were negatively correlated with NSSI frequency. Furthermore, in a subset of patients exhibiting high levels of compulsivity, PIT positively moderated the relationship between compulsivity and NSSI frequency. CONCLUSIONS: These results indicate that D-NSSI patients have difficulties in using different CSs to control ongoing behavior in a goal-directed manner, and the dysfunction of goal-directed control may contribute to NSSI.

Imbalance in functional and structural connectivity underlying goal-directed and habitual learning systems in obsessive-compulsive disorder.

An imbalance between the goal-directed and habitual learning systems has been proposed to underlie compulsivity in obsessive-compulsive disorder (OCD). In addition, the overall balance between these systems may be influenced by stress hormones. We examined the multimodal networks underlying these dual learning systems. Both functional and structural measures indicated reduced connectivity within the goal-directed subnetwork (FC: P = 0.042; SC-FN: P = 0.014) and reduced connectivity between the goal-directed and habitual subnetworks (FC: P = 0.014; SC-FA: P = 0.052), but no differences within the habitual subnetwork in patients with OCD compared with controls. Path modeling indicated that anatomical connectivity in the goal-directed subnetwork influenced compulsive symptoms (R2 = 0.41), whereas functional connectivity within the habit subnetwork and between goal-directed and habitual subnetworks influenced obsessive symptoms (R2 = 0.63). In addition, the relationship between anatomical connectivity in the goal-directed subnetwork and compulsion was moderated by the stress hormone ACTH (adrenocorticotropic hormone), such that at low levels of ACTH greater connectivity resulted in lower compulsion, but at high levels of ACTH this relationship was reversed. These results provide new insights into the neural correlates of the imbalance between dual learning systems, and their relationship with symptom dimensions in patients with OCD. It may further support the reconceptualization of OCD as "compulsive-obsessive disorder," with a greater focus on the transdiagnostic dimension of compulsivity.

Aberrant rich club organization in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

Recent studies suggested that the rich club organization promoting global brain communication and integration of information, may be abnormally increased in obsessive-compulsive disorder (OCD). However, the structural and functional basis of this organization is still not very clear. Given the heritability of OCD, as suggested by previous family-based studies, we hypothesize that aberrant rich club organization may be a trait marker for OCD. In the present study, 32 patients with OCD, 30 unaffected first-degree relatives (FDR) and 32 healthy controls (HC) underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). We examined the structural rich club organization and its interrelationship with functional coupling. Our results showed that rich club and peripheral connection strength in patients with OCD was lower than in HC, while it was intermediate in FDR. Finally, the coupling between structural and functional connections of the rich club, was decreased in FDR but not in OCD relative to HC, which suggests a buffering mechanism of brain functions in FDR. Overall, our findings suggest that alteration of the rich club organization may reflect a vulnerability biomarker for OCD, possibly buffered by structural and functional coupling of the rich club.

White Matter Alterations of the Goal-Directed System in Patients With Obsessive-Compulsive Disorder and Their Unaffected First-Degree Relatives.

BACKGROUND: It has been postulated that the neurobiological mechanism responsible for the onset of symptoms of obsessive-compulsive disorder (OCD), especially compulsive behavior, is related to alterations of the goal-directed and habitual learning systems. However, little is known about whether changes in these learning systems co-occur with changes in the white matter structure of patients with OCD and their unaffected first-degree relatives (UFDRs). METHODS: Diffusion tensor imaging data were acquired from 32 patients with OCD (21 male), 32 UFDRs (16 male), and 32 healthy control subjects (16 male). White matter tracts in the goal-directed and habitual networks were reconstructed with seed-based probabilistic tractography. Partial least squares path modeling was used to measure the covariation between white matter connectivity, psychiatric symptoms, and cognitive flexibility. RESULTS: Patients with OCD showed reduced connectivity in the fiber tracts within the goal-directed but not within the habitual network compared with healthy control subjects. Using partial least squares path modeling, patients' symptoms were negatively associated with connectivity within the goal-directed but not within the habitual network. Cognitive flexibility was correlated negatively with caudate-dorsolateral prefrontal cortex tracts in patients with OCD. UFDRs also exhibited reduced white matter connectivity in the goal-directed network. CONCLUSIONS: These findings suggest that the balance of learning systems in OCD may be disrupted, mainly impairing white matter in the goal-directed network. Alterations of the goal-directed network could explain overt symptoms and impaired cognitive flexibility in patients with OCD. Similar alterations in the goal-directed network are present in UFDRs. The impaired goal-directed system may be an endophenotype of OCD.

Abnormal Anhedonia as a Potential Endophenotype in Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is often accompanied by cognitive, particularly executive function, impairments. Recently, anhedonia has emerged as an apparently important symptom of OCD reflecting altered emotion regulation. These two aspects are often comorbid in OCD. However, little is known about whether anhedonia may be a trait marker for OCD. METHODS: To verify the role of executive function and evaluate the role of anhedonia in OCD and its relationship with OCD symptoms, we recruited 60 OCD patients, 30 unaffected first-degree relatives (FDRs), and 60 healthy controls (HCs). Participants completed psychometric testing to assess depression, anxiety, and anhedonia symptoms, as well as two cognitive tests to assess executive function, namely the Wisconsin Card Sorting Test (WCST) and the Stroop Color-Word Test (SCWT). RESULTS: Compared to HCs, OCD patients and FDRs had significantly lower anticipatory and consummatory pleasure scores. The severity of anticipatory anhedonia correlated positively with obsessive-compulsive symptoms (r = 0.253, p = 0.009), even after controlling for depression and anxiety symptoms. Compared to HCs, OCD patients and FDRs made more errors and achieved fewer categories in the WCST. For all three SWCT components, OCD patients and FDRs took more time to name colors than HCs, but the three groups had similar numbers of errors. CONCLUSION: This family-based study showed dampened pleasure together with cognitive dysfunction in OCD patients. The similar consummatory pleasure findings between OCD and FDR groups suggest anhedonia may be considered as a candidate OCD endophenotype.

Modeling essential connections in obsessive-compulsive disorder patients using functional MRI.

OBJECT: Obsessive-compulsive disorder (OCD) is a mental disease in which people experience uncontrollable and repetitive thoughts or behaviors. Clinical diagnosis of OCD is achieved by using neuropsychological assessment metrics, which are often subjectively affected by psychologists and patients. In this study, we propose a classification model for OCD diagnosis using functional MR images. METHODS: Using functional connectivity (FC) matrices calculated from brain region of interest (ROI) pairs, a novel Riemann Kernel principal component analysis (PCA) model is employed for feature extraction, which preserves the topological information in the FC matrices. Hierarchical features are then fed into an ensemble classifier based on the XGBoost algorithm. Finally, decisive features extracted during classification are used to investigate the brain FC variations between patients with OCD and healthy controls. RESULTS: The proposed algorithm yielded a classification accuracy of 91.8%. Additionally, the well-known cortico-striatal-thalamic-cortical (CSTC) circuit and cerebellum were found as highly related regions with OCD. To further analyze the cerebellar-related function in OCD, we demarcated cerebellum into three subregions according to their anatomical and functional property. Using these three functional cerebellum regions as seeds for brain connectivity computation, statistical results showed that patients with OCD have decreased posterior cerebellar connections. CONCLUSIONS: This study provides a new and efficient method to characterize patients with OCD using resting-state functional MRI. We also provide a new perspective to analyze disease-related features. Despite of CSTC circuit, our model-driven feature analysis reported cerebellum as an OCD-related region. This paper may provide novel insight to the understanding of genetic etiology of OCD.

An Effect of Chronic Stress on Prospective Memory via Alteration of Resting-State Hippocampal Subregion Functional Connectivity.

The alteration of hippocampal function by chronic stress impairs higher order cognitive functions such as prospective memory (PM). However, how chronic stress affects hippocampal subregions related to PM remains largely unknown. In this study, the altered functional network of hippocampal subregions related to PM in chronic stress was explored. College students (N = 21) completed PM tasks and resting-state functional magnetic resonance imaging scans one month prior to (baseline) and during the final examination week (chronic stress). Hippocampal subregions' seed-based functional connectivity (FC) and PM were compared between baseline and chronic stress. PM performance declined in chronic stress. The FC of the cornu ammonis 2, 3 and dentate gyrus (CA23DG) with the bilateral caudate and precuneus was increased in chronic stress, while the FC of the subicular complex (SUBC) with the left middle frontal gyrus, the left inferior parietal gyrus and the right supramarginal gyrus was decreased. There was a negative correlation between PM performance and the FC of hippocampal subregions. We found chronic stress impairs PM by decreasing the FC of SUBC and increasing the FC of CA23DG. These findings suggest functional changes in hippocampal subregion networks as a mechanism underlying the impairment of PM in chronic stress.