Insular dysfunction reflects altered between-network connectivity and severity of negative symptoms in schizophrenia during psychotic remission

Schizophrenia is characterized by aberrant intrinsic functional connectivity (iFC) within and between intrinsic connectivity networks (ICNs), including the Default Mode- (DMN), Salience- (SN), and Central Executive Network (CEN). The anterior insula (AI) of the SN has been demonstrated to modulate DMN/CEN interactions. Recently, we found that the dependence of DMN/CEN interactions on SN's right AI activity is altered in patients with schizophrenia in acute psychosis and related to psychotic symptoms, indicating a link between aberrant AI, DMN, CEN, and psychosis. However, since structural alterations of the insula are also present during psychotic remission and associated with negative symptoms, impaired AI interaction might be relevant even for psychotic remission and corresponding symptoms. Twelve patients with schizophrenia during psychotic remission (SR) and 12 healthy controls were assessed using resting-state fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed ICNs including DMN, SN, and CEN. Scores of iFC within (intra-iFC) and between (inter-iFC) distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Intra-iFC was altered in patients SN, DMN, and CEN, including decreased intra-iFC in the left AI within the SN. Patients' inter-iFC between SN and CEN was increased and correlated with the severity of negative symptoms. Furthermore, decreased intra-iFC of the left AI correlated with both severity of negative symptoms and increased inter-iFC between SN and CEN. Our result provides first evidence for a relationship between AI dysfunction and altered between-network interactions in schizophrenia during psychotic remission, which is related to the severity of negative symptoms. Together with our previous results, data suggest specific SN/DMN/CEN reorganization in schizophrenia with distinct insular pathways for distinct symptom dimensions

Intrinsic functional network contributions to the relationship between trait empathy and subjective happiness

幸福感と共感性を関連付ける安静時脳機能ネットワークの解明 --前頭前皮質の機能的結合性の役割--. 京都大学プレスリリース. 2021-01-08.Subjective happiness (well-being) is a multi-dimensional construct indexing one's evaluations of everyday emotional experiences and life satisfaction, and has been associated with different aspects of trait empathy. Despite previous research identifying the neural substrates of subjective happiness and empathy, the mechanisms mediating the relationship between the two constructs remain largely unclear. Here, we performed a data-driven, multi-voxel pattern analysis of whole-brain intrinsic functional connectivity to reveal the neural mechanisms of subjective happiness and trait empathy in a sample of young females. Behaviorally, we found that subjective happiness was negatively associated with personal distress (i.e., self-referential experience of others’ feelings). Consistent with this inverse relationship, subjective happiness was associated with the dorsolateral prefrontal cortex exhibiting decreased functional connectivity with regions important for the representation of unimodal sensorimotor information (e.g., primary sensory cortices) or multi-modal summaries of brain states (e.g., default mode network) and increased functional connectivity with regions important for the attentional modulation of these representations (e.g., frontoparietal, attention networks). Personal distress was associated with the medial prefrontal cortex exhibiting functional connectivity differences with similar networks––but in the opposite direction. Finally, intrinsic functional connectivity within and between these networks fully mediated the relationship between the two behavioral measures. These results identify an important contribution of the macroscale functional organization of the brain to human well-being, by demonstrating that lower levels of personal distress lead to higher subjective happiness through variation in intrinsic functional connectivity along a neural representation vs. modulation gradient