Dysconnectivity of the Agency Network in Schizophrenia: A Functional Magnetic Resonance Imaging Study

Abstract

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the “agency network” may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the “agency network.” Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia ( n = 15) and matched controls ( n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

Baseline Cortical Thickness Reductions in Clinical High Risk for Psychosis: Brain Regions Associated with Conversion to Psychosis Versus Non-Conversion as Assessed at One-Year Follow-Up in the Shanghai-At-Risk-for-Psychosis (SHARP) Study

“…68,[81][82][83] Functions that have been ascribed to these regions include semantic, phonological, and orthographic processes (IPG and FG), 84 multimodal association functions involved in word reading, comprehension, and semantic analyses (angular gyrus; see Seghier 85 ), interfacing between phonetic and articulatory representations (sMG; Gow 86 ), and between phonetic and semantic representations (MTG). Furthermore, the fronto-temporo-parietal regions contribute to cognitive flexibility: self-agency processing, 87 working memory processes, 88 bottom-up attention, undirected thinking, episodic memory, and social cognition (see ref. 89 for a review), delayed reward discounting, 90 theory of mind 91 (important for facilitating the development of inferences about complex linguistic messages), and face processing.…”

Potential Locations for Non-Invasive Brain Stimulation in Treating Schizophrenia: A Resting-State Functional Connectivity Analysis

“…There are other brain regions identified in our study, involving the bilateral IPL, the right temporal pole (TPO), and the medial prefrontal cortex (mPFC). IPL is one of the structures in the sense of agency and the dysconnectivity of the agency network ( 78 ), considered as a center of multisensory integration ( 79 ). The bilateral IPL, especially the angular gyrus (AG), may be directly involved in the pathophysiology of SCZ and extremely correlate with the SCZ network.…”

Right parietotemporal activity predicts sense of agency under uncertain delays of sensory outcomes

“…The observed signal prior to motor action (Figure 3) is speculated to be a signature of an internal predictive mechanism originating from the right inferior parietal lobule (Figure 3). This region has been shown to be involved in the formation of sense of agency (Chambon et al 2015;Chambon et al 2012;Farrer et al 2003;Farrer and Frith 2002;Koreki et al 2019;Yomogida et al 2010) , and more likely involved in sense of external-agency rather than sense of self-agency (Seghezzi et al 2019;Sperduti et al 2011). This signal was absent in the overall performance block where motor-outcome delay uncertainty was low, so the delay could be used as a more reliable agency cue.…”