Altered Functional Connectivity of Striatum Based on the Integrated Connectivity Model in First-Episode Schizophrenia

Abstract

Background: The human striatum is a heterogeneous structure involved in diverse functional domains that related to distinct striatum subregions. Striatal dysfunction was thought to be a fundamental element in schizophrenia. However, the connectivity pattern of striatum solely based on functional or structural characteristics leads to inconsistent findings in healthy adult and also schizophrenia. This study aims to develop an integrated striatal model and reveal the altered functional connectivity pattern of the striatum in schizophrenia.Methods: Two data-driven approaches, task-dependent meta-analytic connectivity modeling (MACM) and task-independent resting-state functional connectivity (RSFC), were used for seven anatomical connectivity-based striatum subregions to provide an integrated striatal model. Then, RSFC analyses of seven striatal subregions were applied to 45 first-episode schizophrenia (FES) and 27 healthy controls to examine the difference, based on the integrated model, of functional connectivity pattern of striatal subregions.Results: MACM and RSFC results showed that striatum subregions were associated with discrete cortical regions and involved in distinct cognitive processes. Besides, RSFC results overlapped with MACM findings but showed broader distributions. Importantly, significantly reduced functional connectivity was identified between limbic subregion and thalamus, medial prefrontal cortex, anterior cingulate cortex, and insula and also between executive subregions and thalamus, supplementary motor area, and insula in FES.Conclusions: Combing functional and structural connectivity information, this study provides the integrated model of corticostriatal subcircuits and confirms the abnormal functional connectivity of limbic and executive striatum subregions with different networks and thalamus, supporting the important role of the corticostriatal-thalamic loop in the pathophysiology of schizophrenia.

The alternations of nucleus accumbent in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment

“…Decreased FC of NAcc with the frontal cortices (e.g., right superior frontal gyrus and inferior frontal gyrus) and anterior cingulate gyrus was also observed in patients at baseline relative to controls. The results are consistent with previous studies that reported hypoconnectivity of the frontostriatal loop in schizophrenia ( 18 , 54 ). Specifically, Broca's region and its right hemisphere counterpart in the inferior frontal gyrus are involved in language processing ( 55 , 56 ).…”

Circuit-Based Approaches to Understanding Corticostriatothalamic Dysfunction Across the Psychosis Continuum

“…Thus, while the consistent identification of disrupted dorsal CST and hippocampal-striatal FC across the psychosis continuum aligns with preclinical models emphasizing cortical and hippocampal control over dopamine signalling (23,60,61,(68)(69)(70)97,104), the fMRI findings do not allow us to determine whether cortical or hippocampal abnormalities are primary. Indeed, it is possible that hippocampal dysregulation is linked to a diminished influence from cortex, given that reduced FC between the medial PFC and the hippocampus has been reported only in people with clinically diagnosable illness (i.e., FEP and schizophrenia patients); in this sense, disrupted cortico-hippocampal communication may be a trigger for clinically significant symptom expression by altering hippocampal regulation over dopamine transmission (136,(179)(180)(181)(182). It is also important to note that, due to the small size of the midbrain, wholebrain fMRI studies have limited sensitivity for mapping effects in this region unless they specifically try to investigate the area.…”

Capturing functional connectomics using Riemannian partial least squares

“…The role of the basal ganglia in schizophrenic patients has been previously observed, particularly the decrease in connectivity between the salience network and the basal ganglia 38 , 39 and the decreased connectivity between the cerebellum and basal ganglia 40 . Similarly, the importance of the thalamus in schizophrenia, identified when using the AAL atlas, is well-known 41 , 42 .…”