Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [¹⁸F]fallypride PET and functional MRI study

Abstract

In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlations of dopamine D receptor availability between striatal and extrastriatal regions using [ F]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [ F]fallypride binding potential (BP ) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter-correlations. Correlations between BP in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed-based resting-state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic-naïve patients to determine if these relationships are illness-related characteristics, or arising due to chronic antipsychotic treatment.

Functional brain networks in never-treated and treated long-term Ill schizophrenia patients

“…Antipsychotic drugs are well known to block D2 receptors in striatum and amygdala [52], and they can have neuroplastic effects on the brain, including increased synapse number and connections of striatum [53]. Numerous neurochemical studies have also provided robust evidence of the close link between dopamine receptor availability in striatum and the antipsychotic treatment efficacy [54,55].…”

Relationship of self‐transcendence traits with in vivo dopamine D2/3 receptor availability and functional connectivity: An [18F]fallypride PET and fMRI study

“…The seeds (referred to as [ 18 F]fallypride BP ND ‐based seeds in the text) such as (ST) insula_lt and (ST3) insula_lt were derived from voxel‐based regression analysis between [ 18 F]fallypride BP ND and self‐transcendence scores (age as a covariate), and were based on the brain regions with significant clusters (FWE p < 0.05) and peak voxel coordinates (uncorrected p < 0.001). In target regions, AAL and network regions were defined by the templates provided from the functional connectivity toolbox (CONN) software, and the prefrontal cortex was defined by an in‐house mask (Kim et al, ).…”

“…Seeds were defined as statistically significant clusters with family‐wise error (FWE)‐corrected p < 0.05 and with peak voxels of uncorrected p < 0.001. The AAL atlas regions, network regions defined by the template provided from the CONN software, and the prefrontal cortex defined by an in‐house mask (Kim et al, ) were used as the target ROIs in the seed‐to‐ROI rs‐fMRI analysis.…”

“…The AAL atlas regions, network regions defined by the template provided from the CONN software, and the prefrontal cortex defined by an in-house mask (Kim et al, 2018) were used as the target ROIs in the seed-to-ROI rs-fMRI analysis.…”

“…, and were based on the brain regions with significant clusters (FWEp < 0.05) and peak voxel coordinates (uncorrected p < 0.001). In target regions, AAL and network regions were defined by the templates provided from the functional connectivity toolbox (CONN) software, and the prefrontal cortex was defined by an in-house mask (Kim et al, 2018…”