WHITE MATTER ABNORMALITIES OF THE FRONTAL-STRIATAL-THALAMIC CIRCUITS IN INDIVIDUALS WITH ATTENUATED POSITIVE SYMPTOM SYNDROMES A PROBABILISTIC TRACTOGRAPHY STUDY

Abstract Background Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis. Disturbances in the frontal-striatal-thalamic circuit have been implicated in the neuropathology of APSS. This study aimed to systematically investigate white matter (WM) alterations in the frontal -striatal- thalamic circuit in APSS. Methods Diffusion magnetic resonance imaging (dMRI) and T1-weighted images were acquired from 43 individuals with APSS and 50 healthy controls (HCs). The dMRI data were preprocessed using FSL software. Brainnetome Atlas (BNA) was utilized to extract regions of interest (ROIs) in the frontal lobe, striatum, and thalamus. Bidirectional probabilistic tractography was performed to construct the frontal-striatal-thalamic circuit. Multiple linear regression was employed to compare the connectivity probability (CP) and diffusion index values between the APSS and HC groups. Results Compared to HCs, individuals with APSS exhibited significantly lower CP values in right Orbital gyrus_area 13- right nucleus accumbens (R: OrG_A13-NAC) fiber tract. Higher mean diffusivity values were observed in the L: OrG_A13-NAC and left ventral caudate– left caudal temporal thalamus (L: vCa- cTtha) fiber tract. Additionally, higher radial diffusivity values were found in the R: NAC-OrG_A13 fiber tract, while higher axial diffusivity values were observed in multiple frontal lobe ROIs-striatum ROIs and striatum ROIs-thalamus ROIs fiber tracts. No significant differences were found in fractional anisotropy values. Conclusions Individuals with APSS demonstrated reduced fiber connection strength, impaired myelin and inflammatory changes in the R: NAC-OrG_A13 fiber tract, and possible inflammatory changes in the L: vCa-cTtha fiber tract. These alterations may contribute to the neuropathology of APSS. Additionally, increased fiber coherence in multiple fiber tracts suggests potential compensatory mechanisms.