Neural Correlates of Formal Thought Disorder Dimensions in Psychosis

Abstract

Background and hypothesis: Formal thought disorder (FTD) is a core symptom of psychosis, but its neural correlates remain poorly understood. This study tested whether four FTD dimensions differ in their association with brain perfusion and brain structure.

Study design: This cross-sectional study investigated 110 patients with schizophrenia spectrum disorders using 3T magnetic resonance imaging (MRI). The Thought and Language Disorder scale (TALD) was utilized, which comprises four subscales: Objective Positive (OP), Objective Negative (ON), Subjective Positive (SP), and Subjective Negative (SN). Resting-state cerebral blood flow (rsCBF), cortical thickness (CortTh), gray matter volume (GMV), and diffusion MRI tractography were tested for associations with TALD subscales controlling for age, medication, total intracranial volume, and for variance of the 3 other TALD subscales.

Study results: Following Bonferroni correction, the FTD dimensions presented distinct neural correlates. OP scores were associated with increased rsCBF and increased GMV in the right cerebellum lingual gyrus. Higher SP scores were linked to increased GMV in bilateral prefrontal cortex. In contrast, ON was associated with increased GMV in the right premotor cortex. At more liberal statistical thresholds, higher SP was associated with increased CortTh in the right inferior frontal gyrus, whereas SN scores were linked to decreased GMV in the right prefrontal lobe, the left inferior temporal gyrus, and the left supplementary motor area. Unadjusted analyses mostly corroborated these findings.

Conclusion: These findings stress the heterogeneity in FTD, suggesting distinct neural patterns for specific FTD experiences. In sum, FTD in psychosis may require distinct treatment strategies and further mechanistic investigations on single-item levels.

Keywords: disorganization; emptiness; pathobiology.

Fig. 1.

Associations of TALD total score, as well as TALD sub-scores (OP, ON, SP, SN) severity with rsCBF, CorthTh, and GMV analyses corrected for each other subscale, age, medication (OLZ eq), and TIV. Red/yellow denotes a positive association (corrected P-value < .05), while blue denotes a negative association (corrected P-value < .05). Specific statistics of significant clusters are given in table 2. Detailed associations of TALD sub-scores with GMV are presented in Supplementary figure 5. TALD, Thought and Language Disorder scale; OP, objective positive, ON, objective negative; SP, subjective positive, SN, subjective negative; rsCBF, resting-state cerebral blood flow; CortTh, cortical thickness; GMV, gray matter volume; OLZ eq, olanzapine equivalents..

Fig. 2.

(A) Example correlation plots for 2 bundles (superior longitudinal fasciculus II and left inferior frontal-occipital fasciculus) showing the association between mean FA and total TALD score. (B) TBSS results. Significant association between SP TALD sub-score severity and MD (red [in print: dark grey], TFCE FWE P = .045, 5000 simulations) and at trend level FA (green [in print: light grey], TFCE FWE P = .09) when controlling for age, medication (OLZ eq), TIV, and the other sub-scores. Blue = Skeleton. TALD, Thought and Language Disorder scale; SP, subjective positive; MD, mean diffusivity; TBSS, Tract-Based Spatial Statistics; OLZ eq, olanzapine equivalents..