Semantic Processing and Thought Disorder in Childhood-Onset Schizophrenia: Insights from fMRI

Abstract

Impairments in language processing and thought disorder are core symptoms of schizophrenia. Here we used fMRI to investigate functional abnormalities in the neural networks subserving sentence-level language processing in childhood-onset schizophrenia (COS). Fourteen children with COS (mean age: 13.34; IQ: 95) and 14 healthy controls (HC; mean age: 12.37; IQ: 104) underwent fMRI while performing a semantic judgment task previously shown to differentially engage semantic and syntactic processes. We report four main results. First, different patterns of functional specialization for semantic and syntactic processing were observed within each group, despite similar level of task performance. Second, after regressing out IQ, significant between-group differences were observed in the neural correlates of semantic and, to a lesser extent, syntactic processing, with HC children showing overall greater activity than COS children. Third, while these group differences were not related to effects of medications, a significant negative correlation was observed in the COS group between neuroleptic dosage and activity in the left inferior frontal gyrus for the semantic condition. Finally, COS children's level of thought disorder was significantly correlated with task-related activity in language-relevant networks. Taken together, these findings suggest that children with COS exhibit aberrant patterns of neural activity during semantic, and to a lesser extent syntactic, processing and that these functional abnormalities in language-relevant networks are significantly related to severity of thought disorder.

Figure 1

Several clusters of significant activity in fronto-temporal language regions were observed in HC children for both the semantic (top) and syntactic (bottom) conditions as compared to resting baseline. Activation maps are displayed at a threshold of t > 3.85, p < 0.001 for magnitude, p < .05, corrected for spatial extent.

Figure 2

Children with COS also showed significant task-related activity during the semantic (top) and syntactic (bottom) conditions as compared to resting baseline, albeit to a lesser degree than observed in the HC group. Activation maps are displayed at a threshold of t >3.85, p < 0.001 for magnitude, p < .05, corrected for spatial extent.

Figure 3

Percent signal change from resting baseline during the semantic condition was significantly greater in the healthy control children than the children with COS in the left STG, MTG, and putamen as well as the right IFG, ACC, DMPFC, and cerebellum.

Figure 4

Percent signal change from resting baseline during the syntactic condition was significantly greater in the healthy control children than the children with COS in the left IFG, premotor cortex and putamen, as well as the DMPFC bilaterally and the right presupplemental motor area and caudate.

Figure 5

Significant negative correlations were observed between COS children's formal thought disorder scores and activity during the semantic condition in left IFG and STG (shown here at t > 2.68, p < 0.01 for magnitude, p < .05, uncorrected for spatial extent), as well as in DMPFC and DLPFC (see Table 5). The scatter plot illustrates the negative relationship between formal thought disorder scores and activity within the left IFG and STG (r = -0.84; p < 0.001; r = -0.75; p < 0.002, respectively).

Figure 6

Significant negative correlations were also observed between COS children's repair of organization of thought scores and activity during the semantic condition in bilateral MTG and DMPFC (shown here at t > 2.68, p < 0.01 for magnitude, p < .05, uncorrected for spatial extent), as well as in the right caudate nucleus (see Table 5). The scatter plot illustrates the negative correlations between repair of organization of thought scores and activity within left and right MTG and DMPFC (r = -0.80; p < 0.001; r = -0.81; p < 0.001; r = -0.72; p < 0.003, respectively).