Faulty suppression of irrelevant material in patients with thought disorder linked to attenuated frontotemporal activation

Abstract

Formal thought disorder is a feature schizophrenia that manifests as disorganized, incoherent speech, and is associated with a poor clinical outcome. The neurocognitive basis of this symptom is unclear but it is thought to involve an impairment in semantic processing classically described as a loosening of meaningful associations. Using a paradigm derived from the n400 event-related, potential, we examined the extent to which regional activation during semantic processing is altered in schizophrenic patients with formal thought disorder. Ten healthy control and 18 schizophrenic participants (9 with and 9 without formal thought disorder) performed a semantic decision sentence task during an event-related functional magnetic resonance imaging experiment. We employed analysis of variance to estimate the main effects of semantic congruency and groups on activation and specific effects of formal thought disorder were addressed using post-hoc comparisons. We found that the frontotemporal network, normally engaged by a semantic decision task, was underactivated in schizophrenia, particularly in patients with FTD. This network is implicated in the inhibition of automatically primed stimuli and impairment of its function interferes with language processing and contributes to the production of incoherent speech.

Figure 1

fMRI task design.

Figure 2

(a) 3-Group ANOVA: semantic congruency (congruent versus incongruent) trials. Comparison of healthy controls (n = 10) versus schizophrenic patients with formal thought disorder (FTD, n = 9) versus schizophrenic patients without formal thought disorder (Non-FTD, n = 9). Attenuated activation in the left inferior frontal gyrus was observed in FTD relative to Non-FTD and to controls. The latter showed greater activation in this region also relative to non-FTD. The left side of the brain images corresponds to the right side of the brain. The superior part of the brain images corresponds to the anterior brain region. (b) Scatter plot of the activity in the left inferior frontal cortex as a function of the score in formal thought disorder (FTD) within schizophrenic patients (n = 18). We observe that FTD higher scores in a sample of psychotic schizophrenic patients are negatively correlated with activity in the left inferior frontal cortex (x = −43.33, y = 14.81, z = 14.85).

Figure 3

Post-hoc 2 group comparisons: semantic congruency (congruent versus incongruent trials). (a) healthy controls (n = 10) versus schizophrenic patients with formal thought disorder (FTD, n = 9) (b, c) FTD versus schizophrenic patients without formal Thought Disorder (Non-FTD, n = 9). (a) Controls show greater activation relative to FTD in the inferior frontal gyrus bilaterally, dorsal portions, in the left middle temporal gyrus (BA 22), in the left lingual gyrus, in the left precuneus, and in the cerebellum (posterior lobe) bilaterally. (b) Non-FTD patients showed greater activation of bilateral middle frontal gyrus and bilateral anterior cingulate, relative to FTD. (c) FTD patients show greater activation relative to Non-FTD patients in the right posterior cingulate. The left side of the brain images correspond to the right side of the brain. The superior part of the brain images correspond to the anterior brain region.

Figure 4

Semantic decision match fMRI task: performance accuracy in semantic congruent and incongruenet trials. Control (n = 10) versus NON-FTD (n = 9) versus FTD (n = 9).

Figure 5

Semantic decision match fMRI task: reaction times in semantic congruent and incongruent trials. Control (n = 10) versus NON-FTD (n = 9) versus FTD (n = 9).