Correlations between fMRI activation and individual psychotic symptoms in un-medicated subjects at high genetic risk of schizophrenia

Abstract

Background: It has been proposed that different types of psychopathology in schizophrenia may reflect distinguishable pathological processes. In the current study we aimed to address such associations in the absence of confounders such as medication and disease chronicity by examining specific relationships between fMRI activation and individual symptom severity scores in un-medicated subjects at high genetic risk of schizophrenia.

Methods: Associations were examined across two functional imaging paradigms: the Hayling sentence completion task, and an encoding/retrieval task, comprising encoding (at word classification) and retrieval (old word/new word judgement). Symptom severity was assessed using the positive and negative syndrome scale (PANSS). Items examined were hallucinations, delusions, and suspiciousness/persecution.

Results: Associations were seen in the anterior middle temporal gyrus in relation to hallucination scores during the sentence completion task, and in the medial temporal lobe in association with suspiciousness/persecution scores in the encoding/retrieval task. Cerebellar activation was associated with delusions and suspiciousness/persecution scores across both tasks with differing patterns of laterality.

Conclusion: These results support a role for the lateral temporal cortex in hallucinations and medial temporal lobe in positive psychotic symptoms. They also highlight the potential role of the cerebellum in the formation of delusions. That the current results are seen in un-medicated high risk subjects indicates these associations are not specific to the established illness and are not related to medication effects.

Figure 1

Distribution of symptom dimensions in high risk individuals. Values represent the number of subjects with PANSS scores >2 for each symptom type examined. Pair-wise correlation values between the symptom dimensions were as follows: Delusions × hallucinations r = 0.34 (p < 0.01); delusions × suspiciousness/persecution r = 0.48 (p < 0.01); hallucinations × suspiciousness/persecution r = 0.32 (p < 0.01).

Figure 2

Within group activation maps for sentence completion task (a, b) and verbal encoding/retrieval task (c-e). For the Hayling sentence completion test, contrasts shown are (a) sentence completion versus rest and (b) the parametric contrast representing increasing activation with increasing difficulty. For the encoding/retrieval task, contrasts shown are (c) word classification versus experimental baseline, (d) correct recognition versus experimental baseline, and (e) correct rejection versus experimental baseline. For illustration purposes maps are thresholded at T = 4.5, 4, 6, 5, 5 respectively, extent threshold = 50 voxels. Left hemisphere shown on left of image.

Figure 3

Correlations with symptom scores in hypothesised regions. (a) significant positive correlation between severity of hallucinations and activation in left middle temporal gyrus for sentence completion task, (b) significant negative correlation between severity of suspiciousness/persecution score and activation in bilateral MTL for the retrieval task. Maps thresholded at p = 0.005, K_E = 300 voxels. Left hemisphere shown on left of image

Figure 4

Correlations with symptoms scores in cerebellar regions. Negative correlations with suspiciousness/persecution score for (a) sentence completion, (b) verbal retrieval. Positive correlations with delusions score for (c) sentence completion, (d) verbal encoding. Maps thresholded at p = 0.005 uncorrected, extent threshold = 100 voxels. Left hemisphere shown on left of image