Reduced parietofrontal effective connectivity during a working-memory task in people with high delusional ideation

Abstract

Background: Working-memory impairment is a core cognitive dysfunction in people with schizophrenia and people at mental high risk. Recent imaging studies on working memory have suggested that abnormalities in prefrontal activation and in connectivity between the frontal and parietal regions could be neural underpinnings of the different stages of psychosis. However, it remains to be explored whether comparable alterations are present in people with subclinical levels of psychosis, as experienced by a small proportion of the general population who neither seek help nor show constraints in daily functioning.

Methods: We compared 24 people with subclinical high delusional ideation and 24 people with low delusional ideation. Both groups performed an n-back working-memory task during functional magnetic resonance imaging. We characterized frontoparietal effective connectivity using dynamic causal modelling.

Results: Compared to people who had low delusional ideation, people with high delusional ideation showed a significant increase in dorsolateral prefrontal activation during the working-memory task, as well as reduced working-memory-dependent parietofrontal effective connectivity in the left hemisphere. Group differences were not evident at the behavioural level.

Limitations: The current experimental design did not distinguish among the working-memory subprocesses; it remains unexplored whether differences in connectivity exist at that level.

Conclusion: These findings suggest that alterations in the working-memory network are also present in a nonclinical population with psychotic experiences who do not display cognitive deficits. They also suggest that alterations in working-memory-dependent connectivity show a putative continuity along the spectrum of psychotic symptoms.

Fig. 1

Model space adapted from Deserno and colleagues. (A) The 3 model families based on frontoparietal connectivity with (1) bidirectional, (2) forward and (3) backward modulation. (B) A 16-model subspace with additional modulations of the connections from the visual cortex to the dlPFC and the parietal cortex (example shown for the bidirectional family only). dlPFC = dorsolateral prefrontal cortex; WM = working memory.

Fig. 2

Local activation during working memory. (A) Frontoparietal activation during working-memory performance in participants with high and low delusional ideation taken together (displayed at p_{FWE, WBC} < 0.05 for the 2-back > 0-back contrast; x, y, z = −40, 15, 36). (B) Higher left dlPFC activation in people with high versus low delusional ideation for the 2-back > 0-back contrast (t = 3.97, p_{FWE, SVC} = 0.026; x, y, z = −52, 34, 12). Literature-based dlPFC mask displayed in yellow. (C) Plot of parameter estimates extracted from peak voxels of the task × group interaction effect. dlPFC = dorsolateral prefrontal cortex; FWE = family-wise-error–corrected; PDI = Peters Delusion Inventory; SVC = small-volume–corrected; WBC = whole-brain–corrected.

Fig. 3

Results of Bayesian model selection for each hemisphere across all participants taken together, as well as separately for people with low and high delusional ideation (low PDI and high PDI, respectively). The measure of relative model evidence is given as exceedance probability. Family selection of bidirectional, forward or backward modulation of frontoparietal connectivity for the left and right hemisphere, respectively. PDI = Peters Delusion Inventory.

Fig. 4

Parameter estimates from Bayesian model averaging over the entire model space (i.e., 48 models). Within-group results for people with low and high delusional ideation (low PDI and high PDI, respectively). Group differences were found for 3 dynamic causal modelling parameters: working-memory-induced (modulatory) parietofrontal connectivity was reduced in people with high delusional ideation compared to those with low delusional ideation; people with high delusional ideation showed enhanced intrinsic frontovisual connectivity; and we observed a group difference in the modulatory influence on frontovisual connectivity. All effects were observed in the left hemisphere. *Significant at p < 0.05. dlPFC = dorsolateral prefrontal cortex; PDI = Peters Delusion Inventory; WM = working memory.