Impaired functional connectivity in patients with psychosis and visual hallucinations

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Abstract
Background: more than one-third of patients with psychosis experience visual hallucinations, but the underlying pathomechanism remains largely unknown. Although schizophrenia is related to altered brain functional connectivity, it is unknown how this could predispose patients to experience visual hallucinations. Previous work suggested that this predisposition is caused by alterations in vision-related networks, including the Visual Network, possibly with a specific focus on the Ventral Attention Network 1 . This network responds to salient stimuli from the Visual Network and operates as a switch between the internally-focused Default Mode Network and the outside-world-focused Dorsal Attention Network. Methods: in this case control study we investigated the role of these networks in three groups: 14 participants with a psychotic disorder and visual hallucinations, 15 participants with a psychotic disorder without visual hallucinations, and 16 healthy controls. All patients underwent resting state functional Magnetic Resonance Imaging after which we determined the intra- and inter-network functional connectivity of these networks in all participants. We also used fast Eigenvector Centrality Mapping to determine the most central regions, i.e. the most functionally communicating regions, within these networks. Results: compared to healthy controls, patients with visual hallucinations had lower functional connectivity, both intra-network and inter-network, in all vision-related networks. This decrease was most prominent for the Ventral Attention Network and the Dorsal Attention Network for intra-network functional connectivity. Moreover, Eigenvector Centrality Mapping showed a severe decrease in functional communication within the Visual Network in the right intracalcarine sulcus, with a simultaneous increase in functional communication in the lateral part of the left middle occipital gyrus, a region involved in object recognition. The results of patients without hallucinations were generally in between patients with visual hallucinations and healthy controls. Discussion: our study shows that widespread dysconnectivity of predominantly vision-related functional networks may predispose patients with psychosis to generate visual hallucinations. These results are in line with previous models of hallucinations in psychosis which suggested that the processing deficits in the Visual Network may cause or exacerbate inadequate co-functioning and switching between the Default Mode Network and the Dorsal Attentional Network, possibly due to impaired Ventral Attention Network functioning. In combination with impaired attending of visual signals by the Dorsal Attentional Network, this may lead to inappropriate saliency processing and wrongly attributing an external origin to internally generated events and, consequently, to visual hallucinations. The often complex nature of psychotic visual hallucinations may be explained by the more central role of object processing regions.

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