Network dynamics during the different stages of hallucinations in schizophrenia

Abstract

The majority of patients with schizophrenia suffer from hallucinations. While the triple-network model, which includes the default mode network (DMN), the central executive network (CEN) and the salience network (SAL), has recently been applied to schizophrenia, how this framework could explain the emergence of hallucinations remains unclear. Therefore, complementary brain regions that have been linked to hallucinations, such as the left hippocampus, should also be considered and added to this model. Accordingly, the present study explored the effective connectivity across these four components (i.e., the quadripartite model) during the different stages of hallucinations. Twenty-five patients with schizophrenia participated in a single session of resting-state functional magnetic resonance imaging to capture hallucinatory experiences. Based on the participants' self-report of the psychosensory experiences that occurred during scanning, hallucinatory experiences were identified and divided into four stages: periods without hallucination ("OFF"), periods with hallucination ("ON"), transition periods between "OFF" and "ON", and the extinction of the hallucinatory experience ("END"). Using stochastic dynamic causal modeling analysis, this study first confirmed that the SAL played a critical and causal role in switching between the CEN and the DMN in schizophrenia. In addition, effective connectivity within the quadripartite model depended on the hallucinatory stage. In particular, "ON" periods were linked to memory-based sensory input from the hippocampus to the SAL, while "END" periods were associated with a takeover of the CEN in favor of a voluntary process. Finally, the pathophysiological and therapeutic implications of these findings are critically discussed. Hum Brain Mapp 37:2571-2586, 2016. © 2016 Wiley Periodicals, Inc.

Prediction of activation patterns preceding hallucinations in patients with schizophrenia using machine learning with structured sparsity

“…Interestingly, this PC revealed activation of the brain regions involved in auditory hallucination‐related processes and in self‐other distinction, such as the right temporo‐parietal junction (Jardri et al, ; Decety & Lamm, ; Plaze et al, ), together with a deactivation of key nodes of the DMN, including the posterior cingulate cortex, medial prefrontal cortex, medial temporal cortex, and lateral parietal cortex (Buckner, Andrews‐Hanna, & Schacter, ). Our results appeared fully compatible with recent fMRI‐capture findings demonstrating that aberrant activations of speech‐related areas concomitant with hallucinatory experiences follow complex interactions between ICNs, such as the DMN and the CEN (Lefebvre et al, ). A disengagement of the DMN during goal‐directed behaviors has been seminally evidenced in the resting‐state literature (Fox et al, ; Lefebvre et al, ; Raichle et al, ), and similar mechanisms might be involved in hallucinatory occurrences (Jardri et al, ; Leroy et al, ).…”

fMRI capture of auditory hallucinations: Validation of the two‐steps method

“…By replicating previous findings, these results provide further support for the existence of anti‐correlation between the DMN and sensory cortices during AVH experiences and of a central role of DMN dynamics in these phenomena (Alderson‐Day et al, ; Lefebvre et al, ). This finding allows us to add the anti‐correlation of DM‐/AVH‐related time courses as a complementary selection criterion for the component of interest in the “2S” method (Lefebvre et al, ). These findings reinforce the consistency of the method as applied to fMRI capture of hallucinations.…”

Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions

“…Another possible explanation for the observed dissociation between structural and functional connectivity is that functional connectivity compensates the reduced integrity of structural connections [Fornito et al, ; Honey et al, ], at least during the early stages of the disease. Indeed, while preserved functional connectivity was evident in the present study, which mostly included patients with 22q11DS at‐risk but not diagnosed with schizophrenia, this is not the case in schizophrenic patients [Chang et al, ; Iwabuchi et al, ; Lefebvre et al, ; Manoliu et al, ; Moran et al, ; Orliac et al, ; Palaniyappan et al, ]. This may suggest that the structure‐function relationship may change at different stages of the disease, and that functional connectivity impairments would correspond to later, more severe stages.…”

“…However, we did not observe a relationship between altered triple network connectivity and psychotic symptoms in patients with 22q11DS. Of note, the studies conducted in schizophrenic patients reported functional connectivity impairments related to psychotic symptoms [Lefebvre et al, ; Manoliu et al, ], while no evidence exists of a relationship between triple network structural dysconnectivity and the symptomatic profile [Chen et al, ; Iwabuchi et al, ]. As discussed in the previous paragraphs, functional connectivity seems to be preserved in patients with 22q11DS, and this might explain the lack of correlations with psychotic symptoms in this population.…”