Auditory Verbal Hallucinations and Brain Dysconnectivity in the Perisylvian Language Network: A Multimodal Investigation

Abstract

Neuroimaging studies of schizophrenia have indicated that the development of auditory verbal hallucinations (AVHs) is associated with altered structural and functional connectivity within the perisylvian language network. However, these studies focussed mainly on either structural or functional alterations in patients with chronic schizophrenia. Therefore, they were unable to examine the relationship between the 2 types of measures and could not establish whether the observed alterations would be expressed in the early stage of the illness.We used diffusion tensor imaging and functional magnetic resonance imaging to examine white matter integrity and functional connectivity within the left perisylvian language network of 46 individuals with an at risk mental state for psychosis or a first episode of the illness, including 28 who had developed AVH group and 18 who had not (nonauditory verbal hallucination [nAVH] group), and 22 healthy controls. Inferences were made at P < .05 (corrected). The nAVH group relative to healthy controls showed a reduction of both white matter integrity and functional connectivity as well as a disruption of the normal structure−function relationship along the fronto-temporal pathway. For all measures, the AVH group showed intermediate values between healthy controls and the nAVH group. These findings seem to suggest that, in the early stage of the disorder, a significant impairment of fronto-temporal connectivity is evident in patients who do not experience AVHs. This is consistent with the hypothesis that, whilst mild disruption of connectivity might still enable the emergence of AVHs, more severe alterations may prevent the occurrence of the hallucinatory experience.

Interaction of language, auditory and memory brain networks in auditory verbal hallucinations

“…Four out of five papers retained in the meta-analysis reported decreased FA of the left (but not right) AF of patients with AVH as compared to patients without AVH (Seok et al, 2007, Catani et al, 2011, De Weijer et al, 2011, Ćurčić-Blake et al, 2015). Similar results were recently obtained when comparing ultra-high-risk and first-episode-psychosis individuals following AVH episodes with NoAVH subject (Benetti et al, 2015). …”

“…In healthy people with hallucinations, an increase in inter-hemispheric connectivity has been observed, similar to early stage patients. The majority of large studies on chronic schizophrenia patients that incorporate both a control group and a group of patients without AVH find decreases in anatomical or functional connectivity of language areas (De Weijer et al, 2013, Oestreich et al, 2015, McCarthy-Jones et al, 2015, Ćurčić-Blake et al, 2013), but other studies (with smaller sample sizes; see Table 2) have found exactly the opposite (Hoffman et al, 2011a, Benetti et al, 2015). Most of these studies, excluding those that limited investigation to just a few regions of interest, found abnormalities in a combination of networks rather than in a single network.…”

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study

“…In our results, this leftward lateralization of the arcuate fasciculus is found in AVH + patients but not in no-AVH patients. One can hypothesize that whilst disruption of connectivity might be present to ensure the emergence of AVH as compared with healthy controls (Geoffroy et al, 2014), more severe WM alterations may prevent the occurrence of AVH in patients with predominantly negative symptoms as suggested by Benetti et al (2015). This hypothesis is consistent with McCarthy-Jones and collaborators findings showing that patients with larger FA decreases in the arcuate were less likely to have current AVH (McCarthy-Jones et al, 2015).…”

“…Two studies reported a positive correlation between AVH severity and FA in the SLF either in the left part (Seok et al, 2007) or bilaterally (Shergill et al, 2007). Finally, a recent study in unmedicated subjects at risk to develop psychosis reported larger abnormalities in WM integrity and functional connectivity within the left perisylvian language network in subjects who had not developed AVH as compared with subjects who had developed AVH (Benetti et al, 2015). …”

Reduced integrity of the left arcuate fasciculus is specifically associated with auditory verbal hallucinations in schizophrenia

“…First, given the role of the AF L in language (Catani et al, 2005), we hypothesised decreases in FA-AF L in patients with AVH compared to patients with hallucinations restricted to other modalities (e.g., visual hallucinations). Second, as some previous studies have employed patients with both current and remitted AVH (e.g., Benetti et al, 2015), we aimed to test whether FA-AF L changes associated with AVH reflected a state or trait phenomena. Finally, we aimed to undertake the first empirical test based on the proposal that if AVH represent the brain's attempt to incorporate disjointed neural activity then this integration may only be possible up to a certain level of temporal desynchronisation (Whitford et al, 2010).…”