Deficit in parietal memory network underlies auditory hallucination: a longitudinal study

Auditory hallucination is a prominent and common symptom in schizophrenia. Previous neuroimaging studies have yielded mixed results of its brain network deficits. We proposed a novel hypothesis that parietal memory network, centered at the precuneus, plays a critical role in auditory hallucination. This network is adjacent and partially overlaps with the default mode network, and has been associated with brain function of familiarity labelling in memory processing. Using a longitudinal design and a large cohort of first-episode, drug-naïve schizophrenia patients, we examined this hypothesis and further investigated whether the functional connectivity patterns of the parietal memory network can serve as a neuroimaging marker for auditory hallucination and help to predict future treatment effects. Resting-state scans from 59 first-episode drug-naïve schizophrenic patients (27 with and 32 without hallucination) and 53 healthy control subjects were acquired at the baseline test, and 56 of them were scanned again after two months. Functional connectivity strength within the parietal memory network and between this network and memory hubs was across the three groups at baseline and follow-up scans. Results showed that decreased functional connectivity strength within the parietal memory network was specific to the auditory hallucination group (p = 0.009, compare to the healthy subjects; p = 0.029, compare to the patients without hallucination), with the precuneus representing the largest group difference. The intra-network connectivity strength of the precuneus negatively correlated with the severity of hallucination at the baseline scan (r = −0.437, p = 0.029), and it was significantly increased after two-month medication (p = 0.039). Logistic regression analysis and crossvalidation test demonstrated that the functional connectivity strength of the precuneus and precuneus-hippocampus connectivity could differentiate patients with or without auditory hallucination with a sensitivity of 0.750 and a specificity of 0.708. Moreover, crossvalidation test showed that these imaging features at the baseline scan well predicted the extents of positive symptom improvement in the hallucination group after the two-month medication (R2 = 0.433, p = 0.022). Our results provide evidence for a critical role of the parietal memory network underlying auditory hallucination, and further propose a novel neuroimaging marker for identifying patients, accessing severity, and prognosis of treatment effect for auditory hallucination.AbbreviationsAHauditory hallucinationAHRSAuditory Hallucination Rating ScaleAUCArea-under-curveBPRSBrief Psychiatric Rating ScaleDMNdefault mode networkDSM-IVDiagnostic and Statistical Manual of Mental Disorders, Fourth EditionDUPduration of untreated psychosisFCSfunctional connectivity strengthHChealthy controlICindependent componentPMNparietal memory networkNMDAN-methyl-D-aspartateRSNresting state networkrs-fMRIresting-state functional MRIrTMSrepetitive transcranial magnetic stimulationSANSExpanded Version and the Scale for Assessment of Negative Symptoms