Abnormal development and dysconnectivity of distinct thalamic nuclei in patients with 22q11.2 deletion syndrome experiencing auditory hallucinations

Abstract Background Several studies in patients with schizophrenia have demonstrated an abnormal thalamic volume and thalamocortical connectivity. Specifically, hyperconnectivity with somatosensory areas has been related to the presence of auditory hallucinations (AH). The 22q11.2 deletion syndrome is a neurogenetic disorder conferring proneness to develop schizophrenia and deletion carriers (22qdel) experience hallucinations to a greater extent than the general population. Methods We acquired 442 consecutive MRI scans from 120 22qdel and 110 controls every 3 years (age-range:8-35). The volume of thalamic nuclei was obtained with FreeSurfer and compared between 22qdel and controls and between 22qdel with or without AH. In a subgroup of 76 22qdel, we evaluated the functional connectivity between thalamic nuclei affected in patients experiencing AH and cortical regions. Results As compared to controls, 22qdel had respectively lower and higher volume of nuclei involved in sensory processing and cognitive functions. 22qdel with AH had a smaller volume of the medial geniculate nucleus (MGN) with deviant trajectories showing a steeper volume decrease from childhood with respect to those without AH. Moreover, we showed an aberrant development of nuclei intercalated between prefrontal cortex and the hippocampus (the anteroventral (AV) and medioventral-reuniens nuclei) and hyperconnectivity of MGN and AV with the auditory cortex (AC) and Wernicke’s area. Conclusions The increased connectivity of the MGN and AV to AC might be interpreted as a lack of maturation of thalamocortical connectivity. Overall, our findings point towards an aberrant development of thalamic nuclei and an immature pattern of connectivity with temporal regions in relation to AH.