Mancini Valentina, Zöller Daniela, Schneider Maude, Schaer Marie, Eliez Stephan
Developmental Imaging and Psychopathology Laboratory, University of Geneva School of Medicine, Geneva, Switzerland.
Developmental Imaging and Psychopathology Laboratory, University of Geneva School of Medicine, Geneva, Switzerland; Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Sep;5(9):875-890. doi: 10.1016/j.bpsc.2020.04.015. Epub 2020 May 8.
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 (AHs). The 22q11.2 deletion syndrome is a neurogenetic disorder conferring proneness to develop schizophrenia, and deletion carriers (22qdel carriers) experience hallucinations to a greater extent than the general population.
We acquired 442 consecutive magnetic resonance imaging scans from 120 22qdel carriers and 110 control subjects every 3 years (age range: 8-35 years). The volume of thalamic nuclei was obtained with FreeSurfer and was compared between 22qdel carriers and control subjects and between 22qdel carriers with and without AHs. In a subgroup of 76 22qdel carriers, we evaluated the functional connectivity between thalamic nuclei affected in patients experiencing AHs and cortical regions.
As compared with control subjects, 22qdel carriers had lower and higher volumes of nuclei involved in sensory processing and cognitive functions, respectively. 22qdel carriers with AHs had a smaller volume of the medial geniculate nucleus, with deviant trajectories showing a steeper volume decrease from childhood with respect to those without AHs. Moreover, we showed an aberrant development of nuclei intercalated between the prefrontal cortex and hippocampus (the anteroventral and medioventral reuniens nuclei) and hyperconnectivity of the medial geniculate nucleus and anteroventral nucleus with the auditory cortex and Wernicke's area.
The increased connectivity of the medial geniculate nucleus and anteroventral nucleus to the auditory cortex might be interpreted as a lack of maturation of thalamocortical connectivity. Overall, our findings point toward an aberrant development of thalamic nuclei and an immature pattern of connectivity with temporal regions in relation to AHs.
多项针对精神分裂症患者的研究表明，丘脑体积及丘脑皮质连接存在异常。具体而言，与躯体感觉区的过度连接与幻听（AHs）的存在有关。22q11.2缺失综合征是一种神经遗传性疾病，易患精神分裂症，缺失携带者（22qdel携带者）比普通人群更容易出现幻觉。
我们每3年从120名22qdel携带者和110名对照受试者中获取442次连续的磁共振成像扫描（年龄范围：8 - 35岁）。使用FreeSurfer获取丘脑核体积，并在22qdel携带者与对照受试者之间以及有和没有AHs的22qdel携带者之间进行比较。在76名22qdel携带者的亚组中，我们评估了经历AHs的患者中受影响的丘脑核与皮质区域之间的功能连接。
与对照受试者相比，22qdel携带者参与感觉处理和认知功能的核体积分别较低和较高。有AHs的22qdel携带者内侧膝状体体积较小，与没有AHs的人相比，其异常轨迹显示从童年期开始体积下降更陡峭。此外，我们还发现前额叶皮质和海马之间插入的核（前腹侧和内侧腹侧 reuniens 核）发育异常，以及内侧膝状体核和前腹侧核与听觉皮质和韦尼克区的过度连接。
内侧膝状体核和前腹侧核与听觉皮质之间连接性增加可能被解释为丘脑皮质连接成熟度不足。总体而言，我们的研究结果表明，与AHs相关的丘脑核发育异常以及与颞叶区域的连接模式不成熟。
