Williams John C, Tubiolo Philip N, Gil Roberto B, Zheng Zu Jie, Silver-Frankel Eilon B, Haubold Natalka K, Abeykoon Sameera K, Pham Dathy T, Ojeil Najate, Bobchin Kelly, Slifstein Mark, Weinstein Jodi J, Perlman Greg, Horga Guillermo, Abi-Dargham Anissa, Van Snellenberg Jared X
Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794.
medRxiv. 2024 Dec 22:2024.12.18.24319241. doi: 10.1101/2024.12.18.24319241.
Converging evidence from clinical neuroimaging and animal models has strongly implicated dysfunction of thalamocortical circuits in the pathophysiology of schizophrenia. Preclinical models of genetic risk for schizophrenia have shown reduced synaptic transmission from auditory thalamus to primary auditory cortex, which may represent a correlate of auditory disturbances such as hallucinations. Human neuroimaging studies, however, have found a generalized increase in resting state functional connectivity (RSFC) between whole thalamus and sensorimotor cortex in people with schizophrenia (PSZ). We aimed to more directly translate preclinical findings by specifically localizing auditory and visual thalamic nuclei in unmedicated PSZ and measuring RSFC to primary sensory cortices.
In this case-control study, 82 unmedicated PSZ and 55 matched healthy controls (HC) completed RSFC functional magnetic resonance imaging (fMRI). Auditory and visual thalamic nuclei were localized for 55 unmedicated PSZ and 46 HC who additionally completed a sensory thalamic nuclei localizer fMRI task (N = 101). Using localized nuclei as RSFC seeds we assessed group differences in auditory and visual thalamocortical connectivity and associations with positive symptom severity.
Auditory thalamocortical connectivity was not significantly different between PSZ and HC, but hyperconnectivity was associated with greater positive symptom severity in bilateral superior temporal gyrus. Visual thalamocortical connectivity was significantly greater in PSZ relative to HC in secondary and higher-order visual cortex, but not predictive of positive symptom severity.
These results indicate that visual thalamocortical hyperconnectivity is a generalized marker of schizophrenia, while hyperconnectivity in auditory thalamocortical circuits relates more specifically to positive symptom severity.
临床神经影像学和动物模型的越来越多的证据强烈表明丘脑皮质回路功能障碍与精神分裂症的病理生理学有关。精神分裂症遗传风险的临床前模型显示，从听觉丘脑到初级听觉皮层的突触传递减少，这可能是幻觉等听觉障碍的一个相关因素。然而，人类神经影像学研究发现，精神分裂症患者（PSZ）全丘脑与感觉运动皮层之间的静息态功能连接（RSFC）普遍增加。我们旨在通过在未用药的PSZ中特异性定位听觉和视觉丘脑核，并测量其与初级感觉皮层的RSFC，更直接地转化临床前研究结果。
在这项病例对照研究中，82名未用药的PSZ和55名匹配的健康对照（HC）完成了RSFC功能磁共振成像（fMRI）。对55名未用药的PSZ和46名HC进行了听觉和视觉丘脑核的定位，这些人还额外完成了一项感觉丘脑核定位fMRI任务（N = 101）。以定位的核为RSFC种子，我们评估了听觉和视觉丘脑皮质连接的组间差异以及与阳性症状严重程度的关联。
PSZ和HC之间的听觉丘脑皮质连接没有显著差异，但双侧颞上回的高连接性与更严重的阳性症状相关。相对于HC，PSZ在次级和高级视觉皮层的视觉丘脑皮质连接显著更强，但不能预测阳性症状的严重程度。
这些结果表明，视觉丘脑皮质高连接性是精神分裂症的一个普遍标志，而听觉丘脑皮质回路的高连接性更具体地与阳性症状严重程度相关。
