Department of Psychology, Northwestern University, Evanston, IL, USA.
Department of Psychology, University of Colorado Boulder, Boulder, CO, USA.
Psychol Med. 2021 Jun;51(8):1289-1298. doi: 10.1017/S0033291719004161. Epub 2020 Feb 3.
Consistent with pathophysiological models of psychosis, temporal disturbances in schizophrenia spectrum populations may reflect abnormal cortical (e.g. prefrontal cortex) and subcortical (e.g. striatum) cerebellar connectivity. However, few studies have examined associations between cerebellar connectivity and timing dysfunction in psychosis populations, and none have been conducted in youth at clinical high-risk (CHR) for psychosis. Thus, it is currently unknown if impairments in temporal processes are present in CHR youth or how they may be associated with cerebellar connectivity and worsening of symptoms.
A total of 108 (56 CHR/52 controls) youth were administered an auditory temporal bisection task along with a resting state imaging scan to examine cerebellar resting state connectivity. Positive and negative symptoms at baseline and 12 months later were also quantified.
Controlling for alcohol and cannabis use, CHR youth exhibited poorer temporal accuracy compared to controls, and temporal accuracy deficits were associated with abnormal connectivity between the bilateral anterior cerebellum and a right caudate/nucleus accumbens striatal cluster. Poor temporal accuracy accounted for 11% of the variance in worsening of negative symptoms over 12 months.
Behavioral findings suggest CHR youth perceive durations of auditory tones as shortened compared to objective time, which may indicate a slower internal clock. Poorer temporal accuracy in CHR youth was associated with abnormalities in brain regions involved in an important cerebellar network implicated in prominent pathophysiological models of psychosis. Lastly, temporal accuracy was associated with worsening of negative symptoms across 12 months, suggesting temporal dysfunction may be sensitive to illness progression.
与精神分裂症谱系人群的精神病理性模型一致，时间紊乱可能反映了皮质（例如前额叶皮层）和皮质下（例如纹状体）小脑连接的异常。然而，很少有研究检查精神分裂症谱系人群的小脑连接与计时功能障碍之间的关联，也没有在精神病高危（CHR）的年轻人中进行过此类研究。因此，目前尚不清楚 CHR 青少年是否存在时间过程障碍，以及它们如何与小脑连接和症状恶化相关。
共对 108 名（56 名 CHR/52 名对照）年轻人进行了听觉时间二分法任务和静息状态成像扫描，以检查小脑静息状态连接。还在基线和 12 个月后量化了阳性和阴性症状。
在控制酒精和大麻使用的情况下，CHR 青少年的时间准确性较对照组差，时间准确性缺陷与双侧前小脑与右侧尾状核/伏隔核纹状体簇之间的异常连接有关。在 12 个月内，较差的时间准确性解释了阴性症状恶化的 11%的方差。
行为学发现表明，CHR 青少年感知的听觉音的时长比客观时间短，这可能表明内部时钟较慢。CHR 青少年较差的时间准确性与参与重要小脑网络的大脑区域异常有关，该网络与精神病理模型中的突出病理生理学有关。最后，时间准确性与 12 个月内的阴性症状恶化有关，这表明时间功能障碍可能对疾病进展敏感。
