Aberrant cerebellar neural activity and cerebro-cerebellar functional connectivity involving executive dysfunction in schizophrenia with primary negative symptoms

  • Ju Gao
  • Xiaowei Tang
  • Congjie Wang
  • Miao Yu
  • Weiwei Sha
  • Xiang Wang
  • Hongying Zhang
  • Xiangrong ZhangEmail author
  • Xiaobin ZhangEmail author


Deficit schizophrenia (DS) is a distinct subtype of schizophrenia characterized by primary and enduring negative symptoms. More severe executive dysfunctions were observed in DS patients, however, the associated neuroimaging characteristics, especially cerebellar functional anomalies in DS, remain largely unknown. We employed resting-state functional and structural MRI data of 106 male participants, including data from 29 DS patients, 39 non-deficit schizophrenia (NDS) patients and 38 healthy controls (HCs). Z-standardized fractional amplitude of low-frequency fluctuation (zfALFF) values were calculated in order to examine spontaneous regional brain activity. Cerebro-cerebellar functional connectivity and changes in the volume of gray matter in the cerebellum were also examined. Relative to the HCs, both DS and NDS patients exhibited decreased zfALFF in the bilateral cerebellar lobules VIII and IX. The zfALFF in the left Crus II was lower in DS patients compared to NDS patients. No significant difference was observed in the volume of cerebellar gray matter among the three groups. Compared with NDS patients, cerebro-cerebellar functional connectivity analysis revealed increased connectivity in the left orbital medial frontal cortex and right putamen regions in DS patients. Reduced zfALFF in the left Crus II in the DS group was significantly positively correlated with Stroop Color and Word scores, while negatively correlated with Trail-Making Test part B scores. The increased functional connectivity in the right putamen in DS patients was significantly positively correlated with Animal Naming Test and semantic Verbal Fluency Test scores. These results highlight cerebellar functional abnormality in DS patients and provide insight into the pathophysiological mechanism of executive dysfunction.


Deficit schizophrenia Executive function Cerebellum Resting-state fMRI Cerebro-cerebellar circuit 



We sincerely thank Gavin P. Reynold for polishing the article.

Author contributions

All authors reviewed and contributed to the final version of the manuscript. Additional contributions are stated below.

Ju Gao was responsible for data analyses and preparation of the manuscript. Xiaowei Tang and Hongying Zhang performed the experiments. Congjie Wang and Miao Yu contributed to the data analyses and interpretation of findings. Weiwei Sha and Xiaobin Zhang were responsible for obtaining ethical approval and performing neurocognitive assessment. Xiang Wang offered the Chinese version of SDS. Xiangrong Zhang formulated the hypothesis, designed the experimental strategy and obtained funding for the study.


This study was supported by the National Natural Science Foundation of China (NSFC) (Nos. 81371474, 81571314, 91132727 and 31671144), National Key Research and Development Program (2016YFC1307002 and 2018YFC1314303), Medical key talent projects in Jiangsu, Province (ZDRCA2016075), the six talent peaks projects in Jiangsu Province (No.2015-WSN-071) and the Shanghai Changning Medical Research Program (CNKW2016Y17).

Compliance with ethical standards

Ethical statements

Informed consent was obtained from all individual participants included in the study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

All authors declare no conflict of interest.

Supplementary material

11682_2018_32_MOESM1_ESM.docx (72 kb)
ESM 1 (DOCX 71 kb)


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Authors and Affiliations

  • Ju Gao
    • 1
    • 2
  • Xiaowei Tang
    • 1
    • 3
  • Congjie Wang
    • 4
  • Miao Yu
    • 1
  • Weiwei Sha
    • 3
  • Xiang Wang
    • 5
  • Hongying Zhang
    • 6
  • Xiangrong Zhang
    • 1
    Email author
  • Xiaobin Zhang
    • 3
    Email author
  1. 1.Department of Geriatric PsychiatryNanjing Brain Hospital Affiliated to Nanjing Medical UniversityNanjingChina
  2. 2.Department I of Geriatric PsychiatryShanghai Changning Mental Health CenterShanghaiChina
  3. 3.Department of PsychiatryWutaishan Hospital of YangzhouYangzhouChina
  4. 4.Department of PsychiatryHuai’an No. 3 People’s HospitalHuai’anChina
  5. 5.Medical Psychological Institute of the Second Xiangya HospitalChangshaChina
  6. 6.Department of RadiologySubei People’s Hospital of Jiangsu provinceYangzhouChina

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