Patterns of co-altered brain structure and function underlying neurological soft signs in schizophrenia spectrum disorders

Dusan Hirjak, Mahmoud Rashidi, Stefan Fritze, Alina L. Bertolino, Lena S. Geiger, Zhenxiang Zang, Katharina M. Kubera, Mike M. Schmitgen, Fabio Sambataro, Vince D. Calhoun, Matthias Weisbrod, Heike Tost, Robert C. Wolf

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Neurological soft signs (NSS) comprise a broad range of subtle neurological deficits and are considered to represent external markers of sensorimotor dysfunction frequently found in mental disorders of presumed neurodevelopmental origin. Although NSS frequently occur in schizophrenia spectrum disorders (SSD), specific patterns of co-altered brain structure and function underlying NSS in SSD have not been investigated so far. It is unclear whether gray matter volume (GMV) alterations or aberrant brain activity or a combination of both, are associated with NSS in SSD. Here, 37 right-handed SSD patients and 37 matched healthy controls underwent motor assessment and magnetic resonance imaging (MRI) at 3 T. NSS were examined on the Heidelberg NSS scale. We used a multivariate data fusion technique for multimodal MRI data—multiset canonical correlation and joint independent component analysis (mCCA + jICA)—to investigate co-altered patterns of GMV and intrinsic neural fluctuations (INF) in SSD patients exhibiting NSS. The mCCA + jICA model indicated two joint group-discriminating components (temporoparietal/cortical sensorimotor and frontocerebellar/frontoparietal networks) and one modality-specific group-discriminating component (p <.05, FDR corrected). NSS motor score was associated with joint frontocerebellar/frontoparietal networks in SSD patients. This study highlights complex neural pathomechanisms underlying NSS in SSD suggesting aberrant structure and function, predominantly in cortical and cerebellar systems that critically subserve sensorimotor dynamics and psychomotor organization.

Original languageEnglish (US)
Pages (from-to)5029-5041
Number of pages13
JournalHuman Brain Mapping
Issue number17
StatePublished - Dec 1 2019


  • gray matter volume
  • mCCA + jICA
  • motor abnormalities
  • neurological soft signs
  • resting-state functional MRI
  • schizophrenia spectrum disorders

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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