Neurological soft signs (NSS) have been considered to be one of the most promising biomarkers and endophenotypes for schizophrenia spectrum disorders. However, one of the main unresolved issues is the definition in NSS which have been conventionally considered as clinical neurological signs without localized brain regions. Increasing evidence from neuroimaging studies has suggested these NSS are partly localizable and maybe associated with deficits in specific brain areas.

Dr. CHAN Raymond and his team from the Institute of Psychology of Chinese Academy of Sciences have been challenging their traditional view of NSS. They recently provided a rigorous meta-analysis of neuroimaging data on schizophrenia and showed that f NSS are associated with both localized brain structures and connection concerning the “cerebello-thalamo-prefrontal” brain network.

Based on the results, Dr. CHAN and his collaborators further examined whether there would be similar functional connectivity abnormalities demonstrated in people with first-episode schizophrenia and their unaffected first-degree relatives. By so doing, they administered the motor coordination signs, Fist-Edge-Palm (FEP) imaging paradigm (a functional imaging paradigm designed by Dr. CHAN’s team), to 13 people with first-episode schizophrenia, 14 unaffected first-degree relatives, and 14 healthy controls. Functional connectivity was performed using the psychophysiological interaction (PPI) analysis in order to evaluate the abnormalities between the sensorimotor cortex and frontal regions when participants performed the FEP task compared to simple motor tasks.

Their findings showed that people with schizophrenia demonstrated hypoactivation of the left frontal-parietal region comparing to healthy controls. Interestingly, the unaffected first-degree relatives of the patients also showed a significant but milder hypoactivation in the same regions comparing to healthy controls. In contrast, healthy controls and the first-degree relatives of patients with schizophrenia showed significant activation of the left middle frontal gyrus. Moreover, with increase in task complexity, significant functional connectivity was observed between the sensorimotor cortex and the right frontal gyrus in healthy controls but not in patients with first episode schizophrenia.

These findings suggest that activity of the left frontal-parietal and frontal regions may be neurofunctional correlates of neurological soft signs, which in turn may be a potential endophenotype of schizophrenia. These findings add valuable information to the understanding of the origin and underlying neural mechanism of motor coordination neurological soft signs. Dr. CHAN and his team are now recruiting a larger sample of first-episode and their non-psychotic siblings to replicate their current findings.

This study was supported by grants from the National Science Fund China Outstanding Investigator Award, the Beijing Training Project for the Leading Talents in Science & Technology, the Key Laboratory of Mental Health, and the International Partnership Programme for Creative Research Team.

The paper is now available online in NeuroImage: Clinical.