Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis

Abstract

Background: Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas.

Method: We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included.

Results: The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus.

Conclusions: Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.

Keywords: activation; brain; estimation; imaging; likelihood; meta-analysis; neurological; psychosis; schizophrenia; signs; soft.

Fig. 1.

The flow chart of articles selecting for activation likelihood estimation-structural magnetic resonance imaging (ALE-sMRI) and activation likelihood estimation-functional magnetic resonance imaging (ALE-fMRI) analyses.

Fig. 2.

Activation likelihood estimation-structural magnetic resonance imaging (ALE-sMRI) results. ALE meta-analysis results of the sMRI. Red labels (neurological soft signs [NSS] gray matters) are the ALE meta-analysis results of the NSS scores negative correlated gray matter foci. Blue labels (NSS white matters) are the ALE meta-analysis results of the NSS scores negative correlated white matter foci (P < .05, false discovery rate [FDR] corrected).

Fig. 3.

Activation likelihood estimation-functional magnetic resonance imaging (ALE-fMRI) results of individual groups. ALE meta-analysis results of the fMRI (go/no-go task) of mental disorders and healthy controls separately. Red labels (patients) are the ALE meta-analysis results of the brain activation foci of the mental disorder patients when doing the inhibition response. Blue labels (healthy controls) are the ALE meta-analysis results of the brain activation foci of the healthy controls when doing the inhibition response (P < .01, false discovery rate [FDR] corrected).

Fig. 4.

Activation likelihood estimation-functional magnetic resonance imaging (ALE-fMRI) results of groups difference. ALE meta-analysis results of the fMRI (go/no-go task) for the group difference between mental disorders and healthy controls. Red labels (patients > healthy controls) are the ALE meta-analysis results of the hyperactivated brain foci of the mental disorder patients when doing the inhibition response. Blue labels (healthy controls > patients) are the ALE meta-analysis results of the attenuated activation brain foci of the mental disorders when doing the inhibition response (P < .01, false discovery rate [FDR] corrected).