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

Abstract

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.

MultimodalMRIassessment for first episode psychosis: A major change in the thalamus and an efficient stratification of a subgroup

“…Schizophrenia is known to affect multiple domains (Fitzsimmons, Kubicki, & Shenton, 2013; Hirjak et al, 2019; Karlsgodt, Sun, & Cannon, 2010) and set up the ground for the initial attempts of multimodal analysis. (Aine et al, 2017; Calhoun & Sui, 2016; Meng et al, 2017; Shile et al, 2016; Sui, Huster, Yu, Segall, & Calhoun, 2014; Wang et al, 2015).…”

Neurological Soft Signs (NSS) in Census-Based, Decade-Adjusted Healthy Adults, 20 to >70 Years of Age

“…Contrary to their previous findings, Hirjak et al ( 103 ) showed that in addition to the cerebellum, the brainstem and basal ganglia play a role in motor regulation. Moreover, the visuospatial control of motor acts along with the sensorimotor control, as described by the above researchers ( 63 , 101 ), bridges motor and sensory activation—thus supporting Dazzan's introduction of “integrative signs.” The group ( 104 ) even suggested a meaningful integration in terms of a dimensional or brain network approach as being more appropriate to understand motor abnormalities. Thus, they built on Andreasen's cortico-cerebellar-thalamo-cortical circuit (CCTCC) ( 64 ), a hypothetical large network which has influenced schizophrenia research during several decades.…”

“…Thus, they built on Andreasen's cortico-cerebellar-thalamo-cortical circuit (CCTCC) ( 64 ), a hypothetical large network which has influenced schizophrenia research during several decades. Hirjak et al ( 104 ) supposed that motor function or dysfunction is related to networks which encompass the cerebello-thalamo-cortical, basal ganglia and cortico-motor circuits, as well as serotonergic in addition to dopaminergic neurotransmitters. Correspondingly, the degeneration of the indicated neurotransmitter systems may contribute to age-related fine and gross motor declines, as well as to higher cognitive deficits along with peripheral factors such as a decrease in muscle strength and slowing of movements ( 105 ).…”

Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study

“… 54 Finally, recent evidence that volume alterations co-occur with aberrant brain activity in cortical and cerebellar systems subserving sensory- and psychomotor organization adds to the concept of sensorimotor dysfunctions as potential biomarkers for psychosis. 14 As such, it is not surprising that motor coordination problems would be associated with more severe manifestations of the disease.…”

“… 13 Furthermore, multimodal imaging data have shown that gray matter volume alterations co-occur with aberrant brain activity in cortical and cerebellar systems subserving sensorimotor dynamics and psychomotor organization, pointing to a defined pathophysiological substrate for sensorimotor dysfunctions and contributing to their definition as potential biomarkers for psychosis. 14 …”