Cerebellar contributions to neurological soft signs in healthy young adults

Abstract

Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin, e.g., in patients with schizophrenia and autism. Yet NSS are also present in healthy individuals suggesting a neurodevelopmental signature of motor function, probably as a continuum between health and disease. So far, little is known about the neural mechanisms underlying these motor phenomena in healthy persons, and it is even less known whether the cerebellum contributes to NSS expression. Thirty-seven healthy young adults (mean age = 23 years) were studied using high-resolution structural magnetic resonance imaging (MRI) and "resting-state" functional MRI at three Tesla. NSS levels were measured using the "Heidelberg Scale." Cerebellar gray matter volume was investigated using cerebellum-optimized voxel-based analysis methods. Cerebellar function was assessed using regional homogeneity (ReHo), a measure of local network strength. The relationship between cerebellar structure and function and NSS was analyzed using regression models. There was no significant relationship between cerebellar volume and NSS (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). Positive associations with cerebellar lobule VI activity were found for the "motor coordination" and "hard signs" NSS domains. A negative relationship was found between lobule VI activity and "complex motor task" domain (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). The data indicate that in healthy young adults, distinct NSS domains are related to cerebellar activity, specifically with activity of cerebellar subregions with known cortical somatomotor projections. In contrast, cerebellar volume is not predictive of NSS in healthy persons.

Neural mechanism and heritability of complex motor sequence and audiovisual integration: A healthy twin study

“…Activation of the pre‐ and postcentral gyri, the temporal gyrus, the insula and the cerebellar areas during the FEP motor sequence, and activation of the precentral, superior temporal and fusiform gyri during audiovisual integration were consistent with evidence from previous structural MRI studies of complex motor sequencing in healthy individuals (Dazzan et al, ; Hirjak et al, ; Thomann et al, ). These findings suggest that the FEP and AVI tasks can capture the complex motor sequencing and sensory integration functions.…”

“…Although many studies have focused on these impairments in psychiatric disorders, their underlying neural mechanism and whether these impairments are heritable is not known. Empirical evidence has demonstrated that the grey matter volumes of the pre‐ and postcentral gyri, and the frontal and temporal lobes were associated with impairments in complex motor sequencing, sensory integration, or both in healthy individuals (Dazzan et al, ; Hirjak, Thomann, Kubera, Stieltjes, & Wolf, ; Hirjak, Wolf, Kubera, Stieltjes, & Thomann, ; Thomann, Hirjak, Kubera, Stieltjes, & Wolf, ). While the evidence for the association between complex motor sequencing/sensory integration and subcortical volumes was found in patients with schizophrenia, similar associations have not been found in healthy controls (Bottmer et al, ; Dazzan et al, ; Heuser et al, 2011; Ho, Mola, & Andreasen, ; Kong, Bachmann, Thomann, Essig, & Schroder, ; Mouchet‐Mages et al, ; Thomann et al, ; Venkatasubramanian, Jayakumar, Gangadhar, & Keshavan, ).…”

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

“…We chose to investigate neural correlates of NSS with restingstate fMRI because functional brain alterations underlying NSS in SSD are intrinsic and therefore they may be better examined without the confounders of a non-ecological setting (e.g., scanner and paradigm) and the patient's motivational bias. Previous MRI studies have confirmed this notion and successfully used resting-state fMRI (e.g., regional homogeneity (ReHo) to study NSS in healthy individuals (Hirjak, Thomann, Kubera, Stieltjes, & Wolf, 2016;. ReHo is a voxel-based measure of focal connectivity that evaluates the synchronicity of the time series between a given voxel and each of its 26 neighboring voxels (Zang, Jiang, Lu, He, & Tian, 2004).…”

Morphological and functional alterations in patients with schizophrenia spectrum disorders

“…In patients with schizophrenia, a dysfunction of the cerebellum has been related to neurological soft signs. Hirjak et al [4] performed a structural and resting-state magnetic resonance imaging (MRI) investigation in 37 healthy young adults symptoms can be described by a reverse U-shaped curve. Neurocognitive assessments show that schizophrenia patients have deficits in Theory of Mind (ToM), which refers to the capacity to make inferences about one's own and others' thoughts and intentions.…”