Neurological soft signs in adolescents are associated with brain structure and postural control

Bonke, Elena (2023): Neurological soft signs in adolescents are associated with brain structure and postural control. Dissertation, LMU München: Fakultät für Biologie
Graduate School of Systemic Neurosciences (GSN)

Abstract

Neurological soft signs (NSS) are minor deviations from the norm in sensory and motor performance. NSS exist in the general population but are more frequently found in cohorts with neurodevelopmental disorders. NSS are considered a diffuse and unspecific marker of altered neurodevelopment but receive increasing attention since the presence of NSS in children has been found to be predictive of psychiatric disorders in late adolescence. To date, only little is known about potential neurodevelopmental alterations that may underlay the presence of NSS. The prevalence of NSS has been shown to decrease during adolescence as part of continued neural development and brain re-wiring processes. Therefore, adolescence has been proposed as an important phase for the manifestation or outgrowing of NSS. The underlying mechanisms that may underly this process, however, are largely unknown. As NSS are subtle signs and commonly identified by subjective observer-based neurological examinations, quantitative tools may help to objectively investigate functional and structural correlates associated with NSS. For the work included in this dissertation, healthy adolescent athletes from three European countries were investigated. All participants underwent a neurological examination, resulting in a categorization of participants into groups with and without NSS (NSS+/NSS-). A total NSS score was calculated to provide a continuous measure spanning the whole spectrum of NSS. Two quantitative tools were used to investigate functional and structural correlates of NSS in healthy adolescents: Study I) Instrumented force plate measures to investigate postural control (Bonke et al., 2023), and Study II) Structural magnetic resonance imaging to investigate brain morphology and white matter microstructure (Bonke et al., 2022). Study I aimed to investigate the incremental value of instrumented force plate measures in addition to observer-based neurological examinations. Such associations have not been assessed before but are important for capturing subtle alterations in postural control. This will help to acquire a more comprehensive assessment of motor development. We found no statistically significant differences in postural control between NSS+ and NSS- group. However, participants performing non-optimal in the diadochokinesis sub-test measuring pronation/supination of forearms showed significantly reduced postural control in the medial-lateral (ML) direction. Moreover, the total NSS score correlated significantly with postural control performance in the ML direction. Findings from this study reveal that adolescents with NSS, and in particular adolescents that perform non-optimal in pronation/supination movements of the forearms also perform worse in ML postural control assessed by force plate assessments. As pronation/supination movements of forearms and ML postural control continue to mature until adolescence, it can be assumed that these functions are related and may indicate altered motor development. Study II aimed to identify and characterize NSS-related brain structure alterations using structural magnetic resonance imaging. NSS-related brain structure alterations have not yet been investigated in healthy adolescents. However, this investigation is of high relevance to better understand potential alterations in adolescent brain-rewiring processes related to NSS. Using T1-weighted imaging, we found significantly higher gyrification in the left superior frontal and parietal lobe in the group of adolescents with NSS, likely reflecting alterations in synaptic pruning. We did not find differences in cortical volume or thickness. Using diffusion tensor imaging, we found lower tissue fractional anisotropy (FAt) and higher tissue radial diffusivity (RDt) in widespread white matter clusters in the group of adolescents with NSS, likely indicating alterations in myelination. Findings from this study reveal that NSS in healthy adolescents are associated with brain structure alterations that can be objectively quantified using magnetic resonance imaging. As of now, the relevance of NSS-related brain structure alterations in otherwise healthy adolescents is not fully understood. Future studies should assess whether these alterations may explain the described association between NSS and psychiatric disorders. In summary, the work presented in this doctoral dissertation uses two different quantitative measures to objectively investigate functional and structural differences between adolescents with and without NSS. Insights derived from this work show the beneficial use of instrumented tools to complement neurological examinations for a better understanding of functional and structural correlates of NSS. This work will help to generate a more complete picture of NSS-related developmental alterations and potentially related psychiatric vulnerabilities. Future research should make use of larger and more representative datasets to replicate, as well as extend our findings. Specific attention should be drawn on the investigation of factors that contribute to the development of NSS, longitudinal studies that allow to capture NSS-related alterations in developmental trajectories, as well as on investigating the underlying neural mechanisms of NSS.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie ; Graduate School of Systemic Neurosciences (GSN)
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 18. September 2023
• 1. Bericht­erstatter:in: Koerte, Inga