Cortical microstructure and hemispheric specialization – a diffusion-imaging analysis in younger and older adults

Characterizing cortical plasticity becomes increasingly important for identifying compensatory mechanisms and structural reserve in the aging population. While cortical thickness (CT) largely contributed to systems neuroscience, it incompletely informs about the underlying neuroplastic pathophysiology. In turn, microstructural characteristics may correspond to atrophy mechanisms in a more sensitive way, indicating a potentially necessary paradigm shift in neuroimaging. Fractional anisotropy (FA), a diffusion tensor imaging (DTI) measure, is inversely related to cortical histologic complexity. Axial (AD) and radial diffusivity (RD) are assumed to be linked to density of structures oriented perpendicular and parallel to cortical surface respectively. We hypothesized ([1][1]) that cortical DTI will reveal microstructural correlates for hemispheric specialization, particularly in the language and motor systems and ([2][2]) that lateralization of cortical DTI parameters will show an age effect, paralleling age-related changes in activation, especially in the prefrontal cortex. We re-analyzed data of healthy younger and older adult participants (n=91). DTI measures and CT were extracted from Destrieux atlas regions. Diffusion measures showed lateralization in specialized motor, language, visual, auditory, and inferior parietal cortices. Age-dependent increased lateralization was observed for DTI measures in the prefrontal, angular, superior temporal, and lateral occipital cortex. CT did not show any age-dependent alterations in lateralization. Our observations argue that cortical DTI is able to capture correlates of microstructural properties associated with functional specialization, resembling findings from histology. Age effects on diffusion measures in the integrative prefrontal and parietal areas may shed novel light on the atrophy-related plasticity in healthy aging. Significance statement Cortical thickness significantly contributed to systems neuroscience research related to cortical neuroplasticity. However, regarding the underlying cortical microstructure it remains an unspecific measure. With a strong lateralization in diffusion measures but not in thickness in specialized areas we demonstrate that cortical diffusion MRI is suitable to grasp microstructural features linked to specialization already described in histology literature. The findings in the lateralization of prefrontal and parietal cortical features may reflect age-related dynamic in cerebral activation. These results indicate the great potential of cortical diffusion tensor imaging in neuroscience and may even emphasize a necessary paradigm shift from the assessment of cortical macrostructure towards cortical microstructure for a better understanding of neuroplasticity and structure-function relationships in health and disease. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the German Research Foundation (DFG) and the National Science Foundation of China (NSFC) in project Crossmodal Learning, TRR-169/A3 (C.G.), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB936-178316478 - C1 (C.G) & C2 (G.T., B.C.), Werner Otto Stiftung (4/90, R.S.), Else Kroner-Fresenius-Stiftung (grant numbers 2020_EKES.16, R.S.). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Physician Chamber of Hamburg gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability is limited by the approval of Ethics Committee [1]: #ref-1 [2]: #ref-2