Indices of callosal axonal density and radius from diffusion MRI relate to upper and lower limb motor performance

Understanding the relationship between human brain structure and functional outcome is of critical importance in systems neuroscience. Diffusion MRI (dMRI) studies show that fractional anisotropy (FA) is predictive of motor control, underscoring the importance of white matter (WM). However, as FA is a surrogate marker of WM, we aim to shed new light on the structural underpinnings of this relationship by applying a multi-compartment microstructure model providing axonal density/radius indices. Sixteen young adults (7 males / 9 females), performed a hand/foot tapping task and a Multi Limb Reaction Time task. Furthermore, diffusion (STEAM &HARDI) and fMRI (localizer hand/foot activations) data were obtained. Sphere ROIs were placed on activation clusters with highest t value to guide interhemispheric WM tractography. Axonal radius/density indices of callosal parts intersecting with tractography were calculated from STEAM, using the diffusion-time dependent AxCaliber model, and correlated with behavior. Results indicated a possible association between larger apparent axonal radii of callosal motor fibers of the hand and higher tapping scores of both hands, and faster selection-related processing (normalized reaction) times (RTs) on diagonal limb combinations. Additionally, a trend was present for faster selection-related processing (normalized reaction) times for lower limbs being related with higher axonal density of callosal foot motor fibers, and for higher FA values of callosal motor fibers in general being related with better tapping and faster selection-related processing (normalized reaction) times. Whereas FA is sensitive in demonstrating associations with motor behavior, axon radius/density (i.e., fiber geometry) measures are promising to explain the physiological source behind the observed FA changes, contributing to deeper insights into brain-behavior interactions.

[1]  Timothy Edward John Behrens,et al.  The CONNECT project: Combining macro- and micro-structure , 2013, NeuroImage.

[2]  J. Klein,et al.  Human Motor Corpus Callosum: Topography, Somatotopy, and Link between Microstructure and Function , 2007, The Journal of Neuroscience.

[3]  Stephen E. Rose,et al.  Brain microstructure and morphology of very preterm-born infants at term equivalent age: Associations with motor and cognitive outcomes at 1 and 2 years , 2020, NeuroImage.

[4]  P. Basser,et al.  In vivo measurement of axon diameter distribution in the corpus callosum of rat brain. , 2009, Brain : a journal of neurology.

[5]  Rachael D. Seidler,et al.  Differential Callosal Contributions to Bimanual Control in Young and Older Adults , 2011, Journal of Cognitive Neuroscience.

[6]  Andrea Tacchino,et al.  Structural integrity of callosal midbody influences intermanual transfer in a motor reaction‐time task , 2011, Human brain mapping.

[7]  Tao Guo,et al.  Fixel-based analysis reveals fiber-specific alterations during the progression of Parkinson’s disease , 2020, NeuroImage: Clinical.

[8]  A. Scheibel,et al.  Fiber composition of the human corpus callosum , 1992, Brain Research.

[9]  M. Gazzaniga,et al.  Dissociation of Spatial and Temporal Coupling in the Bimanual Movements of Callosotomy Patients , 1996 .

[10]  Timothy Edward John Behrens,et al.  Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skills , 2007, NeuroImage.

[11]  S. Swinnen,et al.  Bimanual coordination and corpus callosum microstructure in young adults with traumatic brain injury: a diffusion tensor imaging study. , 2010, Journal of neurotrauma.

[12]  F. Castellanos,et al.  Constrained by Our Connections: White Matter's Key Role in Interindividual Variability in Visual Working Memory Capacity , 2014, The Journal of Neuroscience.

[13]  Peter Boesiger,et al.  Combining fMRI and DTI: A framework for exploring the limits of fMRI-guided DTI fiber tracking and for verifying DTI-based fiber tractography results , 2008, NeuroImage.

[14]  Derek K. Jones,et al.  Estimating axon conduction velocity in vivo from microstructural MRI , 2019, NeuroImage.

[15]  Oren Civier,et al.  Fixel-based Analysis of Diffusion MRI: Methods, Applications, Challenges and Opportunities , 2021, NeuroImage.

[16]  John Ashburner,et al.  An Image Registration-Based Method for EPI Distortion Correction Based on Opposite Phase Encoding (COPE) , 2020, WBIR.

[17]  Alard Roebroeck,et al.  Robust and Fast Markov Chain Monte Carlo Sampling of Diffusion MRI Microstructure Models , 2018, Front. Neuroinform..

[18]  G. Yovel,et al.  In vivo correlation between axon diameter and conduction velocity in the human brain , 2014, Brain Structure and Function.

[19]  Alexander Leemans,et al.  Transcallosal connectivity of the human cortical motor network , 2016, Brain Structure and Function.

[20]  Mariana Lazar,et al.  Axonal deficits in young adults with High Functioning Autism and their impact on processing speed , 2014, NeuroImage: Clinical.

[21]  Steen Moeller,et al.  Evaluation of slice accelerations using multiband echo planar imaging at 3T , 2013, NeuroImage.

[22]  J. Tanji,et al.  Neuronal activity in cortical motor areas related to ipsilateral, contralateral, and bilateral digit movements of the monkey. , 1988, Journal of neurophysiology.

[23]  S. Lange,et al.  Adjusting for multiple testing--when and how? , 2001, Journal of clinical epidemiology.

[24]  Tim B. Dyrby,et al.  Orientationally invariant indices of axon diameter and density from diffusion MRI , 2010, NeuroImage.

[25]  S. Swinnen,et al.  Diffusion tensor imaging metrics of the corpus callosum in relation to bimanual coordination: Effect of task complexity and sensory feedback , 2013, Human brain mapping.

[26]  F. Esposito,et al.  Distributed corpus callosum involvement in amyotrophic lateral sclerosis: a deterministic tractography study using q-ball imaging , 2013, Journal of Neurology.

[27]  Alexander Leemans,et al.  Structural and Functional Cortical Connectivity Mediating Cross Education of Motor Function , 2017, The Journal of Neuroscience.

[28]  Mark Jenkinson,et al.  Evaluating fibre orientation dispersion in white matter: Comparison of diffusion MRI, histology and polarized light imaging , 2017, NeuroImage.

[29]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[30]  P. Basser,et al.  Axcaliber: A method for measuring axon diameter distribution from diffusion MRI , 2008, Magnetic resonance in medicine.

[31]  Rainer Goebel,et al.  Robust and fast nonlinear optimization of diffusion MRI microstructure models , 2017, NeuroImage.

[32]  M. Peters,et al.  A nontrivial motor performance difference between right-handers and left-handers: attention as intervening variable in the expression of handedness. , 1987, Canadian journal of psychology.

[33]  Stuart Crozier,et al.  Apparent Fibre Density: A novel measure for the analysis of diffusion-weighted magnetic resonance images , 2012, NeuroImage.

[34]  Yaniv Assaf,et al.  Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the human brain , 2005, NeuroImage.

[35]  Y. Assaf,et al.  Diffusion Tensor Imaging (DTI)-based White Matter Mapping in Brain Research: A Review , 2007, Journal of Molecular Neuroscience.

[36]  J. Buonaccorsi,et al.  Rapid foot-tapping but not hand-tapping ability is different between relapsing-remitting and progressive multiple sclerosis. , 2020, Multiple sclerosis and related disorders.

[37]  C. Beaulieu The Biological Basis of Diffusion Anisotropy , 2009 .

[38]  Yaniv Assaf,et al.  Micro-structural assessment of short term plasticity dynamics , 2013, NeuroImage.

[39]  Stephan P. Swinnen,et al.  Complexity of Central Processing in Simple and Choice Multilimb Reaction-Time Tasks , 2014, PloS one.

[40]  J. Polimeni,et al.  Blipped‐controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g‐factor penalty , 2012, Magnetic resonance in medicine.

[41]  Stephan P. Swinnen,et al.  Bimanual motor deficits in older adults predicted by diffusion tensor imaging metrics of corpus callosum subregions , 2013, Brain Structure and Function.

[42]  Derek K. Jones,et al.  White matter organization in developmental coordination disorder: A pilot study exploring the added value of constrained spherical deconvolution , 2018, NeuroImage: Clinical.

[43]  Jan Sijbers,et al.  ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data , 2009 .

[44]  Derek K. Jones,et al.  Including diffusion time dependence in the extra-axonal space improves in vivo estimates of axonal diameter and density in human white matter , 2016, NeuroImage.

[45]  S. P. Swinnen,et al.  Interactions between brain structure and behavior: The corpus callosum and bimanual coordination , 2014, Neuroscience & Biobehavioral Reviews.

[46]  B. Preilowski,et al.  Possible contribution of the anterior forebrain commissures to bilateral motor coordination. , 1972, Neuropsychologia.

[47]  Julien Cohen-Adad,et al.  In vivo histology of the myelin g-ratio with magnetic resonance imaging , 2015, NeuroImage.

[48]  T. S. Monteiro,et al.  Prefronto-Striatal Structural Connectivity Mediates Adult Age Differences in Action Selection , 2020, The Journal of Neuroscience.

[49]  Daihong Liu,et al.  Fiber-specific white matter reductions in amyotrophic lateral sclerosis , 2020, NeuroImage: Clinical.

[50]  Virginia B Penhune,et al.  Annals of the New York Academy of Sciences a Sensitive Period for Musical Training: Contributions of Age of Onset and Cognitive Abilities , 2022 .

[51]  Steen Moeller,et al.  Multiband multislice GE‐EPI at 7 tesla, with 16‐fold acceleration using partial parallel imaging with application to high spatial and temporal whole‐brain fMRI , 2010, Magnetic resonance in medicine.

[52]  H. Vanharanta,et al.  Influences of Aging, Gender, and Handedness on Motor Performance of Upper and Lower Extremities , 1996, Perceptual and motor skills.

[53]  Dante Mantini,et al.  Fiber-specific variations in anterior transcallosal white matter structure contribute to age-related differences in motor performance , 2020, NeuroImage.

[54]  L. Wald,et al.  Corpus callosum axon diameter relates to cognitive impairment in multiple sclerosis , 2019, Annals of clinical and translational neurology.

[55]  C. Barut,et al.  RELATIONSHIPS BETWEEN HAND AND FOOT PREFERENCES , 2007, The International journal of neuroscience.

[56]  Jelle Veraart,et al.  On the scaling behavior of water diffusion in human brain white matter , 2019, NeuroImage.

[57]  M S Gazzaniga,et al.  Anterior and posterior callosal contributions to simultaneous bimanual movements of the hands and fingers. , 2000, Brain : a journal of neurology.

[58]  Thomas R. Knösche,et al.  White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI , 2013, NeuroImage.

[59]  Onur Güntürkün,et al.  The Relationship Between Axon Density, Myelination, and Fractional Anisotropy in the Human Corpus Callosum. , 2020, Cerebral cortex.

[60]  S. Berman,et al.  Modeling conduction delays in the corpus callosum using MRI-measured g-ratio , 2019, NeuroImage.

[61]  Alan Connelly,et al.  Investigating white matter fibre density and morphology using fixel-based analysis , 2017, NeuroImage.

[62]  Jan Sijbers,et al.  Multi-tissue constrained spherical deconvolution for improved analysis of multi-shell diffusion MRI data , 2014, NeuroImage.

[63]  Derek K. Jones,et al.  Noninvasive quantification of axon radii using diffusion MRI , 2020, eLife.

[64]  P. Basser Diffusion MRI: From Quantitative Measurement to In vivo Neuroanatomy , 2009 .

[65]  Stephen E. Rose,et al.  Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions , 2015, NeuroImage: Clinical.

[66]  P. Basser,et al.  New modeling and experimental framework to characterize hindered and restricted water diffusion in brain white matter , 2004, Magnetic resonance in medicine.

[67]  Derek K. Jones,et al.  Impact of b‐value on estimates of apparent fibre density , 2020, bioRxiv.

[68]  Bryon A. Mueller,et al.  The development of corpus callosum microstructure and associations with bimanual task performance in healthy adolescents , 2008, NeuroImage.

[69]  Gianfranco Genta,et al.  Features and performance of some outlier detection methods , 2011 .

[70]  S. Swinnen Intermanual coordination: From behavioural principles to neural-network interactions , 2002, Nature Reviews Neuroscience.

[71]  S. P. Swinnen,et al.  White matter organization in relation to upper limb motor control in healthy subjects: exploring the added value of diffusion kurtosis imaging , 2013, Brain Structure and Function.

[72]  Stamatios N. Sotiropoulos,et al.  An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging , 2016, NeuroImage.

[73]  R. Ivry,et al.  Callosotomy patients exhibit temporal uncoupling during continuous bimanual movements , 2002, Nature Neuroscience.