The Relationship Between Axon Density, Myelination, and Fractional Anisotropy in the Human Corpus Callosum.

Published on Apr 14, 2020in Cerebral Cortex5.043
· DOI :10.1093/CERCOR/BHZ221
Patrick Friedrich11
Estimated H-index: 11
(University of Paris),
Christoph Fraenz8
Estimated H-index: 8
(RUB: Ruhr University Bochum)
+ 4 AuthorsErhan Genç16
Estimated H-index: 16
(RUB: Ruhr University Bochum)
The corpus callosum serves the functional integration and interaction between the two hemispheres. Many studies investigate callosal microstructure via diffusion tensor imaging (DTI) fractional anisotropy (FA) in geometrically parcellated segments. However, FA is influenced by several different microstructural properties such as myelination and axon density, hindering a neurobiological interpretation. This study explores the relationship between FA and more specific measures of microstructure within the corpus callosum in a sample of 271 healthy participants. DTI tractography was used to assess 11 callosal segments and gain estimates of FA. We quantified axon density and myelination via neurite orientation dispersion and density imaging (NODDI) to assess intra-neurite volume fraction and a multiecho gradient spin-echo sequence estimating myelin water fraction. The results indicate three common factors in the distribution of FA, myelin content and axon density, indicating potentially shared rules of topographical distribution. Moreover, the relationship between measures varied across the corpus callosum, suggesting that FA should not be interpreted uniformly. More specific magnetic resonance imaging-based quantification techniques, such as NODDI and multiecho myelin water imaging, may thus play a key role in future studies of clinical trials and individual differences.
📖 Papers frequently viewed together
1 Citations
4 Authors (Kiran Thapaliya, ..., Markus Barth)
20 Citations
144 Citations
#1Sebastian Ocklenburg (RUB: Ruhr University Bochum)H-Index: 31
#2Catrona Anderson (University of Otago)H-Index: 4
Last. Erhan Genç (RUB: Ruhr University Bochum)H-Index: 16
view all 14 authors...
Myelination of axons in the central nervous system is critical for human cognition and behavior. The predominant protein in myelin is proteolipid protein—making PLP1, the gene that encodes for proteolipid protein, one of the primary candidate genes for white matter structure in the human brain. Here, we investigated the relation of genetic variation within PLP1 and white matter microstructure as assessed with myelin water fraction imaging, a neuroimaging technique that has the advantage over con...
8 CitationsSource
#1Kaitlyn McLachlan (U of G: University of Guelph)H-Index: 9
#2Irene M. Vavasour (UBC: University of British Columbia)H-Index: 30
Last. Christian Beaulieu (U of A: University of Alberta)H-Index: 63
view all 8 authors...
BACKGROUND: Prenatal alcohol exposure (PAE) is linked to alterations of cerebral white matter, including volume and nonspecific diffusion magnetic resonance imaging (MRI) indices of microstructure in humans. Some animal models of PAE have demonstrated myelination deficiencies, but myelin levels have not yet been evaluated in individuals with PAE. Multiecho T2 MRI offers a quantitative method to estimate myelin water fraction (MWF; related to myelin content) noninvasively, which was used here to ...
4 CitationsSource
#1Judith Schmitz (RUB: Ruhr University Bochum)H-Index: 10
#2Christoph Fraenz (RUB: Ruhr University Bochum)H-Index: 8
Last. Sebastian Ocklenburg (RUB: Ruhr University Bochum)H-Index: 31
view all 8 authors...
Abstract Histological studies have reported microstructural hemispheric asymmetries in several cortical areas of the human brain, but reliable in vivo assessment methods have been lacking so far. Here, we used neurite orientation dispersion and density imaging (NODDI) to examine microstructural asymmetries in in vivo and determine if findings are in accordance with what has been reported in histological studies. We examined intra-neurite volume fraction (INVF), neurite orientation dispersion (OD...
20 CitationsSource
#1Md. Nasir Uddin (UM: University of Manitoba)H-Index: 1
#2Teresa D. Figley (UM: University of Manitoba)H-Index: 5
Last. Chase R. FigleyH-Index: 16
view all 5 authors...
Various MRI techniques, including myelin water imaging, T1w/T2w ratio mapping and diffusion-based imaging can be used to characterize tissue microstructure. However, surprisingly few studies have examined the degree to which these MRI measures are related within and between various brain regions. Therefore, whole-brain MRI scans were acquired from 31 neurologically-healthy participants to empirically measure and compare myelin water fraction (MWF), T1w/T2w ratio, fractional anisotropy (FA), axia...
35 CitationsSource
Myelin Water Fraction (MWF) measurements derived from quantitative Myelin Water Imaging (MWI) may detect demyelinating changes of the cerebral white matter (WM) microstructure. Here, we investigated age-related alterations of the MWF in normal aging brains of healthy volunteers utilizing two fast and clinically feasible 3D gradient and spin echo (GRASE) MWI sequences with 3 mm and 5 mm isotropic voxel size. In 45 healthy subjects (age range: 18–79 years), distinct regions of interest (ROI) were ...
22 CitationsSource
#1Catrona Anderson (University of Otago)H-Index: 4
#2Wanda M. Gerding (RUB: Ruhr University Bochum)H-Index: 13
Last. Sebastian Ocklenburg (RUB: Ruhr University Bochum)H-Index: 31
view all 12 authors...
The corpus callosum is the brain’s largest commissural fiber tract and is crucial for interhemispheric integration of neural information. Despite the high relevance of the corpus callosum for several cognitive systems, the molecular determinants of callosal microstructure are largely unknown. Recently, it was shown that genetic variations in the myelin-related proteolipid 1 gene PLP1 and the axon guidance related contactin 1 gene CNTN1 were associated with differences in interhemispheric integra...
5 CitationsSource
#1Sebastian Ocklenburg (RUB: Ruhr University Bochum)H-Index: 31
#2Patrick Friedrich (RUB: Ruhr University Bochum)H-Index: 11
Last. Erhan Genç (RUB: Ruhr University Bochum)H-Index: 16
view all 7 authors...
The left hemispheric advantage in speech perception is reflected in faster neurophysiological processing. On the basis of postmortem data, it has been suggested that asymmetries in the organization of the intrinsic microcircuitry of the posterior temporal lobe may produce this leftward timing advantage. However, whether this hypothetical structure-function relationship exists in vivo has never been empirically validated. To test this assumption, we used in vivo neurite orientation dispersion and...
33 CitationsSource
#1Erhan Genç (RUB: Ruhr University Bochum)H-Index: 16
#2Christoph Fraenz (RUB: Ruhr University Bochum)H-Index: 8
Last. Rex E. Jung (UNM: University of New Mexico)H-Index: 8
view all 9 authors...
Previous research has demonstrated that individuals with higher intelligence are more likely to have larger gray matter volume in brain areas predominantly located in parieto-frontal regions. These findings were usually interpreted to mean that individuals with more cortical brain volume possess more neurons and thus exhibit more computational capacity during reasoning. In addition, neuroimaging studies have shown that intelligent individuals, despite their larger brains, tend to exhibit lower r...
67 CitationsSource
#1Nasir Uddin (UM: University of Manitoba)H-Index: 5
#2Teresa D. Figley (UM: University of Manitoba)H-Index: 5
Last. Chase R. FigleyH-Index: 16
view all 4 authors...
: Given the growing popularity of T1 -weighted/T2 -weighted (T1 w/T2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T1 w/T2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T2 w image acquisition, and to compare the resulting T1 w/T2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare thes...
32 CitationsSource
#1Rachael G. Grazioplene (Yale University)H-Index: 10
#2Carrie E. Bearden (UCLA: University of California, Los Angeles)H-Index: 79
Last. Tyrone D. Cannon (Yale University)H-Index: 117
view all 7 authors...
Abstract Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with “fixel-based” analysis, the latter of which leverages connectivit...
26 CitationsSource
Cited By17
#1Sankalp Tikoo (Sapienza University of Rome)H-Index: 1
#2Antonio Suppa (Sapienza University of Rome)H-Index: 29
Last. Patrizia Pantano (Sapienza University of Rome)H-Index: 57
view all 8 authors...
Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involve...
#1Steven L. Meisler (Harvard University)H-Index: 1
#2John D. E. Gabrieli (McGovern Institute for Brain Research)H-Index: 157
AO_SCPLOWBSTRACTC_SCPLOWReading involves the functioning of a widely distributed brain network, and white matter tracts are responsible for sending information between constituent network nodes. Several studies have analyzed fiber bundle microstructural properties to shed insights into the neural basis of reading abilities and disabilities. Findings have been inconsistent, potentially due to small sample sizes and varying methodology. To address this, we analyzed a large data set of 690 children...
#1Oskar Hougaard Jefsen (Aarhus University Hospital)H-Index: 6
#2Maria Simonsen Speed (AU: Aarhus University)H-Index: 3
Last. Doug Speed (AU: Aarhus University)H-Index: 21
view all 5 authors...
Brief abstract null Schizophrenia is hypothesized to be caused by impaired functional integration in the brain, and this could hypothetically be caused by white matter disruptions, synaptic dysfunction, or both. Neuroimaging studies consistently show reduced fractional anisotropy, a measure of white matter integrity, in patients with schizophrenia. Using Mendelian randomization, we show that these white matter changes are likely to be the consequence of a primary synaptopathy in schizophrenia.
#1Jolien Gooijers (Allen Institute for Brain Science)H-Index: 2
#2A. De Luca (UU: Utrecht University)
Last. Stephan P. Swinnen (Allen Institute for Brain Science)H-Index: 85
view all 6 authors...
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. S...
#1Julia-Katharina Pfarr (University of Marburg)H-Index: 2
#2Katharina Brosch (University of Marburg)H-Index: 6
Last. Hannah Lemke (WWU: University of Münster)H-Index: 4
view all 21 authors...
Aberrant brain structural connectivity in major depressive disorder (MDD) has been repeatedly reported, yet many previous studies lack integration of different features of MDD with structural connectivity in multivariate modeling approaches. In n = 595 MDD patients, we used structural equation modeling (SEM) to test the intercorrelations between anhedonia, anxiety, neuroticism, and cognitive control in one comprehensive model. We then separately analyzed diffusion tensor imaging (DTI) connectivi...
#1Timothy T. Griffiths (University of Leeds)H-Index: 1
#2Robert Flather (University of Leeds)H-Index: 1
Last. Ryckie G. Wade (University of Leeds)H-Index: 12
view all 8 authors...
Cubital tunnel syndrome (CuTS) is the 2nd most common compressive neuropathy. To improve both diagnosis and the selection of patients for surgery, there is a pressing need to develop a reliable and objective test of ulnar nerve ‘health’. Diffusion tensor imaging (DTI) characterises tissue microstructure and may identify differences in the normal ulnar from those affected by CuTS. The aim of this study was to compare the DTI metrics from the ulnar nerves of healthy (asymptomatic) adults and patie...
#1Nabin Koirala (Haskins Laboratories)
#2Meaghan V. Perdue (Haskins Laboratories)H-Index: 3
Last. Nicole Landi (Haskins Laboratories)H-Index: 21
view all 5 authors...
Abstract null null Background null Studies exploring neuroanatomic correlates of reading have associated white matter tissue properties with reading disability and related componential skills (e.g., phonological and single-word reading skills). Mean diffusivity (MD) and fractional anisotropy (FA) are widely used surrogate measures of tissue microstructure with high sensitivity; however, they lack specificity for individual microstructural features. Here we investigated neurite features with high...
#1Massimo Lumaca (Royal Academy of Music)H-Index: 5
#2Giosuè Baggio (NTNU: Norwegian University of Science and Technology)H-Index: 15
Last. Peter Vuust (Royal Academy of Music)H-Index: 38
view all 3 authors...
The cultural transmission of spoken language and music relies on human capacities for encoding and recalling auditory patterns. In this experiment, we show that interindividual differences in this ability are associated with variation in the organization of cross-callosal white matter pathways. First, high-angular resolution diffusion MRI (dMRI) data were analyzed in a large participant sample (N = 51). Subsequently, these participants underwent a behavioral test that models in the laboratory th...
2 CitationsSource
#1Sebastian Ocklenburg (RUB: Ruhr University Bochum)H-Index: 31
#2Gesa Berretz (RUB: Ruhr University Bochum)H-Index: 4
Last. Patrick Friedrich (University of Bordeaux)H-Index: 11
view all 4 authors...
In the 2010s, significant progress has been made in several key areas of laterality research, including neuroimaging, genetics and comparative research. In the present article, we discuss which tre...
20 CitationsSource
#1Nakul Aggarwal (UW: University of Wisconsin-Madison)H-Index: 1
#2Jason F. Moody (UW: University of Wisconsin-Madison)
Last. Ned H. Kalin (UW: University of Wisconsin-Madison)H-Index: 87
view all 8 authors...
White matter (WM) development early in life is a critical component of brain development that facilitates the coordinated function of neuronal pathways. Additionally, alterations in WM have been implicated in various neurodevelopmental disorders, including psychiatric disorders. Because of the need to understand WM development in the weeks immediately following birth, we characterized changes in WM microstructure throughout the postnatal macaque brain during the first year of life. This is a per...