TY - JOUR
T1 - A macroscopic link between interhemispheric tract myelination and cortico-cortical interactions during action reprogramming
AU - Lazari, Alberto
AU - Salvan, Piergiorgio
AU - Verhagen, Lennart
AU - Cottaar, Michiel
AU - Papp, Daniel
AU - van der Werf, Olof Jens
AU - Gavine, Bronwyn
AU - Kolasinski, James
AU - Webster, Matthew
AU - Stagg, Charlotte J
AU - Rushworth, Matthew F S
AU - Johansen-Berg, Heidi
N1 - © 2022. The Author(s).
PY - 2022/7/22
Y1 - 2022/7/22
N2 - Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them. As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects. We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics. These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.
AB - Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them. As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects. We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics. These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.
KW - Adult
KW - Animals
KW - Axons
KW - Brain
KW - Brain Mapping
KW - Humans
KW - Myelin Sheath
KW - White Matter
KW - INTERINDIVIDUAL DIFFERENCES
KW - VENTRAL PREMOTOR CORTEX
KW - CONDUCTION-VELOCITY
KW - IMPULSE CONDUCTION
KW - MEDIAL FRONTAL-CORTEX
KW - FUNCTIONAL CONNECTIVITY
KW - PRIMARY MOTOR CORTEX
KW - INDIVIDUAL-DIFFERENCES
KW - WHITE-MATTER MICROSTRUCTURE
KW - THEORETICAL BASIS
U2 - 10.1038/s41467-022-31687-5
DO - 10.1038/s41467-022-31687-5
M3 - Article
C2 - 35869067
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4253
ER -