A review of evidences for macroscopic reorganisation from in vivo imaging studies Written by András Jakab University of Debrecen / ETH Zürich Contact: firstname.lastname@example.org
Overview The recent advent of in vivo imaging techniques like diffusion tensor or functional magnetic resonance imaging gave rise to studies that „reinvent” classical or forgotten aspects of the human macroscopic brain anatomy One such topic is to investigate the structure of major white matter structures and their connections („hodology”- Catani, 2007), this new-old aim was electrified by the diffusion weighted and diffusion tensor imaging (the former now An illustration of the arcuate fasciculus celebrating 25th anniversary: Johansen- signifies the role of neuroimaging in Berg et al., 2012) anatomical studiesCatani M (2007) From hodology to function. Brain 130: 602-605.Le Bihan D, Johansen-Berg H (2012) Diffusion MRI at 25: Exploring brain tissuestructure and function. Neuroimage, in press
Overview The brain’s response to reinforced stimuli and adaptation to a changing environment is considered the backbone of neuroplasticity, which is predominantly understood as the synaptic reorganization within the cortex Significant effort is now carried out to reveal macroscopic changes to the brain structure after learning tasks, which vastly challenges the classical views of neuroplasticity as a phenomenon embedded in the electrical and chemical milieu We aimed at reviewing studies that convey evidence for the possible macroscopic change after extensive learning tasks or challenging environments. We focused on imaging studies describing changes to white matter structure and studies that try to elucidate the possible mechanisms that realize and modulate such an effect. Illustration by H. Cushing
Plastic changes in grey matter thickness 3 months of intensive juggling training is performed in a group of 12 people whereas 12 controls are provided as „non-jugglers” (experiment: 3-ball cascade juggling) Voxel-based morphometry is employed to reveal fine changes of grey matter volume on anatomical MR images Transient changes take place in grey matter in specific motion-selective areas Though the microscopic changes underlying dynamic structural alterations remain unclear Figure by Draganski et al.Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A (2004): Neuroplasticity:Changes in grey matter induced by training. Nature 427: 311-312.
Plastic changes in grey matter thickness Licensed London taxi drivers with extensive navigation experience were analyzed and compared with those of control subjects who did not drive taxis Voxel-based morphometry is employed to reveal fine changes of grey matter volume on anatomical MR images Key findings included: The posterior hippocampi of taxi drivers were significantly larger Hippocampal volume correlated with the amount of time spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus) Figure by Maguire et al.Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J, Frackowiak RSJ, Frith CD(2000): Navigation-related structural change in the hippocampi of taxi drivers.Proceedings of the National Academy of Sciences 97: 4398-4403.
Plastic changes in white matter properties Experience-dependent structural changes have been found in adult gray matter, there is little evidence for such changes in white matter A longitudinal study with juggling training is conducted in a group of 24+24 human subjects, DTI is used to quantify the changes in diffusion anisotropy The anisotropy, i.e. the orderedness of diffusion is increased after training, located in the parieto-occipital sulcus Figure by Scholz et al.Scholz J, Klein MC, Behrens TEJ, Johansen-Berg H (2009): Training induces changes inwhite-matter architecture. Nat Neurosci 12: 1370-1371.
Plastic changes in white matter properties They examined whether 100 hr of intensive remedial instruction affected the white matter of 8- to 10-year-old poor readers Prior to instruction, poor readers had signiﬁcantly lower FA than good readers in a region of the left anterior centrum semiovale Poor readers were given remedial instruction which helps to improve reading skills The region where significant difference was found between poor and normal readers coincides with the region which showed FA increase after the mediation FA increased, meaning an increased orderedness of axonal diffusion (mechanism unkown) Figure by Keller et al.Keller TA, Just MA (2009): Altering Cortical Connectivity: Remediation-Induced Changesin the White Matter of Poor Readers. Neuron 64: 624-631.
Learning-related white matter properties The following studies give indirect evidence that long („lifelong”) conditioning induce macroscopic changes in white matter structure or affect development The time-dependency and timecourse of such changes is not yet understood Diverse regions are reported to repond to these stimuli by increased diffusion anisotropy valuesImfeld A, Oechslin MS, Meyer M, Loenneker T, Jancke L (2009): White matter plasticity inthe corticospinal tract of musicians: A diffusion tensor imaging study. Neuroimage 46: 600-607.Bengtsson SL, Nagy Z, Skare S, Forsman L, Forssberg H, Ullen F (2005): Extensive pianopracticing has regionally specific effects on white matter development. Nat Neurosci 8:1148-1150.Lee B, Park J, Jung WH, Kim HS, Oh JS, Choi C, Jang JH, Kang D, Kwon JS (2010): Whitematter neuroplastic changes in long-term trained players of the game of “Baduk” (GO): Avoxel-based diffusion-tensor imaging study. Neuroimage 52: 9-19.
Plastic changes in white matter properties Using voxel-based analysis (VBA) of fractional anisotropy (FA) measures of fiber tracts, the authors investigated the effect of working memory training on structural connectivity in an interventional study The amount of working memory training correlated with increased FA in the white matter regions adjacent to the intraparietal sulcus and the anterior part of the body of the corpus callosum after training. Figure by Takeuchi et al. Takeuchi H, Sekiguchi A, Taki Y, Yokoyama S, Yomogida Y, Komuro N, Yamanouchi T, Suzuki S, Kawashima R (2010): Training of Working Memory Impacts Structural Connectivity. The Journal of Neuroscience 30: 3297-3303.
White matter plasticity in adults and the elderly? If the hypothesis is justifiable that anisotropy (FA) increase is the sign of plastic changes in white matter, it still remains unclear if this ability is available through the entire lifespan Over a period of 180 days training, Lövdén and colleagues revealed that white matter changes were presend in older subjects as well (indicated by a slight increase in axial diffusivities (i.e. diffusion magnitude along the axonal direction) The potential application relying on such basic knowledge is of vast importance for the rehabilitation science Figure by Lövdén et al. Lövdén M, Bodammer NC, Kühn S, Kaufmann J, Schütze H, Tempelmann C, Heinze H, Düzel E, Schmiedek F, Lindenberger U (2010): Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia 48: 3878-3883.
Plastic changes affected diffusion anisotropy.Where does anisotropy originate from? Two major mechanisms were found to affect anisotropy: The dense packaging of axons where the cell membranes delimit diffusion (90% effect) Myelin sheet: myelin layers affect diffusion anisotropy (approx. 10% effect) Neither neurofilaments nor intracellular organella affects anisotropy according to experimental studies Figures by Beaulieu et al. Beaulieu C (2002): The basis of anisotropic water diffusion in the nervous system ? a technical review. NMR Biomed 15: 435-455.
Age related changes of white matter anisotropy White matter anisotropy changes during development until adulthood Different regions follow different myelination patterns relative to each other, some areas continuing changes in the 20s However, the potential to dynamically change myelination in the adulthood is questionable Figure by Jakab et al. Schmithorst VJ, Wilke M, Dardzinski BJ, Holland SK (2002) Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study. Radiology. 222(1):212-8.
Possible mechanisms for white matterneuroplastic chages Significant changes in the axonal membrane structure or new growth of axons are not viable and unproven mechanisms for neuroplastic changes in white matter It has been proposed that learning-associated myelination could be responsible for the observations Synaptic efficiency could be regulated by changing the transmission speed of axons by modifying myelin Figure by Bengtsson et al.: piano content; „wiring together” could therefore mean a practice improves FA values in commissural pathways. more efficient synchronization of remote connectionsFields RD (2005): Myelination: An Overlooked Mechanism of Synaptic Plasticity? TheNeuroscientist 11: 528-531.Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, Fields RD (2006):Astrocytes Promote Myelination in Response to Electrical Impulses. Neuron 49: 823-832.
Possible mechanisms for white matterneuroplastic chages Oligodendrocytes mediate the myelin production in response to electrical signals, insulating the axon Electrically active axons signal adjacent oligodendrocytes, triggering local cellular signaling pathways that promote specific myelination of active axons. Vesicular glutamate released from axons signals neighboring oligodendrocytes to form cholesterol-rich signaling domains and locally produce myelin basic protein.Araque A, Navarrete M (2011): Electrically Driven Insulation in the Central NervousSystem. Science 333: 1587-1588.H. Wake, P. R. Lee, R. D. Fields (2011) Control of Local Protein Synthesis and InitialEvents in Myelination by Action Potentials Science 333, 1647.
Perspectives In vivo imaging delivered interesting but contradictory results on the possible changes of white matter during neuroplasticity It is not yet obvious which mechanisms are most responsible for this effect Myelination is potentially modulated in the adulthood representing a meaningful way to retune and synchronize brain circuits Still far from the practical application of this knowledge, there is no mean to intervene into this mechanism to facilitate better brain regeneration after neuronal (axonal) loss Horacio Salinas: „Brain Repair” for the New York Time Magazine