A review of evidences for macroscopic reorganisation from in vivo imaging studies

Written by András JakabUniversity of Debrecen / ETH Zürich

Contact: jakab@vision.ee.ethz.ch

Neuroplasticity

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 celebrating 25th anniversary: Johansen-Berg et al., 2012)

Catani M (2007) From hodology to function. Brain 130: 602-605.

Le Bihan D, Johansen-Berg H (2012) Diffusion MRI at 25: Exploring brain tissue structure and function. Neuroimage, in press

An illustration of the arcuate fasciculus signifies the role of neuroimaging in

anatomical studies

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

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.

Figure by Draganski et al.

Though the microscopic changes underlying dynamic structural alterations remain unclear

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)

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.

Figure by Maguire et al.

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

Scholz J, Klein MC, Behrens TEJ, Johansen-Berg H (2009): Training induces changes in white-matter architecture. Nat Neurosci 12: 1370-1371.

Figure by Scholz et al.

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

Keller TA, Just MA (2009): Altering Cortical Connectivity: Remediation-Induced Changes in the White Matter of Poor Readers. Neuron 64: 624-631.

Figure by Keller et al.

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)

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 values

Imfeld A, Oechslin MS, Meyer M, Loenneker T, Jancke L (2009): White matter plasticity in the 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 piano practicing 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): White matter neuroplastic changes in long-term trained players of the game of “Baduk” (GO): A voxel-based diffusion-tensor imaging study. Neuroimage 52: 9-19.

Plastic changes in white matter properties

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.

Figure by Takeuchi et al.

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.

White matter plasticity in adults and the elderly?

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.

Figure by Lövdén et al.

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

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

Beaulieu C (2002): The basis of anisotropic water diffusion in the nervous system ? a technical review. NMR Biomed 15: 435-455.

Figures by Beaulieu et al.

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

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.

Figure by Jakab et al.

Possible mechanisms for white matter neuroplastic 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 content; „wiring together” could therefore mean a more efficient synchronization of remote connections

Fields RD (2005): Myelination: An Overlooked Mechanism of Synaptic Plasticity? The Neuroscientist 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.

Figure by Bengtsson et al.: piano practice improves FA values in commissural pathways.

Possible mechanisms for white matter neuroplastic chages Oligodendrocytes mediate the myelin production in response to electrical signals,

insulating the axon

Araque A, Navarrete M (2011): Electrically Driven Insulation in the Central Nervous System. Science 333: 1587-1588.

H. Wake, P. R. Lee, R. D. Fields (2011) Control of Local Protein Synthesis and Initial Events in Myelination by Action Potentials Science 333, 1647.

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.

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