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1.  Motor Skill Learning Induces Changes in White Matter Microstructure and Myelination 
The Journal of Neuroscience  2013;33(50):19499-19503.
Learning a novel motor skill is associated with well characterized structural and functional plasticity in the rodent motor cortex. Furthermore, neuroimaging studies of visuomotor learning in humans have suggested that structural plasticity can occur in white matter (WM), but the biological basis for such changes is unclear. We assessed the influence of motor skill learning on WM structure within sensorimotor cortex using both diffusion MRI fractional anisotropy (FA) and quantitative immunohistochemistry. Seventy-two adult (male) rats were randomly assigned to one of three conditions (skilled reaching, unskilled reaching, and caged control). After 11 d of training, postmortem diffusion MRI revealed significantly higher FA in the skilled reaching group compared with the control groups, specifically in the WM subjacent to the sensorimotor cortex contralateral to the trained limb. In addition, within the skilled reaching group, FA across widespread regions of WM in the contralateral hemisphere correlated significantly with learning rate. Immunohistological analysis conducted on a subset of 24 animals (eight per group) revealed significantly increased myelin staining in the WM underlying motor cortex in the hemisphere contralateral (but not ipsilateral) to the trained limb for the skilled learning group versus the control groups. Within the trained hemisphere (but not the untrained hemisphere), myelin staining density correlated significantly with learning rate. Our results suggest that learning a novel motor skill induces structural change in task-relevant WM pathways and that these changes may in part reflect learning-related increases in myelination.
doi:10.1523/JNEUROSCI.3048-13.2013
PMCID: PMC3858622  PMID: 24336716
2.  Deprivation-related and use-dependent plasticity go hand in hand 
eLife  2013;2:e01273.
Arm-amputation involves two powerful drivers for brain plasticity—sensory deprivation and altered use. However, research has largely focused on sensory deprivation and maladaptive change. Here we show that adaptive patterns of limb usage after amputation drive cortical plasticity. We report that individuals with congenital or acquired limb-absence vary in whether they preferentially use their intact hand or residual arm in daily activities. Using fMRI, we show that the deprived sensorimotor cortex is employed by whichever limb individuals are over-using. Individuals from either group that rely more on their intact hands (and report less frequent residual arm usage) showed increased intact hand representation in the deprived cortex, and increased white matter fractional anisotropy underlying the deprived cortex, irrespective of the age at which deprivation occurred. Our results demonstrate how experience-driven plasticity in the human brain can transcend boundaries that have been thought to limit reorganisation after sensory deprivation in adults.
DOI: http://dx.doi.org/10.7554/eLife.01273.001
eLife digest
The loss of a limb will have a profound impact on an individual’s daily life. Nevertheless, individuals can employ a variety of behavioural strategies to adapt to the loss of, say, a hand. Some become skilled at using the residual part of their arm, while others prefer to rely on their other hand. Their brain, too, will undergo major changes. Many studies have shown that the region of the brain that controlled a given limb can be “taken over” by another part of the body if that limb is lost. This process has been previously considered to be harmful, as it has been linked to experiences of pain arising from the missing limb.
Now, Makin et al. have explored the links between changes in the behaviour of individuals missing a hand and changes in their brains. People who had been born without a hand or who had lost a hand in later life were asked to wear a device that recorded their movements as they went about their daily lives. The data revealed that people who had been born without a hand made relatively more use of their residual limb, while those who had lost their hand made relatively more use of their remaining hand.
Moreover, these differences were reflected in patterns of brain activity. In the subjects born without a hand (who were making relatively extensive use of their residual limb), the area of the brain that would otherwise control the ‘missing’ hand was activated when the subjects moved their residual limb. And in the subjects who had lost their hand, this brain region was activated when they moved their remaining hand. However, in individual subjects, the size of the effect depended on the usage preferences of the subject: for example, the minority of people who were born without a hand but nevertheless make extensive use of their intact hand showed a pattern of activation that resembled the average pattern seen in those who had lost a hand in later life.
By providing new insights into the plasticity of brain and behaviour following the loss of a hand, the work of Makin et al. may aid the development of rehabilitation techniques to help patients to optimise the use of both their residual and their intact limbs.
DOI: http://dx.doi.org/10.7554/eLife.01273.002
doi:10.7554/eLife.01273
PMCID: PMC3823186  PMID: 24220510
plasticity; neuroimaging; deprivation; Human
3.  Structural correlates of skilled performance on a motor sequence task 
The brain regions functionally engaged in motor sequence performance are well-established, but the structural characteristics of these regions and the fiber pathways involved have been less well studied. In addition, relatively few studies have combined multiple magnetic resonance imaging (MRI) and behavioral performance measures in the same sample. Therefore, the current study used diffusion tensor imaging (DTI), probabilistic tractography, and voxel-based morphometry (VBM) to determine the structural correlates of skilled motor performance. Further, we compared these findings with fMRI results in the same sample. We correlated final performance and rate of improvement measures on a temporal motor sequence task (TMST) with skeletonized fractional anisotropy (FA) and whole brain gray matter (GM) volume. Final synchronization performance was negatively correlated with FA in white matter (WM) underlying bilateral sensorimotor cortex—an effect that was mediated by a positive correlation with radial diffusivity. Multi-fiber tractography indicated that this region contained crossing fibers from the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). The identified SLF pathway linked parietal and auditory cortical regions that have been shown to be functionally engaged in this task. Thus, we hypothesize that enhanced synchronization performance on this task may be related to greater fiber integrity of the SLF. Rate of improvement on synchronization was positively correlated with GM volume in cerebellar lobules HVI and V—regions that showed training-related decreases in activity in the same sample. Taken together, our results link individual differences in brain structure and function to motor sequence performance on the same task. Further, our study illustrates the utility of using multiple MR measures and analysis techniques to specify the interpretation of structural findings.
doi:10.3389/fnhum.2012.00289
PMCID: PMC3486688  PMID: 23125826
superior longitudinal fasciculus; individual differences; motor sequence performance; fractional anisotropy; diffusion tensor imaging; gray matter volume
4.  Fornix microstructure correlates with recollection but not familiarity memory 
The fornix is the main tract between the medial temporal lobe (MTL) and medial diencephalon, both of which are critical for episodic memory. The precise involvement of the fornix in memory, however, has been difficult to ascertain since damage to this tract in human amnesics is invariably accompanied by atrophy to surrounding structures. We used diffusion-weighted imaging to investigate whether individual differences in fornix white matter microstructure in neurologically healthy participants were related to differences in memory as assessed by two recognition tasks. Higher microstructural integrity in the fornix tail was found to be associated with significantly better recollection memory. In contrast, there was no significant correlation between fornix microstructure and familiarity memory or performance on two non-mnemonic tasks. Our findings support the idea that there are distinct MTL-diencephalon pathways that subserve differing memory processes.
doi:10.1523/JNEUROSCI.4707-09.2009
PMCID: PMC2825810  PMID: 19940194
Recognition Memory; Fornix; Hippocampal function; Memory; Hippocampus; Imaging
5.  Training induces changes in white matter architecture 
Nature neuroscience  2009;12(11):1370-1371.
Although experience-dependent structural changes have been demonstrated in adult gray matter, there is little evidence for such changes in white matter. Using diffusion imaging, we detected a localised increase in fractional anisotropy, a measure of microstructure, in white matter underlying the intraparietal sulcus, following training of a complex visuo-motor skill. This provides the first evidence for training related changes in white matter structure in the healthy human adult brain.
doi:10.1038/nn.2412
PMCID: PMC2770457  PMID: 19820707
6.  Relevance of Structural Brain Connectivity to Learning and Recovery from Stroke 
The physical structure of white matter fiber bundles constrains their function. Any behavior that relies on transmission of signals along a particular pathway will therefore be influenced by the structural condition of that pathway. Diffusion-weighted magnetic resonance imaging provides localized measures that are sensitive to white matter microstructure. In this review, we discuss imaging evidence on the relevance of white matter microstructure to behavior. We focus in particular on motor behavior and learning in healthy individuals and in individuals who have suffered a stroke. We provide examples of ways in which imaging measures of structural brain connectivity can inform our study of motor behavior and effects of motor training in three different domains: (1) to assess network degeneration or damage with healthy aging and following stroke, (2) to identify a structural basis for individual differences in behavioral responses, and (3) to test for dynamic changes in structural connectivity with learning or recovery.
doi:10.3389/fnsys.2010.00146
PMCID: PMC2990506  PMID: 21119774
MRI; diffusion imaging; white matter; stroke; recovery; motor learning; human
7.  Phantom pain is associated with preserved structure and function in the former hand area 
Nature Communications  2013;4:1570-.
Phantom pain after arm amputation is widely believed to arise from maladaptive cortical reorganization, triggered by loss of sensory input. We instead propose that chronic phantom pain experience drives plasticity by maintaining local cortical representations and disrupting inter-regional connectivity. Here we show that, while loss of sensory input is generally characterized by structural and functional degeneration in the deprived sensorimotor cortex, the experience of persistent pain is associated with preserved structure and functional organization in the former hand area. Furthermore, consistent with the isolated nature of phantom experience, phantom pain is associated with reduced inter-regional functional connectivity in the primary sensorimotor cortex. We therefore propose that contrary to the maladaptive model, cortical plasticity associated with phantom pain is driven by powerful and long-lasting subjective sensory experience, such as triggered by nociceptive or top–down inputs. Our results prompt a revisiting of the link between phantom pain and brain organization.
Reorganization of the sensorimotor cortex due to loss of sensory input is implicated in phantom pain. Makin and colleagues use functional MRI to show that phantom pain experience is instead associated with maintained local functional and structural cortical representations but disrupted inter-regional connectivity.
doi:10.1038/ncomms2571
PMCID: PMC3615341  PMID: 23463013

Results 1-7 (7)