Jan Scholz

Training induces changes in white-matter architecture

Although experience-dependent structural changes have been found in adult gray matter, there is little evidence for such changes in white matter. Using diffusion imaging, we detected a localized 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, to the best of our knowledge, the first evidence for training-related changes in white-matter structure in the healthy human adult brain.

Motor skill learning induces changes in white matter microstructure and myelination.

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.

MRI characteristics of the substantia nigra in Parkinson's disease: a combined quantitative T1 and DTI study.

The substantia nigra contains dopaminergic cells that project to the striatum and are affected by the neurodegenerative process that appears in Parkinsons disease (PD). For accurate differential diagnosis and for disease monitoring the availability of a sensitive and non-invasive biomarker for Parkinsons disease would be essential. Although there has been notable progress in studying correlates of nigral degeneration by means of magnetic resonance imaging (MRI) in the past decade, MRI and analysis techniques that allow accurate high-resolution mapping of the SN within a clinically acceptable acquisition time are still elusive. The main purpose of the preliminary study was to evaluate the potential role of the driven equilibrium single pulse observation of T1 (DESPOT1) method for delineation of the SN and differentiation of PD patients from healthy control subjects (n=10 in each group). We also investigated whether additional measures that can be obtained with diffusion tensor imaging (DTI) can further improve the MRI-guided discrimination between PD patients and controls. Our results show that the DESPOT1 method allows for a clear visualisation of the SN as a whole. Volumetric comparisons between ten PD patients and ten healthy subjects revealed significantly smaller volumes in patients for both the left and the right sides when the whole SN was considered. Combining SN volumetry and its connectivity with the thalamus improved the classification sensitivity to 100% and specificity to 80% for PD (discriminant function analysis with leave-one-out cross validation). Combining DESPOT1 imaging and DTI could therefore serve as a diagnostic marker for idiopathic Parkinsons disease in the future.

Phantom pain is associated with preserved structure and function in the former hand area

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.

White matter integrity in the vicinity of Broca's area predicts grammar learning success.

Humans differ substantially in their ability to implicitly extract structural regularities from experience, as required for learning the grammar of a language. The mechanisms underlying this fundamental inter-individual difference, which may determine initial success in language learning, are incompletely understood. Here, we use diffusion tensor magnetic resonance imaging (DTI) to determine white matter integrity around Brocas area, which is crucially involved in both natural and artificial language processing. Twelve young, right-handed individuals completed an artificial grammar learning task, and DTI of their brains were acquired. Inter-individual variability in performance correlated with white matter integrity (increasing fractional anisotropy (FA)) in fibres arising from Brocas area (left BA 44/45), but not from its right-hemispheric homologue. Variability in performance based on superficial familiarity did not show this association. Moreover, when Brocas area was used as a seed mask for probabilistic tractography, we found that mean FA values within the generated tracts was higher in subjects with better grammar learning. Our findings provide the first evidence that integrity of white matter fibre tracts arising from Brocas area is intimately linked with the ability to extract grammatical rules. The relevance of these findings for acquisition of a natural language has to be established in future studies.

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.

Differences between chimpanzees and bonobos in neural systems supporting social cognition

Our two closest living primate relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), exhibit significant behavioral differences despite belonging to the same genus and sharing a very recent common ancestor. Differences have been reported in multiple aspects of social behavior, including aggression, sex, play and cooperation. However, the neurobiological basis of these differences has only been minimally investigated and remains uncertain. Here, we present the first ever comparison of chimpanzee and bonobo brains using diffusion tensor imaging, supplemented with a voxel-wise analysis of T1-weighted images to specifically compare neural circuitry implicated in social cognition. We find that bonobos have more gray matter in brain regions involved in perceiving distress in both oneself and others, including the right dorsal amygdala and right anterior insula. Bonobos also have a larger pathway linking the amygdala with the ventral anterior cingulate cortex, a pathway implicated in both top-down control of aggressive impulses as well as bottom-up biases against harming others. We suggest that this neural system not only supports increased empathic sensitivity in bonobos, but also behaviors like sex and play that serve to dissipate tension, thereby limiting distress and anxiety to levels conducive with prosocial behavior.

Addressing a systematic vibration artifact in diffusion-weighted MRI

We have identified and studied a pronounced artifact in diffusion‐weighted MRI on a clinical system. The artifact results from vibrations of the patient table due to low‐frequency mechanical resonances of the system which are stimulated by the low‐frequency gradient switching associated with the diffusion‐weighting. The artifact manifests as localized signal‐loss in images acquired with partial Fourier coverage when there is a strong component of the diffusion‐gradient vector in the left–right direction. This signal loss is caused by local phase ramps in the image domain which shift the apparent k‐space center for a particular voxel outside the covered region. The local signal loss masquerades as signal attenuation due to diffusion, severely disrupting the quantitative measures associated with diffusion‐tensor imaging (DTI). We suggest a way to improve the interpretation of affected DTI data by including a co‐regressor which accounts for the empirical response of regions affected by the artifact. We also demonstrate that the artifact may be avoided by acquiring full k‐space data, and that subsequent increases in TE can be avoided by employing parallel acceleration. Hum Brain Mapp, 2010.

Reassessing cortical reorganization in the primary sensorimotor cortex following arm amputation

The brain’s ability to reorganise itself is key to our recovery from injuries, but the subsequent mismatch between old and new organisation may lead to pain. Makin et al. argue against this ‘maladaptive plasticity’ theory by showing that phantom pain in upper limb amputees is independent of cortical remapping.

The rate of visuomotor adaptation correlates with cerebellar white-matter microstructure.

Convergent experimental evidence points to the cerebellum as a key neural structure mediating adaptation to visual and proprioceptive perturbations. In a previous study, we have shown that activity in the anterior cerebellum varies with the rate of learning, with fast learners exhibiting more activity in this region than slow learners. Here, we investigated whether this variability in behavior may partly reflect inter‐individual differences in the structural properties of cerebellar white‐matter output tracts. For this purpose, we used diffusion‐weighted magnetic resonance imaging to estimate fractional anisotropy (FA), and correlated the FA with the rate of adaptation to an optical rotation in 11 subjects. We found that FA in a region consistent with the superior cerebellar peduncle (SCP), containing fibers connecting the cerebellar cortex with motor and premotor cortex, was positively correlated with the rate of adaptation but not with the general level of performance or the initial deviation. The same pattern was observed in a region of the lateral posterior cerebellum. In contrast, FA in the angular gyrus of the posterior parietal cortex correlated positively both with the rate of adaptation and the overall level of performance. Our results show that the rate of learning a visuomotor task is associated with FA of cerebellar pathways. Hum Brain Mapp, 2009.