Virginia Conde

Structural brain plasticity in Parkinson's disease induced by balance training

We investigated morphometric brain changes in patients with Parkinsons disease (PD) that are associated with balance training. A total of 20 patients and 16 healthy matched controls learned a balance task over a period of 6 weeks. Balance testing and structural magnetic resonance imaging were performed before and after 2, 4, and 6 training weeks. Balance performance was re-evaluated after ∼20 months. Balance training resulted in performance improvements in both groups. Voxel-based morphometry revealed learning-dependent gray matter changes in the left hippocampus in healthy controls. In PD patients, performance improvements were correlated with gray matter changes in the right anterior precuneus, left inferior parietal cortex, left ventral premotor cortex, bilateral anterior cingulate cortex, and left middle temporal gyrus. Furthermore, a TIME × GROUP interaction analysis revealed time-dependent gray matter changes in the right cerebellum. Our results highlight training-induced balance improvements in PD patients that may be associated with specific patterns of structural brain plasticity. In summary, we provide novel evidence for the capacity of the human brain to undergo learning-related structural plasticity even in a pathophysiological disease state such as in PD.

Dynamic modulation of intrinsic functional connectivity by transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique capable of modulating cortical excitability and thereby influencing behavior and learning. Recent evidence suggests that bilateral tDCS over both primary sensorimotor cortices (SM1) yields more prominent effects on motor performance in both healthy subjects and chronic stroke patients than unilateral tDCS over SM1. To better characterize the underlying neural mechanisms of this effect, we aimed to explore changes in resting-state functional connectivity during both stimulation types. In a randomized single-blind crossover design, 12 healthy subjects underwent functional magnetic resonance imaging at rest before, during, and after 20 min of unilateral, bilateral, and sham tDCS stimulation over SM1. Eigenvector centrality mapping (ECM) was used to investigate tDCS-induced changes in functional connectivity patterns across the whole brain. Uni- and bilateral tDCS over SM1 resulted in functional connectivity changes in widespread brain areas compared with sham stimulation both during and after stimulation. Whereas bilateral tDCS predominantly modulated changes in primary and secondary motor as well as prefrontal regions, unilateral tDCS affected prefrontal, parietal, and cerebellar areas. No direct effect was seen under the stimulating electrode in the unilateral condition. The time course of changes in functional connectivity in the respective brain areas was nonlinear and temporally dispersed. These findings provide evidence toward a network-based understanding regarding the underpinnings of specific tDCS interventions.

Anodal transcranial direct current stimulation (tDCS) over supplementary motor area (SMA) but not pre-SMA promotes short-term visuomotor learning

BACKGROUND Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability and thereby influencing motor behaviour and learning. HYPOTHESIS While there is increasing knowledge about the importance of the primary motor cortex (M1) in short- and long-term motor skill learning, little is known about the role of secondary motor areas such as the supplementary and pre-supplementary motor area (SMA/pre-SMA) especially in short-term motor performance. Since SMA but not pre-SMA is directly connected to M1, we hypothesize that anodal tDCS over SMA but not pre-SMA will facilitate visuomotor learning. METHODS We applied anodal tDCS (tDCS(anodal)) over left SMA, pre-SMA or M1 (n=12 in each group) while subjects performed a visuomotor pinch force task (VPFT) with their right hand and compared VPFT performance relative to sham (tDCS(sham)). RESULTS For the first time, we could show that apart from tDCS(anodal) over left M1 also SMA but not pre-SMA stimulation promotes short-term improvements in visuomotor learning relative to tDCS(sham). CONCLUSIONS Our findings provide novel evidence about the role of SMA in short-term visuomotor performance. This knowledge might be beneficial in developing hypothesis-driven clinical studies in neurorehabilitation.

Cortical thickness in primary sensorimotor cortex influences the effectiveness of paired associative stimulation

Non-invasive brain stimulation protocols in general and paired associative stimulation (PAS) in particular seem to alter corticospinal excitability and thereby to influence behaviour with a high degree of inter-subject variability. The cause of this variability is multidimensional and to some extent still unknown. Here, we tested the hypothesis that individual variations in cortical thickness can explain some of the variability of PAS-induced excitability changes. Ten minutes of a facilitatory PAS protocol (PAS(LTP)) rapidly increased corticospinal excitability in the majority of the subjects (14/19 subjects) while others showed no such effect (5/19 subjects). A whole brain correlation analysis based on high resolution T1-weighted images revealed a significant positive relationship of PAS(LTP)-induced excitability changes with cortical thickness of the underlying left sensorimotor cortex (SM1) only. Cortical thickness alone, among other potential influencing factors, explained about half of the PAS(LTP) variance, indicating that subjects with a strong after-effect were those with thicker gray matter in this region. Based on these findings, we provide novel evidence that local brain structure influences the individual amount of functional plasticity induced by PAS(LTP). While the underlying neurophysiological and/or anatomical reasons for this effect still remain elusive at this point, we conclude that cortical thickness should be considered as an important and until now not recognized modulating factor in studies employing non-invasive brain stimulation techniques.

Bidirectional gray matter changes after complex motor skill learning

Long-term motor skill learning has been consistently shown to result in functional as well as structural changes in the adult human brain. However, the effect of short learning periods on brain structure is not well understood. In the present study, subjects performed a sequential pinch force task (SPFT) for 20 min on 5 consecutive days. Changes in brain structure were evaluated with anatomical magnetic resonance imaging (MRI) scans acquired on the first and last day of motor skill learning. Behaviorally, the SPFT resulted in sequence-specific learning with the trained (right) hand. Structural gray matter (GM) alterations in left M1, right ventral premotor cortex (PMC) and right dorsolateral prefrontal cortex (DLPFC) correlated with performance improvements in the SPFT. More specifically we found that subjects with strong sequence-specific performance improvements in the SPFT also had larger increases in GM volume in the respective brain areas. On the other hand, subjects with small behavioral gains either showed no change or even a decrease in GM volume during the time course of learning. Furthermore, cerebellar GM volume before motor skill learning predicted (A) individual learning-related changes in the SPFT and (B) the amount of structural changes in left M1, right ventral PMC and DLPFC. In summary, we provide novel evidence that short-term motor skill learning is associated with learning-related structural brain alterations. Additionally, we showed that practicing a motor skill is not exclusively accompanied by increased GM volume. Instead, bidirectional structural alterations explained the variability of the individual learning success.

Effect of transcranial direct current stimulation (tDCS) during complex whole body motor skill learning

The aim of the study was to investigate tDCS effects on motor skill learning in a complex whole body dynamic balance task (DBT). We hypothesized that tDCS over the supplementary motor area (SMA), a region that is known to be involved in the control of multi-joint whole body movements, will result in polarity specific changes in DBT learning. In a randomized sham-controlled, double-blinded parallel design, we applied 20 min of tDCS over the supplementary motor area (SMA) and prefrontal cortex (PFC) while subjects performed a DBT. Anodal tDCS over SMA with the cathode placed over contralateral PFC impaired motor skill learning of the DBT compared to sham. This effect was still present on the second day of training. Reversing the polarity (cathode over SMA, anode over PFC) did not affect motor skill learning neither on the first nor on the second day of training. To better disentangle whether the impaired motor skill learning was due to a modulation of SMA or PFC, we performed an additional control experiment. Here, we applied anodal tDCS over SMA together with a larger and presumably more ineffective electrode (cathode) over PFC. Interestingly this alternative tDCS electrode setup did not affect the outcome of DBT learning. Our results provide novel evidence that a modulation of the (right) PFC seems to impair complex multi-joint motor skill learning. Hence, future studies should take the positioning of both tDCS electrodes into account when investigating complex motor skill learning.

Reversed timing-dependent associative plasticity in the human brain through interhemispheric interactions

Spike timing-dependent plasticity (STDP) has been proposed as one of the key mechanisms underlying learning and memory. Repetitive median nerve stimulation, followed by transcranial magnetic stimulation (TMS) of the contralateral primary motor cortex (M1), defined as paired-associative stimulation (PAS), has been used as an in vivo model of STDP in humans. PAS-induced excitability changes in M1 have been repeatedly shown to be time-dependent in a STDP-like fashion, since synchronous arrival of inputs within M1 induces long-term potentiation-like effects, whereas an asynchronous arrival induces long-term depression (LTD)-like effects. Here, we show that interhemispheric inhibition of the sensorimotor network during PAS, with the peripheral stimulation over the hand ipsilateral to the motor cortex receiving TMS, results in a LTD-like effect, as opposed to the standard STDP-like effect seen for contralateral PAS. Furthermore, we could show that this reversed-associative plasticity critically depends on the timing interval between afferent and cortical stimulation. These results indicate that the outcome of associative stimulation in the human brain depends on functional network interactions (inhibition or facilitation) at a systems level and can either follow standard or reversed STDP-like mechanisms.

Instrument specific use-dependent plasticity shapes the anatomical properties of the corpus callosum: a comparison between musicians and non-musicians

Long-term musical expertise has been shown to be associated with a number of functional and structural brain changes, making it an attractive model for investigating use-dependent plasticity in humans. Physiological interhemispheric inhibition (IHI) as examined by transcranial magnetic stimulation has been shown to be correlated with anatomical properties of the corpus callosum as indexed by fractional anisotropy (FA). However, whether or not IHI or the relationship between IHI and FA in the corpus callosum can be modified by different musical training regimes remains largely unknown. We investigated this question in musicians with different requirements for bimanual finger movements (piano and string players) and non-expert controls. IHI values were generally higher in musicians, but differed significantly from non-musicians only in string players. IHI was correlated with FA in the posterior midbody of the corpus callosum across all participants. Interestingly, subsequent analyses revealed that this relationship may indeed be modulated by different musical training regimes. Crucially, while string players had greater IHI than non-musicians and showed a positive structure-function relationship, the amount of IHI in pianists was comparable to that of non-musicians and there was no significant structure-function relationship. Our findings indicate instrument specific use-dependent plasticity in both functional (IHI) and structural (FA) connectivity of motor related brain regions in musicians.

Enhancing the effect of repetitive I-wave paired-pulse TMS (iTMS) by adjusting for the individual I-wave periodicity.

BackgroundRepeated application of paired-pulse TMS over the primary motor cortex (M1) in human subjects with an inter-pulse interval (IPI) of 1.5 ms (iTMS1.5 ms) has been shown to significantly increase paired-pulse MEP (ppMEP) amplitudes during the stimulation period and increased single-pulse MEP amplitudes for up to 10 minutes after termination of iTMS.ResultsHere we show in a cross-over design that a modified version of the iTMS1.5 ms protocol with an I-wave periodicity adjusted to the individual I1-peak wave latency (iTMSadj) resulted in a stronger effect on ppMEPs relative to iTMS1.5 ms.ConclusionsBased on these findings, our results indicate that the efficiency of iTMS strongly depends on the individual choice of the IPI and that parameter optimization of the conventional iTMS1.5 ms protocol might improve the outcome of this novel non-invasive brain stimulation technique.

Task-irrelevant auditory feedback facilitates motor performance in musicians

An efficient and fast auditory–motor network is a basic resource for trained musicians due to the importance of motor anticipation of sound production in musical performance. When playing an instrument, motor performance always goes along with the production of sounds and the integration between both modalities plays an essential role in the course of musical training. The aim of the present study was to investigate the role of task-irrelevant auditory feedback during motor performance in musicians using a serial reaction time task (SRTT). Our hypothesis was that musicians, due to their extensive auditory–motor practice routine during musical training, have superior performance and learning capabilities when receiving auditory feedback during SRTT relative to musicians performing the SRTT without any auditory feedback. Behaviorally, we found that auditory feedback reinforced SRTT performance of the right hand (referring to absolute response speed) while learning capabilities remained unchanged. This finding highlights a potential important role for task-irrelevant auditory feedback in motor performance in musicians, a finding that might provide further insight into auditory–motor integration independent of the trained musical context.