Bernhard Sehm

A Comparison between Uni- and Bilateral tDCS Effects on Functional Connectivity of the Human Motor Cortex.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been shown to induce changes in motor performance and learning. Recent studies indicate that tDCS is capable of modulating widespread neural network properties within the brain. However the temporal evolution of online- and after-effects of tDCS on functional connectivity (FC) within and across the stimulated motor cortices (M1) still remain elusive. In the present study, two different tDCS setups were investigated: (i) unilateral M1 tDCS (anode over right M1, cathode over the contralateral supraorbital region) and (ii) bilateral M1 tDCS (anode over right M1, cathode over left M1). In a randomized single-blinded cross-over design, 12 healthy subjects underwent functional magnetic resonance imaging at rest before, during and after 20 min of either bi-, unilateral, or sham M1 tDCS. Seed-based FC analysis was used to investigate tDCS-induced changes across and within M1. We found that bilateral M1 tDCS induced (a) a decrease in interhemispheric FC during stimulation and (b) an increase in intracortical FC within right M1 after termination of the intervention. While unilateral M1 tDCS also resulted in similar effects during stimulation, no such changes could be observed after termination of tDCS. Our results provide evidence that depending on the electrode montage, tDCS acts upon a modulation of either intracortical and/or interhemispheric processing of M1.

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.

Impairment of emotional facial expression and prosody discrimination due to ischemic cerebellar lesions

A growing literature points to a specific role of the cerebellum in affect processing. However, understanding of affect processing disturbances following discrete cerebellar lesions is limited. We administered the Tübingen Affect Battery to assess recognition of emotional facial expression and emotional prosody in 15 patients with a cerebellar infarction and 10 age-matched controls. On emotional facial expression tasks, patients compared to controls showed impaired selection and matching of facial affect. On prosody tasks, patients showed marked impairments in naming affect and discriminating incongruencies. These deficits were more pronounced for negative affects. Our results confirm a significant role of the cerebellum in processing emotional recognition, a component of social cognition.

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.

Facilitation of Inferior Frontal Cortex by Transcranial Direct Current Stimulation Induces Perceptual Learning of Severely Degraded Speech

Perceptual learning requires the generalization of categorical perceptual sensitivity from trained to untrained items. For degraded speech, perceptual learning modulates activation in a left-lateralized network, including inferior frontal gyrus (IFG) and inferior parietal cortex (IPC). Here we demonstrate that facilitatory anodal transcranial direct current stimulation (tDCSanodal) can induce perceptual learning in healthy humans. In a sham-controlled, parallel design study, 36 volunteers were allocated to the three following intervention groups: tDCSanodal over left IFG, IPC, or sham. Participants decided on the match between an acoustically degraded and an undegraded written word by forced same-different choice. Acoustic degradation varied in four noise-vocoding levels (2, 3, 4, and 6 bands). Participants were trained to discriminate between minimal (/Tisch/-FISCH) and identical word pairs (/Tisch/-TISCH) over a period of 3 d, and tDCSanodal was applied during the first 20 min of training. Perceptual sensitivity (d′) for trained word pairs, and an equal number of untrained word pairs, was tested before and after training. Increases in d′ indicate perceptual learning for untrained word pairs, and a combination of item-specific and perceptual learning for trained word pairs. Most notably for the lowest intelligibility level, perceptual learning occurred only when tDCSanodal was applied over left IFG. For trained pairs, improved d′ was seen on all intelligibility levels regardless of tDCS intervention. Over left IPC, tDCSanodal did not modulate learning but instead introduced a response bias during training. Volunteers were more likely to respond “same,” potentially indicating enhanced perceptual fusion of degraded auditory with undegraded written input. Our results supply first evidence that neural facilitation of higher-order language areas can induce perceptual learning of severely degraded speech.

Language learning without control: The role of the pfc

Learning takes place throughout lifetime but differs in infants and adults because of the development of the PFC, a brain region responsible for cognitive control. To test this hypothesis, adults were investigated in a language learning paradigm under inhibitory, cathodal transcranial direct current stimulation over PFC. The experiment included a learning session interspersed with test phases and a test-only session. The stimulus material required the learning of grammatical dependencies between two elements in a novel language. In a parallel design, cathodal transcranial direct current stimulation over the left PFC, right PFC, or sham stimulation was applied during the learning session but not during the test-only session. Event-related brain potentials (ERPs) were recorded during both sessions. Whereas no ERP learning effects were observed during the learning session, different ERP learning effects as a function of prior stimulation type were found during the test-only session, although behavioral learning success was equal across conditions. With sham stimulation, the ERP learning effect was reflected in a centro-parietal N400-like negativity indicating lexical processes. Inhibitory stimulation over the left PFC, but not over the right PFC, led to a late positivity similar to that previously observed in prelinguistic infants indicating associative learning. The present data demonstrate that adults can learn with and without cognitive control using different learning mechanisms. In the presence of cognitive control, adult language learning is lexically guided, whereas it appears to be associative in nature when PFC control is downregulated.