Causal evidence for a coordinated temporal interplay within the language network.

Recent neurobiological models on language suggest that auditory sentence comprehension is supported by a coordinated temporal interplay within a left-dominant brain network, including the posterior inferior frontal gyrus (pIFG), posterior superior temporal gyrus and sulcus (pSTG/STS), and angular gyrus (AG). Here, we probed the timing and causal relevance of the interplay between these regions by means of concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG). Our TMS-EEG experiments reveal region- and time-specific causal evidence for a bidirectional information flow from left pSTG/STS to left pIFG and back during auditory sentence processing. Adapting a condition-and-perturb approach, our findings further suggest that the left pSTG/STS can be supported by the left AG in a state-dependent manner.

A touching advantage: cross-modal stop-signals improve reactive response inhibition.

The ability to inhibit an already initiated response is crucial for navigating the environment. However, it is unclear which characteristics make stop-signals more likely to be processed efficiently. In three consecutive studies, we demonstrate that stop-signal modality and location are key factors that influence reactive response inhibition. Study 1 shows that tactile stop-signals lead to better performance compared to visual stop-signals in an otherwise visual choice-reaction task. Results of Study 2 reveal that the location of the stop-signal matters. Specifically, if a visual stop-signal is presented at a different location compared to the visual go-signal, then stopping performance is enhanced. Extending these results, study 3 suggests that tactile stop-signals and location-distinct visual stop-signals retain their performance enhancing effect when visual distractors are presented at the location of the go-signal. In sum, these results confirm that stop-signal modality and location influence reactive response inhibition, even in the face of concurrent distractors. Future research may extend and generalize these findings to other cross-modal setups.

Age-related reorganization of functional network architecture in semantic cognition.

Cognitive aging is associated with widespread neural reorganization processes in the human brain. However, the behavioral impact of such reorganization is not well understood. The current neuroimaging study investigated age differences in the functional network architecture during semantic word retrieval in young and older adults. Combining task-based functional connectivity, graph theory and cognitive measures of fluid and crystallized intelligence, our findings show age-accompanied large-scale network reorganization even when older adults have intact word retrieval abilities. In particular, functional networks of older adults were characterized by reduced decoupling between systems, reduced segregation and efficiency, and a larger number of hub regions relative to young adults. Exploring the predictive utility of these age-related changes in network topology revealed high, albeit less efficient, performance for older adults whose brain graphs showed stronger dedifferentiation and reduced distinctiveness. Our results extend theoretical accounts on neurocognitive aging by revealing the compensational potential of the commonly reported pattern of network dedifferentiation when older adults can rely on their prior knowledge for successful task processing. However, we also demonstrate the limitations of such compensatory reorganization and show that a youth-like network architecture in terms of balanced integration and segregation is associated with more economical processing.

Differential contributions of inferior frontal gyrus subregions to sentence processing guided by intonation.

Auditory sentence comprehension involves processing content (semantics), grammar (syntax), and intonation (prosody). The left inferior frontal gyrus (IFG) is involved in sentence comprehension guided by these different cues, with neuroimaging studies preferentially locating syntactic and semantic processing in separate IFG subregions. However, this regional specialisation has not been confirmed with a neurostimulation method. Consequently, the causal role of such a specialisation remains unclear. This study probed the role of the posterior IFG (pIFG) for syntactic processing and the anterior IFG (aIFG) for semantic processing with repetitive transcranial magnetic stimulation (rTMS) in a task that required the interpretation of the sentence's prosodic realisation. Healthy participants performed a sentence completion task with syntactic and semantic decisions, while receiving 10 Hz rTMS over either left aIFG, pIFG, or vertex (control). Initial behavioural analyses showed an inhibitory effect on accuracy without task-specificity. However, electric field simulations revealed differential effects for both subregions. In the aIFG, stronger stimulation led to slower semantic processing, with no effect of pIFG stimulation. In contrast, we found a facilitatory effect on syntactic processing in both aIFG and pIFG, where higher stimulation strength was related to faster responses. Our results provide first evidence for the functional relevance of left aIFG in semantic processing guided by intonation. The stimulation effect on syntactic responses emphasises the importance of the IFG for syntax processing, without supporting the hypothesis of a pIFG-specific involvement. Together, the results support the notion of functionally specialised IFG subregions for diverse but fundamental cues for language processing.

Age-Dependent Contribution of Domain-General Networks to Semantic Cognition.

Aging is characterized by a decline of cognitive control. In semantic cognition, this leads to the paradox that older adults usually show poorer task performance than young adults despite their greater semantic knowledge. So far, the underlying neural changes of these behavioral differences are poorly understood. In the current neuroimaging study, we investigated the interaction of domain-specific and domain-general networks during verbal semantic fluency in young and older adults. Across age groups, task processing was characterized by a strong positive integration within the multiple-demand as well as between the multiple-demand and the default mode network during semantic fluency. However, the behavioral relevance of strengthened connectivity differed between groups: While within-network functional connectivity in both networks predicted greater efficiency in semantic fluency in young adults, it was associated with slower performance in older adults. Moreover, only young adults profited from connectivity between networks for their semantic memory performance. Our results suggest that the functional coupling of usually anticorrelated networks is critical for successful task processing, independent of age, when access to semantic memory is required. Furthermore, our findings lend novel support to the notion of reduced efficiency in the aging brain due to neural dedifferentiation in semantic cognition.

Task-specific network interactions across key cognitive domains.

Human cognition is organized in distributed networks in the brain. Although distinct specialized networks have been identified for different cognitive functions, previous work also emphasizes the overlap of key cognitive domains in higher level association areas. The majority of previous studies focused on network overlap and dissociation during resting states whereas task-related network interactions across cognitive domains remain largely unexplored. A better understanding of network overlap and dissociation during different cognitive tasks may elucidate flexible (re-)distribution of resources during human cognition. The present study addresses this issue by providing a broad characterization of large-scale network dynamics in three key cognitive domains. Combining prototypical tasks of the larger domains of attention, language, and social cognition with whole-brain multivariate activity and connectivity approaches, we provide a spatiotemporal characterization of multiple large-scale, overlapping networks that differentially interact across cognitive domains. We show that network activity and interactions increase with increased cognitive complexity across domains. Interaction patterns reveal a common core structure across domains as well as dissociable domain-specific network activity. The observed patterns of activation and deactivation of overlapping and strongly coupled networks provide insight beyond region-specific activity within a particular cognitive domain toward a network perspective approach across diverse key cognitive functions.

Motor Cortex Causally Contributes to Vocabulary Translation following Sensorimotor-Enriched Training.

The role of the motor cortex in perceptual and cognitive functions is highly controversial. Here, we investigated the hypothesis that the motor cortex can be instrumental for translating foreign language vocabulary. Human participants of both sexes were trained on foreign language (L2) words and their native language translations over 4 consecutive days. L2 words were accompanied by complementary gestures (sensorimotor enrichment) or pictures (sensory enrichment). Following training, participants translated the auditorily presented L2 words that they had learned. During translation, repetitive transcranial magnetic stimulation was applied bilaterally to a site within the primary motor cortex (Brodmann area 4) located in the vicinity of the arm functional compartment. Responses within the stimulated motor region have previously been found to correlate with behavioral benefits of sensorimotor-enriched L2 vocabulary learning. Compared to sham stimulation, effective perturbation by repetitive transcranial magnetic stimulation slowed down the translation of sensorimotor-enriched L2 words, but not sensory-enriched L2 words. This finding suggests that sensorimotor-enriched training induced changes in L2 representations within the motor cortex, which in turn facilitated the translation of L2 words. The motor cortex may play a causal role in precipitating sensorimotor-based learning benefits, and may directly aid in remembering the native language translations of foreign language words following sensorimotor-enriched training. These findings support multisensory theories of learning while challenging reactivation-based theories.SIGNIFICANCE STATEMENT Despite the potential for sensorimotor enrichment to serve as a powerful tool for learning in many domains, its underlying brain mechanisms remain largely unexplored. Using transcranial magnetic stimulation and a foreign language (L2) learning paradigm, we found that sensorimotor-enriched training can induce changes in L2 representations within the motor cortex, which in turn causally facilitate the translation of L2 words. The translation of recently acquired L2 words may therefore rely not only on auditory information stored in memory or on modality-independent L2 representations, but also on the sensorimotor context in which the words have been experienced.

Coherent theta oscillations in the cerebellum and supplementary motor area mediate visuomotor adaptation.

The cerebellum and its interaction with cortical areas play a key role in our ability to flexibly adapt a motor program in response to sensory input. Current knowledge about specific neural mechanisms underlying the process of visuomotor adaptation is however lacking. Using a novel placement of EEG electrodes to record electric activity from the cerebellum, we studied local cerebellar activity, as well as its coupling with neocortical activity to obtain direct neurophysiological markers of visuomotor adaptation in humans. We found increased theta (4-8 Hz) power in "cerebellar" as well as cortical electrodes, when subjects first encountered a visual manipulation. Theta power decreased as subjects adapted to the perturbation, and rebounded when the manipulation was suddenly removed. This effect was observed in two distinct locations: a cerebellar cluster and a central cluster, which were localized in left cerebellar crus I (lCB) and right supplementary motor area (rSMA) using linear constrained minimum variance beamforming. Importantly, we found that better adaptation was associated with increased theta power in left cerebellar electrodes and a right sensorimotor cortex electrode. Finally, increased rSMA -> lCB connectivity was significantly decreased with adaptation. These results demonstrate that: (1) cerebellar theta power is markedly modulated over the course of visuomotor adaptation and (2) theta oscillations could serve as a key mechanism for communication within a cortico-cerebellar loop.

Resolution of diaschisis contributes to early recovery from post-stroke aphasia.

Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site. We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis. Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect. We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients.

The use of noninvasive brain stimulation techniques to improve reading difficulties in dyslexia: A systematic review.

Noninvasive brain stimulation (NIBS) allows to actively and noninvasively modulate brain function. Aside from inhibiting specific processes, NIBS may also enhance cognitive functions, which might be used for the prevention and intervention of learning disabilities such as dyslexia. However, despite the growing interest in modulating learning abilities, a comprehensive, up-to-date review synthesizing NIBS studies with dyslexics is missing. Here, we fill this gap and elucidate the potential of NIBS as treatment option in dyslexia. The findings of the 15 included studies suggest that repeated sessions of reading training combined with different NIBS protocols may induce long-lasting improvements of reading performance in child and adult dyslexics, opening promising avenues for future research. In particular, the "classical" reading areas seem to be most successfully modulated through NIBS, and facilitatory protocols can improve various reading-related subprocesses. Moreover, we emphasize the need to further explore the potential to modulate auditory cortex function as a preintervention and intervention approach for affected children, for example, to avoid the development of auditory and phonological difficulties at the core of dyslexia. Finally, we outline how future studies may increase our understanding of the neurobiological basis of NIBS-induced improvements in dyslexia.

Task-Dependent Functional and Effective Connectivity during Conceptual Processing.

Conceptual knowledge is central to cognition. Previous neuroimaging research indicates that conceptual processing involves both modality-specific perceptual-motor areas and multimodal convergence zones. For example, our previous functional magnetic resonance imaging (fMRI) study revealed that both modality-specific and multimodal regions respond to sound and action features of concepts in a task-dependent fashion (Kuhnke P, Kiefer M, Hartwigsen G. 2020b. Task-dependent recruitment of modality-specific and multimodal regions during conceptual processing. Cereb Cortex. 30:3938-3959.). However, it remains unknown whether and how modality-specific and multimodal areas interact during conceptual tasks. Here, we asked 1) whether multimodal and modality-specific areas are functionally coupled during conceptual processing, 2) whether their coupling depends on the task, 3) whether information flows top-down, bottom-up or both, and 4) whether their coupling is behaviorally relevant. We combined psychophysiological interaction analyses with dynamic causal modeling on the fMRI data of our previous study. We found that functional coupling between multimodal and modality-specific areas strongly depended on the task, involved both top-down and bottom-up information flow, and predicted conceptually guided behavior. Notably, we also found coupling between different modality-specific areas and between different multimodal areas. These results suggest that functional coupling in the conceptual system is extensive, reciprocal, task-dependent, and behaviorally relevant. We propose a new model of the conceptual system that incorporates task-dependent functional interactions between modality-specific and multimodal areas.

Visual Sensory Cortices Causally Contribute to Auditory Word Recognition Following Sensorimotor-Enriched Vocabulary Training.

Despite a rise in the use of "learning by doing" pedagogical methods in praxis, little is known as to how the brain benefits from these methods. Learning by doing strategies that utilize complementary information ("enrichment") such as gestures have been shown to optimize learning outcomes in several domains including foreign language (L2) training. Here we tested the hypothesis that behavioral benefits of gesture-based enrichment are critically supported by integrity of the biological motion visual cortices (bmSTS). Prior functional neuroimaging work has implicated the visual motion cortices in L2 translation following sensorimotor-enriched training; the current study is the first to investigate the causal relevance of these structures in learning by doing contexts. Using neuronavigated transcranial magnetic stimulation and a gesture-enriched L2 vocabulary learning paradigm, we found that the bmSTS causally contributed to behavioral benefits of gesture-enriched learning. Visual motion cortex integrity benefitted both short- and long-term learning outcomes, as well as the learning of concrete and abstract words. These results adjudicate between opposing predictions of two neuroscientific learning theories: While reactivation-based theories predict no functional role of specialized sensory cortices in vocabulary learning outcomes, the current study supports the predictive coding theory view that these cortices precipitate sensorimotor-based learning benefits.

Inferring Causality from Noninvasive Brain Stimulation in Cognitive Neuroscience.

Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. Transcending the limitations of purely correlative neuroimaging measures and experimental sensory stimulation, they allow to experimentally manipulate brain activity and study its consequences for perception, cognition, and eventually, behavior. Although this is true in principle, particular caution is advised when interpreting brain stimulation experiments in a causal manner. Research hypotheses are often oversimplified, disregarding the underlying (implicitly assumed) complex chain of causation, namely, that the stimulation technique has to generate an electric field in the brain tissue, which then evokes or modulates neuronal activity both locally in the target region and in connected remote sites of the network, which in consequence affects the cognitive function of interest and eventually results in a change of the behavioral measure. Importantly, every link in this causal chain of effects can be confounded by several factors that have to be experimentally eliminated or controlled to attribute the observed results to their assumed cause. This is complicated by the fact that many of the mediating and confounding variables are not directly observable and dose-response relationships are often nonlinear. We will walk the reader through the chain of causation for a generic cognitive neuroscience NIBS study, discuss possible confounds, and advise appropriate control conditions. If crucial assumptions are explicitly tested (where possible) and confounds are experimentally well controlled, NIBS can indeed reveal cause-effect relationships in cognitive neuroscience studies.

Probing rapid network reorganization of motor and language functions via neuromodulation and neuroimaging.

Motor and cognitive functions are organized in large-scale networks in the human brain that interact to enable flexible adaptation of information exchange to ever-changing environmental conditions. In this review, we discuss the unique potential of the consecutive combination of repetitive transcranial magnetic stimulation (rTMS) and functional neuroimaging to probe network organization and reorganization in the healthy and lesioned brain. First, we summarize findings highlighting the flexible (re-)distribution and short-term reorganization in motor and cognitive networks in the healthy brain. Plastic after-effects of rTMS result in large-scale changes on the network level affecting both local and remote activity within the stimulated network as well as interactions between the stimulated and distinct functional networks. While the number of combined rTMS-fMRI studies in patients with brain lesions remains scarce, preliminary evidence suggests that the lesioned brain flexibly (re-)distributes its computational capacities to functionally reorganize impaired brain functions, using a similar set of mechanisms to achieve adaptive network plasticity compared to short-term reorganization observed in the healthy brain after rTMS. In general, both short-term reorganization in the healthy brain and stroke-induced reorganization seem to rely on three general mechanisms of adaptive network plasticity that allow to maintain and recover function: i) interhemispheric changes, including increased contribution of homologous regions in the contralateral hemisphere and increased interhemispheric connectivity, ii) increased interactions between differentially specialized networks and iii) increased contributions of domain-general networks after disruption of more specific functions. These mechanisms may allow for computational flexibility of large-scale neural networks underlying motor and cognitive functions. Future studies should use complementary approaches to address the functional relevance of adaptive network plasticity and further delineate how these general mechanisms interact to enable network flexibility. Besides furthering our neurophysiological insights into brain network interactions, identifying approaches to support and enhance adaptive network plasticity may result in clinically relevant diagnostic and treatment approaches.

Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression.

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field. Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modeled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin. We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results. Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications.

Neural modelling of the semantic predictability gain under challenging listening conditions.

When speech intelligibility is reduced, listeners exploit constraints posed by semantic context to facilitate comprehension. The left angular gyrus (AG) has been argued to drive this semantic predictability gain. Taking a network perspective, we ask how the connectivity within language-specific and domain-general networks flexibly adapts to the predictability and intelligibility of speech. During continuous functional magnetic resonance imaging (fMRI), participants repeated sentences, which varied in semantic predictability of the final word and in acoustic intelligibility. At the neural level, highly predictable sentences led to stronger activation of left-hemispheric semantic regions including subregions of the AG (PGa, PGp) and posterior middle temporal gyrus when speech became more intelligible. The behavioural predictability gain of single participants mapped onto the same regions but was complemented by increased activity in frontal and medial regions. Effective connectivity from PGa to PGp increased for more intelligible sentences. In contrast, inhibitory influence from pre-supplementary motor area to left insula was strongest when predictability and intelligibility of sentences were either lowest or highest. This interactive effect was negatively correlated with the behavioural predictability gain. Together, these results suggest that successful comprehension in noisy listening conditions relies on an interplay of semantic regions and concurrent inhibition of cognitive control regions when semantic cues are available.

Intonation processing increases task-specific fronto-temporal connectivity in tonal language speakers.

Language comprehension depends on tight functional interactions between distributed brain regions. While these interactions are established for semantic and syntactic processes, the functional network of speech intonation - the linguistic variation of pitch - has been scarcely defined. Particularly little is known about intonation in tonal languages, in which pitch not only serves intonation but also expresses meaning via lexical tones. The present study used psychophysiological interaction analyses of functional magnetic resonance imaging data to characterise the neural networks underlying intonation and tone processing in native Mandarin Chinese speakers. Participants categorised either intonation or tone of monosyllabic Mandarin words that gradually varied between statement and question and between Tone 2 and Tone 4. Intonation processing induced bilateral fronto-temporal activity and increased functional connectivity between left inferior frontal gyrus and bilateral temporal regions, likely linking auditory perception and labelling of intonation categories in a phonological network. Tone processing induced bilateral temporal activity, associated with the auditory representation of tonal (phonemic) categories. Together, the present data demonstrate the breadth of the functional intonation network in a tonal language including higher-level phonological processes in addition to auditory representations common to both intonation and tone.

Dynamics of language reorganization after left temporo-parietal and frontal stroke.

The loss and recovery of language functions are still incompletely understood. This longitudinal functional MRI study investigated the neural mechanisms underlying language recovery in patients with post-stroke aphasia putting particular emphasis on the impact of lesion site. To identify patterns of language-related activation, an auditory functional MRI sentence comprehension paradigm was administered to patients with circumscribed lesions of either left frontal (n = 17) or temporo-parietal (n = 17) cortex. Patients were examined repeatedly during the acute (≤1 week, t1), subacute (1-2 weeks, t2) and chronic phase (>6 months, t3) post-stroke; healthy age-matched control subjects (n = 17) were tested once. The separation into two patient groups with circumscribed lesions allowed for a direct comparison of the contributions of distinct lesion-dependent network components to language reorganization between both groups. We hypothesized that activation of left hemisphere spared and perilesional cortex as well as lesion-homologue cortex in the right hemisphere varies between patient groups and across time. In addition, we expected that domain-general networks serving cognitive control independently contribute to language recovery. First, we found a global network disturbance in the acute phase that is characterized by reduced functional MRI language activation including areas distant to the lesion (i.e. diaschisis) and subsequent subacute network reactivation (i.e. resolution of diaschisis). These phenomena were driven by temporo-parietal lesions. Second, we identified a lesion-independent sequential activation pattern with increased activity of perilesional cortex and bilateral domain-general networks in the subacute phase followed by reorganization of left temporal language areas in the chronic phase. Third, we observed involvement of lesion-homologue cortex only in patients with frontal but not temporo-parietal lesions. Fourth, irrespective of lesion location, language reorganization predominantly occurred in pre-existing networks showing comparable activation in healthy controls. Finally, we detected different relationships of performance and activation in language and domain-general networks demonstrating the functional relevance for language recovery. Our findings highlight that the dynamics of language reorganization clearly depend on lesion location and hence open new perspectives for neurobiologically motivated strategies of language rehabilitation, such as individually-tailored targeted application of neuro-stimulation.

Task-Dependent Recruitment of Modality-Specific and Multimodal Regions during Conceptual Processing.

Conceptual knowledge is central to cognitive abilities such as word comprehension. Previous neuroimaging evidence indicates that concepts are at least partly composed of perceptual and motor features that are represented in the same modality-specific brain regions involved in actual perception and action. However, it is unclear to what extent the retrieval of perceptual-motor features and the resulting engagement of modality-specific regions depend on the concurrent task. To address this issue, we measured brain activity in 40 young and healthy participants using functional magnetic resonance imaging, while they performed three different tasks-lexical decision, sound judgment, and action judgment-on words that independently varied in their association with sounds and actions. We found neural activation for sound and action features of concepts selectively when they were task-relevant in brain regions also activated during auditory and motor tasks, respectively, as well as in higher-level, multimodal regions which were recruited during both sound and action feature retrieval. For the first time, we show that not only modality-specific perceptual-motor areas but also multimodal regions are engaged in conceptual processing in a flexible, task-dependent fashion, responding selectively to task-relevant conceptual features.

Interleaving Motor Sequence Training With High-Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Consolidation.

The acquisition of novel motor skills is a fundamental process of lifelong learning and crucial for everyday behavior. Performance gains acquired by training undergo a transition from an initially labile state to a state that is progressively robust towards interference, a phenomenon referred to as motor consolidation. Previous work has demonstrated that the primary motor cortex (M1) is a neural key region for motor consolidation. However, it remains unknown whether physiological processes underlying posttraining motor consolidation in M1 are active already during an ongoing training phase or only after completion of the training. We examined whether 10-Hz interleaved repetitive transcranial magnetic stimulation (i-rTMS) of M1 during rest periods between active motor training in an explicit motor learning task affects posttraining offline consolidation. Relative to i-rTMS to the vertex (control region), i-rTMS to the M1hand area of the nondominant hand facilitated posttraining consolidation assessed 6 h after training without affecting training performance. This facilitatory effect generalized to delayed performance of the mirror-symmetric sequence with the untrained (dominant) hand. These findings indicate that posttraining consolidation can be facilitated independently from training-induced performance increments and suggest that consolidation is initiated already during offline processing in short rest periods between active training phases.