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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.

Conceptual knowledge is central to human cognition. The left posterior inferior parietal lobe (pIPL) is implicated by neuroimaging studies as a multimodal hub representing conceptual knowledge related to various perceptual-motor modalities. However, the causal role of left pIPL in conceptual processing remains unclear. Here, we transiently disrupted left pIPL function with transcranial magnetic stimulation (TMS) to probe its causal relevance for the retrieval of action and sound knowledge. We compared effective TMS over left pIPL with sham TMS, while healthy participants performed three different tasks-lexical decision, action judgment, and sound judgment-on words with a high or low association to actions and sounds. We found that pIPL-TMS selectively impaired action judgments on low sound-low action words. For the first time, we directly related computational simulations of the TMS-induced electrical field to behavioral performance, which revealed that stronger stimulation of left pIPL is associated with worse performance for action but not sound judgments. These results indicate that left pIPL causally supports conceptual processing when action knowledge is task-relevant and cannot be compensated by sound knowledge. Our findings suggest that left pIPL is specialized for the retrieval of action knowledge, challenging the view of left pIPL as a multimodal conceptual hub.

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 STATEMENTDespite 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.

Uniquely human cognitive faculties arise from flexible interplay between specific local neural modules, with hemispheric asymmetries in functional specialization. Here, we discuss how these computational design principles provide a scaffold that enables some of the most advanced cognitive operations, such as semantic understanding of world structure, logical reasoning, and communication via language. We draw parallels to dual processing theories of cognition by placing a focus on Kahneman’s System 1 and System 2. We propose integration of these ideas with the global workspace theory to explain dynamic relay of information products between both systems. Deepening the current understanding of how neurocognitive asymmetry makes humans special can ignite the next wave of neuroscience-inspired artificial intelligence.

Semantic composition, the ability to combine single words to form complex meanings, is a core feature of human language. Despite growing interest in the basis of semantic composition, the neural correlates and the interaction of regions within this network remain a matter of debate. We designed a well-controlled two-word fMRI paradigm in which phrases only differed along the semantic dimension while keeping syntactic information alike. Healthy participants listened to meaningful (“fresh apple”), anomalous (“awake apple”) and pseudoword phrases (“awake gufel”) while performing an implicit and an explicit semantic task. We identified neural signatures for distinct processes during basic semantic composition. When lexical information is kept constant across conditions and the evaluation of phrasal plausibility is examined (meaningful vs. anomalous phrases), a small set of mostly left-hemispheric semantic regions, including the anterior part of the left angular gyrus, is found active. Conversely, when the load of lexical information—independently of phrasal plausibility—is varied (meaningful or anomalous vs. pseudoword phrases), conceptual combination involves a wide-spread left-hemispheric network comprising executive semantic control regions and general conceptual representation regions. Within this network, the functional coupling between the left anterior inferior frontal gyrus, the bilateral pre-supplementary motor area and the posterior angular gyrus specifically increases for meaningful phrases relative to pseudoword phrases. Stronger effects in the explicit task further suggest task-dependent neural recruitment. Overall, we provide a separation between distinct nodes of the semantic network, whose functional contributions depend on the type of compositional process under analysis. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-020-02196-2.

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., The present functional magnetic resonance imaging study investigated task‐specific functional connectivity in intonation and tone processing in Mandarin speakers.Intonation processing increased functional interactions between left inferior frontal and bilateral temporal regions and between lateral‐medial frontal regions, likely reflecting higher‐level phonological processes and verbal response preparation.Tone processing only induced bilateral temporal activity, likely associated with auditory representation of tone (phonemic) categories.

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.

An intrinsic characteristic of the motor system is the preference of one side of the body. Lateralization is found in motor behavior and in the structural and functional correlates of cortical motor networks. While genetic factors have been elucidated as mechanisms leading to such asymmetries, findings in motor learning and experience from clinical experience demonstrate considerable additional plasticity during the lifespan. If and how functional lateralization develops in short timeframes during training of motor skills involving both sides of the body is still largely unclear. In the present exploratory study, we investigate lateralization of theta-, alpha- and beta-band oscillations during training of an ecologically valid skill - archery. We relate lateralization shift to performance improvement and elucidate the underlying cortical areas. To this end, healthy participants without any previous experience in archery underwent intensive training with 100 shots on each of three days. 64-channel electroencephalography was recorded simultaneously during the individual shots. We found that a central-parietal theta lateralization shift to the left immediately before the shot was associated with performance improvement. Lateralization of alpha or beta did not yield a significant association. Importantly, areas of maximum activation were not identical with areas showing the strongest associations with performance improvement. These data suggest that learning a complex bimanual motor skill is associated with a shift of theta-band oscillations to the left in central-parietal areas. The relationship with performance improvement may reflect increased cortical efficiency of task-relevant processing.

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.

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., The findings of this review 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 NIBS protocols may improve various reading‐related subprocesses. Moreover, we emphasize the need to further explore the potential to modulate auditory cortex function as prevention and intervention approaches for affected children, to prevent the development of auditory and phonological difficulties at the core of many dyslexics.

Objective: Alpha oscillations are linked to inhibitory capabilities in higher cognitive processing. Transcranial alternating current stimulation (tACS) at 10 Hz can enhance alpha oscillations and modulate behaviour. One possibility to increase the efficacy of tACS may be stimulating at the individual alpha frequency (IAF). The present work addresses this issue (among others) to increase the current understanding of the functional role of alpha oscillations in higher cognitive tasks. Methods: Twenty-two healthy and 13 dyslexic participants performed two word decision tasks while receiving IAF-tACS over the left prefrontal cortex. Resting EEG was recorded to detect electrophysiological changes. Cortical excitability was assessed with TMS. Results: Dyslexic participants performed worse in the phonological task. However, no significant tACS effects were found. Interestingly, higher cortical excitability was correlated with faster responses in healthy controls. In dyslexics this association significantly differed in the phonological task. Conclusion: The non-significant modulation by tACS might be explained by methodological limitations. Alternatively, it may indicate that alpha oscillations do not play a functional role in phonological decisions. The findings on cortical excitability expands the existing literature and may reflect the specific phonological deficit in dyslexics. Significance: Our critical discussion of these null findings expands the systematic knowledge on alpha-tACS for future studies. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Speech comprehension is often challenged by increased background noise, but can be facilitated via the semantic context of a sentence. This predictability gain relies on an interplay of language-specific semantic and domain-general brain regions. However, age-related differences in the interactions within and between semantic and domain-general networks remain poorly understood. Using functional neuroimaging, we investigated commonalities and differences in network interactions enabling processing of degraded speech in healthy young and old participants. Participants performed a sentence repetition task while listening to sentences with high and low predictable endings and varying intelligibility. Stimulus intelligibility was adjusted to individual hearing abilities. Older adults showed an undiminished behavioural predictability gain. Likewise, both groups recruited a similar set of semantic and cingulo-opercular brain regions. However, we observed age-related differences in effective connectivity for high predictable speech of increasing intelligibility. Young adults exhibited stronger connectivity between regions of the cingulo-opercular network and between left insula and the posterior middle temporal gyrus. Moreover, these interactions were excitatory in young adults but inhibitory in old adults. Finally, the degree of the inhibitory influence between cingulo-opercular regions was predictive of the behavioural sensitivity towards changes in intelligibility for high predictable sentences in older adults only. Our results demonstrate that the predictability gain is relatively preserved in older adults when stimulus intelligibility is individually adjusted. While young and old participants recruit similar brain regions, differences manifest in underlying network interactions. Together, these results suggest that ageing affects the network configuration rather than regional activity during successful speech comprehension under challenging listening conditions.

Background: The precise cortical origins of the electrophysiological and behavioral effects of transcranial magnetic stimulation (TMS) remain largely unclear. Addressing this question is further impeded by substantial inter-individual response variability to TMS. Objective: We present a novel method to reliably and user-independently determine the effectively stimulated cortical site at the individual subject level. This generic approach combines physiological measurements with electric field simulations and leverages information from random coil positions, electric field estimations, and electromyography. Methods: We applied ~1000 single biphasic TMS pulses with standard TMS hardware to 13 subjects with random coil positions & orientations over the primary motor hand area. Motor evoked potentials (MEPs) of three finger muscles were recorded concurrently. We calculated the corresponding electric fields for all TMS pulses and regressed them against the elicited MEPs in each cortical element. This yields a cortical map of congruency between induced field strength and generated response. Results: We observed high congruence between the electric fields and the elicited MEPs in hotspots located primarily on the crowns and rims of the precentral gyrus. The three cortical digit representations could be distinguished at the individual subject level with a high spatial resolution. A post-hoc convergence analysis revealed a possible lower bound of only 180 pulses to obtain qualitatively identical results. Conclusions: Leveraging information from many different TMS pulses significantly reduces the number of necessary stimulations and mapping time. The protocol is easy to implement due to the realization of arbitrary coil positions & orientations and is suitable for practical and clinical use such as preoperative mapping.

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 (4-8Hz) power in “cerebellar” as well as cortical electrodes, when subjects first encountered a visual perturbation. Theta power decreased as subjects adapted to the perturbation, and rebounded when the perturbation 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.

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.

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.

Non-invasive brain stimulation (NIBS) has gained increasing popularity as a modulatory tool for drawing causal inferences and exploring task-specific network interactions. Yet, a comprehensive synthesis of reading-related NIBS studies is still missing. We fill this gap by synthesizing the results of 78 NIBS studies investigating the causal involvement of brain regions for reading processing, and then link these results to a neurobiological model of reading. The included studies provide evidence for a functional-anatomical double dissociation for phonology versus semantics during reading-related processes within left inferior frontal and parietal areas. Additionally, the posterior parietal cortex and the anterior temporal lobe are identified as critical regions for reading-related processes. Overall, the findings provide some evidence for a dual-stream neurobiological model of reading, in which a dorsal stream (left temporo-parietal and inferior frontal areas) processes unfamiliar words and pseudowords, and a ventral stream (left occipito-temporal and inferior frontal areas, with assistance from the angular gyrus and the anterior temporal lobe) processes known words. However, individual differences in reading abilities and strategies, as well as differences in stimulation parameters, may impact the neuromodulatory effects induced by NIBS. We emphasize the need to investigate task-specific network interactions in future studies by combining NIBS with neuroimaging.

The language system uses syntactic, semantic, as well as prosodic cues to efficiently guide auditory sentence comprehension. Prosodic cues, such as pitch accents, can build expectations about upcoming sentence elements. This study investigates to what extent syntactic and semantic expectations generated by pitch accents can be dissociated and if so, which cues take precedence when contradictory information is present. We used sentences in which one out of two nominal constituents was placed in contrastive focus with a third one. All noun phrases carried overt syntactic information (case-marking of the determiner) and semantic information (typicality of the thematic role of the noun). Two experiments (a sentence comprehension and a sentence completion task) show that focus, marked by pitch accents, established expectations in both syntactic and semantic domains. However, only the syntactic expectations, when violated, were strong enough to interfere with sentence comprehension. Furthermore, when contradictory cues occurred in the same sentence, the local syntactic cue (case-marking) took precedence over the semantic cue (thematic role), and overwrote previous information cued by prosody. The findings indicate that during auditory sentence comprehension the processing system integrates different sources of information for argument role assignment, yet primarily relies on syntactic information.

The left posterior inferior frontal gyrus in the prefrontal cortex is a key region for phonological aspects of language processing. A previous study has shown that alpha-tACS over the prefrontal cortex applied before task processing facilitated phonological decision-making and increased task-related theta power. However, it is unclear how alpha-tACS affects phonological processing when applied directly during the task. Moreover, the frequency specificity of this effect is also unclear since the majority of neurostimulation studies tested a single frequency only. The present study addressed the question whether and how 10 Hz online tACS affects phonological decisions. To this end, 24 healthy participants received tACS at 10 Hz or 16.18 Hz (control frequency) or sham stimulation over the left prefrontal cortex during task processing in three sessions. As an unexpected finding, 16.18 Hz significantly impaired task accuracy relative to sham stimulation, without affecting response speed. There was no significant difference in phonological task performance between 10 Hz and 16.18 Hz tACS or between 10 Hz and sham stimulation. Our results support the functional relevance of the left prefrontal cortex for phonological decisions and suggest that online beta-tACS may modulate language comprehension.

Transcranial direct current stimulation (tDCS) is widely used to explore the role of various cortical regions for reactive response inhibition. In recent years, tDCS studies reported polarity-, time- and stimulation-site dependent effects on response inhibition. Given the large parameter space in which study designs, tDCS procedures and task procedures can differ, it is crucial to systematically explore the existing tDCS literature to increase the current understanding of potential modulatory effects and limitations of different approaches. We performed a systematic review on the modulatory effects of tDCS on response inhibition as measured by the Stop-Signal Task. The final dataset shows a large variation in methodology and heterogeneous effects of tDCS on performance. The most consistent result across studies is a performance enhancement due to anodal tDCS over the right prefrontal cortex. Partially sub-optimal choices in study design, methodology and lacking consistency in reporting procedures may impede valid conclusions and obscured the effects of tDCS on response inhibition in some previous studies. Finally, we outline future directions and areas to improve research.

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.

The inferior parietal lobe (IPL) is a key neural substrate underlying diverse mental processes, from basic attention to language and social cognition, that define human interactions. Its putative domain-global role appears to tie into poorly understood differences between cognitive domains in both hemispheres. Across attentional, semantic, and social cognitive tasks, our study explored functional specialization within the IPL. The task specificity of IPL subregion activity was substantiated by distinct predictive signatures identified by multivariate pattern-learning algorithms. Moreover, the left and right IPL exerted domain-specific modulation of effective connectivity among their subregions. Task-evoked functional interactions of the anterior and posterior IPL subregions involved recruitment of distributed cortical partners. While anterior IPL subregions were engaged in strongly lateralized coupling links, both posterior subregions showed more symmetric coupling patterns across hemispheres. Our collective results shed light on how under-appreciated functional specialization in the IPL supports some of the most distinctive human mental capacities.

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.

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.

Intonation, the modulation of pitch in speech, is a crucial aspect of language that is processed in right‐hemispheric regions, beyond the classical left‐hemispheric language system. Whether or not this notion generalises across languages remains, however, unclear. Particularly, tonal languages are an interesting test case because of the dual linguistic function of pitch that conveys lexical meaning in form of tone, in addition to intonation. To date, only few studies have explored how intonation is processed in tonal languages, how this compares to tone and between tonal and non‐tonal language speakers. The present fMRI study addressed these questions by testing Mandarin and German speakers with Mandarin material. Both groups categorised mono‐syllabic Mandarin words in terms of intonation, tone, and voice gender. Systematic comparisons of brain activity of the two groups between the three tasks showed large cross‐linguistic commonalities in the neural processing of intonation in left fronto‐parietal, right frontal, and bilateral cingulo‐opercular regions. These areas are associated with general phonological, specific prosodic, and controlled categorical decision‐making processes, respectively. Tone processing overlapped with intonation processing in left fronto‐parietal areas, in both groups, but evoked additional activity in bilateral temporo‐parietal semantic regions and subcortical areas in Mandarin speakers only. Together, these findings confirm cross‐linguistic commonalities in the neural implementation of intonation processing but dissociations for semantic processing of tone only in tonal language speakers.

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.

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.

Previous work has emphasized that cognitive functions in the human brain are organized into large-scale networks. However, the mechanisms that allow these networks to compensate for focal disruptions remain elusive. I suggest a new perspective on the compensatory flexibility of cognitive networks. First, I demonstrate that cognitive networks can rapidly change the functional weight of the relative contribution of different regions. Second, I argue that there is an asymmetry in the compensatory potential of different kinds of networks. Specifically, recruitment of domain-general functions can partially compensate for focal disruptions of specialized cognitive functions, but not vice versa. Considering the compensatory potential within and across networks will increase our understanding of functional adaptation and reorganization after brain lesions and offers a new perspective on large-scale neural network (re-)organization.

Storage and reordering of incoming information are two core processes required for successful sentence comprehension. Storage is necessary whenever the verb and its arguments (i.e., subject and object) are separated over a long distance, while reordering is necessary whenever the argument order is atypical (e.g., object-first order in German, where subject-first order is typical). Previous neuroimaging work has associated storage with the left planum temporale (PT), and reordering with the left posterior inferior frontal gyrus (pIFG). Here, we tested the causal role of the PT and pIFG in storage and reordering using repetitive transcranial magnetic stimulation (rTMS). We applied either effective rTMS over PT or pIFG, or sham rTMS, while subjects listened to sentences that independently varied storage demands (short vs. long argument-verb distance) and reordering demands (subject- vs. object-first argument order). We found that rTMS over pIFG, but not PT, selectively affected reordering during the processing of sentences with a long argument-verb distance. Specifically, relative to sham rTMS, rTMS over pIFG significantly increased the performance difference between object- and subject-first long-distance sentences. These results demonstrate a causal involvement of left pIFG in reordering during sentence comprehension and thus contribute to a better understanding of the role of the pIFG in language processing.

Previous studies helped unraveling the functional architecture of the human cerebral cortex. However, a comprehensive functional segregation of right lateral prefrontal cortex is missing. Here, we delineated cortical clusters in right area 44 and 45 based on their task-constrained whole-brainactivation patterns across neuroimaging experiments obtained from a large database. We identified five clusters that differed with respect to their coactivation patterns, which were consistent with resting-state functional connectivity patterns of an independent dataset. Two clusters in theposterior inferior frontal gyrus (IFG) were functionally associated with action inhibition and execution, while two anterior clusters were related to reasoning and social cognitive processes. A fifth cluster was associated with spatial attention. Strikingly, the functional organization of the right IFG can thus be characterized by a posterior-to-anterior axis with action-related functions on the posterior and cognition-related functions on the anterior end. We observed further subdivisions along a dorsal-to-ventral axis in posterior IFG between action execution and inhibition, and in anterior IFG between reasoning and social cognition. The different clusters were integrated in distinct large-scale networks for various cognitive processes. These results provide evidence for a general organization of cognitive processes along axes spanning from more automatic to more complex cognitive processes.

Previous neuroimaging studies demonstrated that a network of left-hemispheric frontal and temporal brain regions contributes to the integration of contextual information into a sentence. However, it remains unclear how these cortical areas influence and drive each other during contextual integration. The present study used dynamic causal modeling (DCM) to investigate task-related changes in the effective connectivity within this network. We found increased neural activity in left anterior inferior frontal gyrus (aIFG), posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and anterior superior temporal sulcus/MTG (aSTS/MTG) that probably reflected increased integration demands and restructuring attempts during the processing of unexpected or semantically anomalous relative to expected endings. DCM analyses of this network revealed that unexpected endings increased the inhibitory influence of left aSTS/MTG on pSTS/MTG during contextual integration. In contrast, during the processing of semantically anomalous endings, left aIFG increased its inhibitory drive on pSTS/MTG. Probabilistic fiber tracking showed that effective connectivity between these areas is mediated by distinct ventral and dorsal white matter association tracts. Together, these results suggest that increasing integration demands require an inhibition of the left pSTS/MTG, which presumably reflects the inhibition of the dominant expected sentence ending. These results are important for a better understanding of the neural implementation of sentence comprehension on a large-scale network level and might influence future studies of language in post-stroke aphasia after focal lesions.

Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both “online” NTBS effects immediately following the stimulation and “offline” NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology.

Objectives Awake craniotomy is a well-established procedure in surgery of intracranial tumors in eloquent areas. However, sufficiently standardized instruments for the assessment of sensory-motor function before, during and after the operation are currently lacking, despite their importance for evaluation of operative outcome. Patients and methods To address this issue, we designed a standardized assessment tool (the “sensory-motor profile awake scale”; SMP-a). The final scale consists of three motor sections (face, arm and leg) assessing both gross and fine motor skills and one sensory section. It differentiates between six grades of impairment and its tasks are applicable for intraoperative continuous monitoring of sensory-motor functions and supporting processes. We analyzed the data of 17 patients with intracranial tumors eligible for awake craniotomy who were preoperatively assessed with the SMP-a. In addition, we present an exemplary case. Results Our data support the assumption that the SMP-a is feasible in patients eligible for awake craniotomy, even in patients with symptoms of mild aphasia or more severe sensory-motor deficits caused by tumor recurrence. The exemplary case demonstrates the feasibility of repeated measures with the SMP-a in a tumor patient, including the adaption of tasks to the individual requirements of an intraoperative setting. Conclusion This exploratory study suggests that the SMP-a might be a feasible rating scale in patients with intracranial tumors. The flexibility of the scale enables individual adaption, but preserves the standardized scoring system to allow comparison between assessment dates, patients and, hopefully in the future, institutions. However, future studies are mandatory to provide data on the instrument’s diagnostic properties with respect to feasibility, objectivity, validity and reliability.

We present the first case report describing a craniotomy for a glioblastoma in a patient with hemihydranencephaly (HHE). Ten years ago our patient had average cognitive and language functions, indicating very good adaption of his single right hemisphere. Due to the tumour he developed a deceleration, deficits in language functions and mild impairments of basic cognitive functions. Further neuroplastic reorganisations of his right hemisphere in response to the tumour growth are discussed. The favourable postoperative outcome supported the decision for careful tumour resection in this patient with HHE.

Despite the widespread use of transcranial magnetic stimulation (TMS), the precise cortical locations underlying the resulting physiological and behavioral effects are still only coarsely known. To date, mapping strategies have relied on projection approaches (often termed "center of gravity" approaches) or maximum electric field value evaluation, and therefore localize the stimulated cortical site only approximately and indirectly. Focusing on the motor cortex, we present and validate a novel method to reliably determine the effectively stimulated cortical site at the individual subject level. The approach combines measurements of motor evoked potentials (MEPs) at different coil positions and orientations with numerical modeling of induced electric fields. We identify sharply bounded cortical areas, around the gyral crowns and rims of the motor hand area, as the origin of MEPs and show that the magnitude of the tangential component and the overall magnitude of the electric field are most relevant for the observed effect. To validate our approach, we identified the coil location and orientation that produces the maximal electric field at the predicted stimulation site, and then experimentally show that this location produces MEPs more efficiently than other tested locations/orientations. Moreover, we used extensive uncertainty and sensitivity analyses to verify the robustness of the method and identify the most critical model parameters. Our generic approach improves the localization of the cortical area effectively stimulated by TMS and may be transferred to other modalities such as language mapping.

Background. Hypokinetic dysarthria is highly prevalent in idiopathic Parkinson disease (PD), and effectiveness of high-intensity voice treatment is well established. However, the neural correlates remain largely unknown. Objective. We aimed to specify cerebral pathophysiology of hypokinetic dysarthria and treatment-induced changes using functional magnetic resonance imaging (fMRI). Methods. We used fMRI to investigate healthy controls (HCs) and patients with idiopathic PD–associated dysarthria before and after treatment according to the Lee Silverman Voice Treatment LOUD (LSVT). During fMRI, participants covertly read sentences with normal (eg, conversation in a quiet room) or high (eg, shouting on a windy beach) intensity. In addition, we tested LSVT effects on intelligibility and different speech features (intensity, pitch, articulation). Results. LSVT effectively improved intelligibility, articulation, and pitch in patients. Covert high-intensity speech compared with covert normal-intensity speech led to increased activation of mainly secondary motor areas and bilateral superior and medial temporal regions. Prior to LSVT, patients showed less activity in several speech-associated areas compared with HCs. As a neural correlate of effective LSVT, increased right-sided superior temporal activity correlated with improved intelligibility. Conclusion. This is the first brain imaging study using a covert speech paradigm in PD, which revealed cortical hypoactivation as correlate of hypokinetic dysarthria. Furthermore, cortical correlates of effective LSVT treatment colocalized with the neuronal network, showing increased activation during high- versus normal-intensity speech generation.

Introduction Previous work in the language domain has shown that 10 Hz rTMS of the left or right posterior inferior frontal gyrus (pIFG) in the prefrontal cortex impaired phonological decision-making, arguing for a causal contribution of the bilateral pIFG to phonological processing. However, the neurophysiological correlates of these effects are unclear. The present study addressed the question whether neural activity in the prefrontal cortex could be modulated by 10 Hz tACS and how this would affect phonological decisions. Methods In three sessions, 24 healthy participants received tACS at 10 Hz or 16.18 Hz (control frequency) or sham stimulation over the bilateral prefrontal cortex before task processing. Resting state EEG was recorded before and after tACS. We also recorded EEG during task processing. Results Relative to sham stimulation, 10 Hz tACS significantly facilitated phonological response speed. This effect was task-specific as tACS did not affect a simple control task. Moreover, 10 Hz tACS significantly increased theta power during phonological decisions. The individual increase in theta power was positively correlated with the behavioral facilitation after 10 Hz tACS. Conclusion Our results show a facilitation of phonological decisions after 10 Hz tACS over the bilateral prefrontal cortex. This might indicate that 10 Hz tACS increased task-related activity in the stimulated area to a level that was optimal for phonological performance. The significant correlation with the individual increase in theta power suggests that the behavioral facilitation might be related to increased theta power during language processing.

Speech prosody, the variation in sentence melody and rhythm, plays a crucial role in sentence comprehension. Specifically, changes in intonational pitch along a sentence can affect our understanding of who did what to whom. To date, it remains unclear how the brain processes this particular use of intonation and which brain regions are involved. In particular, one central matter of debate concerns the lateralisation of intonation processing. To study the role of intonation in sentence comprehension, we designed a functional magnetic resonance imaging (MRI) experiment in which participants listened to spoken sentences. Critically, the interpretation of these sentences depended on either intonational or grammatical cues. Our results showed stronger functional activity in the left inferior frontal gyrus (IFG) when the intonational cue was crucial for sentence comprehension compared to when it was not. When instead a grammatical cue was crucial for sentence comprehension, we found involvement of an overlapping region in the left IFG, as well as in a posterior temporal region. A further analysis revealed that the lateralisation of intonation processing depends on its role in syntactic processing: activity in the IFG was lateralised to the left hemisphere when intonation was the only source of information to comprehend the sentence. In contrast, activity in the IFG was right-lateralised when intonation did not contribute to sentence comprehension. Together, these results emphasise the key role of the left IFG in sentence comprehension, showing the importance of this region when intonation establishes sentence structure. Furthermore, our results provide evidence for the theory that the lateralisation of prosodic processing is modulated by its linguistic role.

International audience; Numerous functional neuroimaging studies in humans used univariate group analyses to identify brain areas that show increased activity across participants during specific tasks. However, there is increasing evidence that group-level analyses may obscure important parts of the signal response (Margulies, 2017; Poldrack, 2017). Here, we re-analyzed data from our recent study (Hartwigsen et al., 2017) that investigated functional reorganization in the language network. We show that across-voxel pattern-learning approaches are useful to isolate plastic changes in neural networks underlying cognitive functions at the individual subject level. Using predictive machine-learning tools to identify and exploit subject-specific neural activity patterns have been argued to become an important cornerstone of precision medicine in psychiatry and neurology.

Communication is an inferential process. In particular, language comprehension constantly requires top-down efforts, as often multiple interpretations are compatible with a given sentence. To assess top-down processing in the language domain, our experiment employed ambiguous sentences that allow for multiple interpretations (e.g., The client sued the murderer with the corrupt lawyer., where the corrupt lawyer could either belong to The client or the murderer). Interpretation thus depended on whether participants chunk the words of the sentence into short or long syntactic phrases. In principle, bottom-up acoustic information (i.e., the presence or absence of an intonational phrase boundary at the offset of the murderer) indicates one of the two possible interpretations. Yet, acoustic information often indicates interpretations that require words to be chunked into overly long phrases that would overburden working memory. Processing is biased against these demands, reflected in a top-down preference to chunk words into short rather than long phrases. It is often proposed, but also hotly debated, that the ability to chunk words into short phrases is subserved by the left inferior frontal gyrus (IFG). Here, we employed focal repetitive transcranial magnetic stimulation to perturb the left IFG, which resulted in a further decrease of the aptitude to tolerate long phrases, indicating the inability of the left IFG to assist the chunking of words into phrases. In contrast, the processing of auditory information was not affected. Our findings support a causal top-down role of the left inferior frontal gyrus in the chunking of words into phrases.

Recent studies have shown that the left inferior frontal gyrus (IFG) plays a key role in language learning. Facilitatory stimulation over this region by means of anodal transcranial direct current stimulation (tDCS) can modulate linguistic abilities in healthy individuals and improve language performance in patients with post-stroke aphasia. Neuroimaging studies in healthy participants have suggested that anodal tDCS decreases task-related activity at the stimulated site when applied during different language tasks, and changes resting-state connectivity in a larger network of areas associated with language processing. However, to date, the neural correlates of the potential beneficial effects of tDCS on verb learning remain unclear. The current study investigated how anodal tDCS during verb learning modulates task-related activity and effective connectivity in the healthy language network. To this end, we combined a verb learning paradigm during functional neuroimaging with simultaneous tDCS over the left IFG in healthy human volunteers. We found that, relative to sham stimulation, anodal tDCS significantly decreased task-related activity at the stimulated left IFG and in the right homologue. Effective connectivity analysis showed that anodal tDCS significantly decreased task-related functional coupling between the left IFG and the right insula. Importantly, the individual decrease in connectivity was significantly correlated with the individual behavioural improvement during anodal tDCS. These results demonstrate, for the first time, that the behavioural improvements induced by anodal tDCS might be related to an overall decrease in processing effort both with respect to task-related activity and effective connectivity within a large language network.

This study presents the first validation of the Brief Cognitive Status Exam (BCSE) against two other screening tools for cognitive impairment in patients with intracranial tumors. 58 patients and 22 matched healthy controls completed the BCSE, the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Patients were additionally tested with a comprehensive neuropsychological battery. Based on this assessment, they were classified as cognitively impaired or unimpaired on five cognitive domains. Analyses revealed a comparable feasibility of the BCSE relative to the MoCA and the MMSE, but a smaller range of assessed functions (e.g., no correlation with the domain visual-spatial functions). The ability to separate patients and healthy controls was extremely poor for BCSE and MMSE (sensitivity of 38.6 % and less), but moderate for MoCA (sensitivity 68.97 %). Detection of cognitive impairment in patients was worst with BCSE (sensitivity 37 %; MoCA 92.9 %, MMSE 44.4 %) as compared to neuropsychological testing. Moreover, prediction of cognitive outcome was also worst for the BCSE (AUC = .713, NPV = 50 %). An optimal cut-off of 50.5 increased the results slightly. In summary, the BCSE showed good feasibility but no sufficient results in separating healthy individuals from patients or detecting cognitive impairment in patients. Consequently, as a screening measure, we would recommend the MoCA instead of the BCSE. However, since even the MoCA failed to detect cognitive impairment, our study supports the view that reliable results could only be obtained with a comprehensive neuropsychological battery.

Across the last three decades, the application of noninvasive brain stimulation (NIBS) has substantially increased the current knowledge of the brain’s potential to undergo rapid short-term reorganization on the systems level. A large number of studies applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in the healthy brain to probe the functional relevance and interaction of specific areas for different cognitive processes. NIBS is also increasingly being used to induce adaptive plasticity in motor and cognitive networks and shape cognitive functions. Recently, NIBS has been combined with electrophysiological techniques to modulate neural oscillations of specific cortical networks. In this review, we will discuss recent advances in the use of NIBS to modulate neural activity and effective connectivity in the healthy language network, with a special focus on the combination of NIBS and neuroimaging or electrophysiological approaches. Moreover, we outline how these results can be transferred to the lesioned brain to unravel the dynamics of reorganization processes in poststroke aphasia. We conclude with a critical discussion on the potential of NIBS to facilitate language recovery after stroke and propose a phase-specific model for the application of NIBS in language rehabilitation.

Background The rapid adaptation of actions to changes in the environment is crucial for survival. We previously demonstrated a joint contribution of left dorsal premotor cortex (PMd) and left supramarginal gyrus (SMG) to action reprogramming. However, we did not probe the contribution of PMd to the speed and accuracy of action reprogramming and how the functional relevance of PMd changes in the presence of a dysfunctional SMG. Objective This study further dissociated the unique contribution of left PMd and SMG to action reprogramming. Specifically, we tested whether the critical contribution of PMd during action reprogramming depends on the functional integrity of SMG. Methods Adopting a condition-and-perturb repetitive transcranial magnetic stimulation (rTMS) approach, we first transiently conditioned left SMG with 1 Hz offline rTMS and then perturbed PMd activity with online rTMS whilst human subjects performed a spatially-precued reaction time task. Results Relative to sham rTMS, effective online perturbation of left PMd significantly impaired both the response speed and accuracy in trials that were invalidly pre-cued and required the subject to reprogram the prepared action. Moreover, the disruptive effect of rTMS over left PMd on response speed became stronger after SMG had been conditioned with offline rTMS. Conclusions These results corroborate the notion that left PMd and SMG jointly contribute to rapid action reprogramming. Moreover, the strong virtual lesion effect observed with rTMS over PMd suggest that this area represents a key node for both the suppression of activation based on the precue and response activation based on the response target.

Increased neural activity in left angular gyrus (AG) accompanies successful comprehension of acoustically degraded but highly predictable sentences, as previous functional imaging studies have shown. However, it remains unclear whether the left AG is causally relevant for the comprehension of degraded speech. Here, we applied transient virtual lesions to either the left AG or superior parietal lobe (SPL, as a control area) with repetitive transcranial magnetic stimulation (rTMS) while healthy volunteers listened to and repeated sentences with high- versus low-predictable endings and different noise vocoding levels. We expected that rTMS of AG should selectively modulate the predictability gain (i.e., the comprehension benefit from sentences with high-predictable endings) at a medium degradation level. We found that rTMS of AG indeed reduced the predictability gain at a medium degradation level of 4-band noise vocoding (relative to control rTMS of SPL). In contrast, the behavioral perturbation induced by rTMS changed with increased signal quality. Hence, at 8-band noise vocoding, rTMS over AG versus SPL decreased the number of correctly repeated keywords for sentences with low-predictable endings. Together, these results show that the degree of the rTMS interference depended jointly on signal quality and predictability. Our results provide the first causal evidence that the left AG is a critical node for facilitating speech comprehension in challenging listening conditions.

Sentence comprehension requires the rapid analysis of semantic and syntactic information. These processes are supported by a left hemispheric dominant fronto-temporal network, including left posterior inferior frontal gyrus (pIFG) and posterior superior temporal gyrus/sulcus (pSTG/STS). Previous electroencephalography (EEG) studies have associated semantic expectancy within a sentence with a modulation of the N400 and syntactic gender violations with increases in the LAN and P600. Here, we combined focal perturbations of neural activity by means of short bursts of transcranial magnetic stimulation (TMS) with simultaneous EEG recordings to probe the functional relevance of pIFG and pSTG/STS for sentence comprehension. We applied 10 Hz TMS bursts of three pulses at verb onset during auditory presentation of short sentences. Verb-based semantic expectancy and article-based syntactic gender requirement were manipulated for the sentence final noun. We did not find any TMS effect at the noun. However, TMS had a short-lasting impact at the mid-sentence verb that differed for the two stimulation sites. Specifically, TMS over pIFG elicited a frontal positivity in the first 200 msec post verb onset whereas TMS over pSTG/STS was limited to a parietal negativity at 200–400 msec post verb onset. This indicates that during verb processing in sentential context, frontal brain areas play an earlier role than temporal areas in predicting the upcoming noun. The short-living perturbation effects at the mid-sentence verb suggest a high degree of online compensation within the language system since the sentence final noun processing was unaffected.

Objectives To validate the Fullerton Advanced Balance (FAB) Scale for patients with idiopathic Parkinson disease (PD); and to compare the FAB Scale with the Mini-Balance Evaluation Systems Test (Mini-BESTest) and Berg Balance Scale (BBS). Design Observational study to assess concurrent validity, test-retest, and interrater reliability of the FAB Scale in patients with PD and to compare the distribution of the scale with the Mini-BESTest and BBS. Setting University hospital in an urban community. Participants Patients with idiopathic PD (N=85; Hoehn and Yahr stages 1–4). Interventions Not applicable. Main Outcome Measures FAB Scale, Mini-BESTest, BBS, timed Up and Go test, Unified Parkinson's Disease Rating Scale, and visual analog scale. Results Interrater (3 raters) and test-retest (3±1d) reliability were high for all scales (ICCs≥.95). The FAB Scale was highly correlated with the Mini-BESTest (Spearman ρ=.87) and timed Up and Go test item of the Mini-BESTest (Spearman ρ=.83). In contrast with the BBS, the FAB Scale and Mini-BESTest have only minimal ceiling effects. The FAB Scale demonstrated the most symmetric distribution when compared with the Mini-BESTest and BBS (skewness: FAB scale: −.54; Mini-BESTest: −1.07; BBS: −2.14). Conclusions The FAB Scale is a valid and reliable tool to assess postural control in patients with PD. No ceiling effect was noted for the FAB Scale. Although the items of the FAB Scale are more detailed when compared with the Mini-BESTest, interrater and test-retest reliability were excellent. The scale is a promising tool to detect small changes of the postural control system in individuals with PD.

The role of left and right hemisphere brain regions in language recovery after stroke-induced aphasia remains controversial. Here, we summarize how neuroimaging studies increase the current understanding of functional interactions, reorganization and plasticity in the language network. We first discuss the temporal dynamics across the time course of language recovery, with a main focus on longitudinal studies from the acute to the chronic phase after stroke. These studies show that the functional contribution of perilesional and spared left hemisphere as well as contralesional right hemisphere regions to language recovery changes over time. The second section introduces critical variables and recent advances on early prediction of subsequent outcome. In the third section, we outline how multi-method approaches that combine neuroimaging techniques with non-invasive brain stimulation elucidate mechanisms of plasticity and reorganization in the language network. These approaches provide novel insights into general mechanisms of plasticity in the language network and might ultimately support recovery processes during speech and language therapy. Finally, the neurobiological correlates of therapy-induced plasticity are discussed. We argue that future studies should integrate individualized approaches that might vary the combination of language therapy with specific non-invasive brain stimulation protocols across the time course of recovery. The way forward will include the combination of such approaches with large data sets obtained from multicentre studies.

Postural instability is one of the most disabling and risky symptoms of advanced Parkinson's disease (PD). The purpose of this study was to investigate whether and how this is mediated by a centrally impaired spatial orientation. Therefore, we performed a spatial orientation study in 21 PD patients (mean age 68years, SD 8.5 years, 9 women) in a medically on condition and 21 healthy controls (mean age 68.9years, SD 5.5years, 14 women). We compared their spatial responses to the horizontal axis (Sakashita's visual target cancellation task), the vertical axis (bucket-test), the sagittal axis (tilt table test) and postural stability using the Fullerton Advanced Balance Scale (FAB). We found larger deviations on the vertical axis in PD patients, although the direct comparisons of performance in PD patients and healthy controls did not reveal significant differences. While the total scores of the FAB Scale were significantly worse in PD (25.9 points, SD 7.2 points) compared to controls (35.1 points, SD 2.3 points, p

The adaptive potential of the language network to compensate for lesions remains elusive. We show that perturbation of a semantic region in the healthy brain induced suppression of activity in a large semantic network and upregulation of neighbouring phonological areas. After perturbation, the disrupted area increased its inhibitory influence on another semantic key node. The inhibitory influence predicted the individual delay in response speed, indicating that inhibition at remote nodes is functionally relevant. Individual disruption predicted the upregulation of semantic activity in phonological regions. In contrast, perturbation over a phonological region suppressed activity in the network and disrupted behaviour without inducing upregulation. The beneficial contribution of a neighbouring network might thus depend on the level of functional disruption and may be interpreted to reflect a differential compensatory potential of distinct language networks. These results might reveal generic mechanisms of plasticity in cognitive networks and inform models of language reorganization. DOI: http://dx.doi.org/10.7554/eLife.25964.001, eLife digest Taking part in a conversation requires us to extract meaning from a complex series of sounds by recognising words and phrases. We then need to decide on a response, and plan and execute the lip and tongue movements necessary to generate that response. Each of these processes – from analysing the meaning of words to producing speech – requires a distinct set of brain regions to work together. However, we know relatively little about how these regions interact with one another during specific language processes, or about what happens when key regions are damaged. Hartwigsen et al. have now used a technique called TMS in healthy volunteers to temporarily disrupt the activity of individual brain regions with a role in language. TMS involves applying small magnetic fields to the scalp over a target brain area. The magnetic fields induce electrical currents in the underlying brain tissue and temporarily scramble its activity. Hartwigsen et al. examined how this affected the volunteers’ performance on a language task, as well as the activity of other language areas. Temporarily disrupting a single brain region involved in analysing the meaning of words reduced the activity of multiple other areas in the brain’s language networks. The greater this reduction in activity, the more poorly the volunteers performed on a language task. However, not all brain regions showed reduced activity. Areas adjacent to the disrupted region, which normally process the sounds of words, increased their activity. This increase may have partially compensated for the effects of the TMS to help limit the language impairments. These findings offer insights into how the brain reacts and adapts when key language areas are damaged, for example as a result of stroke. The next step is to determine the extent to which healthy brain tissue can take over from damaged regions, and whether we can target this process to improve recovery after stroke. DOI: http://dx.doi.org/10.7554/eLife.25964.002