Biology subjects

Hartwigsen, G.

Publications and source records attributed to Hartwigsen, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Cortical Adaptation Mechanism in the Delta Band of Post-Stroke Aphasic subjects during Naming Task

AO_SCPLOWBSTRACTC_SCPLOWThis study explores differences in spatiotemporal cortical dynamics between five people with chronic post-stroke aphasia and five healthy subjects. Electroencephalography was recorded during picture naming in both groups. Frequency-specific Global Field Power (GFP) results showed that the delta band has higher power to discriminate between healthy subjects and people with aphasia (PWA) than theta and alpha bands. EEG topologies computed at the time of GFP peaks in the delta band revealed strong activation oscillating between posterior and anterior areas in PWA. On the other hand, EEG topologies from healthy subjects were variable. Then, Spatial ERP (S-ERP) were developed to add spatial resolution to classical ERP analysis. S-ERP and associated analyses confirmed the previously observed oscillatory pattern in the delta frequency band among PWA during picture naming. This oscillating pattern was alternating between occipital and prefrontal areas with almost opposite phases, a characteristic not observed in healthy subjects. In addition, all PWA performed well on the picture naming task, suggesting that this oscillating pattern may be a cortical adaptation mechanism enabling them to succeed. The observation of large-scale oscillating delta activity across the scalp in all post-stroke subjects who have substantially recovered from aphasia holds the potential to inspire innovative rehabilitation methods employing non-invasive brain stimulation techniques such as transcranial alternating current stimulation (tACS).

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bioRxiv2023

Investigating Spatiotemporal Dynamics of Cortical Activity During Language Production in the Healthy and Lesioned Brain

Efficient language production requires rapid interactions between different brain areas. These interactions can be severely affected by brain lesions. However, the neurophysiological correlates of the spatiotemporal dynamics during language production are not well understood. The current pilot study explores differences in spatiotemporal cortical dynamics between five subjects with post-stroke aphasia and five control subjects. Electroencephalography was recorded during picture naming in both groups. Average-based analyses (event-related potential (ERP), frequency-specific Global Field Power (GFP)), reveal a strong synchronization of cortical oscillations, especially within the first 600ms post-stimulus, with a time shift between participants with aphasia and control subjects. ERPs and the corresponding brain microstates indicate coordinated brain activity alternating mainly between frontal and occipital zones. This behavior can be described as standing waves between two main sources. At the single-trial scale, traveling waves (TW) were identified from both phase and amplitude analyses. The spatiotemporal distribution of amplitude TW reveals subject-specific organization of several interconnected hubs. In patients with aphasia this spatial organization of TW reveals zones with no TW notably in the vicinity of stroke lesions. The present results provide important hints for the hypothesis that TW contribute to the synchronization and communication between different brain areas especially by interconnecting cortical hubs. Moreover, our findings show that cortical dynamics is affected by brain lesions. Contribution to the FieldO_LISpatiotemporal cortical dynamics of individual trials reveals the presence of phase and amplitude traveling waves. C_LIO_LIExploration of traveling waves on the 2D cortical surface reveals the presence of interconnected epicenters or hubs in all subjects. C_LIO_LIThe spatiotemporal distribution of traveling waves shows a higher density in the prefrontal area for people with aphasia than for healthy subjects. C_LIO_LIFor subjects with aphasia, a sparser density of traveling waves is observed in the approximated lesion area. C_LIO_LIEvent-related potential analyses reveal a consistent alternating activity between the frontal and occipital regions. C_LIO_LISubjects with aphasia present a larger and/or delayed contribution in the delta range in the GFP patterns compared to control subjects. C_LI

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bioRxiv2023

Conceptual representations in the default, control and attention networks are task-dependent and cross-modal

Conceptual knowledge is central to human cognition. Neuroimaging studies suggest that conceptual processing involves modality-specific and multimodal brain regions in a task-dependent fashion. However, it remains unclear (1) to what extent conceptual feature representations are also modulated by the task, (2) whether conceptual representations in multimodal regions are indeed cross-modal, and (3) how the conceptual system relates to the large-scale functional brain networks. To address these issues, we conducted multivariate pattern analyses on fMRI data. 40 participants performed three tasks--lexical decision, sound judgment, and action judgment--on written words. We found that (1) conceptual feature representations are strongly modulated by the task, (2) conceptual representations in several multimodal regions are cross-modal, and (3) conceptual feature retrieval involves the default, frontoparietal control, and dorsal attention networks. Conceptual representations in these large-scale networks are task-dependent and cross-modal. Our findings support theories that assume conceptual processing to rely on a flexible, multi-level architecture.

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bioRxiv2023

Modeling the Effects of Transcranial Magnetic Stimulation on Spatial Attention

ObjectivesTranscranial magnetic stimulation (TMS) has been widely used to modulate brain activity in healthy and diseased brains, but the underlying mechanisms are not fully understood. Previous research leveraged biophysical modeling of the induced electric field (E-field) to map causal structure-function relationships in the primary motor cortex. This study aims at transferring this localization approach to spatial attention, which helps to understand the TMS effects on cognitive functions, and may ultimately optimize stimulation schemes. ApproachThirty right-handed healthy participants underwent a functional magnetic imaging (fMRI) experiment, and seventeen of them participated in a TMS experiment. The individual fMRI activation peak within the right inferior parietal lobule (rIPL) during a Posner-like attention task defined the center target for TMS. Thereafter, participants underwent 500 Posner task trials. During each trial, a 5-pulse burst of 10 Hz repetitive TMS (rTMS) was given over the rIPL to modulate attentional processing. The TMS-induced E-fields for every cortical target were correlated with the behavioral modulation to identify relevant cortical regions for attentional orientation and reorientation. Main resultsWe did not observe a robust correlation between E-field strength and behavioral outcomes, highlighting the challenges of transferring the localization method to cognitive functions with high neural response variability and complex network interactions. Nevertheless, TMS selectively inhibited attentional reorienting in five out of seventeen subjects, resulting in task-specific behavioral impairments. The BOLD-measured neuronal activity and TMS-evoked neuronal effects showed different patterns, which emphasizes the principal distinction between the neural activity being correlated with (or maybe even caused by) particular paradigms, and the activity of neural populations exerting a causal influence on the behavioral outcome. SignificanceThis study is the first to explore the mechanisms of TMS-induced attentional modulation through electrical field modeling. Our findings highlight the complexity of cognitive functions and provide a basis for optimizing attentional stimulation protocols.

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bioRxiv2022

Meta-analytic evidence for a novel hierarchical model of conceptual processing

Conceptual knowledge plays a pivotal role in human cognition. Grounded cognition theories propose that concepts consist of perceptual-motor features represented in modality-specific perceptual-motor cortices. However, it is unclear whether conceptual processing consistently engages modality-specific areas. Here, we performed an activation likelihood estimation (ALE) meta-analysis across 212 neuroimaging experiments on conceptual processing related to 7 perceptual-motor modalities (action, sound, visual shape, motion, color, olfaction-gustation, and emotion). We found that conceptual processing consistently engages brain regions also activated during real perceptual-motor experience of the same modalities. In addition, we identified multimodal convergence zones that are recruited for multiple modalities. In particular, the left inferior parietal lobe (IPL) and posterior middle temporal gyrus (pMTG) are engaged for three modalities: action, motion, and sound. These "trimodal" regions are surrounded by "bimodal" regions engaged for two modalities. Our findings support a novel model of the conceptual system, according to which conceptual processing relies on a hierarchical neural architecture from modality-specific to multimodal areas up to an amodal hub.

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bioRxiv2022

Facilitatory stimulation of the pre-SMA in healthy aging has distinct effects on task-based activity and connectivity

BackgroundThe continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults. MethodsWe implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, we stimulated each participant once with effective and once with sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand. ResultsEffective stimulation increased activation relative to sham stimulation only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased functional connectivity in task-specific networks for semantic and executive conditions with high cognitive load. Notably, stimulation-induced changes in activation and connectivity related differently to behavior: While increased activation of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. ConclusionsiTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.

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bioRxiv2022

Age-related reorganization of functional network architecture for language processing

Semantic memory is a fundamental human ability which is central to communication. Although it is usually well preserved in healthy aging, memory problems in verbal communication due to slowed access and retrieval processes are a common complaint with increasing age. So far, the neural bases of this paradox remain poorly understood. The current neuroimaging study investigated age differences in the functional network architecture during semantic word retrieval in young and older adults. Using group spatial independent component analysis, we defined functional networks for verbal semantic fluency. 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 processes and demonstrate that a youth-like network architecture in terms of balanced integration and segregation is associated with more economical processing. Significance StatementCognitive aging is associated with widespread neural reorganization processes in the human brain. However, the behavioral impact of such reorganization is not well understood. Here, we used taskbased fMRI to demonstrate a large-scale reorganization of brain networks in older adults even when their semantic abilities are intact. In particular, functional networks of older adults were characterized by increased coupling between different systems, reduced segregation and efficiency, and a larger number of hub regions relative to young adults. Associating these changes with behavior revealed high, albeit less efficient, performance for networks in older adults showing stronger dedifferentiation and reduced distinctiveness. Our results highlight the compensatory potential of network reconfiguration with age, but also reveal the limitations of such reorganization processes.

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bioRxiv2022

Adaptive plasticity in the healthy reading network investigated through combined neurostimulation and neuroimaging

The reading network in the human brain comprises several regions, including the left inferior frontal cortex (IFC), ventral occipito-temporal cortex (vOTC) and dorsal temporo-parietal cortex (TPC). The left TPC is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings. Here, we tested the causal contribution of this area for reading with repetitive transcranial magnetic stimulation (rTMS) and explored the response of the reading network using functional magnetic resonance imaging (fMRI). 28 healthy adult readers overtly read simple and complex words and pseudowords during fMRI after effective or sham TMS over the left TPC. Behaviorally, effective stimulation slowed pseudoword reading. A multivariate pattern analysis showed a shift in activity patterns in the left IFC for pseudoword reading after effective relative to sham TMS. Furthermore, active TMS led to increased effective connectivity from the left vOTC to the left TPC, specifically for pseudoword processing. The observed changes in task-related activity and connectivity suggest compensatory reorganization in the reading network following TMS-induced disruption of the left TPC. Our findings provide first evidence for a causal role of the left TPC for overt pseudoword reading and emphasize the relevance of functional interactions in the healthy reading network for successful pseudoword processing.

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bioRxiv2022

Bayesian stroke modeling details sex biases in the white matter substrates of aphasia

Ischemic cerebrovascular events often lead to aphasia. Previous work provided hints that such strokes may affect women and men in distinct ways. Women tend to suffer strokes with more disabling language impairment, even if the lesion size is comparable to men. In 1,401 patients, we isolated data-led representations of anatomical lesion patterns and hand-tailored a Bayesian analytical solution to carefully model the degree of sex divergence in predicting language outcomes [~]3 months after stroke. We located lesion-outcome effects in the left-dominant language network that highlight the ventral pathway as a core lesion focus across different tests of language performance. We provide newly detailed evidence for sex-specific brain-behavior associations in the domain-general networks associated with cortico-subcortical pathways, with unique contributions of the fornix in women and cingular fiber bundles in men. Our collective findings suggest diverging white matter substrates in how stroke causes language deficits in women and men. Clinically acknowledging such sex disparities has the potential to improve personalized treatment for stroke patients worldwide.

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bioRxiv2021

The role of the angular gyrus in semantic cognition - A synthesis of five functional neuroimaging studies

Semantic knowledge is central to human cognition. The angular gyrus (AG) is widely considered a key brain region for semantic cognition. However, the role of the AG in semantic processing is controversial. Key controversies concern response polarity (activation vs. deactivation) and its relation to task difficulty, lateralization (left vs. right AG), and functional-anatomical subdivision (PGa vs. PGp subregions). Here, we combined the fMRI data of five studies on semantic processing (n = 172) and analyzed the response profiles from the same anatomical regions-of-interest for left and right PGa and PGp. We found that the AG was consistently deactivated during non-semantic conditions, whereas response polarity during semantic conditions was inconsistent. However, the AG consistently showed relative response differences between semantic and non-semantic conditions, and between different semantic conditions. A combined analysis across all studies revealed that AG responses could be best explained by separable effects of task difficulty and semantic processing demand. Task difficulty effects were stronger in PGa than PGp, regardless of hemisphere. Semantic effects were stronger in left than right AG, regardless of subregion. These results suggest that the AG is engaged in both domain-general task-difficulty-related processes and domain-specific semantic processes. In semantic processing, we propose that left AG acts as a "multimodal convergence zone" that binds different semantic features associated with the same concept, enabling efficient access to task-relevant features.

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bioRxiv2021

Age-related differences in the neural network dynamics underlying the predictability gain

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.

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bioRxiv2021

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 (4-8Hz) 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.

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bioRxiv2021

Towards a causal role of Broca's area in language: A TMS-EEG study on syntactic prediction

Categorical predictions have been proposed as the key mechanism supporting the fast pace of syntactic composition in human language. Accordingly, grammar-based expectations facilitate the analysis of incoming syntactic information--e.g., hearing the determiner "the" enhances the prediction of a noun--which is then checked against a single or few other word categories. Previous functional neuroimaging studies point towards Brocas area in the left inferior frontal gyrus (IFG) as one fundamental cortical region involved in categorical prediction during on-line language processing. Causal evidence for this hypothesis is however still missing. In this study, we combined Electroencephalography (EEG) and Transcranial Magnetic Stimulation (TMS) to test whether Brocas area is functionally relevant in predictive mechanisms for language. Specifically, we transiently perturbed Brocas area during the categorical prediction phase in two-word constructions, while simultaneously measuring the Event-Related Potential (ERP) correlates of syntactic composition. We reasoned that if Brocas area is involved in predictive mechanisms for syntax, disruptive TMS during the processing of the first word (determiner/pronoun) would mitigate the difference in ERP responses for predicted and unpredicted categories when composing basic phrases and sentences. Contrary to our hypothesis, perturbation of Brocas area at the predictive stage did not affect the ERP correlates of basic composition. The correlation strength between the electrical field induced by TMS and the magnitude of the EEG response on the scalp further confirmed this pattern. We discuss the present results in light of an alternative account of the role of Brocas area in syntactic composition, namely the bottom-up integration of words into constituents.

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bioRxiv2021

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 modelled 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.

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bioRxiv2020

Predicting speech from a cortical hierarchy of event-based timescales

How can anticipatory neural processes structure the temporal unfolding of context in our natural environment? We here provide evidence for a neural coding scheme that sparsely updates contextual representations at the boundary of events and gives rise to a hierarchical, multi-layered organization of predictive language comprehension. Training artificial neural networks to predict the next word in a story at five stacked timescales and then using model-based functional MRI, we observe a sparse, event-based "surprisal hierarchy". The hierarchy evolved along a temporo-parietal pathway, with model-based surprisal at longest timescales represented in inferior parietal regions. Along this hierarchy, surprisal at any given timescale gated bottom-up and top-down connectivity to neighbouring timescales. In contrast, surprisal derived from a continuously updated context influenced temporo-parietal activity only at short timescales. Representing context in the form of increasingly coarse events constitutes a network architecture for making predictions that is both computationally efficient and semantically rich.

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bioRxiv2020

Age-dependent contribution of domain-general network interactions 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 contribution of domain-general networks to a verbal semantic fluency task in young and older adults. In both 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 system 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 a slower performance in older adults. Moreover, only young adults profited from increased connectivity between networks for their semantic memory performance. Our results suggest that the functional coupling of usually anti-correlated 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.

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bioRxiv2020

Hemispheric specialization within the inferior parietal lobe across cognitive domains

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.

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bioRxiv2019

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 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.

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