559 research outputs found
Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity
Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood-flow independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings, and offers substantial promise to investigate physiological mechanisms, but behaviourally-relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven Hidden Markov Model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both p < 0.001). Hidden Markov Model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared to controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes
Neuroimaging investigations of cortical specialisation for different types of semantic knowledge
Embodied theories proposed that semantic knowledge is grounded in motor and perceptual experiences. This leads to two questions: (1) whether the neural underpinnings of perception are also necessary for semantic cognition; (2) how do biases towards different sensorimotor experiences cause brain regions to specialise for particular types of semantic information. This thesis tackles these questions in a series of neuroimaging and behavioural investigations.
Regarding question 1, strong embodiment theory holds that semantic representation is reenactment of corresponding experiences, and brain regions for perception are necessary for comprehending modality-specific concepts. However, the weak embodiment view argues that reenactment may not be necessary, and areas near to perceiving regions may be sufficient to support semantic representation.
In the particular case of motion concepts, lateral occipital temporal cortex (LOTC) has been long identified as an important area, but the roles of its different subregions are still uncertain. Chapter 3 examined how different parts of LOTC reacted to written descriptions of motion and static events, using multiple analysis methods. A series of anterior to posterior sub-regions were analyzed through univariate, multivariate pattern analysis (MVPA), and psychophysical interaction (PPI) analyses. MVPA revealed strongest decoding effects for motion vs. static events in the posterior parts of LOTC, including both visual motion area (V5) and posterior middle temporal gyrus (pMTG). In contrast, only the middle portion of LOTC showed increased activation for motion sentences in univariate analyses. PPI analyses showed increased functional connectivity between posterior LOTC and the multiple demand network for motion events. These findings suggest that posterior LOTC, which overlapped with the motion perception V5 region, is selectively involved in comprehending motion events, while the anterior part of LOTC contributes to general semantic processing.
Regarding question 2, the hub-and-spoke theory suggests that anterior temporal lobe (ATL) acts as a hub, using inputs from modality-specific regions to construct multimodal concepts. However, some researchers propose temporal parietal cortex (TPC) as an additional hub, specialised in processing and integrating interaction and contextual information (e.g., for actions and locations). These hypotheses are summarized as the "dual-hub theory" and different aspects of this theory were investigated in in Chapters 4 and 5.
Chapter 4 focuses on taxonomic and thematic relations. Taxonomic relations (or categorical relations) occur when two concepts belong to the same category (e.g., ‘dog’ and ‘wolf’ are both canines). In contrast, thematic relations (or associative relations) refer to situations that two concepts co-occur in events or scenes (e.g., ‘dog’ and ‘bone’), focusing on the interaction or association between concepts. Some studies have indicated ATL specialization for taxonomic relations and TPC specialization for thematic relations, but others have reported inconsistent or even converse results. Thus Chapter 4 first conducted an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies contrasting taxonomic and thematic relations. This found that thematic relations reliably engage action and location processing regions (left pMTG and SMG), while taxonomic relations only showed consistent effects in the right occipital lobe. A primed semantic judgement task was then used to test the dual-hub theory’s prediction that taxonomic relations are heavily reliant on colour and shape knowledge, while thematic relations rely on action and location knowledge. This behavioural experiment revealed that action or location priming facilitated thematic relation processing, but colour and shape did not lead to priming effects for taxonomic relations. This indicates that thematic relations rely more on action and location knowledge, which may explain why the preferentially engage TPC, whereas taxonomic relations are not specifically linked to shape and colour features. This may explain why they did not preferentially engage left ATL.
Chapter 5 concentrates on event and object concepts. Previous studies suggest ATL specialization for coding similarity of objects’ semantics, and angular gyrus (AG) specialization for sentence and event structure representation. In addition, in neuroimaging studies, event semantics are usually investigated using complex temporally extended stimuli, unlike than the single-concept stimuli used to investigate object semantics. Thus chapter 5 used representational similarity analysis (RSA), univariate analysis, and PPI analysis to explore neural activation patterns for event and object concepts presented as static images. Bilateral AGs encoded semantic similarity for event concepts, with the left AG also coding object similarity. Bilateral ATLs encoded semantic similarity for object concepts but also for events. Left ATL exhibited stronger coding for events than objects. PPI analysis revealed stronger connections between left ATL and right pMTG, and between right AG and bilateral inferior temporal gyrus (ITG) and middle occipital gyrus, for event concepts compared to object concepts. Consistent with the meta-analysis in chapter 4, the results in chapter 5 support the idea of partial specialization in AG for event semantics but do not support ATL specialization for object semantics. In fact, both the meta-analysis and chapter 5 findings suggest greater ATL involvement in coding objects' associations compared to their similarity.
To conclude, the thesis provides support for the idea that perceptual brain regions are engaged in conceptual processing, in the case of motion concepts. It also provides evidence for a specialised role for TPC regions in processing thematic relations (pMTG) and event concepts (AG). There was mixed evidence for specialisation within the ATLs and this remains an important target for future research
Oscillatory mechanisms of conscious perception and attention
Although the prominent role of neural oscillations in perception and cognition has been continuously investigated, some critical questions remain unanswered. My PhD thesis was aimed at addressing some of them.
First, can we dissociate oscillatory underpinnings of perceptual accuracy and subjective awareness? Current work would strongly suggest that this dissociation can be drawn. While the fluctuations in alpha-amplitude decide perceptual bias and metacognitive abilities, the speed of alpha activity (i.e., alpha-frequency) dictates sensory sampling, shaping perceptual accuracy.
Second, how are these oscillatory mechanisms integrated during attention? The obtained results indicate that a top-down visuospatial mechanism modulates neural assemblies in visual areas via oscillatory re-alignment and coherence in the alpha/beta range within the fronto-parietal brain network. These perceptual predictions are reflected in the retinotopically distributed posterior alpha-amplitude, while perceptual accuracy is explained by the higher alpha-frequency at the to-be-attended location. Finally, sensory input, elaborated via fast gamma oscillations, is linked to specific phases of this slower activity via oscillatory nesting, enabling integration of the feedback-modulated oscillatory activity with sensory information.
Third, how can we relate this oscillatory activity to other neural markers of behaviour (i.e., event-related potentials)? The obtained results favour the oscillatory model of ERP genesis, where alpha-frequency shapes the latency of early evoked-potentials, namely P1, with both neural indices being related to perceptual accuracy. On the other hand, alpha-amplitude dictates the amplitude of later P3 evoked-response, whereas both indices shape subjective awareness.
Crucially, by combining different methodological approaches, including neurostimulation (TMS) and neuroimaging (EEG), current work identified these oscillatory-behavior links as causal and not just as co-occurring events. Current work aimed at ameliorating the use of the TMS-EEG approach by explaining inter-individual differences in the stimulation outcomes, which could be proven crucial in the way we design entrainment experiments and interpret the results in both research and clinical settings
Local Differences in Cortical Excitability – A Systematic Mapping Study of the TMS-Evoked N100 Component
Die transkranielle Magnetstimulation führt zu einer fokalen Aktivierung des Kortex, die durch die elektroenzephalographische Aufzeichnung (TMS-EEG) graphisch dargestellt werden kann. Anhand der TMS-evozierten Potenziale (TEP) kann die kortikale Erregbarkeit untersucht werden. Hierfür eignet sich besonders die negative N100 Komponente, die 100ms nach der Stimulation auftritt und in verschiedenen kortikalen Arealen messbar ist.
Durch ein systematisches Mapping mittels TMS kann die Exzitabilität in verschiedenen Hirnarealen dargestellt werden. In der vorliegenden Studie wurden die Effekte untersucht, die eine systematische Verschiebung der TMS-Spule innerhalb des Motorkortex auf die N100 und MEP Amplitude hat.
Es wurde ein Mapping des Motorkortex bei zwölf gesunden Versuchspersonen durchgeführt. Dafür wurde ein standardisiertes Gitter verwendet mit Mittelpunkt über dem motorischen Hotspot und zwölf Positionen mit einer Entfernung zwischen 5 mm und 10 mm um den Hotspot. Auf allen dreizehn Positionen des Mapping-Gitters wurde ein TMS single-pulse-Protokoll angewendet.
In dieser Studie konnte gezeigt werden, dass TMS über dem primär motorischen Kortex eine ipsilaterale und leicht posteriore Topographie der N100-Komponente generiert. Diese wird vermutlich durch die Anamtomie des primär motorischen Kortex und der lokalen Erregbarkeit der umgebenden kortikalen Areale beeinflusst. Während des kortikalen Mappings zeigten sich charakteristische Unterschiede in der Amplitude und Latenz der N100. Bei Stimulation der antero-medialen Lokalisation zeigte sich eine signifikante Abnahme der N100 Amplitude, während in den anderen Richtungen keine wesentlichen Änderungen der Amplitude auftraten. Dies könnte an einer geringeren Exzitabilität anteriorer Kortexareale liegen, die vermutlich zu der posterioren Topographie der N100 führt. Anhand der Veränderungen der N100 Amplitude könnten somit Unterschiede in der lokalen Exzitabilität verschiedener kortikaler Areale dargestelllt werden
Évaluation et modulation des fonctions exécutives en neuroergonomie - Continuums cognitifs et expérimentaux
Des études en neuroergonomie ont montré que le pilote d’avion pouvait commettre des erreurs en raison d’une incapacité transitoire à faire preuve de flexibilité mentale. Il apparait que certains facteurs, tels qu’une forte charge mentale ou une pression temporelle importante, un niveau de stress trop élevé, la survenue de conflits, ou une perte de conscience de la situation, peuvent altérer temporairement l’efficience des fonctions exécutives permettant cette flexibilité. Depuis mes travaux initiaux, dans lesquels je me suis intéressé aux conditions qui conduisent à une négligence auditive, j’ai souhaité développer une approche scientifique visant à quantifier et limiter les effets délétères de ces différents facteurs. Ceci a été fait à travers l’étude des fonctions exécutives chez l’être humain selon le continuum cognitif (du cerveau lésé au cerveau en parfait état de fonctionnement) et le continuum expérimental (de l’ordinateur au monde réel). L’approche fondamentale de l’étude des fonctions exécutives en neurosciences combinée à l’approche neuroergonomique graduelle avec des pilotes et des patients cérébro-lésés, a permis de mieux comprendre la manière dont ces fonctions sont mises en jeu et altérées. Cette connaissance à contribuer par la suite à la mise en place de solutions pour préserver leur efficacité en situation complexe.
Après avoir rappelé mon parcours académique, je présente dans ce manuscrit une sélection de travaux répartis sur trois thématiques de recherche. La première concerne l’étude des fonctions exécutives impliquées dans l’attention et en particulier la façon dont la charge perceptive et la charge mentale peuvent altérer ces fonctions. La deuxième correspond à un aspect plus appliqué de ces travaux avec l’évaluation de l’état du pilote. Il a été question d’analyser cet état selon l’activité de pilotage elle-même ou à travers la gestion et la supervision d’un système en particulier. La troisième et dernière thématique concerne la recherche de marqueurs prédictifs de la performance cognitive et l’élaboration d’entraînements cognitifs pour limiter les troubles dysexécutifs, qu’ils soient d’origine contextuelle ou lésionnelle.
Ces travaux ont contribué à une meilleure compréhension des troubles cognitifs transitoires ou chroniques, mais ils ont aussi soulevé des questions auxquelles je souhaite répondre aujourd’hui. Pour illustrer cette réflexion, je présente en dernière partie de ce document mon projet de recherche qui vise à développer une approche multifactorielle de l’efficience cognitive, éthique et en science ouverte
Water and Brain Function: Effects of Hydration Status on Neurostimulation and Neurorecording
Introduction: TMS and EEG are used to study normal neurophysiology, diagnose, and treat clinical neuropsychiatric conditions, but can produce variable results or fail. Both techniques depend on electrical volume conduction, and thus brain volumes. Hydration status can affect brain volumes and functions (including cognition), but effects on these techniques are unknown. We aimed to characterize the effects of hydration on TMS, EEG, and cognitive tasks. Methods: EEG and EMG were recorded during single-pulse TMS, paired-pulse TMS, and cognitive tasks from 32 human participants on dehydrated (12-hour fast/thirst) and rehydrated (1 Liter oral water ingestion in 1 hour) testing days. Hydration status was confirmed with urinalysis. MEP, ERP, and network analyses were performed to examine responses at the muscle, brain, and higher-order functioning. Results: Rehydration decreased motor threshold (increased excitability) and shifted the motor hotspot. Significant effects on TMS measures occurred despite being re-localized and re-dosed to these new parameters. Rehydration increased SICF of the MEP, magnitudes of specific TEP peaks in inhibitory protocols, specific ERP peak magnitudes and reaction time during the cognitive task. Rehydration amplified nodal inhibition around the stimulation site in inhibitory paired-pulse networks and strengthened nodes outside the stimulation site in excitatory and CSP networks. Cognitive performance was not improved by rehydration, although similar performance was achieved with generally weaker network activity. Discussion: Results highlight differences between mild dehydration and rehydration. The rehydrated brain was easier to stimulate with TMS and produced larger responses to external and internal stimuli. This is explainable by the known physiology of body water dynamics, which encompass macroscopic and microscopic volume changes. Rehydration can shift 3D cortical positioning, decrease scalp cortex distance (bringing cortex closer to stimulator/recording electrodes), and cause astrocyte swelling-induced glutamate release. Conclusions: Previously unaccounted variables like osmolarity, astrocyte and brain volumes likely affect neurostimulation/neurorecording. Controlling for and carefully manipulating hydration may reduce variability and improve therapeutic outcomes of neurostimulation. Dehydration is common and produces less excitable circuits. Rehydration should offer a mechanism to macroscopically bring target cortical areas closer to an externally applied neurostimulation device to recruit greater volumes of tissue and microscopically favor excitability in the stimulated circuits
„Balancing Vibrations" – Die neurophysiologische Erregbarkeit des primären Motorkortex bei depressiven Jugendlichen im Verlauf einer Sporttherapie - eine Zwischenauswertung -
Die Kombination TMS-EEG stellt eine einzigartige Möglichkeit dar, die kortikale Exzitabilität direkt und zeitlich hochaufgelöst zu untersuchen. Eine Komponente des TMS- evozierten Potentials stellt die N100 dar, welche im Kontext vergangener Arbeiten als Korrelat kortikaler Inhibition etabliert gilt. Veränderungen der N100 wurden bereits mit diversen neuropsychiatrischen Pathologien in Verbindung gebracht und sollen nun erstmals in einem Patientenkollektiv depressiver Jugendlichen untersucht werden. Das Ziel ist es, einen Zusammenhang zwischen Depressivität und N100-Amplituden zu untersuchen und damit den möglichen Einsatz der N100 als Biomarker und Verlaufsparameter für Depression zu evaluieren
TMS combined with EEG: Recommendations and open issues for data collection and analysis
Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS−EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS−EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS−EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS−EEG covered all aspects that should be considered in TMS−EEG experiments, providing methodological recommendations (when possible) for effective TMS−EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS−EEG methodology and thus may promote standardization of experimental and computational procedures across groups
Comparative analysis of TMS-EEG signal using different approaches in healthy subjects
openThe integration of transcranial magnetic stimulation with electroencephalography (TMS-EEG) represents a useful non-invasive approach to assess cortical excitability, plasticity and intra-cortical connectivity in humans in physiological and pathological conditions.
However, biological and environmental noise sources can contaminate the TMS-evoked potentials (TEPs). Therefore, signal preprocessing represents a fundamental step in the analysis of these potentials and is critical to remove artefactual components while preserving the physiological brain activity.
The objective of the present study is to evaluate the effects of different signal processing pipelines, (namely Leodori et al., Rogasch et al., Mutanen et al.) applied on TEPs recorded in five healthy volunteers after TMS stimulation of the primary motor cortex (M1) of the dominant hemisphere. These pipelines were used and compared to remove artifacts and improve the quality of the recorded signals, laying the foundation for subsequent analyses. Various algorithms, such as Independent Component Analysis (ICA), SOUND, and SSP-SIR, were used in each pipeline.
Furthermore, after signal preprocessing, current localization was performed to map the TMS-induced neural activation in the cortex. This methodology provided valuable information on the spatial distribution of activity and further validated the effectiveness of the signal cleaning pipelines.
Comparing the effects of the different pipelines on the same dataset, we observed considerable variability in how the pipelines affect various signal characteristics. We observed significant differences in the effects on signal amplitude and in the identification and characterisation of peaks of interest, i.e., P30, N45, P60, N100, P180. The identification and characteristics of these peaks showed variability, especially with regard to the early peaks, which reflect the cortical excitability of the stimulated area and are the more affected by biological and stimulation-related artifacts.
Despite these differences, the topographies and source localisation, which are the most informative and useful in reconstructing signal dynamics, were consistent and reliable between the different pipelines considered.
The results suggest that the existing methodologies for analysing TEPs produce different effects on the data, but are all capable of reproducing the dynamics of the signal and its components. Future studies evaluating different signal preprocessing methods in larger populations are needed to determine an appropriate workflow that can be shared through the scientific community, in order to make the results obtained in different centres comparable
Graph analysis of TMS–EEG connectivity reveals hemispheric differences following occipital stimulation
(1) Background: Transcranial magnetic stimulation combined with electroencephalography (TMS–EEG) provides a unique opportunity to investigate brain connectivity. However, possible hemispheric asymmetries in signal propagation dynamics following occipital TMS have not been investigated. (2) Methods: Eighteen healthy participants underwent occipital single-pulse TMS at two different EEG sites, corresponding to early visual areas. We used a state-of-the-art Bayesian estimation approach to accurately estimate TMS-evoked potentials (TEPs) from EEG data, which has not been previously used in this context. To capture the rapid dynamics of information flow patterns, we implemented a self-tuning optimized Kalman (STOK) filter in conjunction with the information partial directed coherence (iPDC) measure, enabling us to derive time-varying connectivity matrices. Subsequently, graph analysis was conducted to assess key network properties, providing insight into the overall network organization of the brain network. (3) Results: Our findings revealed distinct lateralized effects on effective brain connectivity and graph networks after TMS stimulation, with left stimulation facilitating enhanced communication between contralateral frontal regions and right stimulation promoting increased intra-hemispheric ipsilateral connectivity, as evidenced by statistical test (p < 0.001). (4) Conclusions: The identified hemispheric differences in terms of connectivity provide novel insights into brain networks involved in visual information processing, revealing the hemispheric specificity of neural responses to occipital stimulation
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