1,721,224 research outputs found
The aging brain as a model to understand motor skill acquisition in humans and its restoration using non-invasive brain stimulation
No full textMotor skill acquisition is essential to our survival, as it enables an efficient interaction with the changing world around us. The acquisition of novel sequential tasks, of particular relevance due to their pervasiveness in everyday life activities, can become more challenging at an advanced age, with structural and functional changes in the brain often resulting in diminished learning abilities. During the pursuit of my doctoral degree, I studied some of the processes leading to the acquisition of a novel sequential motor task, and how some of the mechanisms underlying these processes differ between healthy young and older adults. Young adults acquired the sequential task effectively by prioritizing its accurate execution early in training and focusing on increasing their speed thereafter, resulting in the generation of mechanically efficient execution patterns in the replication of the sequence. In contrast, older adults improved both the accuracy and the speed simultaneously and gradually after more extensive practice, which resulted in an overall decreased performance of the task. However, anodal direct current stimulation applied over the motor cortex partially restored skill acquisition in older adults by facilitating the early improvement of the accuracy, enabling an accelerated generation of efficient execution patterns in the sequence, similar to those seen in young adults. Further investigations into the effects of stimulation to improve skill acquisition in healthy older adults showed age not to be a determinant factor for an individual's proneness to benefit from stimulation; rather, it is the state of the neural system of each individual what likely determines the potential benefits to be had from stimulation. Therefore, a better understanding of the mechanisms targeted by stimulation and the identification of parameters signaling an individual's likelihood to benefit from it are needed to use these techniques to their full potential. Leveraging this knowledge and taking advantage of the portability, robustness and accessibility of this technique could represent an attractive option for applications involving extensive motor training, such as rehabilitative training provided after stroke.UPHUMME
Orchestration of oscillatory activity to improve visual motion discrimination
No full textThis thesis describes advances in the use of novel configurations of non-invasive brain stimulation over the visual system allowing to modulate of modifying electro-physiological activity, interregional interactions and by it, visual behavior such as motion discrimination capacity in healthy subjects. We have implemented three experimental protocols that include the application of a motion discrimination and integration task in combination with bifocal transcranial Alternating Current Stimulation (i.e. tACS) over the primary visual cortex (i.e. V1) and medio-temporal areas (i.e. V5), while varying some of the â orchestraâ parameters in each study. The common objective pursued in the three studies presented in the upcoming chapters was to evaluate physiological changes induced by tACS combined with the visual task, leading to enhanced visual performance expressed by the accurate distinction of the generalized movement orientation of a kinetogram. After introducing the scientific rationale of this thesis in Chapter 1, Chapter 2 describes whether applying two phase-shifted (Alpha) É -tACS conditions (Anti-Phase and In-Phase tACS) within the V1-V5 network were able to positively modulate behavior compared to Sham tACS. Our results suggest that the active Anti-Phase condition significantly increased visual motion discrimination compared to In-phase tACS which rather tended to decrease performances. These two case scenarios were associated with opposite changes in Alpha-Gamma oscillatory modulation (i.e. V1 phase â V5 amplitude coupling) determined by multichannel EEG. Based on these findings, in Chapter 3, we describe testing the effects of modulating Alpha-Gamma interregional interaction. Hence, two conditions V1É V5Æ tACS and vice versa, V1Æ V5É tACS, were behaviorally and electrophysiologically evaluated. The results suggested that there was a common electrophysiological feature between the two Verum tACS, which contrasted with Sham tACS, expressed through WPLIÆ (i.e. Weighted Phase Locking Value) connectivity. Furthermore, WPLIÉ and ZPAC V1amplitude â V5phase (i.e. Z-scored Phase Amplitude Coupling) were the inter-areal mechanisms in which both Verum conditions differed to explain the variance of their corresponding group behavior. However, the electrophysiological changes did not lead to significant difference in behavioral measures. In Chapter 4, we combined the knowledge gained in the first two studies and thus, we time-locked, short bursts of phase-shifted É -tACS to the visual stimulus onset. This permitted to find out that, despite the phase difference between the tACS conditions (i.e. In-Phase vs. Anti-Phase), there was a generalized augmentation of the performance after verum stimulation compared to the results with Sham. This amelioration was generally associated with changes in causal PSI (i.e. Phase Slope Index) flows in Æ , whereas specifically the Î -Æ modulation permitted to explain the differences in behavior between Verum and Sham. Moreover, dynamic PSI-causal β bottom-up and top-down flows revealed the mechanisms behind each type of Verum stimulation. These studies provided first interesting evidence that physiology-inspired bifocal tACS applied to the visual network might be used to modulate visual behavior and respective underlying mechanisms. The induced electrophysiological and behavioural effects achieved are complex and need to be studied in more details in upcoming studies.UPHUMME
Does one size fit all? - Towards the optimization and personalization of non-invasive brain stimulation paradigms to enhance motor learning
No full textThe acquisition and re-acquisition of motor skills is an important aspect of daily life and in the recovery after a stroke. Non-invasive brain stimulation (NIBS) is a technique that is used to improve motor learning and enhance motor recovery in stroke survivors. Although the current results are promising, the outcomes are heterogeneous with responders and non-responders. This thesis aimed to investigate multiple, novel NIBS strategies to enhance stimulation efficacy and to develop approaches for protocol personalization. These alternative strategies include targeting other areas of the motor network than the primary motor cortex (M1), targeting the brain as a network with the use of multifocal stimulation, and using a variety of stimulation techniques (TMS, tACS, tDCS) to study underlying mechanisms.
Study 1 explored the methodological implications of TMS for measuring inhibitory and excitatory neurotransmissions. With the use of TMS, short intracortical inhibition (SICI) and intracortical facilitation (ICF) were measured in healthy young adults. SICI and ICF were studied with different stimulators, waveforms, and current directions using a set of interstimulus intervals. Our findings indicated high comparability among the different stimulation paradigms, except for SICI at 3 ms, which enables data sharing across units and facilitates the conduction of multi-center studies.
Study 2 measured the effect of 50 Hz tACS applied to the cerebellum on a novel motor learning task in healthy young adults. Targeting the cerebellum with NIBS is a relatively new field of research with open questions that need to be addressed. Therefore, we explored for the first time the effect of CB-tACS on a motor learning task. Our results did not show an improvement of learning with 50 Hz CB-tACS. We argue that this might have been related to the task and/or the selected stimulation frequency. Therefore, this stimulation paradigm requires further optimization to be effective for motor learning.
Study 3 compared multifocal sequential stimulation to monofocal tDCS on motor learning in stroke patients. The multifocal paradigm consisted of an orchestrated M1 â CB stimulation setup, the monofocal paradigm targeted the M1. Our results indicated a significant effect of multifocal M1-CB stimulation, mainly driven by CB-tDCS during the early phase of learning. Moreover, baseline performance and neurophysiology were related to stimulation responsiveness that could potentially lead to biomarkers to predict stimulation efficacy in stroke patients.
Study 4 measured the effect of personalized bifocal theta tACS applied to the FPN on motor learning in healthy older adults. Sequence learning has a cognitive component related to working memory (WM) capacity, a process mediated by the FPN. We hypothesized that targeting the FPN might be beneficial for motor learning. tACS to the FPN improved performance, when WM load was high, but not when WM-load was low. Therefore, we conclude that the FPN is a promising new target to enhance motor learning which might be most beneficial for individuals with decreased WM capacity due to age or stroke.
In conclusion, this thesis demonstrates that targeting alternative motor network areas, and multifocal stimulation is promising. These results expand on the current knowledge of NIBS and identified open questions that require further examination but could ultimately lead towards enhanced efficacy and the personalization of study protocols.UPHUMME
Noninvasive deep brain stimulation to modulate human behavior by means of transcranial temporal interference electrical stimulation
No full textAll functions we use in our everyday life depend on a complex interplay between both cortical and subcortical brain areas, communicating in between each others. When a region is affected by either an accident, aging or neurodegenerative diseases, the whole network is disturbed resulting in functional impairments. Hence, it is highly important to find methods allowing to better investigate the role of each brain structure in humans, with the goal of applying this knowledge to improve current rehabilitative and therapeutic solutions.
Noninvasive brain stimulation (NIBS) techniques can help unveiling the functional role of specific brain regions in key behaviors of everyday life, such as motor and cognitive functions. However, current NIBS methods show a major drawback when targeting subcortical areas, the well-known steep depth-focality tradeoff. The higher the distance of the target region from the scalp, the lower the focality as well as the higher the co-activation of no target structures, due to concurrent stimulation of the overlying tissues.
Transcranial Temporal Interference Stimulation (tTIS) is a novel noninvasive deep brain stimulation technique introduced to overcome the depth-focality tradeoff, able to reach deep brain structures in a focal manner. This could provide new insights about the causal role of subcortical regions in humans, which until now was limited to observations from either animals or implanted patients.
First positive results were obtained in mice and phantom modeling, but the translation to humans is still missing. Therefore, the goal of this thesis was to fill this gap, by successfully modulating deep brain regions, leading to behavioral and brain activity changes.
With this purpose, we targeted two main brain regions, the striatum and the hippocampus, known to be key players in non-declarative and declarative memory respectively. Stimulation was delivered in a theta burst pattern, which was previously shown to induce long-term plasticity (LTP)-like effects.
In the first part of the thesis, we investigated the effects of tTIS on striatal and whole brain activity during rest and during a motor learning task in young healthy subjects.
As a next step, behavioral performance of the motor learning task was analysed and a first step towards clinical translation was taken by studying the impact of tTIS in an older cohort compared with a young one.
In a second part of the project, tTIS was applied on the hippocampus in the context of two declarative memory tasks, a spatial navigation task and a face-name association task, to determine the functional role of the hippocampus and the exciting opportunity to neuromodulate its function with respective behavioral and brain activity effects.
This work provides first evidence that tTIS can be used for successful neuromodulation of deep brain structures with good focality in humans. This was proven via both neuroimaging and behavioral data, opening future prospective for the translation of the technique in a rehabilitation setting.UPHUMME
Determining patterns of post-stroke motor recovery through longitudinal multimodal MRI: A step towards patient stratification
No full textMotivated by the need for a better understanding of post-stroke recovery and new biomarkers to improve stroke patient stratification and outcomes, this thesis investigated structure-function coupling and its role in post-stroke recovery. Furthermore, in order to increase data comparability between sessions and centers (a critical challenge in contemporary clinical research), this thesis assessed the reproducibility of microstructure-informed structural connectivity measures in a multi-center dataset.
Stroke is one of the major sources of permanent impairment, frequently of motor origin. However the clinical picture is very heterogeneous: patients show divergent courses of recovery and the underlying mechanisms are still unclear. In addition, current treatments still have limited success and are restricted to a 'one-fits-all' approach, not considering the individual patient's phenotype. As efforts to stratify patients based on structural or functional biomarkers are still needed, we chose to investigate the potential of a multimodal biomarker, the Structural Decoupling Index (SDI) (Preti & Van De Ville, 2019b), a new metric assessing the structure-function coupling strength in the brain.
The first part (Studies 1 and 2) of this thesis investigates the potential of the SDI as a biomarker. In Study 1, the goals were to evaluate the feasibility of applying the SDI on an individual level in healthy older adults and to investigate the effect of an acute stroke on it. Consistent with the literature, we found a network gradient of SDI in healthy older adults, from high coupling in lower-level sensory areas, to low coupling in higher-level cognitive areas. This confirmed the applicability of SDI on an individual level. Furthermore, we showed that stroke impacts the SDI, with a higher decoupling on the ipsi- compared to the contralesional side, and with network-specific effects in RH stroke patients. In Study 2, the goal was to see whether the SDI evolved over time post-stroke and whether it links to behavior. The longitudinal analysis revealed differential network effects of stroke at T1 and T3. Furthermore, we showed that impairment in cognitive and psychological behavioral domains significantly correlates with variations in SDI in a number of key areas including motor regions (e.g., primary motor cortex) and that the brain pattern associated to behavior changes between T1 and T2. Surprisingly, motor performance did not explain variability in key motor areas (e.g., primary motor cortex). The link between post-stroke behavioral performance and SDI underlines its potential clinical relevance.
Driven by the quest for more reproducible analysis pipelines in the context of longitudinal and clinical studies, the second part of this thesis (Study 3) addressed the subject-specific reproducibility and repeatability of microstructure-informed tractography. Through a multi-center study, we demonstrated its high reproducibility and subject-specificity, and we found evidence for increased biological accuracy.
My thesis made a contribution by showing that the SDI is sensitive to pathophysiological changes that occur following a stroke and that it links to clinically relevant behavioral measures. In addition, it confirms the reproducibility and subject-specificity of microstructure-informed tractography. Together, my findings pave the way towards patient stratification and more personalized treatments in stroke rehabilitation.UPHUMME
Longitudinal evaluation of the mechanisms supporting post-stroke motor recovery using TMS-EEG coupling
No full textStroke is the main source of long-lasting disability, affecting dominantly motor functions. The extent and course of recovery are highly heterogeneous between patients, with a minority of patients fully recovering from their initial impairments, leaving 85% persisting deficits. The pathophysiological mechanisms underlying inter-patients heterogeneity are still not fully understood. Most motor recovery is taking place during the first months after a stroke, with limited improvement after that time, emphasizing the importance of this early period. These first months after a stroke are characterized by dynamic modulations of excitatory and inhibitory processes in the brain. Most notably, modulation of intracortical inhibition is thought to promote both neuronal protection from further damage in the hyperacute phase and functional reorganization to compensate for the lesioned brain regions in the following phases. Previous research in animal models and stroke patients has highlighted specifically the importance of the GABAergic system, the main actor of inhibition in the brain. However, the specific functional role and the time course of changes of GABAergic inhibition in the course of recovery are only partially understood.
To better characterize the spatial and temporal properties of the inhibiting mechanisms occurring after a stroke and their association with motor recovery, we investigated the neurophysiological changes of 66 stroke patients longitudinally from the first week to 3 months post stroke. Cortical excitability and inhibition were determined by transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG).
The present results revealed two disinhibition phases with distinct regionality and timing patterns. In Study I, a local ipsilesional disinhibition, expressed by larger evoked activity, in the acute phase was related with better motor recovery at 3 months post stroke. Patients recovering the most showed a return to normal excitatory/inhibitory balance between the acute and early chronic stage. In Study II, global excitatory and inhibitory activity were evaluated through a data-driven analysis of TMS-induced braion oscillatory modes. The late alpha-oscillations, a proxy of GABAergic activity, displayed a small increase in the acute stage followed by a large decrease between the subacute and early chronic stage. This global disinhibition was correlated with greater recovery of fine upper-limb motor function.
This thesis underlines the importance of GABAergic disinhibition, both locally and globally, for motor recovery after a stroke and determined its specific time courses. The acquired knowledge will provide the basis to pave the way to electrophysiological biomarkers for individual phenotyping of patients. Personalized interventional strategies targeting changes in cortical excitability have to potential to maximize functional recovery in each individual patient.UPHUMME
Probing and modulating inter-areal coupling in the cortical visual motion processing pathway with non-invasive brain stimulation
No full textIn the last few years, stroke ranked as the second most common cause of death and is the third most significant condition affecting disability-adjusted life years (DALYs) worldwide. Being the most prevalent and quality of life impacting post-stroke symptoms, rehabilitation of motor deficits, such as paresis or speech impairments, have concentrated most of the stroke rehabilitation research. Nonetheless, approximatively 1 stroke survivor out of 4 will have to deal with permanent Homonimous Hemianopia (HH), the loss of half of the visual field due to postchiasmatic lesions.
This Thesis uses non-invasive brain stimulation techniques to unveil the electrophysiological mechanisms underlying healthy human visual motion perception, and applies these new insights for the development of a novel functional plasticity index and a new biologically-inspired visual rehabilitation protocol. One of the clinically relevant pathways to study and promote in this context, is the neural pathway connecting the ipsilesional middle temporal area (MT) to the primary the visual cortex V1 that mediates motion perception and awareness. First, to measure plasticity induction along this pathway, we tested the potential of cortico-cortical paired associative stimulation (ccPAS) in enhancing spike-timing-dependent plasticity (STDP) between MT and V1. By triggering one TMS pulse first on MT followed 20ms after by a second TMS pulse over V1, we observed a significant connectivity increase in the MT-to-V1 inputs, correlated with motion discrimination improvement. A similar relationship was reported in HH stroke patients, but only in patients with sufficient structural or functional integrity between V1 and MT. Next, we focused on the idea that exogenously modulating the well-reported oscillatory interactions between the two areas would boost visual learning. We developed a cross-frequency (Alpha and Gamma) dual-site transcranial alternate current stimulation (tACS) protocol. We observed an increase in motion perception in the blind field after one tACS session associated with an increase in V1-MT coupling in both healthy and HH stroke patients, when tACS delivered Alpha oscillations over V1 and Gamma oscillations over MT. Furthermore, applied repeatedly during 10 daily training sessions in HH patients, this tACS condition enhanced motion discrimination in the blind field to similar extends to long-term training studies. In line with the previous approach, patients who better responded to the intervention were the ones with preserved structural integrity of the cortical motion pathway. Importantly, improvement in motion discrimination was accompanied by an enlargement of visual field borders assessed with kinetic perimetry, paving the way to a novel intervention for visual field recovery.
In conclusion, this work deepens our understanding of MT-V1 motion discrimination pathway properties and highlights a multimodal marker to index visual system structural and functional integrity potentially predictive of treatment efficacy. Finally, it introduces the first steps towards a promising approach for rehabilitating visual impairments in stroke patients. Further improvements include a novel state-dependent version based on inter-areal coupling, aiming at reducing the variability and increasing the efficacy.UPHUMME
Early motor skill acquisition in healthy older adults: functional MRI and connectome correlates
No full textdecrement have been proposed, such as weakened acquisition of the motor skill. While the processes at play during the initial acquisition phase have been well-characterized in young adults, they were only scarcely investigated in older adults. The goal of this thesis was to assess the neural processes occurring during the acquisition phase of motor learning in older adults. Successful functioning of the brain is complex and relies on complementary types of organization, i.e. the principles of segregation and integration. In other words, the brain is composed of segregated and specialized brain regions that interact with each other by exchanging information. Motor learning, considered as a key function of the brain, does not deviate from this organization scheme. As such, the investigation of motor learning beneficiates from the study of both functional segregation and integration.
The results of this thesis are based on the acquired data of a multiple-day experiment aiming at characterizing motor learning acquisition and improving sleep-dependent motor memory consolidation in older adults and stroke patients. 43 older adults and 15 stroke patients were included in this project and completed multiple measurements involving, among other methods, a novel motor learning task performed concurrently with func-tional magnetic resonance imaging.
In the first study of this thesis, we examined the functional specialization of the brain during acquisition of the motor skill by investigating the within-session dynamics and their relationship with behavioral change. The results demonstrated that motor learning ability relied on the parallel involvement of motor-related cortical areas responsible for action selection and associative parietal areas involved in visuomotor processing. In the second study of this thesis, we assessed the integration of information transfer within functional subnetworks by looking at the changes in functional topology and structure-function correspondence in relation to motor learning ability. We were able to show that motor learning ability was associated with higher flexibility in visual and cognitive/associative networks suggested by increased modularity of the functional subnetworks and a detachment of the functional connectome from the structural connectome.
In conclusion, this thesis demonstrates that the acquisition of a motor skill in healthy aging relies on the in-volvement and flexibility of distributed brain regions organized in networks. The achieved results expand on the existing knowledge of motor learning and offer an indication that multimodal studies are important to comprehend the functional processes of the brain.UPHUMME
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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