No description available.

The primary aim of this thesis is to investigate the physiological effects of transcranial direct current stimulation (tDCS) as applied to the primary motor cortex (M1). This research was largely motivated by the need to understand the basic physiological changes of tDCS, in order to evaluate its use as a potential tool in recovery after stroke, as well as its more general applicability as a tool to modulate plasticity. The experiments in this thesis assess the ability of tDCS to modulate the primary motor cortex in healthy controls. The effects of tDCS on cortical GABA and motor resting state functional connectivity were measured with magnetic resonance spectroscopy (MRS) and resting functional MRI (fMRI). Anodal stimulation reduced GABA concentration and increased functional connectivity in the stimulated M1. Testing these changes within the same individuals demonstrated that the magnitude of changes do not correlate across subjects. Novel evidence on the timecourse of GABA change demonstrated that the reduction in GABA is most prominent in the 30-minute period after stimulation. To determine whether the tDCS-induced modulations in inhibition is restricted to the stimulated hemisphere or whether inhibitory changes could be observed in the nonstimulated M1, or in the interhemispheric connections between the M1s, transcranial magnetic stimulation (TMS) was used to measure intracortical inhibition in each M1 and interhemispheric inhibition and facilitation in the contralateral M1. There were no polarity-specifc effects on intracortical inhibition within either M1, and no changes in interhemispheric excitability from the stimulated to non-stimulated M1. Development of a two-voxel MRS method at ultra high field (7 Tesla) allowed for concurrent measurements of cortical neurotransmitters from both M1s with excellent spectral quality and GABA quantifcation. This method was used to demonstrate the timecourse of tDCS-induced changes in neurochemicals concurrently from both M1s. Anodal stimulation reduced GABA in both the anode-targeted and non-stimulated M1. Cathodal stimulation decreased GABA and glutamate in the non-stimulated M1, with no concurrent changes in the cathode-targeted M1. Bilateral stimulation reduced glutamate in both M1 with no change in GABA.

Le contexte temporel influence profondément la façon dont nous nous comportons. De manière similaire, il donne forme à l'activité du cortex moteur (LFP et potentiels d'action), pendant la préparation motrice, mais aussi en absence de préparation d'un mouvement. / The temporal context deeply shapes the motor cortical activity (spikes and LFPs), during movement preparation but also outside movement preparation.

O exercício físico traz inúmeros benefícios para o sistema nervoso, dentre eles a melhora da memória e cognição, além de um efeito protetor em relação ao declínio mental decorrente do envelhecimento e de lesões do sistema nervoso. Este estudo teve como objetivo observar os efeitos plásticos do exercício moderado de curta duração no hipocampo e em regiões motoras do encéfalo de ratos, frequentemente afetadas por lesões ou doenças neurodegenerativas. As metodologias empregadas nestas análises foram a imuno-histoquímica, o Western blotting,o PCR em tempo real, avaliação dos níveis de neurogênese pela injeção de BrdU e imageamento de Ca2+ de astrócitos corticais. Os resultados encontrados mostram que o exercício moderado de curta duração promoveu alterações plásticas específicas em todas as regiões estudadas, variando na dependência do marcador utilizado e do decurso temporal do exercício. Acreditamos que este é suficiente para promover plasticidade difusa no sistema nervoso, que pode ser parte do substrato do efeito benéfico do exercício no sistema nervoso. / Evidence shows that physical exercise is neuroprotective and enhances brain function by improving cognition, learning and memory. It has also been associated with structural changes such as angiogenesis, synaptogenesis and neurogenesis. The aim of this study was to observe the effects of a moderate, short-term exercise protocol on the hippocampus and brain regions related to motor function, commonly affected by neurodegenerative diseases. The methods used for these analyses were immunohistochemistry, Western blotting, real-time PCR, evaluation of the levels of hippocampal neurogenesis with injections of BrdU and Ca2+ imaging of cortical astrocytes. Our results show that short-term moderate physical exercise induced specific plastic changes in all regions studied, which varied depending on the marker and time course of exercise and is enough to modulate synaptic and structural elements of neurons as well as astrocytes, playing an important role in the diffuse exercise-dependent plasticity which may underlie the beneficial effects of exercise in the brain.

Introdução e objetivos: A estimulação magnética transcraniana (EMT) é um método exclusivo para estimulação cerebral não-invasiva. A diferença fundamental entre EMT e as outras técnicas disponíveis de mapeamento por imagem do cérebro é que se estabelece haver uma relação de causa e efeito entre a resposta fisiológica evocada e o estímulo magnético. A relação entre estrutura e função como a principal característica, constitui uma modalidade de mapeamento cerebral ainda não estabelecido. Os recentes avanços no processamento de imagem permitiram refinar EMT através de sua combinação com a ressonância magnética utilizando-se do sistema de neuronavegação para orientar o posicionamento da bobina em relação ao córtex. Assim a posição da bobina sobre o couro cabeludo pode ser mantida constante conforme verificado pela orientação de navegação em tempo real com registro visual. O objetivo deste estudo foi avaliar a utilidade da EMT no mapeamento cortical motor em comparação com o mapeamento cirúrgico com estimulação cortical direta. Métodos: O estudo foi conduzido com 30 mapeamentos consecutivos em pacientes com programação de cirurgia para tumores adjacentes ao córtex motor. O mapeamento pré-operatório foi realizado com o sistema de estimulação magnética transcraniana navegada. Esta estimulação gera um pulso magnético através de uma bobina. Este método permite estimulação diretamente no córtex cerebral. Eletródios de superfície foram anexados ao abdutor curto do polegar. Em seguida, o limiar motor em repouso (LM) foi determinado através da aplicação de estimulação para região cortical da mão presumida. Mapeamento peritumoral foi realizado na intensidade de 120% do LM. O mapeamento foi realizando com definição de coordenadas vetoriais. Estas coordenadas foram ponderadas previamente por potencial evocado motor. O mapeamento intra-operatório foi realizado pelo cirurgião antes da ressecção do tumor também com neuronavegação. Os locais de estimulação intraoperatória foram selecionados de forma independente dos resultados da EMT. Resultados: Os pontos obtidos na ECD foram comparados ao mapa da EMT segundo coordenadas vetoriais dos centros geométricos da nuvem de pontos obtidos. Verificamos que a distância dos pontos vetoriais médios (centro geométrico) dos pontos obtidos nos dois métodos de mapeamentos diferiu em 4,85 +/- 1,89 mm. A análise de correlação intraclasse revelou uma correlação de 0,901 com p<0,001. As distâncias dos pontos obtidos para o tumor, identificamos uma alta correlação entre estas variáveis com r=0,87, p=0,001. O Limiar motor na EMT é maior no córtex motor do adjacente ao tumor, comparado ao córtex normal. Não há correlação entre os limiares motores de repouso na EMT e na estimulação elétrica. A exatidão do mapeamento com EMT é mantida em pacientes com déficits motores. A condição clínica dos pacientes melhorou significativamente em 3 meses após a cirurgia. Conclusões: A estimulação magnética transcraniana navegada é uma ferramenta confiável e precisa com congruência de pontos obtidos comparados com o mapeamento intraoperatório. EMT navegada é um método promissor para o mapeamento funcional pré-operatória em cirurgia de tumor adjacente ao motor córtex / Introduction and aims: Transcranial magnetic stimulation (TMS) is a unique method for non-invasive brain stimulation. The fundamental difference between TMS and other available non-invasive brain imaging techniques is that when a physiological response is evoked by stimulation of a cortical area, that specific cortical area is causally related to the response. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. The aim of this study was to evaluate the usefulness of navigayed TMS for cortical mapping compared with surgical mapping with direct cirtical stimulation. Methods: The study was performed with 30 neurosurgeries for tumors in or near precentral gyrus. Preoperative mapping was performed with the navigated transcranial brain stimulation system. The TMS system calculates the strength, location, and direction of the stimulating electric field in cortical tissue. It allows online targeting of stimulation directly to peritumoral córtex. The coordinates of TMS mapping were weighted by motor evoked potential. Surface electromyography electrodes were attached to abductor pollicis brevis. Next, the resting motor threshold was determined. The motor threshold was then defined traditionally as the lowest stimulation intensity capable of eliciting motor evoked potentials in at least 5 of 10 trials. The motor threshold was reported both as the percentage of the maximum stimulator intensity. Peritumoral mapping was performed at 120% motor threshold. The intraoperative mapping was performed by the surgeon performing the tumor resection. The Intraoperative direct cortical stimulation locations were chosen independently of the TMS results. The direct electric cortical stimulation points were compared with TMS responses according to original distances of vectorial modules. Results: There is a similarity of the points performed in two mapping methods. We found the distances between geometric centers of TMS and DCS 4,85 +/- 1,89. We identified a strong correlation between these vectorial points (r = 0.901 and p < 0.001). The motor threshold in TMS is the largest in the motor cortex near to the tumor compared to normal cortex (p<0,001). Patients with deficits presented excellent accuracy in two methods. The clinical performance of the patient improved significantly 3 months after surgery. Conclusion: TMS allowed for reliable, precise application in brain mapping and the peritumoral somatotopy corresponded well between the 2 modalities. Navigated TMS is a promising method for preoperative functional mapping in motor cortex tumor surgery

In questa tesi descriviamo una procedura automatizzata per l’analisi della corteccia motoria dello scimpanzè, del Macaca fascicularis e del cavallo, basata su un nuovo metodo computerizzato di analisi delle sezioni colorate attraverso il metodo di Nissl, al fine di studiare la corteccia cerebrale in specie differenti. Le microfotografie delle sezioni sono state elaborate con una procedura standardizzata usando il software ImageJ. Questa procedura ha previsto la suddivisione degli strati corticali, dal primo al sesto, in diversi frames. Per misurare la complessità delle cellule nervose (cioè quanto una cellula fosse diversa dalle adiacenti) abbiamo utilizzato un modello di rappresentazione statistica non-parametrica che mostra come la complessità può essere espressa in termini di un adeguato indice di dispersione statistica quale il MAD (mean absolute deviation). Abbiamo quindi dimostrato che gli strati piramidali della corteccia motoria del cavallo sono più irregolari di quelli di scimpanzè e Macaca fascicularis. La combinazione dell’analisi automatica delle immagini e delle analisi statistiche consente pertanto di confrontare e classificare la complessità della corteccia motoria attraverso diverse specie. Il modello viene proposto come strumento al fine di contribuire a stabilire le somiglianze cerebrali tra umani e animali, rispettando il principio delle 3R. / In this thesis we describe an automated procedure based on a new computerized method of partitioning Nissl-stained sections of the motor cortex of the chimpanzee, crab-eating monkey, and horse, to study the neocortex in different species. Microphotographs of the sections were first processed using a standard procedure in ImageJ, then the stained neuronal profiles were analyzed within continuously adjoining frames from the first to the sixth layer of neocortex. To measure the neuronal complexity (how a given cell is different from its neighbors) we used a general non-parametric data representation model showing that the complexity can be expressed in terms of a suitable measure of statistical dispersion such as the mean absolute deviation. We demonstrated that the pyramidal layers of the motor cortex of the horse are more irregular than those of the monkeys studied. The combination of automated image analysis and statistical analysis made it possible to compare and rank the motor cortex complexity across different species. Therefore, we are confident that our work will help to establish brain similarities between humans and animals used for alimentary purpose, whose brain is often discarded. This, in turn, will allow to carry out the experimental brain research obeying the 3Rs principle.

Les méthodes non-invasives de neuro-imagerie et de neurostimulation peuvent être combinées pour mieux comprendre les connexions dans le cerveau. Pour la première fois, une étude combine de façon séquentielle l’IRM fonctionnelle (fMRI) et un protocole de TMS associative pairée cortico-corticale (TMS-PAScc) sur le cortex moteur primaire (M1) et sur le lobule pariétal inférieur (LPI) dans l’hémisphère gauche. La TMS module-t-elle le couplage neurovasculaire et permet-elle de renforcer une connexion fonctionnelle qui soit détectable à la fMRI à l’état de repos (RS-fMRI)? 10 sujets droitiers et en santé font une session de TMS-PAScc LPI-M1 de courte durée (180 paires d’impulsions, fréquence de stimulation à 0.02 Hz). Les mêmes sujets font 2 sessions de la RS-fMRI, avant et après le protocole PAScc. Les résultats montrent que la corrélation du signal BOLD entre les régions LPI-M1 avant et après la PAScc ne change pas de façon significative (avant-PAS=0.10±0.07 et après-PAS=0.09±0.07, p=0.64), tout comme l’amplitude des potentiels évoqués moteurs (PEM) des impulsions pairées LPI-M1 ne change pas de façon significative du début de la PAScc à 25 minutes après la PAScc (PASdébut=0.71±0.46mV, PASpost25min=0.72±0.89mV, p=0.338). Toutefois, les PEM des impulsions pairées LPI-M1 sont réduites par rapport aux PEM des impulsions simples M1, avant la PAScc et après la PAScc (PEM simples_pré et PASdébut, réduction de 0.32mV, p=0.05; PEM simples_post et PASpost25min, réduction de 0.39mV p=0.008), illustrant la présence d’un lien fonctionnel de nature inhibitrice entre LPI et M1. Toutefois, l’amplitude de cette inhibition n’est pas modulée de façon significative par la TMS-PAScc (ratio mesures pairées/mesures simples préPAS=0.9 et ratio postPAS=0.6, p=0.257). Dans l’ensemble, la TMS-PAScc ne montre pas d’effet soutenu sur la connectivité cérébrale telle que mesurée par la RS-fMRI et la TMS et ce, bien que le LPI montre un lien inhibiteur sur M1 de façon aigue. Plusieurs hypothèses peuvent expliquer cette absence d’effet soutenu, notamment, il est possible que l’altération de la connectivité ne soit visible que lorsque le réseau LPI-M1 est activement sollicité, comme durant l’exécution d’une tâche motrice. Il est aussi possible que le nombre de pairages soit insuffisant pour induire des changements mesurables, mais que la connectivité fonctionnelle suite à des sessions répétées de protocole PAScc pourrait modifier le couplage neurovasculaire et la plasticité cérébrale. / Abstract : Noninvasive neuroimagery and neurostimulation methods can be combined to further the understanding of the human brain connections. For the first time, resting state functional MRI (RS-fMRI) and paired associative cortico-cortical TMS (TMS-PAScc) of the motor cortex (M1) and the cortex of the inferior parietal lobule (LPI) of the left hemisphere are combined in a serial manner. Is TMS able to modify the neurovascular coupling as to facilitate LPI-M1 functional connectivity and change the fMRI BOLD signal? 10 right-handed and healthy subjects did a LPI-M1 TMS-PAScc session of short duration (180 paired pulses at 0.02 Hz, 15 min total). The same subjects underwent 2 fMRI sessions, before and after TMS-PAScc LPI-M1. Results show that the BOLD signal correlation between LPI-M1 does not change significantly before and after PAS (prePAS=0.10±0.07 et postPAS=0.09±0.07, p=0.64). TMS measures of motor evoked potentials (PEM) were taken before and after PAS LPI-M1. The paired pulse PEM measures did not change significantly from the start of PAScc to 25 minutes postPAS (PASstart=0.71 ± 0.46 mV, PASpost25min=0.72±0.89 mV, p=0.338). Paired PEM measures are statistically reduced from PAS PEM single measures, before and afterPAS (sPEM_pre et PASstart, significant 0.32mV reduction, p=0.05; PEMs_post et PASpost25min, 0.39mV reduction, p=0.008). PAScc did not show any significant neuroplasticity effect after 20 minutes because paired pulses did not change before and after PAScc. The PEM reduction of paired pulses is most likely related to the inhibiting effect of the conditioning stimulus of LPI on the test stimulus of M1 at 8ms. This inhibition is an effect limited to the measure itself and does not increase significantly with time (pairedpulse/singlepulsemeasures prePASratio=0.9 and postPASratio=0.6, p=0.257). TMSPAScc did not show a sustained effect on cerebral connectivity as measured by RS-fMRI although stimulation of LPI showed an acute inhibiting effect on M1 during paired measures. LPI-M1 TMS-PAScc did not show sustained connectivity and it could be because no task was involved in our study to actively solicit both cerebral regions during PAS. It is also possible that the number of paired stimulation was not enough to bring a change of connectivity and that PAS needs to be repeated on different days to eventually have a sustainable effect.

This thesis describes a series of experiments in human observers using neurophysiological and behavioural approaches to investigate the effects of varying haptic stimuli, attentional demand and age on motor control and perception during haptic sensing (i.e., using the hand to seek sensory information by touch). In Experiments I-IV, transcranial magnetic stimulation (TMS) was used to explore changes in corticomotor excitability when participants were actively engaged in haptic sensing tasks. These studies showed that corticospinal excitability, as reflected in motor evoked potential (MEP) amplitude, was greatly enhanced when participants were engaged in different forms of haptic sensing. Interestingly, this extra corticomotor facilitation was absent when participants performed finger movements without haptic sensing or when attention was diverted away from haptic input by a concurrent cognitive task (Exp I). This provided strong evidence that the observed corticomotor facilitation was likely central in origin and related to haptic attention. Neuroimaging has shown activation of the parieto-frontal network likely subserves this aspect of haptic perception. Further, this haptic-specific corticomotor facilitation was finely modulated depending on whether participants focused attention on identifying material (texture) as opposed to geometric properties of scanned surfaces (Exp II). With regards to aging effects, haptic-related corticomotor facilitation was associated with higher recognition accuracy in seniors (Exp III). In line with this, seniors exhibited similar levels of haptic-related corticomotor facilitation to young adults when task demands were adjusted for age (Exp IV). Interestingly, both young and senior adults also showed substantial corticomotor facilitation in the ‘resting’ hand when the ipsilateral hand was engaged in haptic sensing (Exp IV). Simply touching the stimulus without being required to identify its properties (no attentional task demands) produced no extra corticomotor facilitation in either hand or age group, attesting again to the specificity of the effects with regards to haptic attention. In Experiments V-VI, the ability to recognise 2-D letters by touch was investigated using kinematic and psychophysical measures. In Experiment V, we characterized how age affected contact forces deployed at the fingertip. This investigation showed that older adults exhibited lower normal force and increased letter-to-letter variability in normal force when compared to young adults. This difference in contact force likely contributed to longer contact times and lower recognition accuracy in older adults, suggesting a central contribution to age-related declines in haptic perception. Consistent with this interpretation, Experiment VI showed that haptic letter recognition in older adults was characterized not only by lower recognition accuracy but also by substantial increases in response times and specific patterns of confusion between letters. All in all, these investigations highlight the critical interaction of central factors such as attentional demand with aging effects on motor and perceptual aspects of haptic sensing. Of particular significance is the clear demonstration that corticomotor excitability is greatly enhanced when a haptic sensing component (i.e., attending to specific haptic features) is added to simple finger movements performed at minimal voluntary effort levels (typically <15 % of the maximal effort). These observations underline the therapeutic potential of active sensory training strategies based on haptic sensing tasks for the re-education of motor and perceptual deficits in hand function (e.g., subsequent to a stroke). The importance of adjusting attentional demands and stimuli is highlighted, particularly with regards to special considerations in the aging population.

No description available.

Transcranial magnetic stimulation (TMS) is a 37-year-old non-invasive tool and can be used for diagnostic, therapeutics, and research purposes. In research, TMS is mostly used to stimulate the motor cortex, resulting in a neuroelectric excitatory response called a motor evoked potential (MEP). The resulting nerve signal leads to muscle movement, which can be measured by electromyography (EMG). Majority of previous research has targeted muscles of the upper limbs, due to the relative inaccessibility of the cortical leg area. Thus, the aim of this study is to investigate whether asymmetry occurs during lower limb stimulation and if there is a difference in stimulated muscles between dominant and non-dominant leg. Nine healthy adults conducted cortical stimulation over the motor cortex using double cone coil. EMG was recorded from the rectus femoris, tibialis anterior and abductor hallucis on both left and right leg. Depending on the subject's tolerance, data was collected by delivering 30 or 35 pulses. For each intensity, five MEPs were recorded, starting at 30% of the intensity and increasing in steps of 10%. Results showed no significant difference (p&gt;0,05) between the dominant and non-dominant leg in all three muscles. In conclusion, the study no stimulus response asymmetry between the dominant and non-dominant leg in the respective muscle.