Transcranial magnetic stimulation (TMS) is commonly used to measure corticospinal and intracortical excitability in basic and clinical neuroscience. However, the effect of glucose on TMS-based measures is not well defined, despite a potentially impactful influence on precision and reliability. Here, a double-blinded placebo-controlled study was used to test the effects of glucose on two commonly used TMS measures: short-interval intracortical inhibition (SICI), and the area under the motor evoked potential recruitment curves (AURC). SICI and AURC are thought to reflect inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmission respectively. Healthy males (N=18) each participated in four sessions. Session 1 involved TMS familiarization and acquisition of an individualized blood glucose response curve. During sessions 2, 3 and 4, dependent measures were taken before (T0) and twice after (T1 & T2) drinking 300 mL of solution containing glucose (75 g), sucralose-sweetened placebo (control for sweetness) or plain water (control for time). The T1 and T2 measurements were started 5 minutes prior to the blood glucose peak observed during Session 1. Blood glucose and mean arterial pressure (MAP) were also monitored. Sucralose, but not water or glucose increased AURC and none of the treatments altered SICI. There was no association between blood glucose level and TMS measures, but in all three conditions MAP rose after consumption of the drink. There was a positive correlation between the rise in blood pressure and the relative increase in AURC at the higher stimulus intensities. Eleven participants returned for a fifth session to quantify the smallest detectible change in the AURC measurements and it was confirmed that significant changes were real while non-significant differences in measurement means fell within the range of expected measurement error. This study also suggests a relationship between corticospinal excitability and autonomic tone. Additional investigation is required to understand the mediating factors of this association. / Thesis / Master of Science (MSc)

Le cortex moteur primaire et le striatum permettent la planification et la sélection de mouvements. La dopamine régule l'activité des neurones dans ces deux structures. La perte des neurones à dopamine projetant de la substance noire compacte vers le striatum est à l'origine de troubles moteurs observés dans la maladie de Parkinson. Nous avons caractérisé le contrôle par la dopamine des neurones du cortex moteur primaire chez la souris et avons démontré que les fibres dopaminergiques innervent préférentiellement la représentation des membres antérieurs dans les couches corticales profondes. Nous avons montré que la dopamine module localement l’activité électrophysiologique des neurones cortico-striataux via les récepteurs D2. Ces résultats montrent que la dopamine peut exercer un contrôle direct sur la motricité au niveau des neurones du cortex moteur primaire. Nous avons par la suite déterminé le potentiel des thérapies cellulaires dans un modèle animal de la maladie de Parkinson. Les approches actuelles privilégient la greffe ectopique de neurones à dopamine dans la région cible, le striatum. Nous avons choisi une approche alternative consistant à pratiquer la greffe au niveau de la région lésée, la substance noire compacte. Nous avons montré chez la souris que la lésion des neurones dopaminergiques altère les propriétés électrophysiologiques des neurones du striatum et que la greffe homotopique de neurones entraîne une meilleure récupération de ces caractéristiques électrophysiologiques que la greffe ectopique dans le striatum.Ces résultats ouvrent des perspectives d'étude des effets de la greffe homotopique sur l'activité des autres structures contrôlant la motricité. / Primary motor cortex and striatum are involved in movement planification and selection. Dopamine regulates the neuronal activity of these two structures. The motor impairments observed in Parkinson's disease originates from the loss of dopamine neurons projecting from the substantia nigra pars compacta to the striatum.We characterized the dopaminergic control of the neurons of primary motor cortex in mice and we demonstrated that dopaminergic fibers preferentially innervate the forelimb representation map in the deep cortical layers. Furthermore, we demonstrated that dopamine locally modulates the electrophysiological activity of the cortico-striatal neurons through D2 receptors. These results show that dopamine can directly control motor function by influencing neuronal activity in primary motor cortex.Thereafter, we determined the potential of cell replacement therapies in an animal model of Parkinson's disease. In most studies, the transplanted dopamine neurons have been placed within the striatum. We have chosen an alternative approach by grafting neurons into the lesioned nucleus, substantia nigra. We showed in mice that the lesion of dopaminergic neurons impaired the electrophysiological properties of the striatal neurons. Whereas these properties are not fully restored with an intra-striatal transplant, all the electrophysiological characteristics are recovered with an intra-nigral graft. This result opens new perspectives to study the homotopic graft effects on the activity of the other structures controlling motor function.

The reticular-activating hypofrontality model of acute exercise (RAH) predicts exercise-induced hypoactivity in frontal cortex which mediates executive function. Connors Continuous Performance Test (CCPT) was used to investigate changes in executive function during- and post treadmill running in healthy volunteers (n=30, 15 male). In a randomized order, subjects performed the CCPT at rest, during low- (LI; 63% maximal heart rate; MHR) and moderate intensity (MI; 75% MHR). Separately, subjects then performed isocalorifically matched exercise bouts of LI, MI and high intensity interval training (HIT) consisting of 4x4 min with 90% MHR and 3 min recovery at 60-70% MHR. Repeated measures ANOVAs revealed main effects of exercise intensity for reaction time RT during- (p≤0.001) and post exercise (p≤0.0001). Subsequent analyses showed an overall increase of RT during exercise compared to rest (p≤0.005). RT decreased significantly from rest to post exercise levels in an exercise intensity dependent, linear fashion (p≤0.0001). Commission errors showed a non significant linear trend to increase both during (p=0.057), and post exercise (p=0.052) as a function of intensity. In a follow up study, we sought to relate observed exercise effects to frontal cortex activity through the use of transcranial direct current stimulation (tDCS) (n=4) and transcranial magnetic stimulation (TMS) over the dorsolateral prefrontal cortex (DLPFC). Prior to TMS stimulation cortical excitability was estimated post running through motor-evoked potentials (MEP) elicited from the primary motor cortex (M1) induced by single burst TMS and measured in the first dorsal interosseous (FDI) muscle using electromyography. At rest, inhibitory cathodal tDCS with left DLPFC cathode and right supraorbital anode led to improved reaction time and increased amount of commission errors, whereas anodal stimulatory tDCS in the immediate post exercise period was unable to recover the post exercise effect. Continuous theta burst stimulation over the left DLPFC post running further impaired inhibitory control and facilitated reaction time. Different findings during- and after- exercise suggests that potential contributing mechanisms such as computational and metabolic factors may be differentially active during these respective conditions. Furthermore, the fact that an inhibitory TMS protocol pronounced the post running effects even more and that we were able to mimic the reported RAH effects at rest with inhibitory frontal tDCS, but observed different patterns during exercise, suggests that the latter state cannot be fully explained by reducing activity in the left frontal cortex alone. Failure to modify the after exercise effect with stimulatory tDCS also supports an interplay of different factors and might emphasize the strong, robust effects of exercise that cannot simply be attenuated by current application. Increases in MEP post running for 35min paired with the observed performance decrements imply an excited state of M1 and might serve as an explanatory cross-link to central fatigue suggesting that a hypofrontal state might enhance the motor cortical drive to activate muscles.

Background and aims: The primary motor cortex (M1) controls voluntary motor behaviours. M1 has been identified to play a major role in the execution of voluntary corticospinal tasks as well as self-initiated corticobulbar tasks. However, the involvement of M1 in more complex corticubulbar tasks, such as swallowing, is not yet fully understood. Swallowing is quite different from other voluntary motor tasks as it has both voluntary and reflexive components. The degree of M1 involvement in the pharyngeal, or more reflexive, component of swallowing is unclear. Studies investigating the role of M1 in swallowing have yielded contradictory findings regarding the specific functional contribution of M1 to swallowing. Therefore, further investigation is warranted to clarify the role of M1 in pharyngeal swallowing. Discrete saliva or water swallowing has been utilized in most studies investigating neurophysiology of swallowing in health and disease. However, individuals most frequently complete multiple, consecutive swallows during the ingestion of liquid. Biomechanical differences between discrete and continuous water swallows have been identified using videofluoroscopic swallowing study (VFSS). However, no studies have investigated the pharyngeal pressure differences between these two swallowing tasks. Additional insights into task differences may be revealed through evaluation of pharyngeal pressure utilizing pharyngeal manometry. This research programme sought to clarify the role of M1 in reflexively and volitionally initiated pharyngeal swallowing. In order to understand M1 involvement in the execution of swallowing, comparative tasks that require known dependence on M1 were also included in this research programme. This research programme addressed the biomechanical changes in motor behaviours as a result of neural disruption during the performance of a number of motor tasks. This neural disruption was intrinsically generated through application of dual task (DT) paradigm and extrinsically generated using single pulse transcranial magnetic stimulation (TMS). A secondary aim of this research programme was to identify the differences in pharyngeal pressure generation between discrete and continuous swallowing. Methods: Twenty-four right handed participants (12 males, average age= 24.4, SD= 6.3) were recruited to this research programme. A number of motor tasks that vary in complexity were tested. These tasks included: volitional swallowing, reflexive swallowing, eyebrow movement, jaw movement and finger tapping with right, left, or bilateral index fingers. Participants performed multiple trials of several tasks in each study. Repetitions of tasks during a single session may affect performance due to factors such as fatigue or practice. A baseline study was undertaken to determine within-participant variability of measures across repeated trials. Following the baseline study, the role of M1 in pharyngeal swallowing was investigated in two main studies in counter balanced order. The role of M1 in pharyngeal swallowing was evaluated by investigating swallowing parameters during neural disruption using a DT paradigm. Participants performed tasks in isolation (baseline) and with interference that consisted of pairing swallowing with comparative task that activates M1 (fingers tapping and eyebrow movement tasks). In the other study, single pulse TMS was utilized to create an electrophysiological disruption to the areas of M1 associated with muscular representation of a number of motor behaviours (swallowing tasks, jaw movement and fingers tapping tasks). Stimulation was provided to both hemispheres in random order to evaluate laterality effects. Swallowing parameters and the performance of the other motor tasks were evaluated when performed with and without electrophysiological disruption. Differences in pharyngeal pressure generation between discrete and continuous swallowing were investigated using pharyngeal manometry. Pharyngeal pressures were recorded at three locations: upper pharynx, mid-pharynx and upper esophageal sphincter (UES) during four swallowing types: discrete saliva swallowing, discrete 10 ml swallowing, volitional continuous swallowing, and reflexive continuous swallowing. The research paradigm used in this research programme identified the effect of experimental conditions on the rate and regularity of task performance. In addition, pharyngeal manometry was utilised to measure the effect of experimental conditions on the pattern of the pharyngeal pressure generation during swallowing. Within subject differences from baseline were identified by means of Repeated Measures Analyses of Variance (RM-ANOVA). Results: Initial analysis of the data revealed that repetition of tasks within a session did not affect the rate and regularity of voluntary corticospinal tasks, voluntary corticiobulbar tasks nor swallowing tasks. In addition, repeating the swallowing tasks during a session did not affect pharyngeal pressure as measured by pharyngeal manometry. When motor tasks were performed concurrently in the DT paradigm, rate and regularity of eyebrow movements were significantly decreased when paired with swallowing tasks, whereas rate and regularity of swallowing were significantly decreased when paired with left finger tapping, but not right finger tapping. However, there was no significant effect of any task on the pattern of pharyngeal pressure generation. Extrinsically generated disruption using TMS significantly reduced rate and regularity of finger tapping tasks and regularity of jaw movement and swallowing tasks. In addition, interruption of pharyngeal M1 during the volitional swallowing task produced significant increase in the duration but not the amplitude of the pharyngeal pressure. Pharyngeal pressure generation differed between swallowing types and boluses types, in that saliva swallowing produced longer pharyngeal pressure duration and lower nadir pressure than water swallows. Discrete water bolus swallowing produced longer UES opening compared to both saliva swallowing or continuous water swallowing. Conclusion: The results of this research programme provided valuable methodological information regarding the effect of trials on task performance as well as identifying pharyngeal pressure differences between discrete and continuous swallowing. In addition to the methodological contribution, this research programme expanded on previous knowledge of neural control of swallowing, in that it extended the findings regarding potential role of M1 in pharyngeal swallowing. Given the absent effect of task repetition on the performance of corticospinal and corticobulbar motor tasks, it is speculated that outcomes of research investigating the effect of experimental manipulation on motor tasks performance is due to the experimental tasks, rather than natural variance in the data. The effect of swallowing on the rate and regularity of eyebrow movement, when performed concurrently using DT paradigm, suggest bilateral functional overlapping to a significant degree between neural substrates that control swallowing and orofacial muscles. These results offer partial support of bilateral representation of swallowing in the cortex. In addition, results further revealed potential involvement of right M1 in the regulation of pharyngeal swallowing as evidenced by a disruptive effect of left finger tapping on the rate and regularity of swallowing. The results from the hemispheric TMS disruption study support the active involvement M1 in the execution of voluntary corticospinal and corticobulbar motor tasks. In addition, the current findings extended previous knowledge of neural control of pharyngeal swallowing by documenting the effect of neural disruption on the regularity and pharyngeal pressure measures during volitional and reflexive swallowing. The current programme documented potential role of M1 in the control of pharyngeal swallowing possibly by modulating the motor plan at the swallowing CPG in the brainstem. This project is the first to document pharyngeal pressure differences between discrete and continuous swallowing. These findings contribute valuable information to the swallowing literature as limited number of studies investigated the biomechanical differences between discrete and continuous liquid ingestion. This knowledge will assist clinicians and researchers in identifying the pharyngeal pressure differences between normal and abnormal swallowing in different swallowing types and ultimately guide their rehabilitation decisions. Data from this research programme will add to the existing knowledge of neurophysiology of swallowing, thereby facilitating understanding of swallowing pathophysiology which is crucial for appropriate management of swallowing disorders.

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.

No description available.

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.

Le contrôle moteur fin et précis des doigts est une habileté importante dans la vie quotidienne pour écrire ou manger par exemple. Ce contrôle moteur est pris en charge par le cortex moteur primaire (M1) qui transmet le signal neuronal à la moelle épinière via la voie corticospinale. Le macaque rhésus est un excellent modèle pour étudier ce système moteur car, comme chez l’humain, il possède cette voie cortico-motoneuronale directe. Bien que les déficits du contrôle moteur de la main suite à des inactivations de M1 aient été étudiés sur des modèles de singes, peu d’études ont décrit les changements musculaires sous-tendant ces déficits. Le but de cette étude était d’évaluer les effets d’une inactivation partielle de M1 sur le comportement et l’activation du patron musculaire du membre supérieur chez le macaque rhésus. Pour ce faire, nous avons effectué des injections intra-corticales de Muscimol, un agoniste du GABA, pour inactiver temporairement l’aire de représentation de la main de M1. Des singes ont été entrainés à réaliser une tâche d’atteinte et de préhension qui requière l’utilisation du pouce et de l’index pour attraper une pastille de nourriture. En parallèle, les activités électromyographiques (EMG) des muscles proximaux et distaux du membre supérieur contralatéral aux sites d’injections ont été enregistrées. L’inactivation partielle de M1 entraine différents déficits moteurs comme une diminution du taux de succès, une perte des mouvements indépendants des doigts, une première flexion de l’index plus lente, et l’apparition de nouvelles stratégies de préhension pour attraper la pastille. Dans le cas de trouble sévère, les singes ont présentés tous ces déficits comportementaux. Ces troubles moteurs étaient sous-tendus par des activités musculaires anormales. En effet, les analyses EMG ont mis en évidence des changements dans les latences et les patrons d’activations musculaires des muscles proximaux et distaux au cours de la phase d’atteinte, d’ajustement et de préhension. Dans le cas de trouble modéré, les patrons d’activations musculaires étaient préservés malgré certain déficits visibles. Cependant, les patrons d’activations musculaires étaient altérés si la tâche demandait une rotation de l’avant-bras et de la main. Ces résultats montrent que les déficits comportementaux et les changements musculaires dépendent de la sévérité des troubles moteurs et/ou de la difficulté de la tâche (i.e. une rotation de l’avant-bras). / Fine digit movements contribute to many different aspects of our daily life and require appropriate muscle coordination. The main pathway through which M1 sends motor commands to spinal motor neurons is via the corticospinal tract. The rhesus macaque, like humans, have this direct corticomotoneuronal pathway of M1, making it a useful model to study this system. Although the effect of M1 inactivation on the control of the hand in term of behavioral changes has been studied in monkeys, little is known of how muscle activation patterns of the upper limb during reaching and grasping in monkeys becomes altered. The goal of this study was to evaluate the effect of a partial inactivation of the primary motor cortex (M1) in rhesus macaques on both behavioral performance and muscle activations. To do so we performed intra-cortical injections of Muscimol, a GABA agonist, to inactivate the hand area of M1. Monkeys performed a reach-to-grasp task that required a precision grip to retrieve a food pellet from a well. Electromyographic (EMG) activity of the proximal and distal muscles of the contralateral upper limb were recorded and quantified relative to the behavioral performance. We found that depending on the severity of the impairment, the Muscimol injection could induce several different movement abnormalities, such as decrease in the success rate, loss of independent finger movements, longer duration of the first flexion of the index finger, and use of alternate types of grasp to retrieve the food pellet. In cases of severe impairment, monkeys displayed all these movement abnormalities concurrently. In addition, we observed that behavioral deficits were associated with muscle discoordination. Indeed, EMG analysis revealed that the latencies and the muscle activation patterns were altered during the reach, hand preshaping and the grasp phases of the movement. These inappropriate EMG activities were visible on both proximal and distal muscles of the upper limb. In cases of mild impairment, monkeys had fewer behavioral deficits, but still showed some changes in the temporal muscle activation patterns. In contrast to the severe cases, the muscle activation patterns were more preserved. Interestingly, in the mild cases, the muscle activation patterns were altered if a rotation of the forearm was required by the task. Thus, we found that behavioral and muscular activation changes were dependent on the severity of the impairment and/or the difficulty of the task (i.e. required a rotation of the forearm).