Serotonin (5-HT) is a well-known modulator of spinal cord excitability and motor output. In the spinal cord, the actions of 5-HT are primarily mediated by the 5-HT1AR, 5-HT2Rs and the 5-HT7R. Following a spinal cord transection, which results in a loss of supraspinal input, 5-HT agonists such as quipazine are used to provide excitation to the spinal cord to facilitate locomotor recovery. This is characterized by rhythmic alteration of left and right hindlimbs and ipsilateral flexor and extensor muscles. However, whether 5-HT has a global effect on spinal cord excitability or is confined to a specific motor group (i.e. flexors or extensors) is currently unknown. Furthermore, quipazine is used in conjunction with activity based interventions to enhance recovery following a spinal cord injury. However, the influence of limb activity on the responsiveness of the injured spinal cord to quipazine has not been examined. Lastly, the recovery of locomotion is at least in part thought to occur through an up-regulation of 5-HT receptors, although this has not been investigated in lumbar spinal cord. Chapter 2 examines whether quipazine had a differential effect on flexor and extensor motor output assessed by recording flexor and extensor reflexes, motoneurons and Ia extracellular field potentials pre- and post-quipazine. It was determined that following an acute spinal transection, quipazine induced a larger flexor monosynaptic reflex (MSR) compared to the extensor MSR due to pre-synaptic but not motoneuron modulation. Chapter 3 examines the influence of a chronic spinal transection with and without passive cycling on the hindlimb flexor and extensor MSR, both pre- and post-quipazine. It was found that three months post STx, the extensor but not flexor MSR demonstrated a hyperexcitable response, which was attenuated with passive cycling. Further, three months of passive cycling extensor MSR response to quipazine was similar to that seen in the control intact group. Chapter 4 examined 5-HT receptor expression in flexor and extensor motoneurons three months post spinalization with or without passive cycling. Following a chronic STx, the 5-HT1AR and 5-HT2CR are down regulated, whereas the 5-HT2AR is up-regulated. Passive cycling further enhanced the 5-HT2AR expression as well as up-regulated the 5-HT7R in extensor but not flexor motoneurons. Chapter 5 discusses the results and significance of these findings in detail.

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<p> Although most muscle spindle investigations have used the cat model and mvasiVe surgical measurement techniques, several investigators have used microneurography to record from the Ia and II fibres in humans during tendon vibration. In these studies the muscle spindle primary (Ia) endings are stimulated using transverse vibration of the tendon at reflex sub-threshold amplitudes. Others have used low amplitude vibration and the H-reflex (monosynaptic electrical response) to determine reflex properties during both agonist and antagonist voluntary contractions. Both of these methods explore only certain parts of the monosynaptic reflex arc; microneurography focus on the properties and firing characteristics of the muscle spindles themselves, whereas the H-reflex response to vibration is a representation of the response of the spinal cord as well as the muscle spindles. </p> <p> In the past we have developed a PC based instrument that uses Lab VIEW and a linear servomotor to study tendon reflex properties by recording H-reflexes (or stretch reflexes for mechanical stimuli) from single tendon taps or electrical stimuli to the afferent nerve. In this thesis we describe a further development of this system to provide precise vibrations of the tendon at up to 55 Hz with amplitudes up to 4 mm. The resultant vibration stretch reflex train is extracted from 2 major background noise sources, 60 Hz power line noise, and vibration artifact noise, of the EMG recording via phase coherent subtractive filtering. </p> <p> To demonstrate the versatility and efficacy of this system in studying the monosynaptic reflex arc, test results from several pilot studies are presented, using the system to vibrate the human distal flexor carpi radialis tendon: (i) whether stretch reflexes could be entrained with high frequency vibration, as contrary to H-reflexes, (ii) whether the responses were affected by low levels of agonist or antagonist contraction, in agreement with the existing pool of work on the subject using the H-reflex, (iii) whether a separation of the Ia (primary) and II (secondary) ending pathways is observable as individual but delayed responses at low vibration frequencies due to different activation characteristics, and axon diameters, of each ending. Possible physiological mechanisms that explain the resultant behaviour are also discussed. </p> / Thesis / Master of Applied Science (MASc)

A manutenção do equilíbrio depende da ativação sinérgica de músculos dos dois hemicorpos, e há evidências de que essa coordenação é mediada por circuitos medulares, que estão sob controle supra-segmentar. O objetivo desse trabalho é descrever mecanismos neurofisiológicos e biomecânicos envolvidos no controle postural de sujeitos saudáveis frente a uma perturbação provocada por uma contração reflexa, enfatizando-se os mecanismos associados à coordenação entre membros. A perturbação postural ocorreu em resposta a um estímulo elétrico unilateral no nervo tibial. Devido a restrições em estudos anteriores, utilizou-se uma ampla abordagem (múltiplos músculos, reflexos cruzados) e estimulação precisamente controlada. Os resultados mostraram um complexo padrão de ativação dos músculos dos membros inferiores bilateralmente. Logo após o estímulo, foram encontradas respostas de curta e média latência em músculos da perna e da coxa. Posteriormente, foram observadas algumas ações musculares de longa latência nos músculos mais distais, que provavelmente foram ativadas em resposta às oscilações posturais. As respostas musculares iniciais sugerem que as informações aferentes e os reflexos medulares possuem uma função muito importante na regulação da coordenação entre membros, durante a manutenção da postura ereta quieta. / Balance depends on the synergic activation of muscles bilaterally, and there is evidence that this coordination is mediated by spinal circuits, which are under supra-spinal control. The objective of this study is to describe neurophysiologic and biomechanical mechanisms involved in the postural control of healthy subjects submitted to a disturbance provoked by a muscular reflex contraction. The postural perturbation was caused by a unilateral electric stimulation to the popliteal fossa. The analysis emphasizes the mechanisms associated with interlimb coordination. In this work, methodological approaches expanded those of previous work, the recordings being done bilaterally and the stimulus being precisely controlled. The results showed a complex pattern of bilateral muscular activation. Short and medium latency responses were found in the leg and thigh muscles. These were followed by some muscular activity at longer latencies, probably occurring due to the postural oscillations. The initial muscular responses suggest that the afferent inflow and the spinal cord reflexes have an important function in the between-limb coordination during the standing posture.

A manutenção do equilíbrio depende da ativação sinérgica de músculos dos dois hemicorpos, e há evidências de que essa coordenação é mediada por circuitos medulares, que estão sob controle supra-segmentar. O objetivo desse trabalho é descrever mecanismos neurofisiológicos e biomecânicos envolvidos no controle postural de sujeitos saudáveis frente a uma perturbação provocada por uma contração reflexa, enfatizando-se os mecanismos associados à coordenação entre membros. A perturbação postural ocorreu em resposta a um estímulo elétrico unilateral no nervo tibial. Devido a restrições em estudos anteriores, utilizou-se uma ampla abordagem (múltiplos músculos, reflexos cruzados) e estimulação precisamente controlada. Os resultados mostraram um complexo padrão de ativação dos músculos dos membros inferiores bilateralmente. Logo após o estímulo, foram encontradas respostas de curta e média latência em músculos da perna e da coxa. Posteriormente, foram observadas algumas ações musculares de longa latência nos músculos mais distais, que provavelmente foram ativadas em resposta às oscilações posturais. As respostas musculares iniciais sugerem que as informações aferentes e os reflexos medulares possuem uma função muito importante na regulação da coordenação entre membros, durante a manutenção da postura ereta quieta. / Balance depends on the synergic activation of muscles bilaterally, and there is evidence that this coordination is mediated by spinal circuits, which are under supra-spinal control. The objective of this study is to describe neurophysiologic and biomechanical mechanisms involved in the postural control of healthy subjects submitted to a disturbance provoked by a muscular reflex contraction. The postural perturbation was caused by a unilateral electric stimulation to the popliteal fossa. The analysis emphasizes the mechanisms associated with interlimb coordination. In this work, methodological approaches expanded those of previous work, the recordings being done bilaterally and the stimulus being precisely controlled. The results showed a complex pattern of bilateral muscular activation. Short and medium latency responses were found in the leg and thigh muscles. These were followed by some muscular activity at longer latencies, probably occurring due to the postural oscillations. The initial muscular responses suggest that the afferent inflow and the spinal cord reflexes have an important function in the between-limb coordination during the standing posture.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective symptomatic treatment for pharmacoresistant dystonic syndromes. The relationship between grey matter volume and intracortical inhibition of the primary motor cortex (MI) in regard to the effectiveness and the state (ON/OFF) of GPi DBS was analysed in the first study. The grey matter of chronically treated patients showed hypertrophy of the supplementary motor area and cerebellar vermis whereas this difference was more significant in patients with a better clinical outcome. The grey matter of the cerebellar hemispheres of the patients showed positive correlation with the improvement of an intracortical inhibition which was generally less effective in patients regardless of the GPi DBS state. Moreover, we showed the same level of SICI in the good responders as in the healthy controls, while in non-responders was the SICI decreased. In the second study, by using paired associative stimulation (PAS) we studied the influence of primary somatosensory cortex (SI) on the MI excitability in dystonia in regards to the effectiveness of GPi DBS. SI PAS decreased the MI excitability in the GPi DBS ON state while switching the stimulation off decreased an inhibitory effect of SI on MI excitability. Non-responders showed a...