More than half of all spinal cord injuries are anatomically incomplete, yet many of these result in complete loss of motor function below the level of injury. One approach to enhance functional recovery is to exploit spared CNS axons (that extend past the point of injury) to sprout and connect to potential targets. We have previously found that application of the neurotrophin; BDNF, to the sensory-motor cortex stimulates expression of regeneration associated genes such as GAP-43, and Tαl tubulin, and results in enhanced sprouting of injured corticospinal fibers rostral to the site of injury. Here, we investigated whether infusion of BDNF into the intact sensorimotor cortex induces sprouting of undamaged corticospinal fibers into denervated cervical spinal cord. We also studied the effect of this treatment using several behavioral tasks: gait analysis, forelimb inhibition during swimming, and food pellet reaching task. The results show that BDNF infusion into the intact sensorimotor cortex subsequent to a unilateral pyramidal lesion increases (3.2 fold) the sprouting of intact corticospinal fibers into the denervated, contralateral grey matter at the lumbar level of the spinal cord when compared with vehicle treated rats. This effect was not seen at the cervical level of the spinal cord. Functionally, unilateral pyramidal injury of corticospinal axons significantly increased toe spread of the contralateral denervated forelimb and hindlimb when compared to the uninjured side. BDNF treatment showed a recovery to presurgical levels. Testing of fine motor control with a food pellet reaching task demonstrated deficits in the impaired forelimb but did not show any improvement due to BDNF treatment.

More than half of all spinal cord injuries are anatomically incomplete, yet many of these result in complete loss of motor function below the level of injury. One approach to enhance functional recovery is to exploit spared CNS axons (that extend past the point of injury) to sprout and connect to potential targets. We have previously found that application of the neurotrophin; BDNF, to the sensory-motor cortex stimulates expression of regeneration associated genes such as GAP-43, and Tαl tubulin, and results in enhanced sprouting of injured corticospinal fibers rostral to the site of injury. Here, we investigated whether infusion of BDNF into the intact sensorimotor cortex induces sprouting of undamaged corticospinal fibers into denervated cervical spinal cord. We also studied the effect of this treatment using several behavioral tasks: gait analysis, forelimb inhibition during swimming, and food pellet reaching task. The results show that BDNF infusion into the intact sensorimotor cortex subsequent to a unilateral pyramidal lesion increases (3.2 fold) the sprouting of intact corticospinal fibers into the denervated, contralateral grey matter at the lumbar level of the spinal cord when compared with vehicle treated rats. This effect was not seen at the cervical level of the spinal cord. Functionally, unilateral pyramidal injury of corticospinal axons significantly increased toe spread of the contralateral denervated forelimb and hindlimb when compared to the uninjured side. BDNF treatment showed a recovery to presurgical levels. Testing of fine motor control with a food pellet reaching task demonstrated deficits in the impaired forelimb but did not show any improvement due to BDNF treatment.

More than half of all spinal cord injuries are anatomically incomplete, yet many of these result in complete loss of motor function below the level of injury. One approach to enhance functional recovery is to exploit spared CNS axons (that extend past the point of injury) to sprout and connect to potential targets. We have previously found that application of the neurotrophin; BDNF, to the sensory-motor cortex stimulates expression of regeneration associated genes such as GAP-43, and Tαl tubulin, and results in enhanced sprouting of injured corticospinal fibers rostral to the site of injury. Here, we investigated whether infusion of BDNF into the intact sensorimotor cortex induces sprouting of undamaged corticospinal fibers into denervated cervical spinal cord. We also studied the effect of this treatment using several behavioral tasks: gait analysis, forelimb inhibition during swimming, and food pellet reaching task. The results show that BDNF infusion into the intact sensorimotor cortex subsequent to a unilateral pyramidal lesion increases (3.2 fold) the sprouting of intact corticospinal fibers into the denervated, contralateral grey matter at the lumbar level of the spinal cord when compared with vehicle treated rats. This effect was not seen at the cervical level of the spinal cord. Functionally, unilateral pyramidal injury of corticospinal axons significantly increased toe spread of the contralateral denervated forelimb and hindlimb when compared to the uninjured side. BDNF treatment showed a recovery to presurgical levels. Testing of fine motor control with a food pellet reaching task demonstrated deficits in the impaired forelimb but did not show any improvement due to BDNF treatment. / Medicine, Faculty of / Graduate

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Injury to the cervical spinal cord is a devastating event that results in a transient to permanent loss of sensory and motor functions following injury. Moderate recovery has been reported to occur in individuals and in animal models after spinal cord injury (SCI). One approach to promote recovery after SCI is rehabilitative training. This thesis examines the relation of reaching training with adaptive changes (i.e. plasticity) and functional recovery following SCI. In my first experiment, I investigated whether plasticity of the corticospinal tract (CST) is the cause for reaching recovery after ablation of the dorsal and lateral CST. Rats that received reaching training were significantly better in reaching than their untrained counterparts. A relesion of the CST revealed that the reaching recovery mainly depended on plasticity of the CST itself. Since it is controversial whether training should be initiated immediately after SCI, I investigated whether a delayed initiation of reaching training after SCI is beneficial. I compared the reaching success of rats that received reaching training on day 4 post SCI with rats that received training on day 12 post SCI. I found that the reaching success in rats that either received reaching training on day 4 or 12 following SCI was similar. Lastly, I investigated whether training efficacy is declined in chronically injured rats. Since it has been shown that the inflammatory response after SCI declines, it is questionable whether there is a relation between the inflammatory response after SCI and training efficacy. In my last experiment I injected chronically injured rats with a substance that induces a systemic inflammation. I found that rehabilitative reaching training in chronic injured rats only resulted in an improved reaching recovery when the training was combined with the administration of the substance that induces inflammation (lipopolysaccharide). Although there are still unanswered questions regarding the underlying mechanism for functional recovery after SCI, the results of this thesis could be used as a basic to improve future rehabilitative training strategies and therefore improve the quality of life in individuals that suffer from SCI.

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The aim of the present thesis was to investigate the relationship between individuals' allocation of overt visual attention during action observation and their consequent pickup of information. Four interrelated studies were conducted to achieve this. In Study 1 we examined the effects of visual guidance - colour highlighting of relevant aspects of the action - on observational learning of the golf swing. The results showed that the visual guides facilitated novices' intake of information pertaining to the model's posture, which was reflected in faster learning. In the remaining studies, transcranial magnetic stimulation and eye tracking data were acquired concurrently to measure the interaction between gaze behaviour and motor resonance - a neurophysiological index of the motor system's engagement with a viewed action, and thus a correlate of information extraction. In Study 2, we directed observers' gaze to distinct locations of the display while they viewed thumb adduction/abduction movements. The results showed that, by directing gaze to a location that maximised the amount of thumb motion across the fovea, motor resonance was maximised relative to a free viewing condition. In Study 3 we examined the link between gaze and motor resonance during the observation of transitive actions. Participants viewed reach-to-grasp actions with natural gaze, or while looking at a target- or an effector- based visual guide. The results showed that the effector-based guide disrupted natural gaze behaviour, and this was associated with a reversal of the motor resonance response. In Study 4 we showed novice and skilled golfers videos of the golf swing and of a reach-grasp-lift action. The results revealed that, for both actions, the extent of motor resonance was related to the location of participants' fixations. The present work provides the first evidence of a relationship between gaze and motor resonance and highlights the importance of appropriate gaze behaviour for observational learning.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.