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1.  Acquisition of internal models of motor tasks in children with autism 
Brain  2008;131(11):2894-2903.
Children with autism exhibit a host of motor disorders including poor coordination, poor tool use and delayed learning of complex motor skills like riding a tricycle. Theory suggests that one of the crucial steps in motor learning is the ability to form internal models: to predict the sensory consequences of motor commands and learn from errors to improve performance on the next attempt. The cerebellum appears to be an important site for acquisition of internal models, and indeed the development of the cerebellum is abnormal in autism. Here, we examined autistic children on a range of tasks that required a change in the motor output in response to a change in the environment. We first considered a prism adaptation task in which the visual map of the environment was shifted. The children were asked to throw balls to visual targets with and without the prism goggles. We next considered a reaching task that required moving the handle of a novel tool (a robotic arm). The tool either imposed forces on the hand or displaced the cursor associated with the handle position. In all tasks, the children with autism adapted their motor output by forming a predictive internal model, as exhibited through after-effects. Surprisingly, the rates of acquisition and washout were indistinguishable from normally developing children. Therefore, the mechanisms of acquisition and adaptation of internal models in self-generated movements appeared normal in autism. Sparing of adaptation suggests that alternative mechanisms contribute to impaired motor skill development in autism. Furthermore, the findings may have therapeutic implications, highlighting a reliable mechanism by which children with autism can most effectively alter their behaviour.
doi:10.1093/brain/awn226
PMCID: PMC2577807  PMID: 18819989
reach adaptation; prism adaptation; motor control; autism
2.  Acquisition of internal models of motor tasks in children with autism 
Brain : a journal of neurology  2008;131(Pt 11):2894-2903.
Children with autism exhibit a host of motor disorders including poor coordination, poor tool use, and delayed learning of complex motor skills like riding a tricycle. Theory suggests that one of the crucial steps in motor learning is the ability to form internal models: to predict the sensory consequences of motor commands and learn from errors to improve performance on the next attempt. The cerebellum appears to be an important site for acquisition of internal models, and indeed the development of the cerebellum is abnormal in autism. Here, we examined autistic children on a range of tasks that required a change in the motor output in response to a change in the environment. We first considered a prism adaptation task in which the visual map of the environment was shifted. The children were asked to throw balls to visual targets with and without the prism goggles. We next considered a reaching task that required moving the handle of a novel tool (a robotic arm). The tool either imposed forces on the hand or displaced the cursor associated with the handle position. In all tasks, the children with autism adapted their motor output by forming a predictive internal model, as exhibited through after-effects. Surprisingly, the rates of acquisition and washout were indistinguishable from normally developing children. Therefore, the mechanisms of acquisition and adaptation of internal models in self-generated movements appeared normal in autism. Sparing of adaptation suggests that alternative mechanisms contribute to impaired motor skill development in autism. Furthermore, the findings may have therapeutic implications, highlighting a reliable mechanism by which children with autism can most effectively alter their behavior.
doi:10.1093/brain/awn226
PMCID: PMC2577807  PMID: 18819989
reach adaptation; prism adaptation; motor control; autism
3.  LOCOMOTOR ADAPTATION ON A SPLIT-BELT TREADMILL CAN IMPROVE WALKING SYMMETRY POST-STROKE 
Brain : a journal of neurology  2007;130(Pt 7):1861-1872.
Human locomotion must be flexible in order to meet varied environmental demands. Alterations to the gait pattern occur on different time scales, ranging from fast, reactive adjustments to slower, more persistent adaptations. A recent study in humans showed the cerebellum to play a key role for slower walking adaptations in inter-limb coordination during split-belt treadmill walking, but not fast reactive changes. It is not known whether cerebral structures are also important in these processes, though some studies of cats have suggested that they are not. In this study, we used a split-belt treadmill walking task to test whether cerebral damage from stroke impairs either type of flexibility. Results showed that stroke involving cerebral structures did not impair either reactive or adaptive abilities and did not disrupt storage of new inter-limb relationships (i.e. after-effects). This suggests that cerebellar interactions with brainstem, rather than cerebral structures, comprise the critical circuit for this type of inter-limb control. Further, the after-effects from a 15-minute adaptation session could temporarily induce symmetry in subjects who demonstrated baseline asymmetry of spatio-temporal gait parameters. In order to re-establish symmetric walking, the choice of which leg is on the fast belt during split-belt walking must be based on the subject’s initial asymmetry. These findings demonstrate that cerebral stroke survivors are indeed able to adapt inter-limb coordination. This raises the possibility that asymmetric walking patterns post-stroke could be remediated utilizing the split-belt treadmill as a long-term rehabilitation strategy.
doi:10.1093/brain/awm035
PMCID: PMC2977955  PMID: 17405765
stroke; motor; locomotion; movement
4.  Sensorimotor dysfunction in multiple sclerosis and column-specific magnetization transfer-imaging abnormalities in the spinal cord 
Brain  2009;132(5):1200-1209.
The human spinal cord contains segregated sensory and motor pathways that have been difficult to quantify using conventional magnetic resonance imaging (MRI) techniques. Multiple sclerosis is characterized by both focal and spatially diffuse spinal cord lesions with heterogeneous pathologies that have limited attempts at linking MRI and behaviour. We used a novel magnetization-transfer-weighted imaging approach to quantify damage to spinal white matter columns and tested its association with sensorimotor impairment. We studied 42 participants with multiple sclerosis who each underwent MRI at 3 Tesla and quantitative tests of sensorimotor function. We measured cerebrospinal-fluid-normalized magnetization-transfer signals in the dorsal and lateral columns and grey matter of the cervical cord. We also measured brain lesion volume, cervical spinal cord lesion number and cross-sectional area, vibration sensation, strength, walking velocity and standing balance. We used linear regression to assess the relationship between sensorimotor impairment and MRI abnormalities. We found that the dorsal column cerebrospinal-fluid-normalized magnetization-transfer signal specifically correlated with vibration sensation (R = 0.58, P < 0.001) and the lateral column signal with strength (R = −0.45, P = 0.003). Spinal cord signal measures also correlated with walking and balance dysfunction. A stepwise multiple regression showed that the dorsal column signal and diagnosis subtype alone explained a significant portion of the variance in sensation (R2 = 0.54, P < 0.001), whereas the lateral column signal and diagnosis subtype explained a significant portion of the variance in strength (R2 = 0.30, P < 0.001). These results help to understand the anatomic basis of sensorimotor disability in multiple sclerosis and have implications for testing the effects of neuroprotective and reparative interventions.
doi:10.1093/brain/awp032
PMCID: PMC2677795  PMID: 19297508
strength; sensation; corticospinal tract; dorsal column medial lemniscal tract; magnetic resonance imaging
5.  Walking flexibility after hemispherectomy: split-belt treadmill adaptation and feedback control 
Brain  2008;132(3):722-733.
Walking flexibility depends on use of feedback or reactive control to respond to unexpected changes in the environment, and the ability to adapt feedforward or predictive control for sustained alterations. Recent work has demonstrated that cerebellar damage impairs feedforward adaptation, but not feedback control, during human split-belt treadmill walking. In contrast, focal cerebral damage from stroke did not impair either process. This led to the suggestion that cerebellar interactions with the brainstem are more important than those with cerebral structures for feedforward adaptation. Does complete removal of a cerebral hemisphere affect either of these processes? We studied split-belt walking in 10 children and adolescents (age 6–18 years) with hemispherectomy (i.e. surgical removal of one entire cerebral hemisphere) and 10 age- and sex-matched control subjects. Hemispherectomy did not impair reactive feedback control, though feedforward adaptation was impaired in some subjects. Specifically, some showed reduced or absent adaptation of inter-leg timing, whereas adaptation of spatial control was intact. These results suggest that the cerebrum is involved in adaptation of the timing, but not spatial, elements of limb movements.
doi:10.1093/brain/awn333
PMCID: PMC2664447  PMID: 19074191
locomotion; children; motor learning

Results 1-5 (5)