Action semantics at the bottom of the brain: Insights from dysplastic cerebellar gangliocytoma

Recent embodied cognition research shows that access to action verbs in shallow-processing tasks becomes selectively compromised upon atrophy of the cerebellum, a critical motor region. Here we assessed whether cerebellar damage also disturbs explicit semantic processing of action pictures and its integration with ongoing motor responses. We evaluated a cognitively preserved 33-year-old man with severe dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease), encompassing most of the right cerebellum and the posterior part of the left cerebellum. The patient and eight healthy controls completed two semantic association tasks (involving pictures of objects and actions, respectively) that required motor responses. Accuracy results via Crawford's modified t-tests revealed that the patient was selectively impaired in action association. Moreover, reaction-time analysis through Crawford's Revised Standardized Difference Test showed that, while processing of action concepts involved slower manual responses in controls, no such effect was observed in the patient, suggesting that motor-semantic integration dynamics may be compromised following cerebellar damage. Notably, a Bayesian Test for a Deficit allowing for Covariates revealed that these patterns remained after covarying for executive performance, indicating that they were not secondary to extra-linguistic impairments. Taken together, our results extend incipient findings on the embodied functions of the cerebellum, offering unprecedented evidence of its crucial role in processing non-verbal action meanings and integrating them with concomitant movements. These findings illuminate the relatively unexplored semantic functions of this region while calling for extensions of motor cognition models.Fil: Cervetto Manciameli, Sabrina Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad de la República; UruguayFil: Abrevaya, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Martorell Caro, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Kozono, Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Muñoz, Edinson. Universidad de Santiago de Chile; ChileFil: Ferrari, Jesica. Instituto de Neurología Cognitiva; ArgentinaFil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Ibáñez Barassi, Agustín Mariano. Australian Research Council; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Autónoma del Caribe; Colombia. Universidad Adolfo Ibañez; ChileFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Nacional de Cuyo; Argentin

Intention Tremor and Deficits of Sensory Feedback Control in Multiple Sclerosis: a Pilot Study

Background Intention tremor and dysmetria are leading causes of upper extremity disability in Multiple Sclerosis (MS). The development of effective therapies to reduce tremor and dysmetria is hampered by insufficient understanding of how the distributed, multi-focal lesions associated with MS impact sensorimotor control in the brain. Here we describe a systems-level approach to characterizing sensorimotor control and use this approach to examine how sensory and motor processes are differentially impacted by MS. Methods Eight subjects with MS and eight age- and gender-matched healthy control subjects performed visually-guided flexion/extension tasks about the elbow to characterize a sensory feedback control model that includes three sensory feedback pathways (one for vision, another for proprioception and a third providing an internal prediction of the sensory consequences of action). The model allows us to characterize impairments in sensory feedback control that contributed to each MS subject’s tremor. Results Models derived from MS subject performance differed from those obtained for control subjects in two ways. First, subjects with MS exhibited markedly increased visual feedback delays, which were uncompensated by internal adaptive mechanisms; stabilization performance in individuals with the longest delays differed most from control subject performance. Second, subjects with MS exhibited misestimates of arm dynamics in a way that was correlated with tremor power. Subject-specific models accurately predicted kinematic performance in a reach and hold task for neurologically-intact control subjects while simulated performance of MS patients had shorter movement intervals and larger endpoint errors than actual subject responses. This difference between simulated and actual performance is consistent with a strategic compensatory trade-off of movement speed for endpoint accuracy. Conclusions Our results suggest that tremor and dysmetria may be caused by limitations in the brain’s ability to adapt sensory feedback mechanisms to compensate for increases in visual information processing time, as well as by errors in compensatory adaptations of internal estimates of arm dynamics

The current state of biomarker research for Friedreich's ataxia: a report from the 2018 FARA biomarker meeting

The 2018 FARA Biomarker Meeting highlighted the current state of development of biomarkers for Friedreich's ataxia. A mass spectroscopy assay to sensitively measure mature frataxin (reduction of which is the root cause of disease) is being developed. Biomarkers to monitor neurological disease progression include imaging, electrophysiological measures and measures of nerve function, which may be measured either in serum and/or through imaging-based technologies. Potential pharmacodynamic biomarkers include metabolic and protein biomarkers and markers of nerve damage. Cardiac imaging and serum biomarkers may reflect cardiac disease progression. Considerable progress has been made in the development of biomarkers for various contexts of use, but further work is needed in terms of larger longitudinal multisite studies, and identification of novel biomarkers for additional use cases

Swayed by sound: sonic guidance as a neurorehabilitation strategy in the cerebellar ataxias

Cerebellar disease leads to problems in controlling movement. The most common difficulties are dysmetria and instability when standing. Recent understanding of cerebellar function has expanded to include non -motor aspects such as emotional, cognitive and sensory processing. Deficits in the acquisition and processing of sensory information are one explanation for the movement problems observed in cerebellar ataxia. Sensory deficits result in an inability to make predictions about future events; a primary function of the cerebellum. A question therefore, is whether augmenting or replacing sensory information can improve motor performance in cerebellar disease. This question is tested in this thesis by augmenting sensory information through the provision of an auditory movement guide.A variable described in motor control theory (tau) was used to develop auditory guides that were continuous and dynamic. A reaching experiment using healthy individuals showed that the timing of peak velocity, audiomotor coordination accuracy, and velocity of approach, could be altered in line with the movement parameters embedded in the auditory guides. The thesis then investigated the use of these sonic guides in a clinical population with cerebellar disease. Performance on neurorehabilitation exercises for balance control was tested in twenty people with cerebellar atrophy, with and without auditory guides. Results suggested that continuous, predictive, dynamic auditory guidance is an effective way of improving iii movement smoothness in ataxia (as measured by jerk). In addition, generating and swaying with imaginary auditory guides was also found to increase movement smoothness in cerebellar disease.Following the tests of instantaneous effects, the thesis then investigated the longterm consequences on motor behaviour of following a two -month exercise with auditory guide programme. Seven people with cerebellar atrophy were assessed pre - and post -intervention using two measures, weight -shifting and walking. The results of the weight -shifting test indicated that the sonic -guide exercise programme does not initiate long -term changes in motor behaviour. Whilst there were minor, improvements in walking, because of the weight -shifting results, these could not be attributed to the sonic guides. This finding confirms the difficulties of motor rehabilitation in people with cerebellar disease.This thesis contributes original findings to the field of neurorehabilitation by first showing that on -going and predictive stimuli are an appropriate tool for improving motor behaviour. In addition, the thesis is the first of its kind to apply externally presented guides that convey continuous meaningful information within a clinical population. Finally, findings show that sensory augmentation using the auditory domain is an effective way of improving motor coordination in some forms of cerebellar disease

Objective assessment of movement disabilities using wearable sensors

The research presents a series of comprehensive analyses based on inertial measurements obtained from wearable sensors to quantitatively describe and assess human kinematic performance in certain tasks that are most related to daily life activities. This is not only a direct application of human movement analysis but also very pivotal in assessing the progression of patients undergoing rehabilitation services. Moreover, the detailed analysis will provide clinicians with greater insights to capture movement disorders and unique ataxic features regarding axial abnormalities which are not directly observed by the clinicians

The advantage of flexible neuronal tunings in neural network models for motor learning

Human motor adaptation to novel environments is often modeled by a basis function network that transforms desired movement properties into estimated forces. This network employs a layer of nodes that have fixed broad tunings that generalize across the input domain. Learning is achieved by updating the weights of these nodes in response to training experience. This conventional model is unable to account for rapid flexibility observed in human spatial generalization during motor adaptation. However, added plasticity in the widths of the basis function tunings can achieve this flexibility, and several neurophysiological experiments have revealed flexibility in tunings of sensorimotor neurons. We found a model, Locally Weighted Projection Regression (LWPR), which uniquely possesses the structure of a basis function network in which both the weights and tuning widths of the nodes are updated incrementally during adaptation. We presented this LWPR model with training functions of different spatial complexities and monitored incremental updates to receptive field widths. An inverse pattern of dependence of receptive field adaptation on experienced error became evident, underlying both a relationship between generalization and complexity, and a unique behavior in which generalization always narrows after a sudden switch in environmental complexity. These results implicate a model that is flexible in both basis function widths and weights, like LWPR, as a viable alternative model for human motor adaptation that can account for previously observed plasticity in spatial generalization. This theory can be tested by using the behaviors observed in our experiments as novel hypotheses in human studies