Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We recently demonstrated that people with FRDA have impairment in motor planning - most likely because of pathology affecting the cerebral cortex and/or cerebello-cortical projections. We used the Simon interference task to examine how effective 13 individuals with FRDA were at inhibiting inappropriate automatic responses associated with stimulus-response incompatibility in comparison with control participants. Participants had to respond to arrow targets according to two features which were either congruent or incongruent. We found that individuals with FRDA were differentially affected in reaction time to incongruent, compared with congruent stimuli, when compared with control participants. There was a significant negative correlation between age of onset and the incongruency effect, suggesting an impact of FRDA on the developmental unfolding of motor cognition, independent of the effect of disease duration. Future neuroimaging studies will be required to establish whether this dysfunction is due to cerebellar impairment disrupting cerebro-ponto-cerebello-thalamo-cerebral loops (and thus cortical function), direct primary cortical pathology, or a possible combination of the two.
"Appreciable between-group differences are visually evident when comparing corresponding slices from the group-averaged track density images Brain Struct Funct the notion of reverse cerebellar diaschisis. However, to establish this hypothesis, future work should assess whether connectivity deficits are correlated with the extent of non-motor symptoms in FRDA, such as depression (da Silva et al. 2012) and cognitive difficulties (Corben et al. 2011a; Georgiou-Karistianis et al. 2012). Except for the Simon effect, which may be considered a non-motor sign, the cognitive functioning of our sample was not quantitatively characterized, thereby precluding this kind of correlation analysis. "
[Show abstract][Hide abstract] ABSTRACT: Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects in distant cortical and subcortical regions. Remote regions affected by primary cerebellar and brainstem pathology include the supplementary motor area, cingulate cortex, frontal cortices, putamen and other subcortical nuclei. The connectivity disruptions identified provide an explanation for some of the non-ataxic symptoms observed in the disease and support the notion of reverse cerebellar diaschisis. This is the first study to comprehensively map white matter connectivity disruptions in Friedreich ataxia using tractography, connectomic techniques and super-resolution track density imaging.
Brain Structure and Function 04/2013; 219(3). DOI:10.1007/s00429-013-0547-1 · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Whole body vibration (WBV) has been extensively studied as an anabolic stimulus for bone and muscle. Therapeutic WBV delivers low magnitude, high frequency vibrations to tissues, eliciting biological and structural responses. This study investigated the effect of 0.3G (Peak-to-Peak), 30Hz sinusoidal vibration on intact flexor carpi ulnaris tendons in rats. Experimental rats were subjected to twenty minutes of WBV daily for five days a week for a total of five weeks. The tendon cross-sectional area and the structural properties of the muscle-tendon-bone unit under tensile loading to failure were evaluated. Initial body weights were similar between the groups and the mean change in body weight of the animals of each group did not differ. The cross-sectional area of the tendons of the vibrated animals was found to be 32% greater (P<0.05) than the controls and the structural stiffness of the vibrated tendons was found to be 41% greater (P<0.05) than the controls. For specimens that failed in the midsubstance of the tendon, a trend (P=0.087) for increased ultimate load was observed in the vibrated tendons compared to the controls. No differences in material properties were observed except for the strain to ultimate load, which was reduced 22% in the vibrated group. These initial findings suggest that vibration may serve as an anabolic stimulus to tendon similar to its effects on bone and muscle. These findings are important as they open the potential that low magnitude, high frequency vibration might serve as a means to accelerate tendon healing.
Journal of Biomechanics 03/2011; 44(6):1189-91. DOI:10.1016/j.jbiomech.2011.02.017 · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Friedreich ataxia (FRDA) is the most common of the inherited ataxias. We have suggested that people with FRDA may have impairment in cognitive and/or psychomotor capacity either due to disturbance of projections of the cerebellum to the cortex, direct cortical pathology or perhaps both. To further explore this possibility, we used a movement task incorporating Fitts' Law, a robust description of the relationship between movement time and accuracy in goal-directed aiming movements. By manipulating task difficulty, according to target size and distance, we were able to quantify processes related to motor planning in 10 individuals with FRDA and 10 matched control participants. Compared to control participants, people with FRDA were significantly disadvantaged in terms of movement time to targets with an increasing index of difficulty. Successful completion of this task requires both preplanning of movement and online error detection and correction. The cerebellum and its connections to the frontal cortex via cerebro-ponto-cerebello-thalamo-cerebral loops are fundamental to both processes. These results lend further support to our contention that in FRDA these loops are impaired, reflecting a failure to access prefrontal/anterior regions necessary for effective management of preplanning of movement and online error correction.
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