Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study

Abstract

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor-sensory tasks of different complexity, i.e. continuous hand tapping and writing of "8" figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age-matched healthy controls were recruited. Task execution was monitored and recorded using MR-compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the "8" by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory-motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo-activation during hand tapping. During writing of the "8" task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the "8" increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance.

Cerebral compensation during motor function in Friedreich ataxia: The IMAGE‐FRDA study

“…Cerebellar deficits were also not apparent during attentionally demanding task performance (even when explored at more liberal uncorrected statistical thresholds). This finding is surprising given that deficits in lobules V and VI are relatively consistent in structural and functional neuroimaging studies of FRDA . However, that we find cerebellar deficits in our simple motor task in the same group of participants, during the same scan session, using similar perceptual stimuli, and employing identical data processing and statistical modeling approaches provides some protection against type II error.…”

“…When the results from Akhlaghi and colleagues are compared to just the FARS High subgroup in the current study, the predominance of hypoactivation in these regions is replicated. Deficits in lobule V/VI and the SMA were also implicated by Ginestroni and colleagues during hand tapping. Taken together, functional changes are consistently evident in the ventral attention/premotor brain regions during motor execution in individuals with FRDA.…”

“…These studies found consistent evidence of functional deficits in cerebellar lobules V and VI, the supplementary motor areas, and the inferior parietal lobules during various finger‐ and hand‐tapping tasks. Other frontal, prefrontal, posterior parietal, and cerebellar brain regions were more inconsistently implicated, and observations included both hypoactivation and hyperactivation relative to healthy controls . This pattern of findings suggests that a common set of brain abnormalities may contribute to the motor deficits in FRDA, whereas task‐specific mechanisms of functional compensation or downstream consequence (ie, diaschisis) may operate elsewhere.…”

“…Motor deficits are the most salient clinical features of FRDA and include limb and gait ataxia; poor balance control; dysmetria, dysdiadochokinesia, and intention tremor; and dysarthria and dysphagia . The neurofunctional correlates of motor dysfunction have been investigated in vivo using functional magnetic resonance imaging (fMRI) in small cohorts of between 7 and 11 individuals with FRDA . These studies found consistent evidence of functional deficits in cerebellar lobules V and VI, the supplementary motor areas, and the inferior parietal lobules during various finger‐ and hand‐tapping tasks.…”

“…The current study had two primary aims. First, we sought to replicate and extend on investigations of simple motor functions in FRDA using a larger research cohort, providing for increased statistical power and more reliable generalizability of results. In addition, by recruiting individuals across a wide range of clinical severity, we sought to cross‐sectionally investigate links between disease severity and detrimental or compensatory functional changes in the brain.…”