Subcortical reorganization in amyotrophic lateral sclerosis

Abstract

The cerebral cortex reorganizes in response to central or peripheral lesions. Although basal ganglia and cerebellum are key components of the network dedicated to movement control, their role in motor reorganization remains elusive. We therefore tested if slowly progressive neurodegenerative motor disease alters the subcortical functional anatomy of the basal ganglia-thalamo-cerebellar circuitry. Ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls underwent functional magnetic resonance imaging (fMRI), while executing a simple finger flexion task. Cued by an acoustic trigger, they squeezed a handgrip force transducer with their right hand at 10% of their maximum voluntary contraction force. Movement frequency, amplitude, and force were controlled. Statistical parametric mapping of task-related BOLD-response revealed increased activation in ALS patients as compared to healthy controls. The main activation increases were found in the supplementary motor area, basal ganglia, brainstem, and cerebellum. These findings suggest that degeneration of cortical and spinal motor neurons in ALS leads to a recruitment of subcortical motor structures. These subcortical activation patterns strongly resemble functional activation in motor learning and might therefore represent adaptations of cortico-subcortical motor loops as a - albeit finally ineffective - mechanism to compensate for the ongoing loss of motor neurons in ALS.

The Present and the Future of Neuroimaging in Amyotrophic Lateral Sclerosis

“…[82][83][84][85] Increased sensorimotor activation was also reported in the hemisphere ipsilateral to the movement. 84 A spatial shift of recruitment to more anterior regions of the premotor cortex during upper limb movement was also observed in patients with ALS.…”

“…83,86 It is suggested that an increase in movement-associated cortical activations beyond the primary motor cortex is associated with the degree of UMN involvement.…”

Neuroimaging in Amyotrophic Lateral Sclerosis

“…A general pattern of cortical reorganization was found for motor function in patients with ALS when compared with that seen in normal subjects [24], with increased activation of the contralateral sensorimotor cortex, supplementary motor area, basal ganglia, and cerebellum demonstrated on fMR images during motor tasks [24,25,80,81]. Increased sensorimotor activation has also been reported in the brain ipsilateral to the movement [80].…”

“…In the search for the UMN markers, several neuroimaging modalities, especially diffusion tensor imaging (DTI) [8][9][10][11][12][13][14][15][16], proton magnetic resonance spectroscopy ( 1 H-MRS) [14,15,[17][18][19][20], perfusion imaging [21], magnetization transfer imaging [22] (MTI) and functional magnetic resonance imaging (fMRI) [23][24][25], have been used with varying success. This article presents an overview of these neuroimaging methods and their potential roles in ALS.…”

Degeneration of the Human Nervous System and Magnetic Resonance Neuroimaging

“…Furthermore, a more pronounced involvement of other motor functional areas at cortical and subcortical levels has been demonstrated in fMRI studies of motor tasks. For motor execution, a stronger involvement of areas involved in motor learning, such as the basal ganglia, cerebellum (Han et al, 2006;Konrad et al, 2006) and/or brainstem (Konrad et al, 2006) is evident. It may be assumed that alterations in functioning of basal ganglia are likely to be related to upper motor neuron pathology since they were observed in patients with exclusive upper motor neuron involvement (Tessitore et al, 2006).…”