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Subcortical reorganization in amyotrophic lateral sclerosis

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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.

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Acknowledgements

This work was supported by the NRW-Nachwuchsgruppe Kn2000 of the Nordrhein-Westfalen Ministry of Education and Research (Fö.1KS9604/0), the Interdisciplinary Center of Clinical Research Münster (IZKF Projects FG2, Kne3/074/04, FG4), the Innovative Medizinische Forschung Münster (KN520301), the Deutsche Forschungsgemeinschaft (Kn 285/6-1 and 6-3), the Amyotrophic Lateral Sclerosis Association, and the Muscular Dystrophy Association—ALS Division.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, IZKF, University of Muenster, Albert-Schweitzer-Str. 11, 48149, Muenster, Germany

    C. Konrad

  2. Department of Neurology, IZKF, University of Muenster, Muenster, Germany

    A. Jansen, J. Sommer & S. Knecht

  3. Department of Neurology, Klinikum Lueneburg, 21339, Lueneburg, Germany

    H. Henningsen

  4. Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA

    P. A. Turski

  5. Department of Neurology, University of Wisconsin-Madison, Madison, WI, USA

    B. R. Brooks

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  1. C. Konrad
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  2. A. Jansen
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  3. H. Henningsen
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  4. J. Sommer
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  5. P. A. Turski
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Correspondence to C. Konrad.

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Konrad C. and Jansen A. contributed equally to their work

Appendix1

Appendix1

In the present study, cortical activation differences between ALS patients and healthy controls were not as pronounced as previously described. However, the post hoc analysis at more liberal statistical thresholds revealed enhanced activation also in the secondary motor areas (SMA and cingulate motor areas, inferior lateral premotor cortex) of ALS patients in comparison to control subjects (Fig. 4).

Fig. 4
figure 4

Brain regions that showed significantly more activation in ALS patients than in healthy subjects during right-hand movement (P<0.01, uncorrected for multiple comparisons)

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Konrad, C., Jansen, A., Henningsen, H. et al. Subcortical reorganization in amyotrophic lateral sclerosis. Exp Brain Res 172, 361–369 (2006). https://doi.org/10.1007/s00221-006-0352-7

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