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Altered cortical activation during a motor task in ALS

Evidence for involvement of central pathways

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Abstract

Objective

To test the hypothesis that patients with amyotrophic lateral sclerosis (ALS) show increased cortical activation during a motor task compared to both healthy controls and patients with muscle weakness due to peripheral lesions.

Methods

Functional magnetic resonance imaging (fMRI) was used to measure activation during a block design paradigm contrasting right hand movements against rest in sixteen patients with ALS, seventeen healthy controls and nine patients with peripheral lesions. The groups were matched for age and gender and the two patient groups were matched for their degree of upper limb weakness. Analysis used a non-parametric approach to perform a 3 way hypothesis-driven comparison between the groups.

Results

During the motor task, patients with ALS showed increased cortical activation bilaterally, extending from the sensorimotor cortex [Brodmann areas (BA) 1, 2, 4] posteriorly into the inferior parietal lobule (BA 40) and inferiorly to the superior temporal gyrus (BA 22) when compared to peripheral lesion patients and controls. In addition, ALS patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) extending to anterior and medial frontal cortex (BA 8, 9, 10, 32).

Conclusions

We conclude that alterations in cortical function in ALS differ in sensorimotor and prefrontal regions. Importantly, we have shown that these changes do not reflect confounding by weakness or task difficulty, but are likely to be related to upper motor neuron pathology in ALS.

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References

  1. Brownell B, Oppenheimer DR, Hughes JT (1970) The central nervous system in motor neurone disease. J Neurol Neurosurg Psychiatry 33:338–357

    Article  CAS  PubMed  Google Scholar 

  2. Ince PG, Evans J, Knopp M, et al. (2003) Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS. Neurology 60:1252–1258

    CAS  PubMed  Google Scholar 

  3. Piao YS, Wakabayashi K, Kakita A, et al. (2003) Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. Brain Pathol 13:10–22

    Article  PubMed  Google Scholar 

  4. Kew JJ, Leigh PN, Playford ED, et al. (1993) Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study. Brain 116:655–680

    Article  PubMed  Google Scholar 

  5. Kew JJ, Brooks DJ, Passingham RE, Rothwell JC, Frackowiak RS, Leigh PN (1994) Cortical function in progressive lower motor neuron disorders and amyotrophic lateral sclerosis: a comparative PET study. Neurology 44:1101–1110

    CAS  PubMed  Google Scholar 

  6. Konrad C, Henningsen H, Bremer J, et al. (2002) Pattern of cortical reorganization in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Exp Brain Res 143:51–56

    Article  PubMed  Google Scholar 

  7. Schoenfeld MA, Tempelmann C, Gaul C, et al. (2005) Functional motor compensation in amyotrophic lateral sclerosis. J Neurol 252:944–952

    Article  PubMed  Google Scholar 

  8. Konrad C, Jansen A, Henningsen H, et al. (2006) Subcortical reorganization in amyotrophic lateral sclerosis. Exp Brain Res 172(3):361–369

    Article  CAS  PubMed  Google Scholar 

  9. Leigh PN, Abrahams S, Al Chalabi A, et al. (2003) The management of motor neurone disease. J Neurol Neurosurg Psychiatry 74(Suppl 4):iv32–iv47

    PubMed  Google Scholar 

  10. Brooks BR, Miller RG, Swash M, Munsat TL (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299

    Article  CAS  PubMed  Google Scholar 

  11. Kleyweg RP, van der Meche FG, Schmitz PI (1991) Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barre syndrome. Muscle Nerve 14:1103–1109

    Article  CAS  PubMed  Google Scholar 

  12. Cedarbaum JM, Stambler N, Malta E, et al. (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21

    Article  CAS  PubMed  Google Scholar 

  13. Evans FJ (1978) Monitoring attention deployment by random number generation: an index to measure subjective randomness. Bull Psychonom Soc 12:35–38

    Google Scholar 

  14. Towse JN, Neil D (1998) Analyzing human random generation behaviour: a review of methods used and a computer programme for describing performance. Behav Res Methods Instrum Comput 30:583–591

    Google Scholar 

  15. Brammer MJ, Bullmore ET, Simmons A, et al. (1997) Generic brain activation mapping in functional magnetic resonance imaging: a nonparametric approach. Magn Reson Imaging 15:763–770

    Article  CAS  PubMed  Google Scholar 

  16. Bullmore E, Brammer M, Williams SC, et al. (1996) Statistical methods of estimation and inference for functional MR image analysis. Magn Reson Med 35:261–277

    Article  CAS  PubMed  Google Scholar 

  17. Bullmore E, Long C, Suckling J, et al. (2001) Colored noise and computational inference in neurophysiological (fMRI) time series analysis: resampling methods in time and wavelet domains. Hum Brain Mapp 12:61–68

    Article  CAS  PubMed  Google Scholar 

  18. Bullmore ET, Brammer MJ, Rabe-Hesketh S, et al. (1999) Methods for diagnosis and treatment of stimulus-correlated motion in generic brain activation studies using fMRI. Hum Brain Mapp 7:38–38

    Article  CAS  PubMed  Google Scholar 

  19. Bullmore ET, Suckling J, Overmeyer S, Rabe-Hesketh S, Taylor E, Brammer MJ (1999) Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Trans Med Imaging 18:32–42

    Article  CAS  PubMed  Google Scholar 

  20. Talairach J, Tornoux P (1988) CoPlanar Sterotaxic Atlas of the human brain. Thieme, Stuttgart

  21. Hirano A (1991) Cytopathology of amyotrophic lateral sclerosis. Adv Neurol 56:91–101

    CAS  PubMed  Google Scholar 

  22. Hughes JT (1982) Pathology of amyotrophic lateral sclerosis. Adv Neurol 36:61–74

    CAS  PubMed  Google Scholar 

  23. Friedman AP, Freedman D (1950) Amyotrophic lateral sclerosis. J Nerv Ment Dis 111:1–18

    Article  CAS  PubMed  Google Scholar 

  24. Kiernan JA, Hudson AJ (1991) Changes in sizes of cortical and lower motor neurons in amyotrophic lateral sclerosis. Brain 114:843–853

    Article  PubMed  Google Scholar 

  25. Martin JE, Swash M (1995) The pathology of motor neuron disease. In: Swash M, Leigh PN (eds) Motor neuron disease: biology and management. Springer-Verlag, London, p 93

  26. Maekawa S, Al Sarraj S, Kibble M, et al. (2004) Cortical selective vulnerability in motor neuron disease: a morphometric study. Brain 127:1237–1251

    Article  CAS  PubMed  Google Scholar 

  27. Chollet F, DiPiero V, Wise RJ, Brooks DJ, Dolan RJ, Frackowiak RS (1991) The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann Neurol 29:63–71

    Article  CAS  PubMed  Google Scholar 

  28. Muller RA, Rothermel RD, Behen ME, Muzik O, Mangner TJ, Chugani HT (1998) Differential patterns of language and motor reorganization following early left hemisphere lesion: a PET study. Arch Neurol 55:1113–1119

    Article  CAS  PubMed  Google Scholar 

  29. Weiller C, Chollet F, Friston KJ, Wise RJ, Frackowiak RS (1992) Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann Neurol 31:463–472

    Article  CAS  PubMed  Google Scholar 

  30. Wunderlich G, Knorr U, Herzog H, Kiwit JC, Freund HJ, Seitz RJ (1998) Precentral glioma location determines the displacement of cortical hand representation. Neurosurgery 42:18–26

    Article  CAS  PubMed  Google Scholar 

  31. Neary D, Snowden J (1996) Frontotemporal dementia: nosology, neuropsychology, and neuropathology. Brain Cogn 31:176–187

    Article  CAS  PubMed  Google Scholar 

  32. Shaw PJ (1994) Excitotoxicity and motor neurone disease: a review of the evidence. J Neurol Sci 124(Suppl):6–13

    Article  PubMed  Google Scholar 

  33. Neary D, Snowden JS, Mann DM (2000) Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS). J Neurol Sci 180:15–20

    Article  CAS  PubMed  Google Scholar 

  34. Abrahams S, Leigh PN, Harvey A, Vythelingum GN, Grise D, Goldstein LH (2000) Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS). Neuropsychologia 38:734–747

    Article  CAS  PubMed  Google Scholar 

  35. Gallassi R, Montagna P, Ciardulli C, Lorusso S, Mussuto V, Stracciari A (1985) Cognitive impairment in motor neuron disease. Acta Neurol Scand 71:480–484

    Article  CAS  PubMed  Google Scholar 

  36. Kew JJ, Goldstein LH, Leigh PN, et al. (1993) The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study. Brain 116:1399–1423

    Article  PubMed  Google Scholar 

  37. Ludolph AC, Langen KJ, Regard M, et al. (1992) Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study. Acta Neurol Scand 85:81–89

    Article  CAS  PubMed  Google Scholar 

  38. Abrahams S, Goldstein LH, Simmons A, et al. (2004) Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Brain 127:1507–1517

    Article  CAS  PubMed  Google Scholar 

  39. Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE, Brooks DJ (1995) Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson’s disease subjects. Brain 118:913–933

    Article  PubMed  Google Scholar 

  40. Frith CD, Friston K, Liddle PF, Frackowiak RS (1991) Willed action and the prefrontal cortex in man: a study with PET. Proc Biol Sci 244:241–246

    Article  CAS  PubMed  Google Scholar 

  41. Frith CD, Friston KJ, Liddle PF, Frackowiak RS (1991) A PET study of word finding. Neuropsychologia 29:1137–1148

    Article  CAS  PubMed  Google Scholar 

  42. Ellis CM, Suckling J, Amaro E Jr, et al. (2001) Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS. Neurology 57:1571–1578

    CAS  PubMed  Google Scholar 

  43. Abrahams S, Goldstein LH, Suckling J, et al. (2005) Frontotemporal white matter changes in amyotrophic lateral sclerosis. J Neurol 252:321–331

    Article  PubMed  Google Scholar 

  44. Abe K, Takanashi M, Watanabe Y, et al. (2001) Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis. Neuroradiology 43:537–541

    Article  CAS  PubMed  Google Scholar 

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Stanton, B.R., Williams, V.C., Leigh, P.N. et al. Altered cortical activation during a motor task in ALS. J Neurol 254, 1260–1267 (2007). https://doi.org/10.1007/s00415-006-0513-4

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  • DOI: https://doi.org/10.1007/s00415-006-0513-4

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