J Clin Neurol.  2016 Apr;12(2):209-217. 10.3988/jcn.2016.12.2.209.

Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia

• Bae JS
• Ferguson M
• Tan R
• Mioshi E
• Simon N
• Burrell J
• Vucic S
• Hodges JR
• Kiernan MC
• Hornberger M

• KMID: 2354142
• DOI: http://doi.org/10.3988/jcn.2016.12.2.209

Abstract

BACKGROUND AND PURPOSE
This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37).
METHODS
Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability.
RESULTS
The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls.
CONCLUSIONS
Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.

Keyword

frontotemporal dementia; amyotrophic lateral sclerosis; voxel-based morphometry; diffusion tensor imaging; transcranial magnetic stimulation

MeSH Terms

Amyotrophic Lateral Sclerosis*
Brain Stem
Cerebellum
Dementia
Diagnosis
Diffusion Tensor Imaging
Frontotemporal Dementia*
Humans
Motor Cortex
Motor Neurons
Transcranial Magnetic Stimulation

Figure

• 

  Fig. 1 Regions of interest (ROIs) included in the study. Gray-matter integrity is indicated by blue shading in the respective ROIs, and white-matter integrity is indicated by dashed lines of different styles (none, partly, and full) surrounding and connecting the regions. BSt: brainstem, CB: cerebellum, MCx: motor cortex, Str/Thal: striatum and thalamus.

• 

  Fig. 2 Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) findings for (A) amyotrophic lateral sclerosis (ALS) vs. controls and (B) behavioral-variant frontotemporal dementia (bvFTD) vs. controls. VBM and DTI findings are shown in blue and red, respectively. Colored voxels show regions that were significant in the analysis at p<0.05 with correction for the family-wise error. For all clusters, t>3.50. Clusters are overlaid on the MNI standard brain atlas. BSt: brainstem, CB: cerebellum, MCx: motor cortex, Str/Thal: striatum and thalamus.

• 

  Fig. 3 VBM and DTI findings for (A) ALS vs. bvFTD and (B) bvFTD vs. ALS. VBM and DTI findings are shown in blue and red, respectively. Colored voxels show regions that were significant in the analysis at p<0.05 with correction for FWE. For all clusters, t>3.50. Clusters are overlaid on the MNI standard brain atlas. ALS: amyotrophic lateral sclerosis, BSt: brainstem, bvFTD: behavioral-variant frontotemporal dementia, CB: cerebellum, DTI: diffusion tensor imaging, FWE: family-wise error, MCx: motor cortex, Str/Thal: striatum and thalamus, VBM: voxel-based morphometry.

• 

  Fig. 4 Threshold-tracking transcranial magnetic stimulation short-interval intracortical inhibition (SICI) results for all groups: across all interstimulus intervals (A) and for the peak interstimulus interval of 3 ms (B). Error bars indicate SEM values. ALS: amyotrophic lateral sclerosis, bvFTD: behavioral-variant frontotemporal dementia, MND: motor neuron disease, SEM: standard error of the mean.

• 

  Fig. 5 Results of VBM (A) and DTI (B) covariation analyses for the average SICI. Results for ALS and bvFTD are shown in light-blue/dark-blue and yellow/red shading, respectively. Colored voxels show regions that were significant in the analysis at p<0.05 with correction for the false discovery rate (FDR). For all clusters, t>3.50. Clusters are overlaid on the MNI standard brain atlas. ALS: amyotrophic lateral sclerosis, bvFTD: behavioral-variant frontotemporal dementia, DTI: diffusion tensor imaging, MNI: Montreal Neurological Institute coordinates, SICI: short-interval intracortical inhibition, VBM: voxel-based morphometry.

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