Abstract
The association between gray matter (GM) density and neurophysiologic changes is still unclear in amyotrophic lateral sclerosis (ALS). We evaluated the relationship between GM density and motor system integrity combining voxel-based morphometry (VBM) and transcranial magnetic stimulation (TMS) in ALS. We included 17 ALS patients and 22 healthy controls (HC) who underwent 3D-T1-weighted imaging. Among the ALS group, we applied left motor cortex single-pulse TMS. We used whole-brain VBM comparing ALS and HC in GM density. We also conducted regression analysis to examine correlations between GM density and the following TMS parameters: motor evoked potential (MEP)/M ratio and central motor conduction time (CMCT). We found significantly decreased GM density in ALS patients in several frontal, temporal, parietal/occipital and cerebellar regions (p < 0.001 uncorrected; cluster-extent threshold k = 100 voxels per cluster). With regards to TMS parameters, ALS patients showed mostly increased MEP/M ratio and modest prolongation of CMCT. MEP/M ratio was associated with GM density in (a) rolandic operculum/inferior frontal gyrus/precentral gyrus; anterior cingulate gyrus; inferior temporal gyrus; superior parietal lobule; cuneus; superior occipital gyrus and cerebellum (positive association) and (b) paracentral lobule/supplementary motor area (negative association). CMCT was associated with GM density in (a) inferior frontal gyrus and middle cingulated gyrus (positive association) and (b) superior parietal lobule; cuneus and cerebellum (negative association). Our findings support a significant interaction between motor and extra-motor structural and functional changes and highlight that motor and extra-motor GM integrity may underlie TMS parameters of motor function in ALS patients.
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Abbreviations
- ALS:
-
Amyotrophic lateral sclerosis
- ALSFRS-R:
-
Revised Amyotrophic Lateral Sclerosis Functional Rating Scale
- APB:
-
Abductor pollicis brevis
- bvFTD:
-
Behavioral variant of frontotemporal dementia
- CMCT:
-
Central motor conduction time
- CSF:
-
Cerebrospinal fluid
- cTBS:
-
Continuous theta burst stimulation
- EMG:
-
Electromyographic
- fMRI:
-
Functional magnetic resonance imaging
- FWE:
-
Family-wise error
- FWHM:
-
Full-width-at-halfmaximum
- GM:
-
Gray matter
- HC:
-
Healthy control
- HR_3DT1w:
-
High resolution 3D–T1-weighted
- LMN:
-
Lower motor neuron
- MEP:
-
Motor evoked potentials
- MNI:
-
Montreal Neurological Institute
- MRI:
-
Magnetic resonance imaging
- MT:
-
Motor threshold
- RMT:
-
Resting motor threshold
- SMA:
-
Supplementary motor area
- SPM8:
-
Statistical Parametric Mapping
- T2-FLAIR:
-
T2-Fluid attenuation inversion recovery
- TE:
-
Echo time
- TIV:
-
Total intracranial volume
- TMS:
-
Transcranial magnetic stimulation
- TR:
-
Time of repetition
- TST:
-
Triple-stimulation technique
- UMN:
-
Upper motor neuron
- VBM:
-
Voxel-based morphometry
- WM:
-
White matter
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Acknowledgements
The study did not receive any funding. F.C. was supported by the IKY FELLOWSHIPS OF EXCELLENCE FOR POSTGRADUATE STUDIES IN GREECE - SIEMENS PROGRAM (SPHA:11118/13a) and IKY SHORT TERMS PROGRAM (2013-ΠΕ2-SHORT TERMS-18671). We acknowledge Odysseas Benekos, Giannis Spandonis and the Philips Medical System for providing all necessary research keys for MRI sequence acquisition. We also acknowledge the radiologists-technologists of Research Radiology & Medical Imaging Department (Ioannis Gkerles, Christos Lioulios, Anestis Passalis, Efstathios Xenos) for conducting participants’ MR scanning. Finally, we would like to thank patients with ALS and their families, as well as healthy volunteers for their willingness to participate to the present study.
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Foteini Christidi and Efstratios Karavasilis shared first authorship. Ioannis Evdokimidis and Nikolaos Karandreas shared last authorship.
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Christidi, F., Karavasilis, E., Velonakis, G. et al. Motor and extra-motor gray matter integrity may underlie neurophysiologic parameters of motor function in amyotrophic lateral sclerosis: a combined voxel-based morphometry and transcranial stimulation study. Brain Imaging and Behavior 12, 1730–1741 (2018). https://doi.org/10.1007/s11682-018-9841-0
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DOI: https://doi.org/10.1007/s11682-018-9841-0