Aberrant interhemispheric homotopic functional and structural connectivity in amyotrophic lateral sclerosis

Zhang, Jiuquan; Ji, Bing; Hu, Jun; Zhou, Changyu; Li, Longchuan; Li, Zhihao; Huang, Xuequan; Hu, Xiaoping

doi:10.1136/jnnp-2016-314567

Cited by 40 publications

(43 citation statements)

References 41 publications

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“…These results were consistent with previous studies reporting decreased interhemispheric FC of the primary motor cortex (Fang et al, 2016;Zhang et al, 2017), and were supported by the findings of decreased degree centrality and FC density in the primary motor cortex in patients with ALS (Li et al, 2018;Zhou et al, 2016). Likewise, the ROI-based FC analysis also showed a lower FC between the precentral ROI and the right cerebellar ROI in patients with ALS.…”

Section: Fc Alterations In Alssupporting

confidence: 92%

“…Indeed, the corticospinal tract is the most important WM tract involved in movement execution of distal extremities (Seo & Jang, 2013), and abnormalities of the corticospinal tract might contribute to the clinical presentations of patients with ALS, such as foot drop, difficulty walking and loss of hand dexterity (Gordon, 2013), and so forth. Therefore, the observed FA decrease in the corpus callosum may suggest altered interhemispheric information transfer in patients with ALS as evidenced by recent reports of impaired interhemispheric structural and FC (Zhang et al, 2017). On the other hand, the corpus callosum, as the largest WM structure interconnecting the two cerebral hemispheres (Li, Wu, Liang, & Huang, 2015), is thought to play an important role in interhemispheric communication.…”

Section: Wm Alterations In Alsmentioning

confidence: 87%

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Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

Qiu

Zhang

Tang

et al. 2019

Human Brain Mapping

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Amyotrophic lateral sclerosis (ALS) is a progressive and intractable neurodegenerative disease of human motor system characterized by progressive muscular weakness and atrophy. A considerable body of research has demonstrated significant structural and functional abnormalities of the primary motor cortex in patients with ALS. In contrast, much less attention has been paid to the abnormalities of cerebellum in this disease. Using multimodal magnetic resonance imagining data of 60 patients with ALS and 60 healthy controls, we examined changes in gray matter volume (GMV), white matter (WM) fractional anisotropy (FA), and functional connectivity (FC) in patients with ALS. Compared with healthy controls, patients with ALS showed decreased GMV in the left precentral gyrus and increased GMV in bilateral cerebellum, decreased FA in the left corticospinal tract and body of corpus callosum, and decreased FC in multiple brain regions, involving bilateral postcentral gyrus, precentral gyrus and cerebellum anterior lobe, among others. Meanwhile, we found significant intermodal correlations among GMV of left precentral gyrus, FA of altered WM tracts, and FC of left precentral gyrus, and that WM microstructural alterations seem to play important roles in mediating the relationship between GMV and FC of the precentral gyrus, as well as the relationship between GMVs of the precentral gyrus and cerebellum. These findings provided evidence for the precentral degeneration and cerebellar compensation in ALS, and the involvement of WM alterations in mediating the relationship between pathologies of the primary motor cortex and cerebellum, which may contribute to a better understanding of the pathophysiology of ALS.

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Section: Fc Alterations In Alssupporting

confidence: 92%

Section: Wm Alterations In Alsmentioning

confidence: 87%

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

Qiu

Zhang

Tang

et al. 2019

Human Brain Mapping

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“…The middle subregion of the corpus callosum serves the homotypically organized interhemispheric connections containing fibers projecting into premotor, primary motor, and primary sensory areas; this implies that damage to this specific corpus callosum region (reflected by decreased MK and RK) might further explain the underlying motor problems in ALS. Indeed, this is supported by a previous study in which the interhemispheric functional coordination between the bilateral motor cortices was reduced and was correlated with impaired microstructural integrity along the interhemispheric fiber bundles through the middle corpus callosum …”

Section: Discussionsupporting

confidence: 78%

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Huang

Zou

Xue

et al. 2019

Magnetic Resonance Imaging

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Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature. Purpose To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time. Study Type Prospective. Subjects Eighteen ALS patients and 20 healthy controls. Field Strength/Sequence DKI images were obtained by a spin‐echo echo‐planar imaging sequence on a 3T MRI scanner, with three b‐values (0, 1000, and 2000 s/mm2) and 64 diffusion encoding directions. Assessment The revised ALS Functional Rating Scale (ALSFRS‐R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel‐based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). Statistical Tests Student's t‐test, chi‐square test, and Pearson correlation analysis. Results ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS‐R score and disease duration. Additionally, several WM regions showed between‐group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics. Data Conclusion The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor‐related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity. Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554–562.

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“…These findings strongly support the notion of cortical primacy in ALS 78. Other contributory evidence for this theory is the demonstration of reduced transcallosal inhibition in ALS 79. Partial normalisation of SICI following the administration of riluzole,80 an antiglutaminergic drug used in ALS, points to a pathogenic role for cortical hyperexcitability in ALS.…”

Section: Cortical Dysfunction In Neurodegenerative Diseasesupporting

confidence: 63%

Interrogating cortical function with transcranial magnetic stimulation: insights from neurodegenerative disease and stroke

Agarwal

Koch

Hillis

et al. 2018

J Neurol Neurosurg Psychiatry

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Transcranial magnetic stimulation (TMS) is an accessible, non-invasive technique to study cortical function in vivo. TMS studies have provided important pathophysiological insights across a range of neurodegenerative disorders and enhanced our understanding of brain reorganisation after stroke. In neurodegenerative disease, TMS has provided novel insights into the function of cortical output cells and the related intracortical interneuronal networks. Characterisation of cortical hyperexcitability in amyotrophic lateral sclerosis and altered motor cortical function in frontotemporal dementia, demonstration of cholinergic deficits in Alzheimer's disease and Parkinson's disease are key examples where TMS has led to advances in understanding of disease pathophysiology and potential mechanisms of propagation, with the potential for diagnostic applications. In stroke, TMS methodology has facilitated the understanding of cortical reorganisation that underlie functional recovery. These insights are critical to the development of effective and targeted rehabilitation strategies in stroke. The present review will provide an overview of cortical function measures obtained using TMS and how such measures may provide insight into brain function. Through an improved understanding of cortical function across a range of neurodegenerative disorders, and identification of changes in neural structure and function associated with stroke that underlie clinical recovery, more targeted therapeutic approaches may now be developed in an evolving era of precision medicine.

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Aberrant interhemispheric homotopic functional and structural connectivity in amyotrophic lateral sclerosis

Abstract: The present data provided direct evidence confirming and extending the view of impaired interhemispheric neural communications mediated by CC, providing a new perspective for examinations and understanding the pathophysiology of ALS.

Cited by 40 publications

References 41 publications

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Interrogating cortical function with transcranial magnetic stimulation: insights from neurodegenerative disease and stroke

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