Purpose: Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS.
Material and methods: Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains.
Results: ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p = 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (ρ = - 0.85, p = 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p < 0.05).
Conclusions: The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.
Keywords: AC, anterior commissure; ALS, amyotrophic lateral sclerosis; ALS-EX, ALS with executive impairment; ALS-NECI, ALS with non-executive cognitive impairment; ALSFRS-R, revised ALS functional rating scale; ATL, anterior temporal lobe; Amyotrophic lateral sclerosis; CC, corpus callosum; CST, corticospinal tract; Corpus callosum; DD, disease duration; DPR, disease progression rate; DTI, diffusion tensor imaging; Diffusion tensor imaging; FA, fractional anisotropy; FTD, frontotemporal dementia; HC, healthy control; Hb, hemoglobin; Interhemispheric connectivity; NIRS, near-infrared spectroscopy; Near-infrared spectroscopy; TBSS, tract based spatial statistics; WM, white matter; fMRI, functional magnetic resonance imaging; pALS, pure ALS no cognitive impairment; rs-FC, resting-state functional connectivity; rs-fNIRS, resting-state functional NIRS.