Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses

Abstract

Resting state functional magnetic resonance imaging (rs-fMRI) has been playing an important role in the study of amyotrophic lateral sclerosis (ALS). Although functional connectivity is widely studied, the patterns of spontaneous neural activity of the resting brain are important mechanisms that have been used recently to study a variety of conditions but remain less explored in ALS. Here we have used fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) to study the regional dynamics of the resting brain of non-demented ALS patients compared with healthy controls. As expected, we found the sensorimotor network (SMN) with changes in fALFF and ReHo but also found the default mode (DMN), frontoparietal (FPN), salience (SN) networks altered and the cerebellum, although no structural changes between ALS patients and controls were reported in the regions with fALFF and ReHo changes. We show an altered pattern in the spontaneous low frequency oscillations that is not confined to the motor areas and reveal a more widespread involvement of nonmotor regions, including those responsible for cognition.

Brain Cortical Complexity Alteration in Amyotrophic Lateral Sclerosis: A Preliminary Fractal Dimensionality Study

“…In addition, we observed a reduction in FD in the posterior cingulate cortex and the insula, suggesting that ALS could result in the damage to structural complexity in these regions and may affect their functions. In line with our results, previous studies have constantly found ALS-associated cortical thinning [4,6], hypometabolism [41], and reduced restingstate neural activity [13] in the posterior cingulate cortex. Consistent with our finding of FD reduction in the insula, researchers have described insula impairment in ALS, such as cortical thinning [5], energy hypometabolism [47], and decreased cerebral blood flow [43].…”

“…For example, the ALS-related neuronal loss has been well documented in the primary motor cortex [38]. Furthermore, the accumulating studies have demonstrated regional structure changes (e.g., reduced cortical thickness [4] and gray matter volume [39]) and functional abnormalities (e.g., reduction of spontaneous brain activity at rest [13] and hypoactivation during motor task [7]) in the primary motor-related cortex in ALS. Thus, our finding provided the convergent evidence that the damage to primary motor cortex is the hallmark of ALS, which may underlie the key mechanism about the impaired initiation and inhibition of movement.…”

“…We also observed a decline of FD in the cingulate gyrus and sulcus (middle part). In fact, middle cingulumassociated cortical atrophy [13,43], functional disconnection [44], and hypoperfusion [43] have been observed in ALS. The middle cingulate cortex has widespread connection with the motor cortex and spinal cord, as well as numerous pyramidal neurons [45].…”

“…Moreover, the structural alteration has been associated with patient cognitive status [5,6], disease severity [8,10], and rate of progression [4]. Additionally, resting-state functional MRI studies have suggested that ALS involves a reduction in spontaneous neuronal activity in the sensorimotor cortex and cingulate cortex [11][12][13], which is also correlated with disease duration and progression rate [12,13]. In terms of blood flow, PET studies have indicated that ALS patients present decreased regional cerebral blood flow in the sensorimotor cortex, cingulate cortex, and insula [14].…”

Peer Review #1 of "Static and dynamic alterations in the amplitude of low-frequency fluctuation in patients with amyotrophic lateral sclerosis (v0.1)"

“…As an effective index to measure local brain activity, amplitude of low frequency fluctuation (ALFF) (Guo et al 2012;Liu et al 2013;Yu-Feng et al 2007) has been extensively employed in ALS research. Using this approach, scholars have discovered that patients with ALS showed aberrant activation in the precentral gyrus, frontal gyrus, and occipital regions; this finding suggests that ALS is a disease involving many system with brain impairment spreading beyond the motor cortex (Bueno et al 2019;Ma et al 2016;Shen et al 2018). In addition, the increased ALFF in the frontal lobe could be a candidate biomarker in ALS (Luo et al 2012).…”