Table 1.
Selected motor task-based and resting-state fMRI studies in ALS.
| Authors | Year | Study design | ALS (n) | Controls (n) | Main study findings/interpretation |
|---|---|---|---|---|---|
| Li et al. (29) | 2009 | Motor task: swallowing, Cross-sectional study |
10 | 10 HC | Reduced somatosensory cortex activation in patients with dysphagia |
| Mohammadi et al. (30) | 2009 | Motor: tongue movement, Cross-sectional study |
22 | 22 HC 5 DC (SBMA) |
ALS patients with bulbar symptoms showed decreased cortical and thalamic activation |
| Palmieri et al. (53) | 2010 | Emotional attribution and recognition task, Cross-sectional study |
9 | 10 HC | Altered emotional processing similar to patents observed in FTD. |
| Lule et al. (55) | 2010 | visual, auditory and somatosensory stimulation, Cross-sectional study |
14 | 18 HC | Decreased response in secondary visual areas in ALS, delayed response in secondary auditory areas, reduced response to somatosensory stimulation |
| Goldstein et al. (52) | 2011 | Cognitive task, Cross-sectional study |
14 | 8 HC | Increased left temporal and decreased precentral and left medial frontal activation: altered inhibitory processing in ALS |
| Kollewe et al. (13) | 2011 | Motor task: hand and tongue movement, Cross-sectional study |
20 | 20 HC | Decreased cortical activation during tongue movements in patients with bulbar symptoms. Increased activation during hand movements. Different functional reorganization in limb and bulbar impairment. |
| Mohammadi et al. (14) | 2011 | Motor task, Cross-sectional study |
22 | 22 HC | Patients stratified into three groups based on disability, Increased activation in early-stage, decreased activation in later stage disease. |
| Poujois et al. (15) | 2013 | Hand motor task Motor imagery, Cross-sectional study |
19 | 13 HC | Motor execution and imagery yields to similar activation patterns. Increased contra- and ipsilateral somatosensory cortex activation. |
| Passamonti (59) | 2013 | Emotional processing task, Cross-sectional study | 11 | 12 HC | Increased activation in prefrontal areas and altered amygdala-prefrontal cortex connectivity in ALS, suggestive of limbic system dysfunction |
| Witiuk et al. (57) | 2014 | Antisaccade task with eye tracking, Cross-sectional study |
12 | 12 HC | ALS patients make more antisaccade direction errors and exhibit reduced DLPFC activation compared to controls i.e. deficits in automatic response inhibition are associated with impaired DLPFC activation |
| Stoppel et al. (43) | 2014 | Go/No-Go paradigm, Longitudinal design |
14 | 14 HC | Increased motor activation compared to controls with subsequent decline on follow-up scanning suggestive of failing adaptive compensation |
| Mohammadi et al. (61) | 2015 | Movement inhibition task (go/no-go), Cross-sectional study |
17 | 17 HC | Increased motor inhibition and execution related activation in patients with ALS compared to controls. |
| Jelsone-Swain et al. (36) | 2015 | Action Observation and Execution task, Cross-sectional study |
19 | 18 HC | Increased activation during action-execution and observation in ALS patients in opercular, premotor and primary motor regions. Mirror neuron system mediated compensation. |
| Li et al. (35) | 2015 | Action observation paradigm, Cross-sectional study |
30 | 30 HC | Action observation activates similar networks to action execution. Increased activation observed in the DLPFC and supplementary motor regions of ALS patients. |
| Aho-Ozhan (60) | 2016 | Cognitive task Cross-sectional study |
15 | 14 HC | Impaired processing of negative emotions such as fear and disgust in ALS |
| Vellage et al. (54) | 2016 | Cognitive task: working memory Cross-sectional study |
14 | 14 HC | Reduced hemodynamic responses in the left occipital cortex and right prefrontal cortex in ALS patients compared to healthy controls |
| Keller et al. (58) | 2018 | Cognitive task: ToM and executive task, Cross-sectional study |
65 | 33 | Increased activation in all ALS patients compared to HC. High performing patients exhibit more activation than those with neuropsychological deficits suggestive of compensation. |
| Mohammadi et al. (66) | 2009 | Resting-state fMRI, Cross-sectional study |
20 | 20 HC | ICA analyses: decreased DMN activation in the anterior and posterior cingulate and parietal regions |
| Jelsone-Swain et al. (84) | 2010 | Resting-state fMRI, Cross-sectional study |
20 | 20 HC | ROI analyses: decreased functional connectivity between the right and left motor cortices |
| Douaud et al. (20) | 2011 | Resting-state fMRI, Cross-sectional study |
25 | 15 HC | Increased SMN, premotor, prefrontal and thalamic functional connectivity, interpreted as compensation and inhibitory dysfunction |
| Agosta et al. (42) | 2011 | Resting-state fMRI, Cross-sectional study |
26 | 15 HC | Increased SMN, cingulate, cerebellar connectivity interpreted as compensation. |
| Fekete et al. (76) | 2013 | Resting state fMRI, Cross-sectional study |
40 | 30 HC | Widespread motor, cerebellar and basal ganglia functional connectivity alterations in the ALS cohort. Accurate subject classification using multiple kernel learning. |
| Zhou et al. (82) | 2013 | Resting-state fMRI, Cross-sectional study |
12 | 12 HC | Positive correlation between disability and functional connectivity |
| Agosta et al. (65) | 2013 | Resting-state fMRI, Cross-sectional study |
20 | 15 HC | ICA analyses: Increased parietal connectivity is associated with cognitive deficits which may represent compensation |
| Welsh et al. (67) | 2013 | Resting state fMRI, Cross-sectional study |
32 | 31 HC | Machine learning (support-vector machine) based on fMRI metrics achieves over 71% accuracy for disease state classification |
| Zhou et al. (73) | 2014 | Resting state fMRI, Cross-sectional study |
12 | 12 HC | Decreased regional brain synchrony in the superior medial SMN detected by regional coherence measures |
| Meoded et al. (38) | 2015 | Resting state fMRI, Cross-sectional study |
14 HC 16 PLS |
Increased functional connectivity between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex in primary lateral sclerosis | |
| Schmidt et al. (77) | 2014 | Resting state fMRI, Cross-sectional study |
64 | 27 HC | A strong positive correlation exist between changes in SC and FC averaged per brain region; suggesting that structural and functional network degeneration in ALS is coupled |
| Chenji et al. (75) | 2016 | Resting state fMRI, Cross-sectional study |
21 | 40 HC | Increased DMN and reduced SMN connectivity associated with greater disability interpreted as inhibitory dysfunction |
| Zhou et al. (69) | 2016 | Resting state fMRI, Cross-sectional study |
44 | 44 HC | Increased cerebellar, occipital and prefrontal degree centrality (DC) and decreased DC in the primary motor cortex and sensory motor regions of ALS patients |
| Menke et al. (79) | 2016 | Resting state fMRI, Presymptomatic study design |
12 | 12 psALS 12 HC |
Increased FC between the cerebellum and precuneus- cingulate-frontal lobe network in asymptomatic mutation carriers compared to controls |
| Trojsi et al. (72) | 2017 | Resting state fMRI, Cross-sectional study |
21 | 15 | Decreased FC in DMN, salience and fronto-parietal network. More significant SLN connectivity changes observed in bulbar onset patients compared to those with spinal onset. |
| Zhang et al. (74) | 2017 | Resting state fMRI, Cross-sectional study |
38 | 35 HC | Impaired interhemispheric functional connectivity eidenceed by voxel mirrored homotopic connectivity (VMHC) reductions, correlations with CC diffusivity metrics |
| Zhang et al. (166) | 2017 | Resting state fMRI, Cross-sectional study |
25 | 25 HC | Reduced occipital surface-based local gyrification index (LGI) is associated with decreased functional connectivity in the bilateral precuneus. |
| Lee et al. (80) | 2017 | Resting state fMRI, Presymptomatic study design |
13 psALS 46 HC |
Connectivity deficits detected in salience, sensorimotor, default mode and thalamic networks in presymptomatic C9orf72 carriers | |
| Li et al. (68) | 2018 | Resting state fMRI, Cross-sectional study |
38 | 35 HC | Graph theory method (functional connectivity density FCD) Decreased FCD in the primary motor cortex, increased long-range FCD in the premotor cortex in ALS patients. |
| Bueno et al. (167) | 2018 | Resting state fMRI, Cross-sectional study |
20 | 15 HC | Focus on Papez circuit integrity. Decreased functional connectivity in ALS patients between hippocampal, parahippocampal and cingulate regions. |
| Menke et al. (39) | 2018 | Resting state fMRI, Longitudinal study |
13 | 3 PLS | Multi-timepoint structural-functional study, ICA and DRA, decreased FC between SMN and frontal pole, increased FC between primary motor cortex and fronto-parietal network |
HC healthy control, DC Disease Control, DLPFC DorsoLateral PreFrontal Cortex, FC functional connectivity, SC Structural Connectivity, SBMA Kennedy's disease, FTD FrontoTemporal Dementia, PLS Primary Lateral Sclerosis, DMN Default Mode Network, SMN SensoriMotor Network, ToM Theory of Mind.