Table 1.
Task-associated fMRI studies in MND patients using motor paradigms.
| Study | Subjects (mean age, years) | Disease duration (months) | ALSFRS-R score | Task design | Main findings in MND patients compared to HCs | Other findings |
|---|---|---|---|---|---|---|
| Konrad (8) | 11 ALS (33), 13 HCs (44) | 35 | NA | Block design: finger flexion with dominant hand | Motor cortex activation located more anteriorly; increased volumes of activation in SMA and cingulate motor areas, contralateral inferior lateral PMC, bilateral parietal cortex | – |
| Schoenfeld (9) | 6 ALS (56.2), 6 HCs (57.1) | 16 | 40 | Block design: consecutive button presses with right hand, fixation/rest as baseline | 1. More activated in bilateral motor areas and PMC; additional activated in bilateral cerebellar areas. 2. Less activated in contralateral M1 | – |
| Konrad (10) | 10 ALS (44), 10 HCs (45) | 21.5 (since diagnosis) | NA | Block design: finger flexion with right hand, rest as baseline | More active in right cerebellar hemisphere, right basal ganglia (especially putamen), bilateral brainstem (especially dorsal pons), right SMA; additional activated in right cingulate areas, bilateral inferior PMC, bilateral basal ganglia, left cerebellar hemisphere | – |
| Han (11) | 15 ALS (51.3), 15 HCs (49.5) | 13.1 | NA | Block design: sequential finger tapping with right and left hands, rest as baseline | Activation larger in bilateral primary sensorimotor cortex, bilateral PMC, bilateral SMA, ipsilateral cerebellum; extra activation in ipsilataral inferior lateral PMC, bilateral posterior limb of internal capsule, contralateral cerebellum | – |
| Tessitore (12) | 16 ALS (53.9), 13 HCs (54) | 39.8 | 27.4 | Block design: visually paced button press with right hand, rest as baseline | 1. Recruited more left anterior putamen. 2. Less activity in left M1, SMA, right posterior parietal cortex | Patients with greater UMN involvement had more robust activation of ACC and right caudate nucleus than patients with greater LMN involvement |
| Lule (13) | 14 ALS (53), 15 HCs (55) | 40 | 33.5 | Block design: grip force task and imagery of the same movement with right, left or both hands, rest as baseline | 1. Stronger response within M1 and PMC for imagery and execution. 2. Differences persisted 6 months later with additional activity in precentral gyrus and frontoparietal network for motor imagery, increased with impairment | – |
| Stanton (14, 15) | 16 ALS (55.1), 9 peripheral lesions (51.9), 17 HCs (55.3) | 25.9 | 41.1 | Block design: moving a joystick with right hand and imagery of the same movement, rest as baseline | 1. Execution: increased activation in primary sensorimotor cortex and extended posteriorly into inferior parietal lobule and inferiorly into superior temporal gyrus, reduced activation in left DLPFC and extended into anterior and medial prefrontal cortex and SMA. 2. Imagery: reduced activation in left inferior parietal lobule, ACC and medial prefrontal cortex | – |
| Li (16) | 10 ALS (45.8), 10 HCs (age matched) | 21.4 | 38.4 | Event-related design: voluntary saliva swallow, rest as baseline | 1. For patients without dysphagia, increased activation in bilateral postcentral gyrus. 2 For patients with dysphagia, reduced activation in bilateral postcentral gyrus | 1. ALS patients without dysphagia showed increased activity in bilateral precentral and postcentral gyri than patients with dysphagia, with additional activity in left thalamus. 2. Cerebral activation map changes correspond to diffusion abnormalities by DTI in ALS |
| Mohammadi (17) | 22 ALS (57), 5 Kennedy syndrome (59), 22 HCs (61) | 14 | 39.5 | Block design: tongue vertical movements, rest as baseline | For patients with bulbar sign, decrease of cortical activity (pre- and postcentral areas) and missing thalamic activity | – |
| Mohammadi (18) | 22 ALS (57), 22 HCs (61) | 14 | 39.5 | Block design: flexion and extension of fingers in right hand, rest as baseline | For patients with MRC-Megascores of 5, increased activation in bilateral M1, S1 and posterior PMC, contralateral putamen, bilateral thalamus, SMA | Movement related signal change and beta weights extracted from the activated cluster were unchanged relative to controls in patients with no weakness, but a marked decrease in patients with weakness |
| Kollewe (19) | 20 ALS (59), 20 HCs (52) | NA | 38.5 | Block design: tongue vertical movements, flexion and extension of fingers in right hand, rest as baseline | 1. During hand movement, increased activity in bilateral M1, S1, posterior PMC and SMA. 2. For tongue movement of patients with bulbar sign, decreased activity in M1, S1 and posterior PMC | ALSFRS-R score was positively correlated with signal change in hand area during hand movements and in tongue area during tongue movements |
| Heimrath (20) | 7 ALS (not given), 14 HCs (not given) | NA | NA | Block design: movement imagery and visual perception including 4 isolated movements, 4 body related movements, 4 movements which can be performed also in later stage ALS, and 1 control movement | 1. During movement perception, more activity in areas for higher order movement representation (e.g., BA 40), less activity in right PMC. 2. During movement imagery, more activity in PMC, less activity in subcortical (e.g., putamen) and cortical (e.g., hippocampus) structures related to motor memory | More advanced disease corresponded to stronger activity in areas of higher order movement representation (e.g., BA 40) |
| Cosottini (21) | 20 ALS (58), 16 HCs (50.6) | 20.1 | 38.2 | Block design: handgrip motor task with right, left or both hands simultaneously, rest as baseline | 1. Enhanced activation in ventral premotor frontal areas and parietal cortex, prevalent in left. 2. Hypoactivation in primary sensory motor cortex and frontal dorsal PMC | 1. Activation in frontoparietal motor circuit paralleled with disease progression rate. 2. Cerebral activation changes corresponded to cortical regions of atrophy by VBM |
| Poujois (22) | 19 ALS (63.8), 21 HCs (60.3) | 18.2 | 35.3 | Block design: execution or imagery of opening and closing right or left hand, rest as baseline | 1. During execution of right-hand movement, higher activity in left M1, bilateral S1 and parietal cortices (including precuneus). 2. During Imagery of right-hand movement, increased activity in left M1 and S1. 3. No difference was found for left-hand tasks | Controlateral parietal activity was inversely correlated with disease progression and ipsilateral S1 activations with the severity of the right-arm deficit |
| Flanagan (23) | 22 ALS (not given), 18 HCs (age matched) | NA | NA | Block design: action observations involved hand-object interactions and no interaction as control condition | Reduced activation in right dorsal, ventral PMC and inferior frontal gyrus | – |
| Li (24) | 30 ALS (53.5), 30 HCs (51.7) | 24.5 | 36.5 | Block design: watch a videotape showing repetitive flexion-extension of fingers in right hand, rest as baseline | 1. Greater activation in bilateral dorsal lateral PMC, inferior parietal gyrus and SMA. 2. Greater activation in M1 and dorsal lateral PMC areas related to movement rate. 3. Greater activation in bilateral superior parietal gyrus and right inferior frontal gyrus related to movement complexity | – |
| Jelsone-Swain (25) | 19 ALS (57.2), 18 HCs (59.9) | 47 | 36.8 | Block design: 1.Action observation and execution (squeezing a ball), rest as baseline. 2. Action understanding | 1. During action-execution and observation, greater activity in right inferior operculum, PMC and M1, left inferior parietal lobe. 2. During action understanding, greater activity in right inferior occipital gyrus, reduced activity in right prefrontal cortex including triangularis, bilateral orbital regions, bilateral temporal lobe and occipital lobe | – |
ACC, anterior cingulate cortex; ALS, amyotrophic lateral sclerosis; BA, Brodmann; DLPFC, dorsolateral prefrontal cortex; DTI, diffusion tensor imaging; fMRI, functional MRI; HC, healthy control; LMN, lower motor neuron; M1, primary motor cortex; MND, motor neuron disease; MRC, medical research council; NA, not available; PMC, premotor cortex; S1, primary sensor cortex; SMA, supplementary motor area; UMN, upper motor neuron; VBM, voxel-based morphometry.