Table 2.
Task-associated fMRI studies in MND patients using extra-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 |
|---|---|---|---|---|---|---|
| Abrahams (26) | 28 ALS (57.3), 18 HCs (55) | 21 | NA | Block design: letter fluency and confrontation naming, say the word “rest” as baseline | 1. Letter fluency: increased activation in left superior frontal gyrus, right middle temporal gyrus and inferior frontal gyrus, reduced activation in left middle temporal gyrus, precuneus, inferior frontal gyrus and inferior parietal lobe, right ACC, bilateral middle frontal gyrus. 2. Confrontation naming: increased activation in right fusiform gyrus, impaired activation in left middle temporal gyrus, middle occipital gyrus and superior temporal gyrus, right cingulate gyrus, bilateral inferior frontal gyrus and cuneus | – |
| Lule (27) | 13 ALS (57.5), 6 tetraplegia (not given), 15 HCs (54.4) | 23 | 36.8 | Event-related design and block design: receive socioemotional stimuli from the International Affective Picture System at inclusion and 6 months later | 1. Larger activity in right supramarginal area. 2. Lower activation in extrastriate visual areas | Within the ALS patients’ group a reduction of brain responses in anterior insula at the follow-up was correlated with the subjective arousal |
| Jawaid (28) | 18 ALS and HCs (not given) | NA | NA | NA: a socioeconomic game called the “Trust task,” patients as trustees | 1. Higher activity of cingulate compared to disease-free investors. 2. Lower activity of cingulated compared to disease-free trustees | – |
| Palmieri (29) | 9 ALS (51.7), 10 HCs (51.1) | 24 (since diagnosis) | 37.9 | Block design: emotional attribution task asked subjects to select one of three unpleasant or neutral words, memory recognition task asked subjects to recognize words presented during previous task | A general increase in activation of left hemisphere, and reduced activation in right hemisphere in both emotional tasks | – |
| Lule (30) | 14 ALS (52.6), 18 HCs (59.6) | 28 | 33.4 | Event-related design: receive visual, auditory and somatosensory stimuli | 1. Auditory stimulation: increased activity in bilateral caudate nucleus and middle frontal gyrus, lower activity in bilateral inferior frontal gyri and right cerebellum. 2. Visual stimulation: lower activity in right occipital lobe. 3. Somatosensory stimulation: no evident difference was found | Several areas with increasing/decreasing activity during different stimuli associated with physical function loss |
| Goldstein (31) | 14 ALS (52.6), 8 HCs (52.4) | NA | NA | Block design: Stroop and negative priming tasks | 1. Stroop effect: increased activation in middle temporal gyrus, superior temporal gyrus, ACC, fusiform and lingual gyri, medial frontal gyrus, inferior parietal cortex, hippocampus, caudate nucleus, insula, cerebellum (all on left). 2. Negative priming effect: reduced activation in left cingulate gyrus, precentral gyrus and medial frontal gyrus, brainstem, lingual and fusiform gyrus, cerebellum | – |
| Meier (32) | 2 ALS (not given), 15 HCs (not given) | NA | NA | Event-related design: reward, punishment and affective-shift trials of the reversal learning task relative to a matched affectively neutral baseline | The orbitofrontal activity of case of mild impairment on neuropsychological tests sensitive to orbitofrontal cortex function and behavioral disturbance was more bilateral and more spatially extensive than controls | – |
| Passamonti (33) | 11 ALS (45.4), 12 HCs (40.3) | 19 | 32.1 | Block design: subjects were asked to identify the emotional faces as the “target” one via a 2-choice button box | 1. Emotional vs. neutral stimuli: greater responses in ventral ACC, dorsal ACC and bilateral DLPFC. 2. Altered left amygdala-prefrontal cortex connectivity. 3. Anxiety modulated right amygdale- prefrontal cortex connectivity in HCs but not in ALS patients | Reduced right PMC activity and altered left amygdale-SMA connectivity were associated with longer disease duration and greater disease severity |
| Witiuk (34) | 12 ALS (61.6), 12 HCs (61.6) | 37.3 (since diagnosis) | 36.3 | Event-related design: 1.anticatch trials, 2.procatch trials, 3.correct antisaccade trials, 4.correct prosaccade trials, 5. corrected antisaccade direction errors, 6.invalid trials, fixation trials as baseline | 1. Increased activation in supplementary eye fields and frontal eye fields. 2. Reductions in DLPFC activation | The ALS group showed reduced saccadic latencies that correlated with increased activation across the oculomotor saccade system |
| Mohammadi (35) | 17 ALS (not given), 17 HCs (age matched) | NA | NA | Block design: go-stop task | 1. Stronger inhibition-related activity in inferior, superior and middle frontal gyrus, putamen and pallidum, Stronger execution-related activity in contralateral sensorimotor cortex. 2. Weaker error-related activity in bilateral insula | – |
| Stoppel (36) | 14 ALS (60.3), 14 HCs (59.7) | 18.3 | 38.2 | Block design: a modified go/no-go task at inclusion and 3 months later | 1. Patients’ motor activations were higher during the initial measurement, and declined during the 3-month interval. 2. Novelty-evoked hippocampal activity increased across 3 months | 1. There was a positive correlation between the ALSFRS-R or MRC-Megascores and the decline in motor activity, but a negative one with the hippocampal activation-increase. 2. There was a close overlap between functional alterations and structural changes by VBM |
| Raaphorst (37) | 21 ALS (60.3), 18 PMA (60.4), 17 HCs (59) | 22.2 (ALS), 26.0 (PMA) | 40.0 (ALS), 41.5 (PMA) | Block design: letter and category fluency tasks, counting backward as baseline | Letter fluency: 1.For patients with PMA, lower activation in left inferior frontal gyrus and ACC; 2. For patients with ALS, lower activation in left inferior frontal gyrus and middle frontal gyrus | – |
ACC, anterior cingulate cortex; ALS, amyotrophic lateral sclerosis; ALSFRS-R, revised ALS functional rating scale; DLPFC, dorsolateral prefrontal cortex; fMRI, functional MRI; HC, healthy control; MND, motor neuron disease; MRC, medical research council; NA, not available; PMA, progressive muscular atrophy; PMC, premotor cortex; SMA, supplementary motor area; VBM, voxel-based morphometry.