Does ipsilateral remapping following hand loss impact motor control of the intact hand?

What happens once a cortical territory becomes functionally redundant? We studied how the brain and behaviour change for the remaining hand in humans (male and female) with either a missing hand from birth (one-handers) or due to amputation. Previous studies reported that in amputees, but not in one-handers, there is increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping). We used a complex finger task to explore whether this observed remapping in amputees involves recruiting more neural resources to support the intact hand to meet greater motor control demand. Using basic fMRI analysis, we found that only amputees had more ipsilateral activity when motor demand increased, however this did not match any noticeable improvement in their task performance. More advanced multivariate fMRI analysis showed that amputees had stronger and more typical representation - relative to controls' contralateral hand representation - compared to one-handers. This suggests that in amputees, both hand areas work together more collaboratively, potentially reflecting the intact hand's efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Additional white matter analysis provided conclusive evidence that the structural connectivity between the two hand areas did not vary across groups. Together, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life. Significant Statement People with congenital hand absence (one-handers) and amputees rely on their intact hand for everyday actions. This extensive daily training could result in increased motor ability, supported by neural resources within the missing-hand territory (i.e., ipsilateral to the intact hand). However, using a demanding multi-finger configuration task, we observed reduced sensorimotor learning in one-handers in the most difficult configuration. Furthermore, despite increased ipsilateral activity, amputees did not show superior intact hand motor ability. Multivariate fMRI analyses suggested a collaborative relationship between the contralateral and ipsilateral hand territories of amputees, which was unique compared to the other two groups. These results suggest that brain plasticity is limited and may depend on the availability of homologous pathways acquired early in life.