Authors
Howell, P., Farner, L., Rabe, F., Freund, P., Wenderoth, N., Gerritzen-Kikkert, S.
Abstract
The early somatosensory nuclei of the brainstem and thalamus are traditionally considered relays of bottom-up peripheral input, yet animal studies indicate that they also receive top-down cortical projections. Whether such top-down processing exists in humans remains unknown. Here, we used cervical spinal cord injury (SCI), in which peripheral somatosensory input is reduced or absent while cortical representations are preserved, to test whether top-down processing can elicit activation across the somatosensory nuclei. We combined 3 Tesla functional and quantitative MRI data to assess activity and structural integrity along the somatosensory hand pathway in 16 individuals with chronic cervical SCI (mean age +/- s.e.m. = 52.4 +/- 3.5 years) and 20 age-, sex-, and handedness-matched able-bodied control subjects (mean age = 50.8 +/- 3.5 years). Participants were visually cued to make overt or, in cases of hand paralysis, attempted right- and left-hand movements. We quantified activation across the cuneate nucleus, ventroposterior lateral thalamus, and primary somatosensory hand cortex, and assessed macro- and microstructural indices sensitive to myelin and tissue integrity (MTsat, R2*). Despite reduced or absent peripheral input, SCI participants exhibited robust and lateralised activation across all levels of the somatosensory pathway. This pattern persisted even in a participant with complete hand paralysis who lacked bottom-up afferent input during the fMRI task, indicating that top-down processing alone is sufficient to drive activity in early somatosensory relays. We simultaneously observed structural degeneration in the cuneate nucleus of SCI participants, marked by reductions in volume and myelin-sensitive metrics, suggestive of secondary degeneration. The extent of atrophy was related to time since injury and reduced sensorimotor hand function, but showed no significant relationship with functional activation, suggesting that preserved corticocuneate signalling is not dependent on the degree of structural degeneration. Together, these findings provide the first evidence in humans that the cuneate nuclei are subject to both bottom-up and top-down somatosensory processing. Although these nuclei are vulnerable to structural atrophy following dorsal column injury, our results suggest that top-down processing remains intact decades after spinal cord injury. This may have implications for the development of rehabilitation treatments targeting preserved somatosensory processing after injury.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 23 Apr 2026.
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