Top-down processing alone activates the early somatosensory nuclei

Abstract

The early somatosensory brainstem and thalamic nuclei are classically viewed as relays of peripheral input, yet research in animal models indicates they also receive top-down cortical signals. Whether such processing exists in humans remains unknown. Using cervical spinal cord injury (SCI), in which peripheral somatosensory input is reduced or absent while cortical processing is preserved, we tested 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 properties along the somatosensory hand pathway in a cross-sectional study of 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. Activation was quantified across the cuneate nucleus, ventroposterior lateral thalamus, and primary somatosensory hand cortex, while structural properties were assessed using quantitative MRI measures sensitive to myelin and tissue integrity, including magnetisation transfer saturation (MTsat) and effective transverse relaxation rate (R2*), alongside morphometric measures. 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 reduced volume and myelin-sensitive metrics (MTsat and R2*), consistent with 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. This provides the first evidence that the cuneate nuclei in humans 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 SCI. This may have implications for the development of rehabilitation treatments targeting preserved somatosensory processing after injury.