Preservation of Neural Activation Along the Somatosensory Processing Stream After Tetraplegia

198 

Abstract Submission 

Paige Howell^1,2,3, Finn Rabe¹, Simon Schading^2,3, Sarah Meissner¹, Patrick Freund^2,3, Nicole Wenderoth^1,3,4, Sanne Kikkert^1,3,2

¹Neural Control of Movement Lab, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland, ²Spinal Cord Injury Center Balgrist, University Hospital Zürich, Zürich, Switzerland, ³Neuroscience Center Zürich, University of Zürich and ETH Zürich, Zürich, Switzerland, ⁴Future Health Technologies, Singapore-ETH Centre, Campus for Research Excellence and Technological Enterprise (CREATE), Singapore, Singapore

Paige Howell  
Neural Control of Movement Lab, Swiss Federal Institute of Technology (ETH)|Spinal Cord Injury Center Balgrist, University Hospital Zürich|Neuroscience Center Zürich, University of Zürich and ETH Zürich
Zürich, Switzerland|Zürich, Switzerland|Zürich, Switzerland

Finn Rabe  
Neural Control of Movement Lab, Swiss Federal Institute of Technology (ETH)
Zürich, Switzerland

Simon Schading  
Spinal Cord Injury Center Balgrist, University Hospital Zürich|Neuroscience Center Zürich, University of Zürich and ETH Zürich
Zürich, Switzerland|Zürich, Switzerland

Sarah Meissner  
Neural Control of Movement Lab, Swiss Federal Institute of Technology (ETH)
Zürich, Switzerland

Patrick Freund  
Spinal Cord Injury Center Balgrist, University Hospital Zürich|Neuroscience Center Zürich, University of Zürich and ETH Zürich
Zürich, Switzerland|Zürich, Switzerland

Nicole Wenderoth  
Neural Control of Movement Lab, Swiss Federal Institute of Technology (ETH)|Neuroscience Center Zürich, University of Zürich and ETH Zürich|Future Health Technologies, Singapore-ETH Centre, Campus for Research Excellence and Technological Enterprise (CREATE)
Zürich, Switzerland|Zürich, Switzerland|Singapore, Singapore

Sanne Kikkert  
Neural Control of Movement Lab, Swiss Federal Institute of Technology (ETH)|Neuroscience Center Zürich, University of Zürich and ETH Zürich|Spinal Cord Injury Center Balgrist, University Hospital Zürich
Zürich, Switzerland|Zürich, Switzerland|Zürich, Switzerland

Following a spinal cord injury (SCI), individuals experience a partial or complete loss of sensorimotor function below the level of injury. This sensory deprivation has long been considered a major driving force for plasticity within the brain (Merzenich et al., 1983). However, in apparent contrast to the notion of deprivation-driven plasticity, we previously found that tetraplegic patients, who lack sensorimotor hand function, could activate somatotopic hand representations in the primary somatosensory cortex (S1) through attempted hand movements (Kikkert et al., 2021). This finding demonstrates that intracortical, i.e., top-down, processes may drive somatotopic activity within S1. While the somatosensory stream primarily relies on bottom-up input, research in cats and primates has indicated that it is also subject to descending cortical modulation through corticothalamic and corticocuneate projections (Liao et al., 2021; Aguilar et al., 2003). It remains unknown to what extent similar top-down processing may activate thalamic and brainstem somatosensory nuclei in humans and whether this processing remains preserved following SCI. Here, we tested the hypothesis that attempted movements in tetraplegic patients, engaging the somatosensory processing stream via a top-down pathway, leads to preserved activation within the ventroposterior lateral (VPL) nuclei of the thalamus and the cuneate nuclei of the brainstem.

We used 3T fMRI (2mm³ resolution) in sixteen chronic tetraplegic patients (mean age ± s.e.m.=52.4 ± 3.5 years) and twenty age-, sex-, and handedness-matched able-bodied control participants (mean age=50.8 ± 3.5 years). The patient sample was heterogeneous in terms of neurological level of injury (C1-C7), the severity of neurological loss (ASIA A-D), and retained hand functioning (GRASSP score 22-188, normal function = 232). Participants were visually cued to make overt or attempted right- and left-hand movements in a blocked-design fashion. We used a region-of-interest approach to analyse right- and left-hand movement activity within the ipsi- and contralateral somatosensory hand nuclei of the brainstem, thalamus and S1. Additionally, we assessed clinical and behavioural traits to explore how they may correlate with functional activation.

We found a clear laterality of hand activity in controls, with significantly higher activation within the ipsilateral cuneate nucleus, contralateral VPL nucleus and the contralateral S1 hand cortex as compared to the opposing stream. Importantly, this canonical pattern of hand activation was similar in tetraplegic patients, suggesting preserved hand representations along the somatosensory processing stream. Indeed, similar activity was observed even within patients with a complete absence of incoming sensory input, suggesting that top-down processing drives activation across the somatosensory processing stream through corticothalamic and corticocuneate projections. Notably, we did not observe any significant correlations between clinical measures and the amount of activation.

Our results reveal preserved activation of the hand somatosensory relay nuclei of tetraplegic patients despite absent or only partially intact transmission of sensory input. This suggests, for the first time, that mere cortical processing can selectively activate the VPL and cuneate nuclei in humans. This finding goes beyond the literature on preserved cortical representations after a loss of sensorimotor function and demonstrates that sensorimotor processing is also preserved subcortically. The results support recent work in non-human primate SCI models, showing that anatomical corticocuneate projections can be preserved post-SCI. Given the sensory gating function of the cuneate nucleus, these findings are also clinically relevant for rehabilitation treatments that attempt to restore somatosensation through the enhanced transmission of spared or restored sensory inputs post-SCI.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ¹

Motor Behavior Other

BOLD fMRI

Perception: Tactile/Somatosensory ²

FUNCTIONAL MRI

Movement Disorder

Neurological

Plasticity

Somatosensory

Spinal Cord

Other - Sensorimotor, Somatotopy