Biology subjects

Pfyffer, D.

Publications and source records attributed to Pfyffer, D..

5 recordsLinked to original sources

bioRxiv2026

Centrally generated movement-related signals engage ipsilateral S1 finger representations after tetraplegia

Ipsilateral primary somatosensory cortex (S1) exhibits somatotopically organized activity during unilateral hand movements, but whether this activity depends on peripheral input remains debated. We addressed this question using functional magnetic resonance imaging (fMRI) in 14 individuals with tetraplegia and 18 able-bodied controls. Participants performed or attempted individual finger movements during 3T fMRI. We quantified movement-related univariate activity and multivariate representational structure within ipsilateral S1. Univariate activity within the anatomically defined ipsilateral S1 hand area did not differ significantly between groups, whereas a continuous spatial analysis identified greater movement-related activity in individuals with tetraplegia in S1 bands lateral to the hand representation. Multivariate analyses revealed reliable separation of finger-specific activity patterns in both groups, with no significant group difference in mean inter-finger distance. The typicality of the overall representational geometry also did not differ significantly between groups. Finally, a person with complete hand paralysis and no measurable feeling or movement still showed clear, finger-specific brain activity patterns and a typical representation of the affected hand. Together, these findings indicate that centrally generated movement-related signals can engage finger-specific representations in ipsilateral S1 without overt movement or measurable hand-related peripheral input. Ipsilateral somatotopic activity therefore cannot be explained solely by sensory reafference from the moving hand.

neuroscience↗

bioRxiv2025

Differential encoding of noxious heat and self-reported pain along corticospinal networks: a simultaneous spinal cord-brain fMRI study

Chronic pain poses a substantial public health burden. Elucidating how the healthy central nervous system (CNS) differentially encodes objective stimulus intensity and subjective experiences of pain perception may offer key insights into the central mechanisms contributing to chronic pain. Functional MRI (fMRI) combined with controlled noxious stimulation provides a powerful means to explore neural representations of nociception and pain perception. Here, we applied noxious heat at three intensities (46 {degrees}C, 47 {degrees}C, 48 {degrees}C, 8 trials each randomized) to the right forearm of 28 healthy women during simultaneous spinal cord-brain fMRI to investigate how distributed corticospinal activity and connectivity encode stimulus intensity and subjective pain. Activity increased with stimulus temperature across regions involved in pain processing--including somatosensory, motor, prefrontal, insular, and subcortical areas--as well as in the ipsilateral dorsal and ventral spinal cord. Spinal- brain functional connectivity was observed between the right dorsal horn and pain-related brain regions such as primary and secondary somatosensory cortex, insula, anterior cingulate cortex, thalamus, and periaqueductal gray, and was positively associated with individual pain ratings. Using representational similarity analysis (RSA), we found that multivoxel activation patterns in the brain and spinal cord, as well as corticospinal connectivity patterns, reliably tracked stimulus temperature, while only subsets of cortical regions (e.g., insula, sensorimotor, and frontal cortices) encoded subjective pain. Notably, spinal cord representations were primarily organized by stimulus temperature rather than perceived pain intensity. These findings demonstrate that simultaneous spinal cord-brain fMRI combined with multivariate modeling can identify sensory and perceptual components of nociceptive processing across the neuroaxis. Such approaches advance mechanistic understanding of pain and may inform the development of CNS-based biomarkers for chronic pain assessment and intervention.

neuroscience↗

bioRxiv2025

Mapping Hand Function with Simultaneous Brain-Spinal Cord Functional MRI

INTRODUCTIONHand motor control depends on intricate brain-spinal cord interactions that regulate muscle activity. Hand function can be disrupted by injury to the brain, spinal cord, and peripheral nerves leading to weakness and impaired coordination. Functional MRI (fMRI) can map motor-related neural activity and potentially characterize the mechanisms underlying hand weakness and diminished coordination. Although brain motor control has been extensively studied, spinal cord mechanisms remain less explored. Here we use simultaneous brain-spinal cord fMRI to map neural activity related to hand strength and dexterity across the central nervous system using force matching and finger tapping tasks. This study pioneers the use of simultaneous brain-spinal cord fMRI to comprehensively map hand function, offering novel insights into coordinated motor processing across the central nervous system. METHODSWe performed simultaneous brain-spinal cord fMRI in 28 right-handed healthy volunteers (age: 40.0 {+/-} 13.8 years, 14 females, 14 males) using a 3T GE SIGNA Premier scanner equipped with a 21-channel head-neck coil. Participants performed a force-matching task at 10%, 20%, and 30% of maximum voluntary contraction using a hand dynamometer. For the finger tapping task, participants completed button-presses at 1 Hz with a 5-button response pad for three task levels: single-digit response with the second digit only (low), single-digit response with all digits in a sequential order (medium), single-digit response with all digits in a random order (high). Visual cues and feedback were provided during the tasks. Brain and spinal cord images were processed separately using FSL and the Spinal Cord Toolbox, with motion correction, physiological noise filtering, and spatial normalization to standard templates. Subject level activity maps were generated and entered into group level analyses to explore both activations and deactivations. For the brain, we used a mixed effect design with a voxelwise threshold of Z score > 3.10 and cluster threshold of p < 0.05. For the spinal cord, we used a fixed effect design with a voxelwise threshold of Z score > 1.64 and cluster threshold of p < 0.05. Region of interest (ROI) analyses were conducted to examine localized changes in activation across task levels RESULTSBoth tasks elicited activation in motor and sensory regions of the brain and spinal cord, with graded responses in the left primary motor (M1), left primary sensory (S1) cortex, and right spinal cord gray matter across task levels. Deactivation of the right M1 and S1 was also present for both tasks. Deactivation of the left spinal cord gray matter was present in the high task level of the force matching task. The ROI analysis findings complemented the group level activity maps. DISCUSSIONOur study provides a detailed map of brain-spinal cord interactions in hand function, revealing graded neural activation and inhibition patterns across motor and sensory regions. Interhemispheric inhibition, reflected in right M1 deactivation, likely restricts extraneous motor output during unilateral tasks. For force matching, the deactivation of the left ventral and dorsal horns of the spinal cord, provides the first evidence that the inhibition of motor areas during a unilateral motor task extends to the spinal cord. Whether this inhibition results from direct descending modulation from the brain or interneuronal inhibition in the cord remains to be interrogated. These findings expand our understanding of central motor control mechanisms and could inform rehabilitation strategies for individuals with motor impairments. CONCLUSIONSOur simultaneous brain-spinal cord fMRI approach provides novel insights into the neural coordination of hand function, enhancing our understanding of motor control and its modulation. This approach may offer a foundation for studying motor dysfunction in conditions such as stroke, spinal cord injury, and neurodegenerative diseases.

neuroscience↗

bioRxiv2025

EPISeg: Automated segmentation of the spinal cord on echo planar images using open-access multi-center data

Functional magnetic resonance imaging (fMRI) of the spinal cord is relevant for studying sensation, movement, and autonomic function. Preprocessing of spinal cord fMRI data involves segmentation of the spinal cord on gradient-echo echo planar imaging (EPI) images. Current automated segmentation methods do not work well on these data, due to the low spatial resolution, susceptibility artifacts causing distortions and signal drop-out, ghosting, and motion-related artifacts. Consequently, this segmentation task demands a considerable amount of manual effort which takes time and is prone to user bias. In this work, we (i) gathered a multi-center dataset of spinal cord gradient-echo EPI with ground-truth segmentations and shared it on OpenNeuro https://openneuro.org/datasets/ds005143/versions/1.3.0, and (ii) developed a deep learning-based model, EPISeg, for the automatic segmentation of the spinal cord on gradient-echo EPI data. We observe a significant improvement in terms of segmentation quality compared to other available spinal cord segmentation models. Our model is resilient to different acquisition protocols as well as commonly observed artifacts in fMRI data. The training code is available at https://github.com/sct-pipeline/fmri-segmentation/, and the model has been integrated into the Spinal Cord Toolbox as a command-line tool.

neuroscience↗

bioRxiv2021

Finger somatotopy is preserved after tetraplegia but deteriorates over time

Following spinal cord injury (SCI), the motor output flow to the limb(s) and sensory input to the brain is largely lost. While attempted movements with the paralysed and sensory deprived body part can still evoke signals in the sensorimotor system, this task-related "net" brain activity of SCI patients differs substantially from healthy controls. Such reorganised and/or altered activity is thought to reflect abnormal processing. It is however possible that this altered net sensorimotor activity in SCI patients conceals preserved somatotopically-specific representations of the paralysed and sensory deprived body parts that could be exploited in a functionally meaningful manner (e.g. via neuroprosthetics). In this cross-sectional study, we investigated whether a functional connection between the periphery and the brain is necessary to maintain somatosensory representations. We used functional MRI and an (attempted) finger movement task to characterise the somatotopic hand layout in the primary somatosensory cortex and structural MRI to assess spared spinal tissue bridges. We tested 14 tetraplegic SCI patients (mean age {+/-} s.e.m.=55 {+/-} 3.6; 1 female) who differed in terms of lesion completeness, retained sensorimotor functioning, and time since injury, as well as 18 healthy control participants (mean age {+/-} s.e.m.=56 {+/-} 3.6 years; 1 female). Our results revealed somatotopically organised representations of patients hands in which neighbouring clusters showed selectivity for neighbouring fingers in contralateral S1, qualitatively similar to those observed in healthy controls. To quantify whether these representations were normal in tetraplegic SCI patients we correlated each participants intricate representational distance pattern across all fingers (revealed using representational similarity analysis) with a canonical inter-finger distance pattern obtained from an independent sample. The resulting hand representation typicality scores were not significantly different between patients and controls. This was even true when considering two individual patients with no sensory hand functioning, no hand motor functioning, and no spared spinal tissue bridges. However, a correlational analysis revealed that over years since SCI the hand representation typicality in primary somatosensory cortex deteriorates. We show that somatosensory representations can be maintained for several years following SCI even in the absence of perhiperhal inputs. Such preserved cortical hand representations could therefore be exploited in a functionally meaningful way by rehabilitation approaches that attempt to establish new functional connections between the hand and the brain after an SCI (e.g. through neuroprosthetics). However, time since injury may critically influence the somatotopic representations of SCI patients and might thereby impact the success of such rehabilitation approaches.

neuroscience↗