Biology subjects

Brooks, J. C. W.

Publications and source records attributed to Brooks, J. C. W..

8 recordsLinked to original sources

bioRxiv2025

Test-retest reliability of sensorimotor activity measured with spinal cord fMRI

Establishing the reliability of spinal cord functional magnetic resonance imaging (fMRI) is critical before employing it to assess experimental or clinical interventions. Previous studies have mapped human motor activity primarily to the ipsilateral ventral horn, aligning with myotomal and dermatomal projections. Despite these insights, the test-retest reliability of spinal fMRI remains under-investigated. Here we assessed spinal cord activation during a sensorimotor paradigm involving right-hand grasping and grip force estimation in 30 healthy volunteers. Participants completed two identical scanning visits, each time performing the same task twice, enabling the investigation of test-retest reliability both within a single experimental visit and between visits performed on different days. Aggregating all task runs, motor-evoked activation was observed in ipsilateral ventro-dorsal regions of spinal segmental levels C5-T1, as well as in medial regions of levels C2-C3. Despite highly reliable task performance (grip force) and fMRI signal quality (temporal signal-to-noise ratio), the reliability of motor activation was predominantly poor-to-fair both within and between visits, with notable variability in spatial distribution observed across task runs. Increasing the number of task runs per individual improved the robustness of group-level activation, as indexed by higher activated voxel count, larger cluster spatial extent, and attenuated t-statistic distribution. Although we demonstrated that motor-evoked activation corresponds to the known neuroanatomical organisation of motor circuits, its low test-retest reliability presents a challenge for wider applications of spinal fMRI. Understanding the drivers of low reliability in functional imaging is warranted, but we suggest that looking beyond measurement error is required, including careful consideration of inherent within-individual variability underpinned by neurophysiological and psychological factors.

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↗

bioRxiv2024

Cortico-spinal Mechanisms of Periphery Neuromodulation induced Analgesia

BackgroundTranscutaneous Electrical Nerve Stimulation (TENS) is widely used for pain management, yet how different parameters--Conventional (high frequency, low intensity) versus Acupuncture-Like (low frequency, high intensity)--modulate pain remains controversial. These modes produce variable analgesic effects, but their underlying brain-spinal mechanisms are unclear. Clarifying these pathways could refine TENS protocols, optimize clinical outcomes, and reduce opioid reliance, highlighting the need for more precise, non-pharmacological approaches to advanced pain care. MethodsThis single-blind, three-arm randomized trial recruited 95 healthy adults (18-30 years) and assigned them (1:1:1) to Conventional TENS, Acupuncture-Like TENS, or sham. Participants underwent a 30-minute TENS intervention on the left forearm (C5-C6 dermatome) with simultaneous brain-spinal fMRI before and after thermal nociceptive stimuli. The primary outcomes were changes in Numeric Rating Scale (NRS) pain scores and brain-spinal BOLD signals. Secondary outcomes included psycho-physiological interaction (PPI) and mediation analyses of periaqueductal gray (PAG) activity and brain- cord connectivity. FindingsBoth TENS modes significantly reduced pain but engaged distinct cortico-spinal pathways. Conventional TENS yielded local analgesia via dlPAG-driven spinal inhibition plus partial cortical involvement (PAG-vmPFC). By contrast, Acupuncture-Like TENS produced diffuse analgesia through vlPAG-linked top-down modulation reliant on spinal gating. Correlation and mediation analyses confirmed that Conventional TENS integrates spinal and cortical synergies, whereas Acupuncture-Like TENS is dominated by robust descending control. InterpretationDifferent TENS parameters yield distinct analgesic mechanisms. Conventional TENS couples direct spinal inhibition with partial cortical regulation, while Acupuncture-Like TENS relies heavily on top-down pathways passing through the spinal cord. Recognizing these unique descending networks can guide targeted TENS protocols for diverse pain conditions, optimizing clinical outcomes and reducing reliance on pharmacological approaches. FundingsThis work was supported by the National Key R&D Program of China (2022YFC3500603), the National Natural Science Foundation of China (32071061, 82072010, 82030121 and 32100861, 82330057), the Beijing Natural Science Foundation (IS23108, JQ22018).

neuroscience↗

bioRxiv2023

A novel implementation of spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test-retest reliability study

Resting fMRI studies have identified intrinsic spinal cord activity, which forms organised motor (ventral) and sensory (dorsal) resting-state networks. However, to facilitate the use of spinal fMRI in, for example, clinical studies, it is crucial to first assess the reliability of the method, particularly given the unique anatomical, physiological, and methodological challenges associated with acquiring the data. Here we demonstrate a novel implementation for acquiring BOLD-sensitive resting-state spinal fMRI, which was used to characterise functional connectivity relationships in the cervical cord and assess their test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways: (1) by extracting the mean timeseries from anatomically constrained seed masks and estimating voxelwise connectivity maps and (2) by calculating seed-to-seed correlations between extracted mean timeseries. Seed regions corresponded to the four grey matter horns (ventral/dorsal and left/right) of C5-C8 segmental levels. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC) in the following ways: for each voxel in the cervical spine; each voxel within an activated cluster; the mean signal as a summary estimate within an activated cluster; and correlation strength in the seed-to-seed analysis. Spatial overlap of clusters derived from voxelwise analysis between sessions was examined using Dice coefficients. Following voxelwise analysis, we observed distinct unilateral dorsal and ventral organisation of cervical spinal resting-state networks that was largely confined in the rostro-caudal extent to each spinal segmental level, with more sparse connections observed between segments (Bonferroni corrected p < 0.003, threshold-free cluster enhancement with 5000 permutations). Additionally, strongest correlations were observed between within-segment ipsilateral dorso-ventral connections, followed by within-segment dorso-dorsal and ventro-ventral connections. Test-retest reliability of these networks was mixed. Reliability was poor when assessed on a voxelwise level, with more promising indications of reliability when examining the average signal within clusters. Reliability of correlation strength between seeds was highly variable, with highest reliability achieved in ipsilateral dorso-ventral and dorso-dorsal/ventro-ventral connectivity. However, the spatial overlap of networks between sessions was excellent. We demonstrate that while test-retest reliability of cervical spinal resting-state networks is mixed, their spatial extent is similar across sessions, suggesting that these networks are characterised by a consistent spatial representation over time.

neuroscience↗

bioRxiv2021

Automated slice-specific z-shimming for fMRI of the human spinal cord

Functional magnetic resonance imaging (fMRI) of the human spinal cord faces many challenges, such as signal loss due to local magnetic field inhomogeneities. This issue can be addressed with slice-specific z-shimming, which compensates for the dephasing effect of the inhomogeneities using a slice-specific gradient pulse. Here, we aim to address outstanding issues regarding this technique by evaluating its effects on several aspects that are directly relevant for spinal fMRI and by developing two automated procedures in order to improve upon the time-consuming and subjective nature of manual selection of z-shims: one procedure finds the z-shim that maximizes signal intensity in each slice of an EPI reference-scan and the other finds the through-slice field inhomogeneity for each EPI-slice in field map data and calculates the required compensation gradient moment. We demonstrate that the beneficial effects of z-shimming are apparent across different echo times, hold true for both the dorsal and ventral horn, and are also apparent in the temporal signal-to-noise ratio (tSNR) of EPI time-series data. Both of our automated approaches were faster than the manual approach, lead to significant improvements in gray matter tSNR compared to no z-shimming and resulted in beneficial effects that were stable across time. While the field-map-based approach performed slightly worse than the manual approach, the EPI-based approach performed as well as the manual one and was furthermore validated on an external corticospinal data-set (N>100). Together, automated z-shimming may improve the data quality of future spinal fMRI studies and lead to increased reproducibility in longitudinal studies.

neuroscience↗

bioRxiv2020

An Age-Specific Atlas for Delineation of White Matter Pathways in Children Aged 6-8 Years

Diffusion MRI allows non-invasive assessment of white matter maturation in typical development and of white matter damage due to brain injury or pathology. Probabilistic white matter atlases provide delineation of white matter tracts, allowing diffusion metrics to be measured in specific white matter pathways. However, given the known age-dependency of developmental change in white matter it may not be optimal to use an adult template when assessing data acquired from children. This study develops an age-specific probabilistic white matter atlas for delineation of 12 major white matter tracts in children aged 6-8 years. By comparing to subject-specific tract tracing in two validation cohorts, we demonstrate that this age-specific atlas gives better overall performance than simply registering to the Johns Hopkins University adult white matter template. Specifically, when normalising diffusion data acquired from children to an adult template, estimates of fractional anisotropy (FA) values for corticospinal tract, uncinate fasciculus, forceps minor, cingulate gyrus part of the cingulum and anterior thalamic radiation were all less accurate than those obtained when using an age-specific atlas, potentially leading to false negatives when performing group comparisons. We then applied the newly developed atlas to compare FA between children treated with therapeutic hypothermia for neonatal encephalopathy and age-matched controls, which revealed significant reductions in the fornix, the left superior longitudinal fasciculus, and both the hippocampal and cingulum parts of the left cingulate gyrus. To our knowledge, this is the first publicly available probabilistic atlas of white matter tracts for this age group.

neuroscience↗

bioRxiv2020

Sensory and motor electrophysiological mapping of the cerebellum in humans.

Damage to the cerebellum during posterior fossa surgery can lead to ataxia and in paediatric cases, the risk of cerebellar mutism syndrome. Animal electrophysiological and human imaging studies have shown compartmentalisation of sensorimotor and cognitive functions within the cerebellum. In the present study, electrophysiological monitoring of sensory and motor pathways was carried out to assess the location of limb sensorimotor representation within the human cerebellum, as a potential approach for real time assessment of neurophysiological integrity to reduce the incidence of cerebellar surgical morbidities. Thirteen adult and paediatric patients undergoing posterior fossa surgery were recruited. For sensory mapping (n=8), electrical stimulation was applied to the median nerves, the posterior tibial nerves, or proximal and distal limb muscles and evoked field potential responses were sought on the cerebellar surface. For motor mapping (n=5), electrical stimulation was applied to the surface of the cerebellum and evoked EMG responses were sought in facial and limb muscles. Evoked potentials on the cerebellar surface were found in two patients (25% of cases). In one patient, the evoked response was located on the surface of the right inferior posterior cerebellum in response to stimulation of the right leg. In the second patient, stimulation of the extensor digitorum muscle in the left forearm evoked a response on the surface of the left inferior posterior lobe. In the motor mapping cases no evoked EMG responses could be found. Intraoperative electrophysiological mapping, therefore, indicates it is possible to record evoked potentials on the surface of the human cerebellum in response to peripheral stimulation.

neuroscience↗

bioRxiv2020

Parallel cortical-brainstem pathways to attentional analgesia

Pain perception is diminished when attention is diverted. Our previous human fMRI study, using a 2x2 factorial design with thermal stimuli and concurrent visual attention task, linked the brainstem triad of locus coeruleus (LC), rostroventromedial medulla (RVM) and periaqueductal grey (PAG) to attentional analgesia. This study was repeated with a larger cohort, replicating our earlier findings. Pain intensity was encoded by the RVM, whilst activity in the contralateral LC correlated with the magnitude of attentional analgesia. Psycho-Physiological Interaction analysis informed subsequent Dynamic Causal Modelling and identified two parallel paths between forebrain and the brainstem regions involved in analgesia. These cortico-brainstem connections were modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) - right-LC loop, and a top-down influence of task on ACC-PAG-RVM. Under conditions of competing attentional demands the ACC recruits discrete brainstem circuits to modulate nociceptive input.

neuroscience↗