William Ryan Willoughby

Background: Spinal cord injury (SCI) results in neurodegeneration both at and above the lesion site. While cervical cord atrophy is well characterised in populations of mixed cervical, thoracic and/or lumbar injuries, the remote morphological changes in cervical cord following thoracic SCI remain unclear. The present study aimed to quantify cervical spinal cord morphology at C2–C3 in individuals with complete thoracic SCI and compare these metrics to matched controls. Methods: Participants were 52 adults with complete thoracic SCI and 55 neurologically healthy, able‐bodied controls matched for age and sex. Extracted cervical metrics included mean cross‐sectional area (CSA), antero‐posterior (AP) and right–left (RL) diameters, eccentricity, solidity, orientation and cord length. Group differences were assessed using linear mixed models adjusted for age, sex and scanning sites. Impacts of experiencing SCI‐related chronic neuropathic pain on these metrics were explored. Results: Compared to controls, the thoracic SCI group showed significantly reduced cervical CSA and AP/RL diameters, consistent with remote atrophy, and increased eccentricity, indicating a more flattened cord profile. Solidity, orientation and cord length showed no group differences, supporting metric reliability and absence of segmentation artefacts. Although no difference was evident among the SCI groups, those experiencing chronic neuropathic pain had larger eccentricity than controls. Conclusions: Complete thoracic SCI is associated with significant remote cervical cord degeneration, even in the absence of direct cervical injury. Results highlight that neurodegenerative processes propagate along ascending and descending spinal pathways. Cervical morphometry metrics, particularly CSA and eccentricity, may represent biomarkers of distal neurodegeneration following thoracic SCI and inform future therapeutic strategies.

Intracranial hemorrhage is a leading cause of long‐term disability, yet clinical focus remains on acute survival and motor recovery. Traditional prognostic tools often overlook neuropsychological sequelae such as deficits in executive function, memory, and processing speed. On the other hand, magnetic resonance imaging (MRI), with its capacity to characterize structural injury, evaluate white matter microstructural integrity, and quantify iron deposition offers a promising framework for improving neuropsychological outcome prediction after intracerebral hemorrhage (ICH).

Background: Spinal cord injury (SCI) results in neurodegeneration both at and above the lesion site. While cervical cord atrophy is well characterized in populations of mixed cervical, thoracic and/or lumbar injuries, the remote morphological changes in cervical cord following thoracic SCI remain unclear. The present study aimed to quantify cervical spinal cord morphology at C2-C3 in individuals with thoracic SCI and compare these metrics to matched controls. Methods: Participants were 60 adults with chronic thoracic SCI and 60 neurologically healthy controls matched for age and sex. Extracted cervical metrics included mean cross-sectional area (CSA), antero-posterior (AP) and right-left (RL) diameters, eccentricity, solidity, orientation, and cord length. Group differences were assessed using linear mixed models adjusted for age, sex and scanning sites. Impacts of experiencing SCI-related chronic neuropathic pain on these metrics were explored. Results: Compared to controls, the thoracic SCI group showed significantly reduced cervical CSA, along with smaller AP and RL diameters, consistent with remote atrophy. Eccentricity was increased, indicating a more flattened cord profile. Solidity, orientation, and cord length showed no group differences, supporting metric reliability and the absence of segmentation artefacts. Compared to controls, increased eccentricity was driven by people with SCI who experience chronic neuropathic pain. The presence of chronic neuropathic pain did not significantly influence other morphometric outcomes. Conclusions: Thoracic SCI is associated with significant remote cervical cord degeneration, even in the absence of direct cervical injury. Results highlight that neurodegenerative processes propagate along ascending and descending spinal pathways. Cervical morphometry metrics, particularly CSA and eccentricity, may represent biomarkers of distal neurodegeneration following thoracic SCI, and inform future therapeutic strategies.

Objective: To investigate the relationship between cerebral blood flow (CBF), seizure control, and mood regulation in idiopathic generalized epilepsy (IGE), we hypothesized that higher CBF in mood‐regulating regions would be associated with greater mood disturbance, particularly in patients with poor seizure control.Methods: Twenty‐three patients with IGE (13 female) and 19 healthy controls (HCs; 9 female) completed 3T MRI. Patients with IGE were categorized into those with seizures controlled for >6 months (IGE−) and those with ≥1 seizure in the last 6 months (IGE+). Participants completed the Profile of Mood States, with the Total Mood Disturbance (TMD) score indexing the current overall mood state. A pulsed arterial spin labeling (PASL) MRI sequence was used to measure CBF. Average CBF within emotion‐related brain regions was estimated. One‐way ANOVA tests examined the main effect of group and seizure control on CBF and TMD. Pearson correlation analyses identified relationships between CBF and TMD in the combined sample and individual groups (significant at FDR‐corrected p < 0.05).Results: Compared to HCs, IGE exhibited significantly higher TMD (mean ± SD: IGE = 57.39 ± 32.32, HC = 2.05 ± 19.86; p < 0.001) and CBF (mean ± SD: IGE = 60.20 ± 10.88, HC = 53.45 ± 10.22; p = 0.046). However, no statistically significant differences in TMD were observed between IGE+ and IGE−, although both demonstrated significantly higher TMD than HCs (both p < 0.001). Additionally, no statistically significant effect of seizure control was found on CBF. In the combined groups, TMD and CBF showed a positive correlation (r = 0.36, p = 0.019).Significance: This is the first study to investigate the relationship between mood disturbance, seizure control, and CBF in IGE. Both neurobiological and mood state measures showed significant differences between IGE patients and HCs. The relationship between greater CBF and worse mood states (higher TMD) suggests changes in CBF may be a potential biomarker for mood disturbance in epilepsy. Larger studies investigating the effects of seizure control on CBF are needed to clarify this relationship in IGE.Plain Language Summary: Patients with idiopathic generalized epilepsy (IGE) often experience mood comorbidities, such as depression and anxiety. This study aimed to investigate whether cerebral blood flow (CBF) could serve as a potential biomarker for mood disturbance in IGE. We found that patients with IGE had higher CBF and greater mood disturbance compared to healthy individuals, and that higher CBF was associated with worse mood across all participants. Our findings suggest that CBF may be a useful biomarker for mood state, providing insights that could improve the mental health outcomes for patients with IGE. However, larger studies that better account for seizure frequency are needed to assess the effects of seizure control on CBF.

Background: Neuropathic pain following spinal cord injury (SCI) affects approximately 60% of individuals with SCI. Effective pharmacological and non-pharmacological treatments remain elusive. We recently demonstrated that our immersive virtual reality walking intervention (VRWalk) may be effective for SCI NP. Additionally, we found that SCI NP may result from a decrease in thalamic γ-aminobutyric-acid (GABA), which disturbs central sensorimotor processing. Objective: While we identified GABAergic changes associated with SCI NP, a critical outstanding question is whether a decrease in SCI NP generated by our VRWalk intervention causes GABA content to rise. Method: A subset of participants (n = 7) of our VRWalk trial underwent magnetic resonance spectroscopy pre- and post-VRWalk intervention to determine if the decrease in SCI NP is associated with an increase in thalamic GABA. Results: The findings revealed a significant increase in thalamic GABA content from pre- to post-VRWalk treatment. Conclusion: While the current findings are preliminary and should be interpreted with caution, pre- to post-VRWalk reductions in SCI NP may be mediated by pre- to post-treatment increases in thalamic GABA by targeting and normalizing maladaptive sensorimotor cortex reorganization. Understanding the underlying mechanisms of pain recovery can serve to validate the efficacy of home-based VR walking treatment as a means of managing pain following SCI. Neuromodulatory interventions aimed at increasing thalamic inhibitory function may provide more effective pain relief than currently available treatments.

Background: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end‐stage liver disease. NAFLD diagnosis and follow‐up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments.Purpose/Hypothesis: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors.Study Type: Cohort.Subjects: Four community‐dwelling adults with obesity.Field strength/Sequence: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE.Assessment: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing.Statistical Tests: Linear regression in MATLAB, ICC analyses using SAS 9.4, one‐sided 95% confidence intervals for the ICC.Results: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF.Conclusions: We demonstrated harmonization of PDFF, MRS, and MRE‐based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD.Level of Evidence: 2Technical Efficacy Stage: 2

Functional magnetic resonance imaging (fMRI) was used to estimate neuronal activity in the primary somatosensory cortex of six participants undergoing cutaneous tactile stimulation on skin areas spread across the entire body. Differences between the accepted somatotopic maps derived from Penfield's work and those generated by this fMRI study were sought, including representational transpositions or replications across the cortex. MR-safe pneumatic devices mimicking the action of a Wartenberg wheel supplied touch stimuli in eight areas. Seven were on the left side of the body: foot, lower, and upper leg, trunk beneath ribcage, anterior forearm, middle fingertip, and neck above the collarbone. The eighth area was the glabella. Activation magnitude was estimated as the maximum cross-correlation coefficient at a certain phase shift between ideal time series and measured blood oxygen level dependent (BOLD) time courses on the cortical surface. Maximally correlated clusters associated with each cutaneous area were calculated, and cortical magnification factors were estimated. Activity correlated to lower limb stimulation was observed in the paracentral lobule and superomedial postcentral region. Correlations to upper extremity stimulation were observed in the postcentral area adjacent to the motor hand knob. Activity correlated to trunk, face and neck stimulation was localized in the superomedial one-third of the postcentral region, which differed from Penfield's cortical homunculus.

A bstract: Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to investigate cortical activity associated with peripheral tactile stimuli in a small cohort of healthy humans. MR-safe automated pneumatic stimulators modeled after the Wartenberg pinwheel were used to generate tactile stimuli at regular intervals on eight disparate areas of skin. The phase-encoded BOLD responses of voxels in the cerebral cortex were characterized by the maximal normalized cross-correlation coefficients at time delays between an idealized response and the measure time course. Overall at the group level, the somatotopic organization of the somatosensory cortex (SI) follows the accepted homunculus model, but a noticeable amount of variation was observed between individual study participants. The surface areas of cortical regions in SI activated by tactile stimulation of different body parts were calculated, giving an estimate of cortical magnification factors. Data collected with the participant actively attending the stimuli were compared to data collected before the attention task. No significant attention-related changes were observed in the somatotopic maps or in time courses of voxels well-correlated to stimuli.