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Resting-state functional MRI (rsfMRI) has recently revealed correlated signals in the spinal cord horns of monkeys and humans. However, the interpretation of these rsfMRI correlations as indicators of functional connectivity in the spinal cord remains unclear. Here, we recorded stimulus-evoked and spontaneous spiking activity and local field potentials (LFPs) from monkey spinal cord in order to validate fMRI measures. We found that both BOLD and electrophysiological signals elicited by tactile stimulation co-localized to the ipsilateral dorsal horn. Temporal profiles of stimulus-evoked BOLD signals covaried with LFP and multiunit spiking in a similar way to those observed in the brain. Functional connectivity of dorsal horns exhibited a U-shaped profile along the dorsal-intermediate-ventral axis. Overall, these results suggest that there is an intrinsic functional architecture within the gray matter of a single spinal segment, and that rsfMRI signals at high field directly reflect this underlying spontaneous neuronal activity. Resting-state fMRI shows networks of correlated activity in the spinal cord, similar to those in the brain, but whether fMRI is a valid measure of functional connectivity in spinal cord is unclear. Here, the authors show that fMRI corresponds well to electrophysiological measures of spinal cord activity.

BackgroundSeveral studies have reported brain activations and functional connectivity (FC) during micturition using functional magnetic resonance imaging (fMRI) and concurrent urodynamics (UDS) testing. However, due to the invasive nature of UDS procedure, non-invasive resting-state fMRI is being explored as a potential alternative. The purpose of this study is to evaluate the feasibility of utilizing resting states as a non-invasive alternative for investigating the bladder-related networks in the brain.MethodsWe quantitatively compared FC in brain regions belonging to the bladder-related network during the following states: ‘strong desire to void’, ‘voiding initiation (or attempt at voiding initiation)’, and ‘voiding (or continued attempt of voiding)’ with FC during rest in nine multiple sclerosis women with voiding dysfunction using fMRI data acquired at 7 T and 3 T.ResultsThe inter-subject correlation analysis showed that voiding (or continued attempt of voiding) is achieved through similar network connections in all subjects. The task-based bladder-related network closely resembles the resting-state intrinsic network only during voiding (or continued attempt of voiding) process but not at other states.ConclusionResting states fMRI can be potentially utilized to accurately reflect the voiding (or continued attempt of voiding) network. Concurrent UDS testing is still necessary for studying the effects of strong desire to void and initiation of voiding (or attempt at initiation of voiding).

Colorectal cancer is the third most commonly diagnosed cancer in the world that affects both men and women. Approximately 40% of colorectal cancer patients exhibit cognitive impairment in executive functions including verbal learning, verbal memory, and information processing that is independent of chemotherapy. However, little information is currently available regarding the neural mechanisms underlying colorectal cancer-related cognitive decline (CRCD). In this study, we utilized highly sensitive 7 Tesla magnetic resonance imaging methods combined with standardized cognitive assessments to investigate the changes in brain local functional connectivity in early-stage colorectal cancer survivors compared to healthy controls. We observed that early-stage colorectal cancer survivors exhibited increased regional homogeneity (ReHo) in the left hippocampus, parahippocampal gyrus, and inferior temporal gyrus, along with decreased ReHo in the left inferior frontal gyrus, which were associated with reduced verbal memory performance compared to healthy controls. Furthermore, survivors exhibited significantly weaker inter-regional functional connectivity, suggesting a potential disruption in coordination among regions critical for verbal memory. Collectively, these findings indicate a maladaptive mechanism in the medial temporal lobes that is associated with declines in verbal memory processes among colorectal cancer survivors. ReHo analysis was found to be a valuable tool for characterizing the neurophysiological basis of colorectal CRCD and presents the medial temporal lobe as a promising target for therapeutic interventions.

The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young’s modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.

Background Voiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a non-invasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the feasibility of a TRPMS trial to address lower urinary tract symptoms in MS patients, through investigating the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals. Methods Ten adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient’s baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive 10 40-min treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement. Discussion Despite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future. Trial registration This trial is registered at ClinicalTrials.Gov ( NCT03574610 , 2 July 2018.) and Houston Methodist Research Institute IRB (PRO00019329)

Subjective cognitive decline (SCD) is one of the earliest noticeable symptoms of AD and is defined as having self-perceived worsening of cognition without exhibiting objective impairments on standardized clinical cognitive tests (PMID: 31958406). Since not all individuals with SCD will convert into MCI or AD, it is important to accurately characterize and model the subtle changes in SCD brains that may be predictive of future trajectory towards AD. Longitudinal MRI data and AD Assessment Scale (ADAS-Cog) scores from 70 subjects with SCD and 100 healthy controls (HC) were acquired from the ADNI 2 and 3 database. Standard resting-state fMRI pre-processing and calculations of 3D regional homogeneity (ReHo) based on 27 neighboring voxels was performed using Data Processing & Analysis for Brain Imaging (DPABI) while site effects were minimized via CovBat harmonization (PMID: 37086875). Within a gray matter mask, two sample t-tests were performed between the HC and SCD groups' ReHo maps using FSL's randomization procedure with 5000 permutations where age, sex, head motion, and voxel-wise GM volume were included as covariates. Significance levels were adjusted for multiple comparisons using threshold-free cluster enhancement correction. An ordinary least squares regression (OLS) model was developed for predicting future ADAS-Cog scores based on baseline (year 0) clinical scores and ReHo values. At baseline compared to HC, SCD revealed significant ReHo decreases in the frontal and occipital regions along with significant increases in the temporal regions (Table 1). Correlation maps of SCD ReHo and ADAS-Cog scores indicated negative correlations in the bilateral insula and temporal regions along with positive correlations in the medial parietal regions (Figure 1). The OLS model developed from these features and baseline clinical scores was able to predict ADAS-Cog scores at year 4 with a goodness-of-fit (r ) of 0.72 among a randomized 50:50 training and test set. Independently, the model's r based on baseline clinical scores alone was 0.64. ReHo reflects neural synchronization within localized regions, providing insights into brain network coherence. Individuals with SCD exhibit significantly different resting-state ReHo features compared to HCs. With predictive modeling, these ReHo features can help augment the long-term projection of early AD trajectories.

Background Subjective cognitive decline (SCD) is one of the earliest noticeable symptoms of AD and is defined as having self‐perceived worsening of cognition without exhibiting objective impairments on standardized clinical cognitive tests (PMID: 31958406). Since not all individuals with SCD will convert into MCI or AD, it is important to accurately characterize and model the subtle changes in SCD brains that may be predictive of future trajectory towards AD. Method Longitudinal MRI data and AD Assessment Scale (ADAS‐Cog) scores from 70 subjects with SCD and 100 healthy controls (HC) were acquired from the ADNI 2 and 3 database. Standard resting‐state fMRI pre‐processing and calculations of 3D regional homogeneity (ReHo) based on 27 neighboring voxels was performed using Data Processing & Analysis for Brain Imaging (DPABI) while site effects were minimized via CovBat harmonization (PMID: 37086875). Within a gray matter mask, two sample t‐tests were performed between the HC and SCD groups' ReHo maps using FSL's randomization procedure with 5000 permutations where age, sex, head motion, and voxel‐wise GM volume were included as covariates. Significance levels were adjusted for multiple comparisons using threshold‐free cluster enhancement correction. An ordinary least squares regression (OLS) model was developed for predicting future ADAS‐Cog scores based on baseline (year 0) clinical scores and ReHo values. Result At baseline compared to HC, SCD revealed significant ReHo decreases in the frontal and occipital regions along with significant increases in the temporal regions (Table 1). Correlation maps of SCD ReHo and ADAS‐Cog scores indicated negative correlations in the bilateral insula and temporal regions along with positive correlations in the medial parietal regions (Figure 1). The OLS model developed from these features and baseline clinical scores was able to predict ADAS‐Cog scores at year 4 with a goodness‐of‐fit (r2) of 0.72 among a randomized 50:50 training and test set. Independently, the model's r2 based on baseline clinical scores alone was 0.64. Conclusion ReHo reflects neural synchronization within localized regions, providing insights into brain network coherence. Individuals with SCD exhibit significantly different resting‐state ReHo features compared to HCs. With predictive modeling, these ReHo features can help augment the long‐term projection of early AD trajectories.

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology.

Introduction There is converging evidence that motor-skill learning is consolidated by sleep spindles during non-rapid eye movement stage 2 (N2) sleep, resulting in improved post-sleep performance. We localized learning-related changes in spindle activity with source localization of simultaneous electroencephalogram (EEG) and magnetoencephalography (MEG) recordings of motor performance and the sleep that followed to identify cortical regions involved in consolidating a finger tapping motor sequence task (MST). Methods Fifteen healthy individuals (age 29.2 ± 4.6 years, 11 males) had a structural MRI and underwent three EEG/MEG sessions, including an adaptation, a non-learning baseline and an MST nap. During the MST visit, participants trained on the MST with their left hand and were tested after a 90 min nap. MST task-activated areas were identified based on mu (8-13 Hz) suppression during tapping compared to rest. We reconstructed cortical source signals during N2 sleep using MRI-anatomically constrained dynamic statistical parametric mapping, and localized spindles in the source space. We then compared spindle density during baseline and MST naps, and the relations of spindle changes to overnap MST improvement. Results MST-training activated different cortical areas than post-sleep MST-testing. While training activated bilateral premotor, primary motor (M1) and primary sensory (S1) cortices, testing activated left M1 and right parietal and prefrontal cortex. Compared to the baseline nap, during the MST nap spindle density increased significantly in MST task-activated (training + testing) areas. In addition, in two regions showing MST activation, pre-supplementary motor area (pre-SMA) and dorsal anterior cingulate cortex (dACC), the change in spindle density between MST and baseline visits correlated with overnap improvement. In contrast, in right premotor and S1, the spindle density change inversely correlated with overnap improvement. Conclusion Motor learning enhances N2 spindle activity in cortical regions involved in task performance and these changes predict sleep-dependent performance improvement. In the right hemisphere, spindle increases in pre-SMA and dACC are associated with task improvement, while spindle increases in premotor and S1 are associated with decreased improvement. Finally, sleep-dependent motor-skill consolidation changes the network involved in task performance. Support (If Any)

Introduction and aim Observational studies have associated oral anticholinergic medications for overactive bladder (OAB) with cognitive impairment. This is the first pilot trial to compare the effects of two classes of OAB medications on brain activity in women. We evaluated the effect of anticholinergic versus non-anticholinergic (Non-Ach) interventions on regional brain activation during a cognitive task. Methods Twelve cognitively normal women seeking OAB therapy were recruited to a randomized, double-blind, parallel, controlled pilot trial. Whole-brain regional activity at baseline and 29 ± 1 days postintervention was assessed with functional magnetic resonance imaging during a working memory task. Average activation strength by region was compared after anticholinergic, beta-3 agonist, or placebo. Two-way ANOVA compared effects of group and time on average activation strength in anticholinergic versus Non-Ach (beta-3 agonists or placebo) groups. Results The mean (SD) age and body mass index of 12 women were 61 (7) years and 36 (7) kg/m 2 . Baseline depression and learning scores differed in the anticholinergic group ( n = 3) versus the Non-Ach group ( n = 9). Right mamillary body activation postintervention was higher after Non-Ach exposure (F 4.9, p < 0.04). In the full sample of participants at follow-up, there was less activation of the right middle frontal gyrus ( p = 0.02), superior frontal gyrus ( p < 0.01), and supramarginal ( p < 0.01) gyrus. Conclusion Activation strength in brain regions underlying working memory was lower over time, and recognition scores improved. A powered trial is needed to adequately evaluate for differential effects of OAB oral medications on regional brain activation.