The effect of age on alpha rhythms in the human brain derived from source localized resting-state electroencephalography.

With increasing age, peak alpha frequency (PAF) is slowed, and alpha power is reduced during resting-states with eyes closed. These age-related changes are evident across the whole scalp but remained unclear at the source level. The purpose of this study was to determine whether age impacts the power and frequency of the dominant alpha rhythm equally across source generators or whether the impact of age varies across sources. A total of 28 young adults and 26 elderly adults were recruited. High-density EEG was recorded for 10 mins with eyes closed. Single dipoles for each independent component were localized and clustered based on their anatomical label, resulting in 36 clusters. Meta-analyses were then conducted to assess effect sizes for PAF and power at PAF for all 36 clusters. Subgroup analyses were then implemented for frontal, sensorimotor, parietal, temporal, and occipital regions. The results of the meta-analyses showed that the elderly group exhibited slower PAF and less power at PAF compared to the young group. Subgroup analyses revealed age effects on PAF in parietal (g = 0.38), temporal (g = 0.65), and occipital regions (g = 1.04), with the largest effects observed in occipital regions. For power at PAF, age effects were observed in sensorimotor (g = 0.84) and parietal regions (g = 0.80), with the sensorimotor region showing the largest effect. Our findings show that age-related slowing and attenuation of the alpha rhythm manifests differentially across cortical regions, with sensorimotor and occipital regions most susceptible to age effects.

Diffusion MRI relates to plasma Aß42/40 in PET negative participants without dementia.

INTRODUCTION: Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-ß (Aß42/40) positivity in Aß positron emission tomography (PET) negative individuals. METHODS: Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aß plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS: Plasma+/PET- demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma-/PET-. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET-. Composite brain FW correlated with plasma Aß42/40 and p-tau181. DISCUSSION: FW imaging changes distinguish plasma Aß42/40 positive and negative groups, independent of group differences in cognitive status, Aß PET status, and other plasma biomarkers (i.e., t-tau, p-tau181, glial fibrillary acidic protein, neurofilament light). HIGHLIGHTS: Plasma Aß42/40 positivity is associated with brain microstructure decline. Plasma+/PET- demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET- demonstrated decreased FAt in 66 total GM and WM regions. Whole-brain FW correlated with plasma Aß42/40 and p-tau181 measures. Plasma+/PET- demonstrated decreased cortical volume and thickness.

Lower individual alpha frequency in individuals with chronic low back pain and fear of movement.

ABSTRACT: Significant progress has been made in linking measures of individual alpha frequency (IAF) and pain. A lower IAF has been associated with chronic neuropathic pain and with an increased sensitivity to pain in healthy young adults. However, the translation of these findings to chronic low back pain (cLBP) are sparse and inconsistent. To address this limitation, we assessed IAFs in a cohort of 70 individuals with cLBP, implemented 3 different IAF calculations, and separated cLBP subjects based on psychological variables. We hypothesized that a higher fear movement in cLBP is associated with a lower IAF at rest. A total of 10 minutes of resting data were collected from 128 electroencephalography channels. Our results offer 3 novel contributions to the literature. First, the high fear group had a significantly lower peak alpha frequency. The high fear group also reported higher pain and higher disability. Second, we calculated individual alpha frequency using 3 different but established methods; the effect of fear on individual alpha frequency was robust across all methods. Third, fear of movement, pain intensity, and disability highly correlated with each other and together significantly predicted IAF. Our findings are the first to show that individuals with cLBP and high fear have a lower peak alpha frequency.

The effect of chronic low back pain on postural control during quiet standing: A meta-analysis.

Low back pain (LBP) has been associated with altered body sway during quiet standing, but the pattern of results is inconsistent. The purpose of this meta-analysis is to examine the effects of vision (eyes open, eyes closed) and changing the support surface (foam surface, firm surface) on postural sway during quiet standing in individuals with chronic LBP (cLBP). Five electronic databases were searched on March 27th, 2022. Of 2,856, 16 studies (n = 663) were included. Across all conditions, we found a positive and medium effect size (g = 0.77 [0.50, 1.04]) that represented greater body sway in individuals with cLBP. Subgroup analyses revealed medium effects during eyes open conditions (firm surface: g = 0.60 [0.33, 0.87]; foam surface: g = 0.68 [0.38, 0.97]), and large effects during eyes closed conditions (firm surface: g = 0.97 [0.60, 1.35]; foam surface: g = 0.89 [0.28, 1.51]). We quantified effects of self-reported pain and found a moderate effect during eyes closed plus firm surface conditions (Q = 3.28; p = 0.070). We conclude that cLBP is associated with increased postural sway, with largest effect sizes evident when vision is removed and when self-reported pain intensity is higher.

Association of longitudinal cognitive decline with diffusion MRI in Gray Matter, Amyloid, and Tau deposition.

Extracellular amyloid plaques in gray matter are the earliest pathological marker for Alzheimer's disease (AD), followed by abnormal tau protein accumulation. The link between diffusion changes in gray matter, amyloid and tau pathology, and cognitive decline is not well understood. We first performed cross-sectional analyses on T1-weighted imaging, diffusion MRI, and amyloid and tau PETs from the ADNI 2/3 database. We evaluated cortical volume, free-water, fractional anisotropy (FA), and amyloid and tau SUVRs in 171 cognitively normal, 103 MCI, and 44 AD individuals. When the 3 groups were combined, increasing amyloid burden was associated with reduced extracellular free-water in the entorhinal cortex and hippocampus in those with amyloid-negative status whereas increasing tau burden was associated with increased extracellular free-water regardless of amyloid status. Next, we found that for the MCI subjects, diffusion measures (free-water, FA) alone predicted MMSE score 2 years later with a high r-square value (87%), as compared to tau SUVRs (27%), T1 volume (36%), and amyloid SUVRs (75%). Diffusion measures represent a potent non-invasive marker for predicting cognitive decline.

Neurophysiology of movement inhibition during full body reaching.

Our current understanding of response inhibition comes from go/no-go studies that draw conclusions based on the overt movement of single limbs (i.e., a single finger pushing a button). In general, go/no-go paradigms have found that an individual's ability to correctly inhibit the motor system is indicative of a healthy central nervous system. However, measuring inhibition by an overt behavioral response may lack the sensitivity to conclude whether the motor system is completely inhibited. Therefore, our goal was to use behavioral and neurophysiological measures to investigate inhibition of the motor system during a full-body reaching task. When directly comparing neurophysiological and behavioral measures, we found that neurophysiological measures were associated with a greater number of errors during no-go trials and faster onset times during go trials. Further analyses revealed a negative correlation between errors and onset times, such that the muscles that activated the earliest during go trials also had the greatest number of errors during no-go trials. Together, our observations show that the absence of an overt behavioral response does not always translate to total inhibition of the motor system.

Advanced diffusion imaging to track progression in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

Advanced diffusion imaging which accounts for complex tissue properties, such as crossing fibers and extracellular fluid, may detect longitudinal changes in widespread pathology in atypical Parkinsonian syndromes. We implemented fixel-based analysis, Neurite Orientation and Density Imaging (NODDI), and free-water imaging in Parkinson's disease (PD), multiple system atrophy (MSAp), progressive supranuclear palsy (PSP), and controls longitudinally over one year. Further, we used these three advanced diffusion imaging techniques to investigate longitudinal progression-related effects in key white matter tracts and gray matter regions in PD and two common atypical Parkinsonian disorders. Fixel-based analysis and free-water imaging revealed longitudinal declines in a greater number of descending sensorimotor tracts in MSAp and PSP compared to PD. In contrast, only the primary motor descending sensorimotor tract had progressive decline over one year, measured by fiber density (FD), in PD compared to that in controls. PSP was characterized by longitudinal impairment in multiple transcallosal tracts (primary motor, dorsal and ventral premotor, pre-supplementary motor, and supplementary motor area) as measured by FD, whereas there were no transcallosal tracts with longitudinal FD impairment in MSAp and PD. In addition, free-water (FW) and FW-corrected fractional anisotropy (FAt) in gray matter regions showed longitudinal changes over one year in regions that have previously shown cross-sectional impairment in MSAp (putamen) and PSP (substantia nigra, putamen, subthalamic nucleus, red nucleus, and pedunculopontine nucleus). NODDI did not detect any longitudinal white matter tract progression effects and there were few effects in gray matter regions across Parkinsonian disorders. All three imaging methods were associated with change in clinical disease severity across all three Parkinsonian syndromes. These results identify novel extra-nigral and extra-striatal longitudinal progression effects in atypical Parkinsonian disorders through the application of multiple diffusion methods that are related to clinical disease progression. Moreover, the findings suggest that fixel-based analysis and free-water imaging are both particularly sensitive to these longitudinal changes in atypical Parkinsonian disorders.

Low Risk for Persistent Back Pain Disability Is Characterized by Lower Pain Sensitivity and Higher Physical Performance.

OBJECTIVE: The STarT Back Tool (SBT) predicts risk for persistent low back pain (LBP)-related disability based on psychological distress levels. Other non-psychological factors associated with LBP, such as pain sensitivity and physical performance, may further characterize SBT-risk subgroups. The purpose of this study was to determine whether a low-risk SBT subgroup demonstrated lower pain sensitivity and/or higher physical performance compared with a medium-/high-risk SBT subgroup. METHODS: In this cross-sectional, secondary analysis, adults with LBP (N = 76) completed SBT and demographics (age, sex, race, chronicity) questionnaires. Participants underwent pain sensitivity (local and remote pressure pain thresholds, temporal summation, conditioned pain modulation) and physical performance (Back Performance Scale, walking speed, obstacle negotiation, Timed "Up & Go" [TUG], TUG Cognitive) testing. Independent samples t tests determined low- versus medium-/high-risk SBT subgroup differences. A follow-up discriminant function analysis was also conducted. RESULTS: The medium-/high-risk subgroup demonstrated a lower proportion of participants with acute pain. The low-risk subgroup demonstrated lower pain sensitivity (higher local pressure pain thresholds and higher conditioned pain modulation) and higher physical performance (superior Back Performance Scale scores, faster walking speeds, faster obstacle approach and crossing speeds, and faster TUG completion). Discriminant function analysis results supported the 2-subgroup classification and indicated strong to moderate relationships with obstacle crossing speed, chronicity, and conditioned pain modulation. CONCLUSION: Lower pain sensitivity and higher physical performance characterized the low-risk SBT subgroup and may represent additional LBP prognostic factors associated with persistent disability. Longitudinal studies are needed to confirm whether these factors can enhance SBT prediction accuracy and further direct treatment priorities. IMPACT: Sensory and physical factors contribute to SBT risk classification, suggesting additional, non-psychological factors are indicative of favorable LBP outcomes. Findings highlight the need for assessment of multiple factors to improve LBP clinical prediction. LAY SUMMARY: People at low risk for back pain disability have less sensitivity to pain and better physical performance. By measuring these factors, physical therapists could guide treatment and improve outcomes for people with back pain.

Recalling fearful memories modifies approach and avoidance behavior based on spatial context.

Motor responses are more efficient when there is a match (or congruency) between the motivational properties of an emotional state and the distance altering characteristics of the movement being executed to the emotion-eliciting stimulus. However, the role of spatial context in shaping motivational orientations to approach and avoid, particularly during whole-body movement tasks, remains less understood. We sought to narrow this knowledge gap by investigating whether an emotion (fear) relived from a previous experience affected movement initiation based on whether motor responses were implicitly coded as approach (i.e., incongruent) or avoidance (i.e., congruent) as per the location of the imagined threat stimulus. Participants (N = 29) completed a tone-initiated forward gait initiation task after recalling a previous fearful experience in which the stimulus from their memory was located either in front (incongruent) or behind (congruent) them. Facilitation versus inhibition of motor responses was indexed by reaction time (RT), displacement and velocity of postural movements prior to stepping, and step kinematics. Analyses revealed that participants initiating forward gait after recalling a fearful experience in which the fearful stimulus was congruent to the movement direction expedited RTs, greater displacement and velocity of anticipatory postural responses, and greater step length and velocity. Results provide support for the theoretical position that motivational orientations to approach and avoid are contextualized based on affective congruency, which includes the spatial orientation of real or imagined emotional stimuli. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Visuomotor brain network activation and functional connectivity among individuals with autism spectrum disorder.

Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and predictive of functional outcomes, though their neural underpinnings remain poorly understood. Using functional magnetic resonance imaging, we examined both brain activation and functional connectivity during visuomotor behavior in 27 individuals with ASD and 30 typically developing (TD) controls (ages 9-35 years). Participants maintained a constant grip force while receiving visual feedback at three different visual gain levels. Relative to controls, ASD participants showed increased force variability, especially at high gain, and reduced entropy. Brain activation was greater in individuals with ASD than controls in supplementary motor area, bilateral superior parietal lobules, and contralateral middle frontal gyrus at high gain. During motor action, functional connectivity was reduced between parietal-premotor and parietal-putamen in individuals with ASD compared to controls. Individuals with ASD also showed greater age-associated increases in functional connectivity between cerebellum and visual, motor, and prefrontal cortical areas relative to controls. These results indicate that visuomotor deficits in ASD are associated with atypical activation and functional connectivity of posterior parietal, premotor, and striatal circuits involved in translating sensory feedback information into precision motor behaviors, and that functional connectivity of cerebellar-cortical sensorimotor and nonsensorimotor networks show delayed maturation.

Association of Cognitive Impairment With Free Water in the Nucleus Basalis of Meynert and Locus Coeruleus to Transentorhinal Cortex Tract.

BACKGROUND AND OBJECTIVES: The goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain. METHODS: Diffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples. RESULTS: FW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen d = 0.54; p fdr < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen d = 1.41; p fdr < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean r 2 = 0.10; p fdr < 0.05). DISCUSSION: These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment.

Unraveling somatotopic organization in the human brain using machine learning and adaptive supervoxel-based parcellations.

In addition to the well-established somatotopy in the pre- and post-central gyrus, there is now strong evidence that somatotopic organization is evident across other regions in the sensorimotor network. This raises several experimental questions: To what extent is activity in the sensorimotor network effector-dependent and effector-independent? How important is the sensorimotor cortex when predicting the motor effector? Is there redundancy in the distributed somatotopically organized network such that removing one region has little impact on classification accuracy? To answer these questions, we developed a novel experimental approach. fMRI data were collected while human subjects performed a precisely controlled force generation task separately with their hand, foot, and mouth. We used a simple linear iterative clustering (SLIC) algorithm to segment whole-brain beta coefficient maps to build an adaptive brain parcellation and then classified effectors using extreme gradient boosting (XGBoost) based on parcellations at various spatial resolutions. This allowed us to understand how data-driven adaptive brain parcellation granularity altered classification accuracy. Results revealed effector-dependent activity in regions of the post-central gyrus, precentral gyrus, and paracentral lobule. SMA, regions of the inferior and superior parietal lobule, and cerebellum each contained effector-dependent and effector-independent representations. Machine learning analyses showed that increasing the spatial resolution of the data-driven model increased classification accuracy, which reached 94% with 1755 supervoxels. Our SLIC-based supervoxel parcellation outperformed classification analyses using established brain templates and random simulations. Occlusion experiments further demonstrated redundancy across the sensorimotor network when classifying effectors. Our observations extend our understanding of effector-dependent and effector-independent organization within the human brain and provide new insight into the functional neuroanatomy required to predict the motor effector used in a motor control task.

Cortical dynamics of movement-evoked pain in chronic low back pain.

KEY POINTS: Cortical activity underlying movement-evoked pain is not well understood, despite being a key symptom of chronic musculoskeletal pain. We combined high-density electroencephalography with a full-body reaching protocol in a virtual reality environment to assess cortical activity during movement-evoked pain in chronic low back pain. Movement-evoked pain in individuals with chronic low back pain was associated with longer reaction times, delayed peak velocity and greater movement variability. Movement-evoked pain was associated with attenuated disinhibition in prefrontal motor areas, as evidenced by an attenuated reduction in beta power in the premotor cortex and supplementary motor area. ABSTRACT: Although experimental pain alters neural activity in the cortex, evidence of changes in neural activity in individuals with chronic low back pain (cLBP) remains scarce and results are inconsistent. One of the challenges in studying cLBP is that the clinical pain fluctuates over time and often changes during movement. The goal of the present study was to address this challenge by recording high-density electroencephalography (HD-EEG) data during a full-body reaching task to understand neural activity during movement-evoked pain. HD-EEG data were analysed using independent component analyses, source localization and measure projection analyses to compare neural oscillations between individuals with cLBP who experienced movement-evoked pain and pain-free controls. We report two novel findings. First, movement-evoked pain in individuals with cLBP was associated with longer reaction times, delayed peak velocity and greater movement variability. Second, movement-evoked pain was associated with an attenuated reduction in beta power in the premotor cortex and supplementary motor area. Our observations move the field forward by revealing attenuated disinhibition in prefrontal motor areas during movement-evoked pain in cLBP.

Functional imaging of the brainstem during visually-guided motor control reveals visuomotor regions in the pons and midbrain.

Integrating visual information for motor output is an essential process of visually-guided motor control. The brainstem is known to be a major center involved in the integration of sensory information for motor output, however, limitations of functional imaging in humans have impaired our knowledge about the individual roles of sub-nuclei within the brainstem. Thus, the bulk of our knowledge surrounding the function of the brainstem is based on anatomical and behavioral studies in non-human primates, cats, and rodents, despite studies demonstrating differences in the organization of visuomotor processing between mammals. fMRI studies in humans have examined activity related to visually-guided motor tasks, however, few have done so while controlling for both force without visual feedback activity and visual stimuli without force activity. Of the studies that have controlled for both conditions, none have reported brainstem activity. Here, we employed a novel fMRI paradigm focused on the brainstem and cerebellum to systematically investigate the hypothesis that the pons and midbrain are critical for the integration of visual information for motor control. Visuomotor activity during visually-guided pinch-grip force was measured while controlling for force without visual feedback activity and visual stimuli without force activity in healthy adults. Using physiological noise correction and multiple task repetitions, we demonstrated that visuomotor activity occurs in the inferior portion of the basilar pons and the midbrain. These findings provide direct evidence in humans that the pons and midbrain support the integration of visual information for motor control. We also determined the effect of physiological noise and task repetitions on the visuomotor signal that will be useful in future studies of neurodegenerative diseases affecting the brainstem.

Empirically derived back pain subgroups differentiated walking performance, pain, and disability.

ABSTRACT: Low back pain (LBP) is a leading cause of disability. However, the processes contributing to disability are not well understood. Therefore, this study (1) empirically derived LBP subgroups and (2) validated these subgroups using walking performance, pain, and disability measures. Seventy adults with LBP underwent testing for a priori determined sensory (temporal summation; conditioned pain modulation), psychological (positive affect/coping; negative coping), and motor (trunk extensor muscle activation during forward bending and walking) measures. A hierarchical cluster analysis determined subgroups that were then validated using walking (walking speed; Timed Up and Go [TUG]; TUG-Cognitive [TUG-Cog]; obstacle negotiation) and clinical (Brief Pain Inventory; Oswestry Disability Index; low back pressure pain threshold) measures. Two subgroups were derived: (1) a "Maladaptive" subgroup (n = 21) characterized by low positive affect/coping, high negative coping, low pain modulation, and atypical trunk extensor activation and (2) an "Adaptive" subgroup (n = 49) characterized by high positive affect/coping, low negative coping, high pain modulation, and typical trunk extensor activation. There were subgroup differences on 7 of 12 validation measures. The Maladaptive subgroup had reduced walking performance (slower self-selected walking speed, TUG completion, and obstacle approach and crossing speed) and worse clinical presentation (higher pain intensity, pain interference, and disability) (moderate to large effect sizes; P's < 0.05). Findings support the construct validity of this multidimensional subgrouping approach. Longitudinal studies are needed to determine whether the Maladaptive subgroup is predictive of poor outcomes, such as pain chronicity or persistent disability.

A Novel Method to Understand Neural Oscillations During Full-Body Reaching: A Combined EEG and 3D Virtual Reality Study.

Virtual reality (VR) can be used to create environments that are not possible in the real-world. Producing movements in VR holds enormous promise for rehabilitation and offers a platform from which to understand the neural control of movement. However, no study has examined the impact of a 3D fully immersive head-mounted display (HMD) VR system on the integrity of neural data. We assessed the quality of 64-channel EEG data with and without HMD VR during rest and during a full-body reaching task. We compared resting EEG while subjects completed three conditions: No HMD (EEG-only), HMD powered off (VR-off), and HMD powered on (VR-on). Within the same session, EEG were collected while subjects completed full-body reaching movements in two conditions (EEG-only, VR-on). During rest, no significant differences in data quality and power spectrum were observed between EEG-only, VR-off, and VR-on conditions. During reaching movements, the proportion of components attributed to the brain was greater in the EEG-only condition compared to the VR-on condition. Despite this difference, neural oscillations in source space were not significantly different between conditions, with both conditions associated with decreases in alpha and beta power in sensorimotor cortex during movements. Our findings demonstrate that the integrity of EEG data can be maintained while individuals execute full-body reaching movements within an immersive 3D VR environment. Clinical impact: Integrating VR and EEG is a viable approach to understanding the cortical processes of movement. Simultaneously recording movement and brain activity in combination with VR provides the foundation for neurobiologically informed rehabilitation therapies.

Chronic jaw pain attenuates neural oscillations during motor-evoked pain.

Motor- and pain-related processes separately induce a reduction in alpha and beta power. When movement and pain occur simultaneously but are independent of each other, the effects on alpha and beta power are additive. It is not clear whether this additive effect is evident during motor-evoked pain in individuals with chronic pain. We combined highdensity electroencephalography (EEG) with a paradigm in which motor-evoked pain was induced during a jaw force task. Participants with chronic jaw pain and pain-free controls produced jaw force at 2% and 15% of their maximum voluntary contraction. The chronic jaw pain group showed exacerbated motor-evoked pain as force amplitude increased and showed increased motor variability and motor error irrespective of force amplitude. The chronic jaw pain group had an attenuated decrease in power in alpha and lower-beta frequencies in the occipital cortex during the anticipation and experience of motor-evoked pain. Rather than being additive, motor-evoked pain attenuated the modulation of alpha and beta power, and this was most evident in occipital cortex. Our findings provide the first evidence of changes in neural oscillations in the cortex during motor-evoked jaw pain.

Plasma Concentrations of Select Inflammatory Cytokines Predicts Pain Intensity 48 Hours Post-Shoulder Muscle Injury.

OBJECTIVES: The relationship between elevated inflammatory cytokine levels and peak pain intensity following acute musculoskeletal injury has not been fully elucidated in high risk subgroups. Identifying the role that these cytokines have on pain responses may help with developing tailored therapeutic approaches. METHODS: Data were collected from 54 participants who were vulnerable to a robust pain response and delayed recovery following musculoskeletal injury. Participants completed baseline active and resting pain measurements and a blood draw before an exercised induced shoulder muscle injury. Participants returned at 24 and 48 hours postinjury for follow-up pain measurements and blood draws. Blood plasma was analyzed for interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor α. Pearson bivariate correlations were performed between cytokines and pain measurements to identify candidate variables for stepwise multiple linear regression predicting pain intensity reports. RESULTS: Pearson bivariate correlation identified 13/45 correlations between inflammatory cytokines and resting pain intensity and 9/45 between inflammatory cytokines and active pain (P<0.05, r≥0.3 or r≤-0.3). This led to 5 stepwise multiple linear regression models, of which 4 met the statistical criterion (P<0.0167); including IL-10 baseline plasma concentrations predicting active pain (r=0.19) and resting pain (r=0.15) intensity 48 hours postinjury. IL-6 and IL-10 plasma concentrations at 48 hours were respectively associated with active and resting pain at 48 hours. DISCUSSION: These findings suggest that elevated concentrations of inflammatory cytokines, specifically IL-10 (at baseline and 48 h) and IL-6 (at 48 h), may play a role in heightened pain responses following exercise-induced muscle injury.

Neurite orientation dispersion and density imaging (NODDI) and free-water imaging in Parkinsonism.

Neurite orientation dispersion and density imaging (NODDI) uses a three-compartment model to probe brain tissue microstructure, whereas free-water (FW) imaging models two-compartments. It is unknown if NODDI detects more disease-specific effects related to neurodegeneration in Parkinson's disease (PD) and atypical Parkinsonism. We acquired multi- and single-shell diffusion imaging at 3 Tesla across two sites. NODDI (using multi-shell; isotropic volume [Viso]; intracellular volume [Vic]; orientation dispersion [ODI]) and FW imaging (using single-shell; FW; free-water corrected fractional anisotropy [FAt]) were compared with 44 PD, 21 multiple system atrophy Parkinsonian variant (MSAp), 26 progressive supranuclear palsy (PSP), and 24 healthy control subjects in the basal ganglia, midbrain/thalamus, cerebellum, and corpus callosum. There was elevated Viso in posterior substantia nigra across Parkinsonisms, and Viso, Vic, and ODI were altered in MSAp and PSP in the striatum, globus pallidus, midbrain, thalamus, cerebellum, and corpus callosum relative to controls. The mean effect size across regions for Viso was 0.163, ODI 0.131, Vic 0.122, FW 0.359, and FAt 0.125, with extracellular compartments having the greatest effect size. A key question addressed was if these techniques discriminate PD and atypical Parkinsonism. Both NODDI (AUC: 0.945) and FW imaging (AUC: 0.969) had high accuracy, with no significant difference between models. This study provides new evidence that NODDI and FW imaging offer similar discriminability between PD and atypical Parkinsonism, and FW had higher effect sizes for detecting Parkinsonism within regions across the basal ganglia and cerebellum.

Altered neural oscillations within and between sensorimotor cortex and parietal cortex in chronic jaw pain.

Pain perception is associated with priming of the motor system and the orienting of attention in healthy adults. These processes correspond with decreases in alpha and beta power in the sensorimotor and parietal cortices. The goal of the present study was to determine whether these findings extend to individuals with chronic pain. Individuals with chronic jaw pain and pain-free controls anticipated and experienced a low pain or a moderate pain-eliciting heat stimulus. Although stimuli were calibrated for each subject, stimulus temperature was not different between groups. High-density EEG data were collected during the anticipation and heat stimulation periods and were analyzed using independent component analyses, EEG source localization, and measure projection analyses. Direct directed transfer function was also estimated to identify frequency specific effective connectivity between regions. Between group differences were most evident during the heat stimulation period. We report three novel findings. First, the chronic jaw pain group had a relative increase in alpha and beta power and a relative decrease in theta and gamma power in sensorimotor cortex. Second, the chronic jaw pain group had a relative increase in power in the alpha and beta bands in parietal cortex. Third, the chronic jaw pain group had less connectivity strength in the beta and gamma bands between sensorimotor cortex and parietal cortex. Our findings show that the effect of chronic pain attenuates rather than magnifies neural responses to heat stimuli. We interpret these findings in the context of system-level changes in intrinsic sensorimotor and attentional circuits in chronic pain.