Neuropsychology of chronic back pain managed with long-term opioid use.

Chronic pain is commonly treated with long-term opioids, but the neuropsychological outcomes associated with stable long-duration opioid use remain unclear. Here, we contrasted the psychological profiles, brain activity, and brain structure of 70 chronic back pain patients on opioids (CBP+O, average opioid exposure 6.2 years) with 70 patients managing their pain without opioids. CBP+O exhibited moderately worse psychological profiles and small differences in brain morphology. However, CBP+O had starkly different spontaneous brain activity, dominated by increased mesocorticolimbic and decreased dorsolateral-prefrontal activity, even after controlling for pain intensity and duration. These differences strongly reflected cortical opioid and serotonin receptor densities and mapped to two antagonistic resting-state circuits. The circuits' dynamics were explained by mesocorticolimbic activity and reflected negative affect. We reassessed a sub-group of CBP+O after they briefly abstained from taking opioids. Network dynamics, but not spontaneous activity, reflected exacerbated signs of withdrawal. Our results have implications for the management and tapering of opioids in chronic pain.

Mechanical hyperalgesia and neuropathic pain qualities impart risk for chronic postoperative pain after total knee replacement.

Total knee replacement (TKR) is the gold-standard treatment for end-stage chronic osteoarthritis pain, yet many patients report chronic postoperative pain after TKR. The search for preoperative predictors for chronic postoperative pain following TKR has been studied with inconsistent findings. This study investigates the predictive value of quantitative sensory testing (QST) and PainDETECT for postoperative pain 3, 6, and 12 months post-TKR. We assessed baseline and postoperative (3- and 6-months) QST measures in 77 patients with knee OA (KOA) and 41 healthy controls, along with neuropathic pain scores in patients (PainDETECT). QST parameters included pressure pain pressure threshold (PPT), pain tolerance threshold (PTT), conditioned pain modulation (CPM), and temporal summation (TS) using cuff algometry, alongside mechanical hyperalgesia, and mechanical temporal summation to repeated pinprick stimulation. Compared to healthy controls, KOA patients at baseline demonstrated hyperalgesia to pinprick stimulation at the medial OA-affected knee and cuff pressure on the ipsilateral calf. Lower cuff algometry PTT and mechanical pinprick hyperalgesia were associated with baseline KOA pain intensity. Moreover, baseline pinprick pain hyperalgesia explained 25% of variance in pain intensity 12 months post-TKR and preoperative neuropathic pain scores also captured 30% and 20% of the variance in postoperative pain at 6- and 12-months, respectively. A decrease in mechanical pinprick hyperalgesia from before surgery to 3 months after TKR was associated with lower postoperative pain at the 12 months post-TKR follow-up, and vice-versa. Our findings suggest that preoperative pinprick hyperalgesia and PainDETECT neuropathic-like pain symptoms show predictive value for the development of chronic post-TKR pain.

Immersive virtual reality-based rehabilitation for subacute stroke: a randomized controlled trial.

OBJECTIVE: Few effective treatments improve upper extremity (UE) function after stroke. Immersive virtual reality (imVR) is a novel and promising strategy for stroke UE recovery. We assessed the extent to which imVR-based UE rehabilitation can augment conventional treatment and explored changes in brain functional connectivity (FC) that were related to the rehabilitation. METHODS: An assessor-blinded, parallel-group randomized controlled trial was performed with 40 subjects randomly assigned to either imVR or Control group (1:1 allocation), each receiving rehabilitation 5 times per week for 3 weeks. Subjects in the imVR received both imVR and conventional rehabilitation, while those in the Control received conventional rehabilitation only. Our primary and secondary outcomes were the Fugl-Meyer assessment's upper extremity subscale (FMA-UE) and the Barthel Index (BI), respectively. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to assess the effectiveness of the trial. For both the FMA-UE/BI, a one-way analysis of covariance (ANCOVA) model was used, with the FMA-UE/BI at post-intervention or at follow-up, respectively, as the dependent variable, the two groups as the independent variable, baseline FMA-UE/BI, age, sex, site, time since onset, hypertension and diabetes as covariates. RESULTS: Both ITT and PP analyses demonstrated the effectiveness of imVR-based rehabilitation. The FMA-UE score was greater in the imVR compared with the Control at the post-intervention (mean difference: 9.1 (95% CI 1.6, 16.6); P = 0.019) and follow-up (mean difference:11.5 (95% CI 1.9, 21.0); P = 0.020). The results were consistent for BI scores. Moreover, brain FC analysis found that the motor function improvements were associated with a change in degree in ipsilesional premotor cortex and ipsilesional dorsolateral prefrontal cortex immediately following the intervention and in ipsilesional visual region and ipsilesional middle frontal gyrus after the 12-week follow-up. CONCLUSIONS: ImVR-based rehabilitation is an effective tool that can improve the recovery of UE functional capabilities of subacute stroke patients when added to standard care. These improvements were associated with distinctive brain changes at two post-stroke timepoints. The study results will benefit future patients with stroke and provide evidence for a promising new method of stroke rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03086889.

Supervision during resistance training positively influences muscular adaptations in resistance-trained individuals.

This study compared the effects of supervised versus unsupervised resistance training (RT) on measures of muscle strength and hypertrophy in resistance-trained individuals. Thirty-six young men and women were randomly assigned to one of two experimental, parallel groups to complete an 8-week RT programme: One group received direct supervision for their RT sessions (SUP); the other group performed the same RT programme in an unsupervised manner (UNSUP). Programme variables were kept constant between groups. We obtained pre- and post-study assessments of body composition via multi-frequency bioelectrical impedance analysis (MF-BIA), muscle thickness of the upper and lower limbs via ultrasound, 1 repetition maximum (RM) in the back squat and bench press, isometric knee extension strength, and countermovement jump (CMJ) height. Results showed the SUP group generally achieved larger increases in muscle thickness for the triceps brachii, all sites of the rectus femoris, and the proximal region of the vastus lateralis. MF-BIA indicated increases in lean mass favoured SUP. Squat 1RM was greater for SUP; bench press 1RM and isometric knee extension were similar between conditions. CMJ increases modestly favoured UNSUP. In conclusion, our findings suggest that supervised RT promotes greater muscular adaptations and enhances exercise adherence in young, resistance-trained individuals.

The Sensitivity of Bipolar Electromyograms to Muscle Excitation Scales With the Inter-Electrode Distance.

The value of surface electromyograms (EMGs) lies in their potential to non-invasively probe the neuromuscular system. Whether muscle excitation may be accurately inferred from bipolar EMGs depends on how much the detected signal is both sensitive and specific to the excitation of the target muscle. While both are known to be a function of the inter-electrode distance (IED), specificity has been of long concern in the physiological literature. In contrast, sensitivity, at best, has been implicitly assumed. Here we provide evidence that the IED imposes a biophysical constraint on the sensitivity of surface EMG. From 20 healthy subjects, we tested the hypothesis that excessively reducing the IED limits EMGs' physiological content. We detected bipolar EMGs with IEDs varying from 5 mm to 50 mm from two skeletal muscles with distinct architectures, gastrocnemius and biceps brachii. Non-parametric statistics and Bayesian hierarchical modelling were used to evaluate the dependence of the onset of muscle excitation and signal-to-noise ratio (SNR) on the IED. Experimental results revealed that IED critically affects the sensitivity of bipolar EMGs for both muscles-indeliberately reducing the IED yields EMGs that are not representative of the whole muscle, hampering validity. Simulation results substantiate the generalization of experimental results to small and large electrodes. Based on current and previous findings, we discuss a potentially valid procedure for defining the most appropriate IED for a single bipolar, surface recording-i.e., the distance from the electrode to the target muscle boundary may heuristically serve as a lower bound when choosing an IED.

Hip thrust and back squat training elicit similar gluteus muscle hypertrophy and transfer similarly to the deadlift.

We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes. Untrained college-aged participants were randomized into HT (n = 18) or SQ (n = 16) groups. Surface electromyograms (sEMG) from the right gluteus maximus and medius muscles were obtained during the first training session. Participants completed 9 weeks of supervised training (15-17 sessions), before and after which gluteus and leg muscle cross-sectional area (mCSA) was assessed via magnetic resonance imaging. Strength was also assessed prior to and after the training intervention via three-repetition maximum (3RM) testing and an isometric wall push test. Gluteus mCSA increases were similar across both groups. Specifically, estimates [(-) favors HT (+) favors SQ] modestly favored the HT versus SQ for lower [effect ±SE, -1.6 ± 2.1 cm2; CI95% (-6.1, 2.0)], mid [-0.5 ± 1.7 cm2; CI95% (-4.0, 2.6)], and upper [-0.5 ± 2.6 cm2; CI95% (-5.8, 4.1)] gluteal mCSAs but with appreciable variance. Gluteus medius + minimus [-1.8 ± 1.5 cm2; CI95% (-4.6, 1.4)] and hamstrings [0.1 ± 0.6 cm2; CI95% (-0.9, 1.4)] mCSA demonstrated little to no growth with small differences between groups. mCSA changes were greater in SQ for the quadriceps [3.6 ± 1.5 cm2; CI95% (0.7, 6.4)] and adductors [2.5 ± 0.7 cm2; CI95% (1.2, 3.9)]. Squat 3RM increases favored SQ [14 ± 2 kg; CI95% (9, 18),] and hip thrust 3RM favored HT [-26 ± 5 kg; CI95% (-34, -16)]. 3RM deadlift [0 ± 2 kg; CI95% (-4, 3)] and wall push strength [-7 ± 12N; CI95% (-32, 17)] similarly improved. All measured gluteal sites showed greater mean sEMG amplitudes during the first bout hip thrust versus squat set, but this did not consistently predict gluteal hypertrophy outcomes. Squat and hip thrust training elicited similar gluteal hypertrophy, greater thigh hypertrophy in SQ, strength increases that favored exercise allocation, and similar deadlift and wall push strength increases.

Rating of perceived effort but relative to what? A comparison between imposed and self-selected anchors.

PURPOSE: Collecting reliable and valid rating of perceived effort (RPE) data requires properly anchoring the scales' upper limits (i.e., the meaning of 10 on a 0-10 scale). Yet, despite their importance, anchoring procedures remain understudied and theoretically underdeveloped. Here we propose a new task-based anchoring procedure that distinguishes between imposed and self-selected anchors. In the former, researchers impose on participants a specific task as the anchor; in the latter, participants choose the most effortful task experienced or imaginable as the anchor. We compared the impact of these conceptually different anchoring procedures on RPE. METHODS: Twenty-five resistance-trained participants (13 females) attended a familiarization and two randomized experimental sessions. In both experimental sessions, participants performed non-fatiguing and fatiguing isometric maximal voluntary contraction (MVC) protocols with the squat followed by the gripper or vice versa. After each MVC, participants reported their RPE on a 0-10 scale relative to an imposed anchor of the performed task (e.g., gripper MVCs anchored to a gripper MVC) or to a self-selected anchor. RESULTS: In the non-fatiguing condition, imposed anchors yielded greater RPEs than self-selected anchors for both the squat [on average, 9.4 vs. 5.5; Δ(CI95%) = 3.9 (3.2, 4.5)] and gripper [9.4 vs. 3.9; Δ = 5.5 (4.7, 6.3)]. Similar results were observed in the fatiguing condition for both the squat [9.7 vs. 6.9; Δ = 2.8 (2.1, 3.5)] and gripper [9.7 vs. 4.5; Δ = 5.2 (4.3, 5.9)]. CONCLUSIONS: We found large differences in RPE between the two anchors, independent of exercises and fatigue state. These findings provide a basis for further development and refinement of anchoring procedures and highlight the importance of selecting, justifying, and consistently applying the chosen anchors.

Surface electromyographic frequency characteristics of the quadriceps differ between continuous high- and low-torque isometric knee extension to momentary failure.

Surface EMG (sEMG) has been used to compare loading conditions during exercise. Studies often explore mean/median frequencies. This potentially misses more nuanced electrophysiological differences between exercise tasks. Therefore, wavelet-based analysis was used to evaluate electrophysiological characteristics in the sEMG signal of the quadriceps under both higher- and lower-torque (70 % and 30 % of MVC, respectively) isometric knee extension performed to momentary failure. Ten recreationally active adult males with previous resistance training experience were recruited. Using a within-session, repeated-measures, randomised crossover design, participants performed isometric knee extension whilst sEMG was collected from the vastus medialis (VM), rectus femoris (RF) and vastus lateralis (VL). Mean signal frequency showed similar characteristics in each condition at momentary failure. However, individual wavelets revealed different frequency component changes between the conditions. All frequency components increased during the low-torque condition. But low-frequency components increased, and high-frequency components decreased, in intensity throughout the high-torque condition. This resulted in convergence of the low-torque and high-torque trial wavelet characteristics towards the end of the low-torque trial. Our results demonstrate a convergence of myoelectric signal properties between low- and high-torque efforts with fatigue via divergent signal adaptations. Further work should disentangle factors influencing frequency characteristics during exercise tasks.

Hip thrust and back squat training elicit similar gluteus muscle hypertrophy and transfer similarly to the deadlift.

Purpose: We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes. Methods: Untrained college-aged participants were randomized into HT or SQ groups. Surface electromyograms (sEMG) from the right gluteus maximus and medius muscles were obtained during the first training session. Participants completed nine weeks of supervised training (15-17 sessions), before and after which we assessed muscle cross-sectional area (mCSA) via magnetic resonance imaging and strength via three-repetition maximum (3RM) testing and an isometric wall push test. Results: Glutei mCSA growth was similar across both groups. Estimates [(-) favors HT; (+) favors SQ] modestly favored the HT compared to SQ for lower [effect ± SE, -1.6 ± 2.1 cm2], mid [-0.5± 1.7 cm2], and upper [-0.5 ± 2.6 cm2], but with appreciable variance. Gluteus medius+minimus [-1.8 ± 1.5 cm2] and hamstrings [0.1 ± 0.6 cm2] mCSA demonstrated little to no growth with small differences between groups. Thigh mCSA changes were greater in SQ for the quadriceps [3.6 ± 1.5 cm2] and adductors [2.5 ± 0.7 cm2]. Squat 3RM increases favored SQ [14 ± 2.5 kg] and hip thrust 3RM favored HT [-26 ± 5 kg]. 3RM deadlift [0 ± 2 kg] and wall push strength [-7 ± 13 N] similarly improved. All measured gluteal sites showed greater mean sEMG amplitudes during the first bout hip thrust versus squat set, but this did not consistently predict gluteal hypertrophy outcomes. Conclusion: Nine weeks of squat versus hip thrust training elicited similar gluteal hypertrophy, greater thigh hypertrophy in SQ, strength increases that favored exercise allocation, and similar strength transfers to the deadlift and wall push.

Subcortical brain anatomy as a potential biomarker of persistent pain after total knee replacement in osteoarthritis.

ABSTRACT: The neural mechanisms for the persistence of pain after a technically successful arthroplasty in osteoarthritis (OA) remain minimally studied, and direct evidence of the brain as a predisposing factor for pain chronicity in this setting has not been investigated. We undertook this study as a first effort to identify presurgical brain and clinical markers of postarthroplasty pain in knee OA. Patients with knee OA (n = 81) awaiting total arthroplasty underwent clinical and psychological assessment and brain magnetic resonance imagining. Postoperative pain scores were measured at 6 months after surgery. Brain subcortical anatomic properties (volume and shape) and clinical indices were studied as determinants of postoperative pain. We show that presurgical subcortical volumes (bilateral amygdala, thalamus, and left hippocampus), together with shape deformations of the right anterior hippocampus and right amygdala, associate with pain persistence 6 months after surgery in OA. Longer pain duration, higher levels of presurgical anxiety, and the neuropathic character of pain were also prognostic of postsurgical pain outcome. Brain and clinical indices accounted for unique influences on postoperative pain. Our study demonstrates the presence of presurgical subcortical brain factors that relate to postsurgical persistence of OA pain. These preliminary results challenge the current dominant view that mechanisms of OA pain predominantly underlie local joint mechanisms, implying novel clinical management and treatment strategies.

Responder Analyses: A Methodological Mess.

SYNOPSIS: Responder analyses are methods for analyzing randomized controlled trials, which purport to identify individuals or subgroups of study participants who experienced a "clinically meaningful" improvement from a treatment. Unfortunately, responder analyses have numerous methodological shortcomings, which preclude inferences concerning individual response to treatments and, thus, adoption into clinical practice. In this Viewpoint, we summarize 2 major limitations of responder analyses: (1) their thresholds of success involve arbitrary criteria and (2) responder analyses do not capture true individual treatment effects. J Orthop Sports Phys Ther 2023;53(XX):1-3. Epub: 20 June 2023. doi:10.2519/jospt.2023.11853.

Biomechanical, Anthropometric and Psychological Determinants of Barbell Bench Press Strength.

The purpose of this study was to improve our understanding of the relative contributions of biomechanical, anthropometric, and psychological factors in explaining maximal bench press (BP) strength in a heterogeneous, resistance-trained sample. Eighteen college-aged participants reported to the laboratory for three visits. The first visit consisted of psychometric testing. The second visit assessed participants' anthropometrics, additional psychometric outcomes, and bench press one repetition maximum (1RM). Participants performed isometric dynamometry testing for horizontal shoulder adduction and elbow extension at a predicted sticking point joint position. Multiple linear regression was used to examine the relationships between the biomechanical, anthropometric, and psychological variables and BP 1RM. Our primary multiple linear regression accounted for 43% of the variance in BP strength (F(3,14) = 5.34, p = 0.01; R2 = 0.53; adjusted R2 = 0.43). The sum of peak isometric net joint moments from the shoulder and elbow had the greatest standardized effect (0.59), followed by lean body mass (0.27) and self-efficacy (0.17). The variance in BP 1RM can be similarly captured (R2 = 0.48) by a single principal component containing anthropometric, biomechanics, and psychological variables. Pearson correlations with BP strength were generally greater among anthropometric and biomechanical variables as compared to psychological variables. These data suggest that BP strength among a heterogeneous, resistance-trained population is explained by multiple factors and is more strongly associated with physical than psychological variables.

Effects of variability in manually contoured spinal cord masks on fMRI co-registration and interpretation.

Functional magnetic resonance imaging (fMRI) of the human spinal cord (SC) is a unique non-invasive method for characterizing neurovascular responses to stimuli. Group-analysis of SC fMRI data involves co-registration of subject-level data to standard space, which requires manual masking of the cord and may result in bias of group-level SC fMRI results. To test this, we examined variability in SC masks drawn in fMRI data from 21 healthy participants from a completed study mapping responses to sensory stimuli of the C7 dermatome. Masks were drawn on temporal mean functional image by eight raters with varying levels of neuroimaging experience, and the rater from the original study acted as a reference. Spatial agreement between rater and reference masks was measured using the Dice Similarity Coefficient, and the influence of rater and dataset was examined using ANOVA. Each rater's masks were used to register functional data to the PAM50 template. Gray matter-white matter signal contrast of registered functional data was used to evaluate the spatial normalization accuracy across raters. Subject- and group-level analyses of activation during left- and right-sided sensory stimuli were performed for each rater's co-registered data. Agreement with the reference SC mask was associated with both rater (F(7, 140) = 32.12, P < 2 × 10-16, η2 = 0.29) and dataset (F(20, 140) = 20.58, P < 2 × 10-16, η2 = 0.53). Dataset variations may reflect image quality metrics: the ratio between the signal intensity of spinal cord voxels and surrounding cerebrospinal fluid was correlated with DSC results (p < 0.001). As predicted, variability in the manually-drawn masks influenced spatial normalization, and GM:WM contrast in the registered data showed significant effects of rater and dataset (rater: F(8, 160) = 23.57, P < 2 × 10-16, η2 = 0.24; dataset: F(20, 160) = 22.00, P < 2 × 10-16, η2 = 0.56). Registration differences propagated into subject-level activation maps which showed rater-dependent agreement with the reference. Although group-level activation maps differed between raters, no systematic bias was identified. Increasing consistency in manual contouring of spinal cord fMRI data improved co-registration and inter-rater agreement in activation mapping, however our results suggest that improvements in image acquisition and post-processing are also critical to address.

Progressive overload without progressing load? The effects of load or repetition progression on muscular adaptations.

Background: Progressive overload is a principle of resistance training exercise program design that typically relies on increasing load to increase neuromuscular demand to facilitate further adaptations. However, little attention has been given to another way of increasing demand-increasing the number of repetitions. Objective: This study aimed to compare the effects of two resistance training programs: (1) increasing load while keeping repetition range constant vs (2) increasing repetitions while keeping load constant. We aimed to compare the effects of these programs on lower body muscle hypertrophy, muscle strength, and muscle endurance in resistance-trained individuals over an 8-week study period. Methods: Forty-three participants with at least 1 year of consistent lower body resistance training experience were randomly assigned to one of two experimental, parallel groups: A group that aimed to increase load while keeping repetitions constant (LOAD: n = 22; 13 men, nine women) or a group that aimed to increase repetitions while keeping load constant (REPS: n = 21; 14 men, seven women). Subjects performed four sets of four lower body exercises (back squat, leg extension, straight-leg calf raise, and seated calf raise) twice per week. We assessed one repetition maximum (1RM) in the Smith machine squat, muscular endurance in the leg extension, countermovement jump height, and muscle thickness along the quadriceps and calf muscles. Between-group effects were estimated using analyses of covariance, adjusted for pre-intervention scores and sex. Results: Rectus femoris growth modestly favored REPS (adjusted effect estimate (CI90%), sum of sites: 2.8 mm [-0.5, 5.8]). Alternatively, dynamic strength increases slightly favored LOAD (2.0 kg [-2.4, 7.8]), with differences of questionable practical significance. No other notable between-group differences were found across outcomes (muscle thicknesses, <1 mm; endurance, <1%; countermovement jump, 0.1 cm; body fat, <1%; leg segmental lean mass, 0.1 kg), with narrow CIs for most outcomes. Conclusion: Both progressions of repetitions and load appear to be viable strategies for enhancing muscular adaptations over an 8-week training cycle, which provides trainers and trainees with another promising approach to programming resistance training.

Loaded inter-set stretch may selectively enhance muscular adaptations of the plantar flexors.

The purpose of this study was to evaluate differences in changes in muscle strength and muscle thickness (MT) of the plantar flexor muscles between traditional resistance training (RT) involving passive rest and RT combined with inter-set stretch in the calf raise exercise. Employing a within-subject design, 21 young, healthy men performed plantar flexion exercises twice per week in both a traditional RT (TRAD) format and combined with a 20-second inter-set stretch (STRETCH). One leg was randomly assigned to the TRAD condition and the contralateral leg performed the STRETCH condition throughout the 8-week study period. Dependent variables included MT of the lateral gastrocnemius (LG), medial gastrocnemius (MG) and the soleus (SOL), and isometric strength of the plantar flexors. Results indicated a potential beneficial hypertrophic effect of STRETCH compared to TRAD for the SOL [0.7 mm, CI90% = (0, 1.6)], while the LG had more ambiguous effects [0.4 mm (-0.4, 1.3)] and MG effects were equivocal [0 mm (-0.6, 0.7)]. In general, LG demonstrated greater standardized growth [z = 1.1 (1, 1.3)] as compared to MG [z = 0.3 (0.2, 0.5)] and SOL [z = 0.3 (0.2, 0.5)]. Measures of isometric strength showed a modest advantage to STRETCH. In conclusion, loaded inter-set stretch may enhance MT of the soleus but effects on the gastrocnemii appear uncertain or unlikely in untrained men; plantar flexor strength appears to be modestly enhanced by the interventional strategy.

On the Relationship Between Pain Variability and Relief in Randomized Clinical Trials.

Previous research reports suggest greater baseline variability is associated with greater pain relief in those who receive a placebo. However, studies that evidence this association do not control for confounding effects from regression to the mean and natural history. In this report, we analyzed data from two randomized clinical trials (Placebo I and Placebo II, total N = 139) while adjusting for the effects of natural history and regression to the mean via a no treatment group. Results agree between the two placebo groups in each study: both placebo groups showed negligible semi-partial correlations between baseline variability and adjusted response [r sp (CI95%) = 0.22 (0.03, 0.42) and 0 (-0.07, 0.07) for Placebo I and II, respectively]. The no treatment group in Placebo I showed a negative correlation [-0.22 (-0.43, -0.02)], but the no treatment and drug groups in Placebo II's correlations were negligible [-0.02 (-0.08, 0.02) and 0.00 (-0.10, 0.12) for the no treatment and drug groups, respectively]. When modeled as a linear covariate, baseline pain variability accounted for <1% of the variance in post-intervention pain across both studies. Even after adjusting for baseline pain and natural history, the inability of baseline pain variability to account for substantial variance in pain response highlights that previous results concerning pain variability and treatment response may be inconsistent. Indeed, the relationship appears to be neither consistently specific nor sensitive to improvements in the placebo group. More work is needed to understand and establish the prognostic value of baseline pain variability-especially its placebo specificity and generalizability across patient populations.

Limits of decoding mental states with fMRI.

A growing number of studies claim to decode mental states using multi-voxel decoders of brain activity. It has been proposed that the fixed, fine-grained, multi-voxel patterns in these decoders are necessary for discriminating between and identifying mental states. Here, we present evidence that the efficacy of these decoders might be overstated. Across various tasks, decoder patterns were spatially imprecise, as decoder performance was unaffected by spatial smoothing; 90% redundant, as selecting a random 10% of a decoder's constituent voxels recovered full decoder performance; and performed similarly to brain activity maps used as decoders. We distinguish decoder performance in discriminating between mental states from performance in identifying a given mental state, and show that even when discrimination performance is adequate, identification can be poor. Finally, we demonstrate that simple and intuitive similarity metrics explain 91% and 62% of discrimination performance within- and across-subjects, respectively. These findings indicate that currently used across-subject decoders of mental states are superfluous and inappropriate for decision-making.

Longing for a Longitudinal Proxy: Acutely Measured Surface EMG Amplitude is not a Validated Predictor of Muscle Hypertrophy.

Surface electromyography amplitudes are commonly measured in acute sports and exercise science studies to make inferences about muscular strength, performance, and hypertrophic adaptations that may result from different exercises or exercise-related variables. Here, we discuss the presumptive logic and assumptions underlying these inferences, focusing on hypertrophic adaptations for simplicity's sake. We present counter-evidence for each of its premises and discuss evidence both for and against the logical conclusion. Given the limited evidence validating the amplitude of surface electromyograms as a predictor of longitudinal hypertrophic adaptations, coupled with its weak mechanistic foundation, we suggest that acute comparative studies that wish to assess stimulus potency be met with scrutiny.

Morphometric similarity networks discriminate patients with lumbar disc herniation from healthy controls and predict pain intensity.

We used a recently advanced technique, morphometric similarity (MS), in a large sample of lumbar disc herniation patients with chronic pain (LDH-CP) to examine morphometric features derived from multimodal MRI data. To do so, we evenly allocated 136 LDH-CPs to exploratory and validation groups with matched healthy controls (HC), randomly chosen from the pool of 157 HCs. We developed three MS-based models to discriminate LDH-CPs from HCs and to predict the pain intensity of LDH-CPs. In addition, we created analogous models using resting state functional connectivity (FC) to perform the above discrimination and prediction of pain, in addition to comparing the performance of FC- and MS-based models and investigating if an ensemble model, combining morphometric features and resting-state signals, could improve performance. We conclude that 1) MS-based models were able to discriminate LDH-CPs from HCs and the MS networks (MSN) model performed best; 2) MSN was able to predict the pain intensity of LDH-CPs; 3) FC networks constructed were able to discriminate LDH-CPs from HCs, but they could not predict pain intensity; and 4) the ensemble model neither improved discrimination nor pain prediction performance. Generally, MSN is sensitive enough to uncover brain morphology alterations associated with chronic pain and provides novel insights regarding the neuropathology of chronic pain.

Developing a Technique for the Imaging-Based Measurement of ACL Elongation: A Proof of Principle.

Towards the goal of obtaining non-invasive biomarkers reflecting the anterior cruciate ligament's (ACL) loading capacity, this project aimed to develop a magnetic resonance imaging (MRI)-based method facilitating the measurement of ACL elongations during the execution of knee stress tests. An MRI-compatible, computer-controlled, and pneumatically driven knee loading device was designed to perform Lachman-like tests and induce ACL strain. A human cadaveric leg was used for test purposes. During the execution of the stress tests, a triggered real-time cine MRI sequence with a temporal resolution of 10 Hz was acquired in a parasagittal plane to capture the resultant ACL elongations. To test the accuracy of these measurements, the results were compared to in situ data of ACL elongation that were acquired by measuring the length changes of a surgical wire directly sutured to the ACL's anteromedial bundle. The MRI-based ACL elongations ranged between 0.7 and 1.7 mm and agreed very well with in situ data (root mean square errors, RMSEs ≤ 0.25 mm), although peak elongation rates were underestimated by the MRI (RMSEs 0.19-0.36 mm/s). The high accuracy of elongation measurements underlines the potential of the technique to yield an imaging-based biomarker of the ACL's loading capacity.