White matter microstructure predicts measures of clinical symptoms in chronic back pain patients.

Chronic back pain (CBP) has extensive clinical and social implications for its sufferers and is a major source of disability. Chronic pain has previously been shown to have central neural factors underpinning it, including the loss of white matter (WM), however traditional methods of analyzing WM microstructure have produced mixed and unclear results. To better understand these factors, we assessed the WM microstructure of 50 patients and 40 healthy controls (HC) using diffusion-weighted imaging. The data were analyzed using fixel-based analysis (FBA), a higher-order diffusion modelling technique applied to CBP for the first time here. Subjects also answered questionnaires relating to pain, disability, catastrophizing, and mood disorders, to establish the relationship between fixelwise metrics and clinical symptoms. FBA determined that, compared to HC, CBP patients had: 1) lower fibre density (FD) in several tracts, specifically the right anterior and bilateral superior thalamic radiations, right spinothalamic tract, right middle cerebellar peduncle, and the body and splenium of corpus callosum; 2) higher FD in the genu of corpus callosum; and 3) lower FDC - a combined fibre density and cross-section measure - in the bilateral spinothalamic tracts and right anterior thalamic radiation. Exploratory correlations showed strong negative relationships between fixelwise metrics and clinical questionnaire scores, especially pain catastrophizing. These results have important implications for the intake and processing of sensory data in CBP that warrant further investigation.

Resting state functional connectivity in SLE patients and association with cognitive impairment and blood-brain barrier permeability.

OBJECTIVE: Extensive blood-brain barrier (BBB) leakage has been linked to cognitive impairment in SLE. This study aimed to examine the associations of brain functional connectivity (FC) with cognitive impairment and BBB dysfunction among patients with SLE. METHODS: Cognitive function was assessed by neuropsychological testing (n = 77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n = 78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (n = 61). Differences in rsFC were compared between SLE patients with cognitive impairment (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls. RESULTS: A whole-brain rsFC comparison found significant differences in intra-network and inter-network FC in SLE-CI vs SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared with SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared with SLE-NC (P = 0.030) and healthy controls (P = 0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P = 0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and cognitive impairment in SLE patients was mediated by alterations in FC. CONCLUSION: SLE patients with cognitive impairment had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and cognitive impairment.

Effects of Confidence-Based Rejection on Usability and Error in Pattern Recognition-Based Myoelectric Control.

Rejection of movements based on the confidence in the classification decision has previously been demonstrated to improve the usability of pattern recognition based myoelectric control. To this point, however, the optimal rejection threshold has been determined heuristically, and it is not known how different thresholds affect the tradeoff between error mitigation and false rejections in real-time closed-loop control. To answer this question, 24 able-bodied subjects completed a real-time Fitts' law-style virtual cursor control task using a support vector machine classifier. It was found that rejection improved information throughput at all thresholds, with the best performance coming at thresholds between 0.60 and 0.75. Two fundamental types of error were defined and identified: operator error (identifiable, repeatable behaviors, directly attributable to the user), and systemic error (other errors attributable to misclassification or noise). The incidence of both operator and systemic errors were found to decrease as rejection threshold increased. Moreover, while the incidence of all error types correlated strongly with path efficiency, only systemic errors correlated strongly with throughput and trial completion rate. Interestingly, more experienced users were found to commit as many errors as novice users, despite performing better in the Fitts' task, suggesting that there is more to usability than error prevention alone. Nevertheless, these results demonstrate the usability gains possible with rejection across a range of thresholds for both novice and experienced users alike.

Rejection of Systemic and Operator Errors in a Real-Time Myoelectric Control Task.

In myoelectric pattern-recognition control, the rejection of movement decisions based on confidence - the likelihood of a correct classification - has been shown to improve system usability, however it is not known to what extent this is due directly to error mitigation, and to what extent this is due to users having opportunities to change the way they contract. To understand this, 24 subjects participated in a real-time pattern recognition control task with rejection at seven different confidence thresholds, and without rejection. Errors were classified into systemic errors (i.e., those produced by the classifier) and operator errors (i.e., those produced by user behavior). It was found that the error permitted by the rejection controller was reduced by about half at high rejection thresholds, with both systemic and operator errors significantly affected, while the errors produced by the user remained essentially constant throughout. Conversely, correct decisions were filtered out by the rejection controller at significantly greater rates at high rejection thresholds, which may be excessive enough to ultimately impair usability. While some subjects reported being experienced in myoelectric control, no significant differences were observed due to experience level.

Enhancement of muscle and locomotor performance by a series compliance: A mechanistic simulation study.

The objective was to better understand how a series compliance alters contraction kinetics and power output of muscle to enhance the work done on a load. A mathematical model was created in which a gravitational point load was connected via a linear spring to a muscle (based on the contractile properties of the sartorius of leopard frogs, Rana pipiens). The model explored the effects of load mass, tendon compliance, and delay between onset of contraction and release of the load (catch) on lift height and power output as measures of performance. Series compliance resulted in increased lift height over a relatively narrow range of compliances, and the effect was quite modest without an imposed catch mechanism unless the load was unrealistically small. Peak power of the muscle-tendon complex could be augmented up to four times that produced with a muscle alone, however, lift height was not predicted by peak power. Rather, lift height was improved as a result of the compliance synchronizing the time courses of muscle force and shortening velocity, in particular by stabilizing shortening velocity such that muscle power was sustained rather than rising and immediately falling. With a catch mechanism, enhanced performance resulted largely from energy storage in the compliance during the period of catch, rather than increased time for muscle activation before movement commenced. However, series compliance introduced a trade-off between work done before versus after release of the catch. Thus, the ability of tendons to enhance locomotor performance (i.e. increase the work done by muscle) appears dependent not only on their established role in storing energy and increasing power, but also on their ability to modulate the kinetics of muscle contraction such that power is sustained over more of the contraction, and maximizing the balance of work done before versus after release of a catch.

Modifying motor unit territory placement in the Fuglevand model.

The Fuglevand model is often used to address challenging questions in neurophysiology; however, there are elements of the neuromuscular system unaccounted for in the model. For instance, in some muscles, slow and fast motor units (MUs) tend to reside deep and superficially in the muscle, respectively, necessarily altering the development of surface electromyogram (EMG) power during activation. Thus, the objective of this study was to replace the randomized MU territory (MUT) placement algorithm in the Fuglevand model with an optimized method capable of reflecting these observations. To accomplish this, a weighting term was added to a previously developed optimization algorithm to encourage regionalized MUT placement. The weighting term consequently produced significantly different muscle fibre type content in the deep and superficial portions of the muscle. The relation between simulated EMG and muscle force was found to be significantly affected by regionalization. These changes were specifically a function of EMG power, as force was unaffected by regionalization. These findings suggest that parameterizing MUT regionalization will allow the model to produce a larger variety of EMG-force relations, as is observed physiologically, and could potentially simulate the loss of specific MU types as observed in ageing and clinical populations.

The superposition principle applied to grasping an object producing moments outside anatomically-defined axes.

The superposition principle suggests that motor commands can be divided into individually controlled components that summate to produce complex motor actions. Previous studies have examined the validity of this principle in human grasping by changing moments acting on an object about a single anatomically-defined axis and asking subjects to hold the object while their forearm was constrained. Superposition was reflected as separate control of the grip force and moments required to prevent object slip and maintain orientation. The objective of this study was to examine the robustness of this principle by: 1) expanding the range of tasks to include those where moments act on an object with respect to moment arms not necessarily in line with the anatomically-defined axes; 2) asking subjects to hold the object in an unconstrained manner. Ten subjects were asked to lift and hold an object vertically under eighteen moment conditions. Force and moment data from all digits were analysed using principal components analysis (PCA). Different PCAs were run for variable sets corresponding to moments about the long axis of the forearm (M(x)), the vertical (M(y)) and grip (M(z)) axes, and for the entire dataset (M(3D)). The PCA showed grip force and moment variables on separate PCs for the M(x), M(y), and M(3D) variable sets. The M(3D) PCA also showed a separation of variables corresponding to moments about each anatomically-defined axis. Thus, the present results show that the superposition principle holds during natural manipulation of an object experiencing external moments outside the anatomically-defined axes.

Variability of middle cerebral artery blood flow with hypercapnia in women.

We examined the effect of euoxic hypercapnia on middle cerebral artery (MCA) blood flow velocity waveform parameters in pre- and postmenopausal women by exposing 24 healthy women (12 pre-, 12 postmenopausal) to hypercapnia for 20 min. MCA blood flow velocity was measured continuously by transcranial Doppler ultrasound. The data were run through an algorithm that detected the feature points of the waveforms and then analyzed for statistically significant group differences. The changes in mean blood flow velocity with euoxic hypercapnia were not significant between the two groups. However, certain feature points, particularly the velocity of the reflected shoulder (V(REFLEC)), increased (89.4 +/- 14.6 to 110.0 +/- 20.5 cm/s and 102.3 +/- 14.1 to 125.1 +/- 14.9 cm/s from euoxic eucapnia to euoxic hypercapnia in pre- and postmenopausal women, respectively), as did the augmentation index (79.9 +/- 10.4 to 85.9 +/- 12.6% and 114.7 +/- 12.8 to 119.0 +/- 12.6%) and pulsatility index (0.86 +/- 0.18 to 0.74 +/- 0.15 and 0.71 +/- 0.11 to 0.66 +/- 0.11). Furthermore, while systolic peak velocity (V(SYS)) was the highest point of the waveform in premenopausal women, V(REFLEC) was the highest point for the postmenopausal cohort. The implications of this finding become obvious when calculating pulsatility index (PI), the values of which varied significantly for the postmenopausal women, depending on whether V(SYS) or the absolute maximum was used. These findings suggest that hypercapnia increases blood flow velocity waveform reflections, and that PI calculations, particularly for older age groups, may need to be considered more carefully, since these reflections often exceed the systolic peak velocity.