Brain Connectivity Associated with Muscle Synergies in Humans.

The human brain is believed to simplify the control of the large number of muscles in the body by flexibly combining muscle coordination patterns, termed muscle synergies. However, the neural connectivity allowing the human brain to access and coordinate muscle synergies to accomplish functional tasks remains unknown. Here, we use a surprising pair of synergists in humans, the flexor hallucis longus (FHL, a toe flexor) and the anal sphincter, as a model that we show to be well suited in elucidating the neural connectivity underlying muscle synergy control. First, using electromyographic recordings, we demonstrate that voluntary FHL contraction is associated with synergistic anal sphincter contraction, but voluntary anal sphincter contraction occurs without FHL contraction. Second, using fMRI, we show that two important medial wall motor cortical regions emerge in relation to these tasks: one located more posteriorly that preferentially activates during voluntary FHL contraction and one located more anteriorly that activates during both voluntary FHL contraction as well as voluntary anal sphincter contraction. Third, using transcranial magnetic stimulation, we demonstrate that the anterior region is more likely to generate anal sphincter contraction than FHL contraction. Finally, using a repository resting-state fMRI dataset, we demonstrate that the anterior and posterior motor cortical regions have significantly different functional connectivity with distinct and distant brain regions. We conclude that specific motor cortical regions in humans provide access to different muscle synergies, which may allow distinct brain networks to coordinate muscle synergies during functional tasks. SIGNIFICANCE STATEMENT: How the human nervous system coordinates activity in a large number of muscles is a fundamental question. The brain and spinal cord are believed to simplify the control of muscles by grouping them into functional units called muscle synergies. Motor cortex is involved in activating muscle synergies; however, the motor cortical connections that regulate muscle synergy activation are unknown. Here, we studied pelvic floor muscle synergies to elucidate these connections in humans. Our experiments confirmed that distinct motor cortical regions activate different muscle synergies. These regions have different connectivity to distinct brain networks. Our results are an important step forward in understanding the cortical control of human muscles synergies, and may also have important clinical implications for understanding movement dysfunction.

Cortical activation associated with muscle synergies of the human male pelvic floor.

Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control.

Reliability of superficial male pelvic floor structural measurements using linear-array transperineal sonography.

This study evaluated reliability of measures for superficial structures of the male pelvic floor (PF) obtained via transperineal sonography. Two embalmed cadavers were dissected to identify positioning of muscles on and around the bulb of the penis and to confirm the PF protocol. Cross-sectional area (CSA) and linear thickness of the bulb of the penis, urethra, bulbospongiosus (BS) muscles, and ischiocavernosus (IC) muscles were measured on 38 transverse images from 20 male patients by three raters with varied study knowledge and sonographic experience. Intra- and inter-rater reliability were calculated with two-way, mixed effects intra-class correlation coefficients. Measures of the bulb of the penis had the best reliability. CSA of all muscles and sagittal thickness of the BS near the central tendon had good reliability. Reliability varied for rater-identified thickest muscle region and measures of the urethra. Our study suggests that structures of the male PF can be reliably evaluated using a transperineal sonographic approach.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study.

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing.

3D curvature of muscle fascicles in triceps surae.

Muscle fascicles curve along their length, with the curvatures occurring around regions of high intramuscular pressure, and are necessary for mechanical stability. Fascicles are typically considered to lie in fascicle planes that are the planes visualized during dissection or two-dimensional (2D) ultrasound scans. However, it has previously been predicted that fascicles must curve in three-dimensional (3D) and thus the fascicle planes may actually exist as 3D sheets. 3D fascicle curvatures have not been explored in human musculature. Furthermore, if the fascicles do not lie in 2D planes, then this has implications for architectural measures that are derived from 2D ultrasound scans. The purpose of this study was to quantify the 3D curvatures of the muscle fascicles and fascicle sheets within the triceps surae muscles and to test whether these curvatures varied among different contraction levels, muscle length, and regions within the muscle. Six male subjects were tested for three torque levels (0, 30, and 60% maximal voluntary contraction) and four ankle angles (-15, 0, 15, and 30° plantar flexion), and fascicles were imaged using 3D ultrasound techniques. The fascicle curvatures significantly increased at higher ankle torques and shorter muscle lengths. The fascicle sheet curvatures were of similar magnitude to the fascicle curvatures but did not vary between contractions. Fascicle curvatures were regionalized within each muscle with the curvature facing the deeper aponeuroses, and this indicates a greater intramuscular pressure in the deeper layers of muscles. Muscle architectural measures may be in error when using 2D images for complex geometries such as the soleus.

3D fascicle orientations in triceps surae.

The aim of this study was to determine the three-dimensional (3D) muscle fascicle architecture in human triceps surae muscles at different contraction levels and muscle lengths. Six male subjects were tested for three contraction levels (0, 30, and 60% of maximal voluntary contraction) and four ankle angles (-15, 0, 15, and 30° of plantar flexion), and the muscles were imaged with B-mode ultrasound coupled to 3D position sensors. 3D fascicle orientations were represented in terms of pennation angle relative to the major axis of the muscle and azimuthal angle (a new architectural parameter introduced in this study representing the radial angle around the major axis). 3D orientations of the fascicles, and the sheets along which they lie, were regionalized in all the three muscles (medial and lateral gastrocnemius and the soleus) and changed significantly with contraction level and ankle angle. Changes in the azimuthal angle were of similar magnitude to the changes in pennation angle. The 3D information was used for an error analysis to determine the errors in predictions of pennation that would occur in purely two-dimensional studies. A comparison was made for assessing pennation in the same plane for different contraction levels, or for adjusting the scanning plane orientation for different contractions: there was no significant difference between the two simulated scanning conditions for the gastrocnemii; however, a significant difference of 4.5° was obtained for the soleus. Correct probe orientation is thus more critical during estimations of pennation for the soleus than the gastrocnemii due to its more complex fascicle arrangement.

In-vivo determination of 3D muscle architecture of human muscle using free hand ultrasound.

Muscle architecture is an important parameter affecting the muscle function. Most of the previous studies on in-vivo muscle architecture have used in 2D ultrasound. The importance of the third dimension has not been much explored due to lack of appropriate methods. DT-MRI has been used to study muscle architecture in 3D, however, due to long scan times of about 15 min DT-MRI has not been suitable to study active muscle contractions. The purpose of this study was to develop and validate methods to determine in-vivo muscle fascicle orientations in 3D using ultrasound. We have used 2D ultrasound and a 3D position tracker system to find the 3D fascicle orientation in 3D space. 2D orientations were obtained by using automated methods developed in our previous studies and we have extended these in the current study to obtain the 3D muscle fascicle orientation in 3D space. The methods were validated using the physical phantom and we found that the mean error in the measurement was less than 0.5° in each of the three co-ordinate planes. These methods can be achieved with short scan times (less than 2 min for the gastrocnemii) and will thus enable future studies to quantify 3D muscle architecture during sub-maximal voluntary contractions.

Computational methods for quantifying in vivo muscle fascicle curvature from ultrasound images.

Muscle fascicles curve during contraction, and this has been seen using B-mode ultrasound. Curvature can vary along a fascicle, and amongst the fascicles within a muscle. The purpose of this study was to develop an automated method for quantifying curvature across the entirety of an imaged muscle, to test the accuracy of the method against synthetic images of known curvature and noise, and to test the sensitivity of the method to ultrasound probe placement. Both synthetic and ultrasound images were processed using multiscale vessel enhancement filtering to accentuate the muscle fascicles, wavelet-based methods were used to quantify fascicle orientations and curvature distribution grids were produced by quantifying local curvatures for each point within the image. Ultrasound images of ramped isometric contractions of the human medial gastrocnemius were acquired in a test-retest study. The methods enabled distinct curvatures to be determined in different regions of the muscle. The methods were sensitive to kernel sizes during image processing, noise within the image and the variability of probe placements during retesting. Across the physiological range of curvatures and noise, curvatures calculated from validation grids were quantified with a typical standard error of less than 0.026 m⁻¹, and this is about 1% of the maximum curvatures observed in fascicles of contracting muscle.

Movement mechanics as a determinate of muscle structure, recruitment and coordination.

During muscle contractions, the muscle fascicles may shorten at a rate different from the muscle-tendon unit, and the ratio of these velocities is its gearing. Appropriate gearing allows fascicles to reduce their shortening velocities and allows them to operate at effective shortening velocities across a range of movements. Gearing of the muscle fascicles within the muscle belly is the result of rotations of the fascicles and bulging of the belly. Variable gearing can also occur as a result of tendon length changes that can be caused by changes in the relative timing of muscle activity for different mechanical tasks. Recruitment patterns of slow and fast fibres are crucial for achieving optimal muscle performance, and coordination between muscles is related to whole limb performance. Poor coordination leads to inefficiencies and loss of power, and optimal coordination is required for high power outputs and high mechanical efficiencies from the limb. This paper summarizes key studies in these areas of neuromuscular mechanics and results from studies where we have tested these phenomena on a cycle ergometer are presented to highlight novel insights. The studies show how muscle structure and neural activation interact to generate smooth and effective motion of the body.

Automated tracking of muscle fascicle orientation in B-mode ultrasound images.

B-mode ultrasound can be used to non-invasively image muscle fascicles during both static and dynamic contractions. Digitizing these muscle fascicles can be a timely and subjective process, and usually studies have used the images to determine the linear fascicle lengths. However, fascicle orientations can vary along each fascicle (curvature) and between fascicles. The purpose of this study was to develop and test two methods for automatically tracking fascicle orientation. Images were initially filtered using a multiscale vessel enhancement (a technique used to enhance tube-like structures), and then fascicle orientations quantified using either the Radon transform or wavelet analysis. Tests on synthetic images showed that these methods could identify fascicular orientation with errors of less than 0.06 degrees . Manual digitization of muscle fascicles during a dynamic contraction resulted in a standard deviation of angle estimates of 1.41 degrees across ten researchers. The Radon transform predicted fascicle orientations that were not significantly different from the manually digitized values, whilst the wavelet analysis resulted in angles that were 1.35 degrees less, and reasons for these differences are discussed. The Radon transform can be used to identify the dominant fascicular orientation within an image, and thus used to estimate muscle fascicle lengths. The wavelet analysis additionally provides information on the local fascicle orientations and can be used to quantify fascicle curvatures and regional differences with fascicle orientation across an image.