Serial sarcomere number is substantially decreased within the paretic biceps brachii in individuals with chronic hemiparetic stroke

2020 ◽  
Author(s):  
Jonaz Moreno
2021 ◽  
Vol 118 (26) ◽  
pp. e2008597118
Author(s):  
Amy N. Adkins ◽  
Julius P. A. Dewald ◽  
Lindsay P. Garmirian ◽  
Christa M. Nelson ◽  
Wendy M. Murray

A muscle’s structure, or architecture, is indicative of its function and is plastic; changes in input to or use of the muscle alter its architecture. Stroke-induced neural deficits substantially alter both input to and usage of individual muscles. We combined in vivo imaging methods (second-harmonic generation microendoscopy, extended field-of-view ultrasound, and fat-suppression MRI) to quantify functionally meaningful architecture parameters in the biceps brachii of both limbs of individuals with chronic hemiparetic stroke and in age-matched, unimpaired controls. Specifically, serial sarcomere number (SSN) and physiological cross-sectional area (PCSA) were calculated from data collected at three anatomical scales: sarcomere length, fascicle length, and muscle volume. The interlimb differences in SSN and PCSA were significantly larger for stroke participants than for participants without stroke (P = 0.0126 and P = 0.0042, respectively), suggesting we observed muscle adaptations associated with stroke rather than natural interlimb variability. The paretic biceps brachii had ∼8,200 fewer serial sarcomeres and ∼2 cm2 smaller PCSA on average than the contralateral limb (both P < 0.0001). This was manifested by substantially smaller muscle volumes (112 versus 163 cm3), significantly shorter fascicles (11.0 versus 14.0 cm; P < 0.0001), and comparable sarcomere lengths (3.55 versus 3.59 μm; P = 0.6151) between limbs. Most notably, this study provides direct evidence of the loss of serial sarcomeres in human muscle observed in a population with neural impairments that lead to disuse and chronically place the affected muscle at a shortened position. This adaptation is consistent with functional consequences (increased passive resistance to elbow extension) that would amplify already problematic, neurally driven motor impairments.


2020 ◽  
Author(s):  
Amy N. Adkins ◽  
Julius P.A. Dewald ◽  
Lindsay Garmirian ◽  
Christa M. Nelson ◽  
Wendy M. Murray

ABSTRACTA muscle’s structure, or architecture, is indicative of its function and is plastic; changes in input to or use of the muscle alter its architecture. Stroke-induced neural deficits substantially alter both input to and usage of individual muscles. Here, we combined novel in vivo imaging methods (second harmonic generation microendoscopy, extended field-of-view ultrasound, and fat-supression MRI) to quantify functionally meaningful muscle architecture parameters in the biceps brachii of both limbs of individuals with chronic hemiparetic stroke and in age-matched, unimpaired controls. Specifically, serial sarcomere number and physiological cross-sectional area were calculated from data collected at three anatomical scales: sarcomere length, fascicle length, and muscle volume. Our data indicate that the paretic biceps brachii had ~8,500 fewer serial sarcomeres compared to the contralateral limb (p=0.0044). In the single joint posture tested, the decreased serial sarcomere number was manifested by significantly shorter fascicles (10.7cm vs 13.6cm; p<0.0001) without significant differences in sarcomere lengths (3.58μm vs. 3.54μm; p=0.6787) in the paretic compared to the contralateral biceps. No interlimb differences were observed in unimpaired controls, suggesting we observed muscle adaptations associated with stroke rather than natural interlimb variability. This study provides the first direct evidence of the loss of serial sarcomeres in human muscle, observed in a population with neural impairments that lead to disuse and chronically place the affected muscle at a shortened position. This adaptation is consistent with functional consequences (increased passive resistance to elbow extension) that would amplify already problematic, neurally driven motor impairments.SIGNIFICANCE STATEMENTSerial sarcomere number determines a muscle’s length during maximum force production and its available length range for active force generation. Skeletal muscle length adapts to functional demands; for example, animal studies demonstrate that chronically shortened muscles decrease length by losing serial sarcomeres. This phenomenon has never been demonstrated in humans. Integrating multi-scale imaging techniques, including two photon microendoscopy, an innovative advance from traditional, invasive measurement methods at the sarcomere scale, we establish that chronic impairments that place a muscle in a shortened position are associated with the loss of serial sarcomeres in humans. Understanding how muscle adapts following impairment is critical to the design of more effective clinical interventions to mitigate such adaptations and to improve function following motor impairments.


2015 ◽  
Vol 96 (10) ◽  
pp. e35
Author(s):  
Heather Tanksley Peters ◽  
Susan White ◽  
Stephen Page

2008 ◽  
Vol 100 (6) ◽  
pp. 3236-3243 ◽  
Author(s):  
Jacob G. McPherson ◽  
Michael D. Ellis ◽  
C. J. Heckman ◽  
Julius P. A. Dewald

Despite the prevalence of hyperactive stretch reflexes in the paretic limbs of individuals with chronic hemiparetic stroke, the fundamental pathophysiological mechanisms responsible for their expression remain poorly understood. This study tests whether the manifestation of hyperactive stretch reflexes following stroke is related to the development of persistent inward currents (PICs) leading to hyperexcitability of motoneurons innervating the paretic limbs. Because repetitive volleys of 1a afferent feedback can elicit PICs, this investigation assessed motoneuronal excitability by evoking the tonic vibration reflex (TVR) of the biceps muscle in 10 awake individuals with chronic hemiparetic stroke and measuring the joint torque and electromyographic (EMG) responses of the upper limbs. Elbow joint torque and the EMG activity of biceps, brachioradialis, and the long and lateral heads of triceps brachii were recorded during 8 s of 112-Hz biceps vibration (evoking the TVR) and for 5 s after cessation of stimulation. Repeated-measures ANOVA tests revealed significantly ( P ≤ 0.05) greater increases in elbow flexion torque and EMG activity in the paretic as compared with the nonparetic limbs, both during and up to 5 s following biceps vibration. The finding of these augmentations exclusively in the paretic limb suggests that contralesional motoneurons may become hyperexcitable and readily invoke PICs following stroke. An enhanced tendency to evoke PICs may be due to an increased subthreshold depolarization of motoneurons, an increased monoaminergic input from the brain stem, or both.


2018 ◽  
Vol 237 (1) ◽  
pp. 121-135 ◽  
Author(s):  
Jacob G. McPherson ◽  
Arno H. A. Stienen ◽  
Brian D. Schmit ◽  
Julius P. A. Dewald

2017 ◽  
Vol 31 (9) ◽  
pp. 814-826 ◽  
Author(s):  
Natalia Sánchez ◽  
Ana Maria Acosta ◽  
Roberto Lopez-Rosado ◽  
Arno H. A. Stienen ◽  
Julius P. A. Dewald

Although global movement abnormalities in the lower extremity poststroke have been studied, the expression of specific motor impairments such as weakness and abnormal muscle and joint torque coupling patterns have received less attention. We characterized changes in strength, muscle coactivation and associated joint torque couples in the paretic and nonparetic extremity of 15 participants with chronic poststroke hemiparesis (age 59.6 ± 15.2 years) compared with 8 age-matched controls. Participants performed isometric maximum torques in hip abduction, adduction, flexion and extension, knee flexion and extension, ankle dorsi- and plantarflexion and submaximal torques in hip extension and ankle plantarflexion. Surface electromyograms (EMGs) of 10 lower extremity muscles were measured. Relative weakness (paretic extremity compared with the nonparetic extremity) was measured in poststroke participants. Differences in EMGs and joint torques associated with maximum voluntary torques were tested using linear mixed effects models. Results indicate significant poststroke torque weakness in all degrees of freedom except hip extension and adduction, adductor coactivation during extensor tasks, in addition to synergistic muscle coactivation patterns. This was more pronounced in the paretic extremity compared with the nonparetic extremity and with controls. Results also indicated significant interjoint torque couples during maximum and submaximal hip extension in both extremities of poststroke participants and in controls only during maximal hip extension. Additionally, significant interjoint torque couples were identified only in the paretic extremity during ankle plantarflexion. A better understanding of these motor impairments is expected to lead to more effective interventions for poststroke gait and posture.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Steven C Cramer ◽  
Robert Zhou ◽  
Morgan Ingemanson ◽  
John J Choi ◽  
Katherine M Wu ◽  
...  

Introduction: Emerging brain mapping methods measure function of individual brain circuits and have the potential to predict a patient’s gains and needs in the context of stroke rehabilitation. We recently described a motor-parietal circuit underlying visuomotor tracking and defined an EEG coherence measure (reflecting connectivity) that predicts visuomotor learning. Here we test the hypothesis that this EEG metric predicts visuomotor learning after stroke. Methods: After baseline dense-array resting EEG, patients with chronic hemiparetic stroke were provided with a home-based gaming system. During 9 half-hour training sessions, patients played games in which the stroke-affected arm tracked objects moving on the tabletop. Games were implemented using augmented reality, which we have found has advantages for motor training and in which virtual objects are projected into the real world and modified during game play. Results: Subjects (n=12) had affected arm Box&Blocks score of 15±12 and were 35±26 mo post-stroke. Visuomotor tracking improved significantly: on a standardized visuomotor test using the gaming system, scores increased from 60.5±11.5% to 74.0±3.2% (p=0.003). Gains were specific, as other behaviors were unchanged. Individual gains in visuomotor tracking score were predicted by the EEG connectivity metric from our prior study, coherence between leads overlying ipsilesional primary motor cortex (M1i) and ipsilesional lateral parietal region in the high beta (20-30 Hz) range, with higher connectivity predicting greater visuomotor tracking gains (r=0.61, p=0.037). This too was specific, as connectivity between M1i and other brain areas did not predict gains. Secondary analysis found that baseline visuomotor tracking scores correlated with several EEG connectivity measures, all inversely and all between M1i and contralesional regions. Conclusions: We found that (1) training that targets a specific brain circuit improves behavioral output of that circuit, and (2) an EEG measure of brain connectivity within that circuit predicts these behavioral gains--both with specificity. This approach may be useful for many neural circuits and their respective rehabilitation-related behaviors.


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