Single Session Effects of Prolonged Continuous Theta Burst Stimulation Targeting Two Brain Regions on Pain Perception in Patients with Painful Diabetic Neuropathy: A Preliminary Study.

BACKGROUND: Painful diabetic neuropathy (pDN) is the most common cause of neuropathic pain (NP) in the United States. Prolonged continuous theta burst stimulation (pcTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is quick (1-4 minutes) and tolerable for most individuals, compared to high frequency rTMS and can modulate pain thresholds in healthy participants. However, its effects on patients with chronic pain are still unclear. The primary purpose of this preliminary study is to investigate the effects of single session pcTBS targeted at the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) on a set of self-report measures of pain (SRMP) that assess the (a) sensory-discriminative; (b) affective-motivational; and (c) cognitive-evaluative aspects of pain experience. METHODS: For this prospective, single-blind study, forty-two participants with pDN were randomized to receive either pcTBS targeting the M1 or the DLPFC brain regions. SRMP were completed at baseline, post pcTBS and 24h-post pcTBS. A two-way mixed model repeated measures analysis of variance (2 brain regions by 3 time points) was conducted to evaluate the effects of pcTBS stimulation at M1 and DLPFC for each subscale of each SRMP. RESULTS: After a single session of pcTBS targeted at M1 or DLPFC in patients with pDN, statistically significant improvements from baseline to post pcTBS and baseline to 24 h-post pcTBS were observed for different SRMP subscales examining the (a) sensory-discriminative, (b) affective-motivational and (c) cognitive-evaluative components of the pain experience. At 24 h-post pcTBS, none of the participants reported any serious adverse events to the pcTBS treatment, thus demonstrating its feasibility. CONCLUSIONS: In pDN patients with NP, our study results demonstrated significant improvement in scores on self-report measures of pain (SRMP) after a single session of pcTBS targeting the M1 and DLPFC brain regions. Future studies should consider utilizing multiple sessions of pcTBS to evaluate its long-term effects on pain perception, safety and tolerability in patients with chronic pain. CLINICAL TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov website (NCT04988321).

Effect of neuroanatomy on corticomotor excitability during and after transcranial magnetic stimulation and intermittent theta burst stimulation.

Individual neuroanatomy can influence motor responses to transcranial magnetic stimulation (TMS) and corticomotor excitability after intermittent theta burst stimulation (iTBS). The purpose of this study was to examine the relationship between individual neuroanatomy and both TMS response measured using resting motor threshold (RMT) and iTBS measured using motor evoked potentials (MEPs) targeting the biceps brachii and first dorsal interosseus (FDI). Ten nonimpaired individuals completed sham-controlled iTBS sessions and underwent MRI, from which anatomically accurate head models were generated. Neuroanatomical parameters established through fiber tractography were fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD) at the point of stimulation. Cortical magnetic field induced electric field strength (EFS) was obtained using finite element simulations. A linear mixed effects model was used to assess effects of these parameters on RMT and iTBS (post-iTBS MEPs). FDI RMT was dependent on interactions between EFS and both FTSA and TFC. Biceps RMT was dependent on interactions between EFS and and both FTSA and BSD. There was no groupwide effect of iTBS on the FDI but individual changes in corticomotor excitability scaled with RMT, EFS, BSD, and FTSA. iTBS targeting the biceps was facilitatory, and dependent on FTSA and TFC. MRI-based measures of neuroanatomy highlight how individual anatomy affects motor system responses to different TMS paradigms and may be useful for selecting appropriate motor targets when designing TMS based therapies.

Intermittent theta burst stimulation modulates biceps brachii corticomotor excitability in individuals with tetraplegia.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (TMS) that can increase corticomotor excitability of hand muscles in individuals with spinal cord injury (SCI). The objective of this study was to determine the effect of iTBS on the corticomotor excitability of the biceps brachii in individuals with tetraplegia. METHODS: Ten individuals with low cervical SCI (C5-C8) and ten nonimpaired individuals completed three independent sessions. Motor evoked potentials (MEPs) served as our measure of corticomotor excitability and were collected before and after iTBS. MEPs were normalized by the electromyography corresponding to maximum voluntary contraction and analyzed using linear mixed effects models to determine the effect of iTBS (active or sham) on normalized MEPs (nMEPs). iTBS effects were compared to a ratio of active and resting motor thresholds as a measurement of corticomotor conductance potential. RESULTS: Relative to sham, active iTBS increased nMEPs over time (p < 0.001) in individuals with SCI, but not nonimpaired individuals (p = 0.915). The amplitude of nMEPs were correlated with the biceps corticomotor conductance potential (p < 0.001), with nMEPs decreasing as the ratio increased at different rates after sham or active iTBS. CONCLUSIONS: Preliminary results suggest that iTBS increases biceps corticomotor excitability in individuals with tetraplegia with effects that may be predicted by corticomotor conductance potential. Clinical trial registration NCT03277521 Registered on clinicaltrials.gov on August 24, 2017.

Withdrawal reflexes in the upper limb adapt to arm posture and stimulus location.

INTRODUCTION: Withdrawal reflexes in the leg adapt in a context-appropriate manner to remove the limb from noxious stimuli, but the extent to which withdrawal reflexes adapt in the arm remains unknown. METHODS: We examined the adaptability of withdrawal reflexes in response to nociceptive stimuli applied in different arm postures and to different digits. Reflexes were elicited at rest, and kinetic and electromyographic responses were recorded under isometric conditions, thereby allowing motorneuron pool excitability to be controlled. RESULTS: Endpoint force changed from a posterior-lateral direction in a flexed posture to predominantly a posterior direction in a more extended posture [change in force angle (mean ± standard deviation) 35.6 ± 5.0°], and the force direction changed similarly with digit I stimulation compared with digit V (change = 22.9 ± 2.9°). CONCLUSIONS: The withdrawal reflex in the human upper limb adapts in a functionally relevant manner when elicited at rest.

The effect of impaired unilateral ankle propulsion on contralateral knee joint loading.

BACKGROUND: Impairments in unilateral ankle propulsion may result from restriction by an external device or pathology such as lower limb amputation. Models of gait suggest this reduction may lead to increased collisional force on the contralateral side, potentially increasing force through the knee and increasing the risk of knee pain or osteoarthritis. RESEARCH QUESTION: How do restrictions in unilateral ankle propulsive force affect contralateral knee joint loading in otherwise healthy individuals? METHODS: 18 individuals without impairment walked on a treadmill at 1.5 m/s for two conditions: one free of restrictions, and one where a randomized limb's ankle propulsive force was restricted using an off-the-shelf ankle-foot orthosis (AFO). Ankle propulsive power, lower extremity joint work, and ground reaction force variables were calculated for the final 3 gait cycles of each condition. Tibiofemoral joint contact force (TJCF) for the limb contralateral to the AFO was calculated through a standard OpenSim workflow utilizing the gait2392 model. Intra-limb pair-wise comparisons were made between conditions. RESULTS: Compared to walking unrestricted, the limb wearing the AFO demonstrated a significant reduction in peak ankle propulsive power and positive ankle work by approximately 50 % each (p<0.01). With ankle restriction, the ipsilateral knee significantly increased positive work (p<0.01). The overall propulsion produced by that limb did not change between conditions, demonstrated by a lack of change in anterior ground reaction force impulse (p=0.11). The knee of the limb contralateral to the AFO did not display differences in any TJCF variable between conditions (all p>0.07). SIGNIFICANCE: These results suggest a unilateral deficit in ankle propulsion will not increase contralateral knee joint forces in individuals who are able to use other joints of the limb to compensate for the loss of ankle function. However, further research should investigate this relationship in those who display pathologies that may prevent more proximal compensations.

Prolonged continuous theta burst stimulation increases motor corticospinal excitability and intracortical inhibition in patients with neuropathic pain: An exploratory, single-blinded, randomized controlled trial.

OBJECTIVES: A new paradigm for Transcranial Magnetic Stimulation (TMS), referred to as prolonged continuous theta burst stimulation (pcTBS), has recently received attention in the literature because of its advantages over high frequency repetitive TMS (HF-rTMS). Clinical advantages include less time per intervention session and the effects appear to be more robust and reproducible than HF-rTMS to modulate cortical excitability. HF-rTMS targeted at the primary motor cortex (M1) has demonstrated analgesic effects in patients with neuropathic pain but their mechanisms of action are unclear and pcTBS has been studied in healthy subjects only. This study examined the neural mechanisms that have been proposed to play a role in explaining the effects of pcTBS targeted at the M1 and DLPFC brain regions in neuropathic pain (NP) patients with Type 2 diabetes. METHODS: Forty-two patients with painful diabetic neuropathy were randomized to receive a single session of pcTBS targeted at the left M1 or left DLPFC. pcTBS stimulation consisted of 1,200 pulses delivered in 1 min and 44 s with a 35-45 min gap between sham and active pcTBS stimulation. Both the activity of the descending pain system which was examined using conditioned pain modulation and the activity of the ascending pain system which was assessed using temporal summation of pain were recorded using a handheld pressure algometer by measuring pressure pain thresholds. The amplitude of the motor evoked potential (MEP) was used to measure motor corticospinal excitability and GABA activity was assessed using short (SICI) and long intracortical inhibition (LICI). All these measurements were performed at baseline and post-pcTBS stimulation. RESULTS: Following a single session of pcTBS targeted at M1 and DLPFC, there was no change in BPI-DN scores and on the activity of the descending (measured using conditioned pain modulation) and ascending pain systems (measured using temporal summation of pain) compared to baseline but there was a significant improvement of >13% in perception of acute pain intensity, increased motor corticospinal excitability (measured using MEP amplitude) and intracortical inhibition (measured using SICI and LICI). CONCLUSION: In patients with NP, a single session of pcTBS targeted at the M1 and DLPFC modulated the neurophysiological mechanisms related to motor corticospinal excitability and neurochemical mechanisms linked to GABA activity, but it did not modulate the activity of the ascending and descending endogenous modulatory systems. In addition, although BPI-DN scores did not change, there was a 13% improvement in self-reported perception of acute pain intensity.

The assessment of biceps voluntary activation with transcranial magnetic stimulation in individuals with tetraplegia.

BACKGROUND: Assessment of voluntary activation is useful in the study of neuromuscular impairments, particularly after spinal cord injury (SCI). Measurement of voluntary activation with transcranial magnetic stimulation (VATMS) is limited by technical challenges, including the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its antagonist may be an important parameter in the assessment of VATMS. OBJECTIVE: The purpose of this study was to evaluate the effect of isometric elbow flexion angle on two metrics in individuals with tetraplegia following SCI: 1) the ratio of biceps/triceps MEP amplitude across a range of voluntary efforts, and 2) VATMS. METHODS: Ten individuals with tetraplegia and ten nonimpaired individuals were recruited to participate in three sessions wherein VATMS was assessed at 45°, 90°, and 120° of isometric elbow flexion. RESULTS: In SCI participants, the biceps/triceps MEP ratio was not modulated by elbow angle. In nonimpaired participants, the biceps/triceps MEP ratio was greater in the more flexed elbow angle (120° flexion) compared to 90° during contractions of 50% and 75% MVC, but VATMS was not different. VATMS assessed in the more extended elbow angle (45° flexion) was lower relative to 90° elbow flexion; this effect was dependent on the biceps/triceps MEP ratio. In both groups, VATMS was sensitive to the linearity of the voluntary moment and superimposed twitch relationship, regardless of elbow angle. Linearity was lower in SCI relative to nonimpaired participants. CONCLUSIONS: Increasing the MEP ratio via elbow angle did not enable estimation of VATMS in SCI participants. VATMS may not be a viable approach to assess neuromuscular function in individuals with tetraplegia.

Paired pulse transcranial magnetic stimulation in the assessment of biceps voluntary activation in individuals with tetraplegia.

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle relative to its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS.

Effects of stimulus waveform on transcranial magnetic stimulation metrics in proximal and distal arm muscles.

OBJECTIVES: The purpose of this study was to determine the effect of common transcranial magnetic stimulation (TMS) waveforms (monophasic and biphasic) on resting motor threshold (RMT), active motor threshold (AMT), and motor evoked potential (MEP) amplitudes in the biceps and first dorsal interosseous (FDI) because waveforms may affect motor targets differently. We also determined test-retest reliability. METHODS: Ten individuals participated in two sessions of TMS delivered to the motor cortex. Monophasic stimulation to induce a posterior-anterior current in the brain (monoPA) and biphasic posterior-anterior then anterior-posterior (biPA-AP) were applied in each session in random order. In each session, there were four blocks of measurements (2 muscles × 2 waveforms) of RMT, AMT and MEPs at the hotspot location. MEPs were normalized to the maximum EMG signal. RESULTS: RMTs and AMTs were lower for monoPA compared to biPA-AP stimulation for the biceps (p<0.01) and FDI (p<0.01). Normalized MEPs were greater for monoPA compared to biPA-AP stimulation in the FDI (p=0.01) and not different in the biceps (p=0.86). Motor thresholds were not different between sessions suggesting high reliability (p<0.01). Normalized MEPs had very low reliability across sessions in the FDI, and moderate reliability in the biceps. DISCUSSION: Preliminary investigation suggests the effect of TMS waveform on motor thresholds is similar in upper limb proximal and distal muscles, but the effect differs per motor target for MEPs. Further, test-retest reliability of waveform effects was sensitive to target muscle. These findings may contribute to improve the efficacy and reliability of TMS for clinical use.

Effect of low-cost transcranial magnetic stimulation navigation on hotspot targeting and motor evoked potential variability in the biceps brachii.

BACKGROUND: Transcranial magnetic stimulation (TMS) can monitor or modulate brain excitability. However, reliability of TMS outcomes depends on consistent coil placement during stimulation. Neuronavigated TMS systems can address this issue, but their cost limits their use outside of specialist research environments. OBJECTIVE: The objective was to evaluate the performance of a low-cost navigated TMS approach in improving coil placement consistency and its effect on motor evoked potentials (MEPs) when targeting the biceps brachii at rest and during voluntary contractions. METHODS: We implemented a navigated TMS system using a low-cost 3D camera system and open-source software environment programmed using the Unity 3D engine. MEPs were collected from the biceps brachii at rest and during voluntary contractions across two sessions in ten non-disabled individuals. Motor hotspots were recorded and targeted via two conditions: navigated and conventional. RESULTS: The low-cost navigated TMS system reduced coil orientation error (pitch: 1.18°±1.2°, yaw: 1.99°±1.9°, roll: 1.18°±2.2° with navigation, versus pitch: 3.7°±5.7°, yaw: 3.11°±3.1°, roll: 3.8°±9.1° with conventional). The improvement in coil orientation had no effect on MEP amplitudes and variability. CONCLUSIONS: The low-cost system is a suitable alternative to expensive systems in tracking the motor hotspot between sessions and quantifying the error in coil placement when delivering TMS. Biceps MEP variability reflects physiological variability across a range of voluntary efforts, that can be captured equally well with navigated or conventional approaches of coil locating.

Assessing the effects of gait asymmetry: Using a split-belt treadmill walking protocol to change step length and peak knee joint contact force symmetry.

Asymmetrical gait may affect important outcomes such as knee joint contact force (KJCF). A split-belt treadmill (SBTM) can be used to provoke changes in step length symmetry (SLsym) and may produce a similar response in KJCF symmetry (KJCFsym) between limbs. The purpose of this study was to explore the utility of employing a SBTM walking paradigm to alter KJCF and KJCFsym and to determine if changes in SLsym coincided with changes in KJCFsym. Twenty healthy individuals performed a standardized SBTM protocol, where baseline and post-adaptation conditions had tied belt speeds of 0.5 m/s and the split-adaptation condition used a 3:1 belt speed ratio. OpenSim techniques were used to produce normalized, averaged stance phase peak KJCF during baseline walking, early- and late-adaptation, and post-adaptation. SLsym and KJCFsym values were determined. Comparisons were made for symmetry values between early- and late-adaptation and between baseline and post-adaptation. SLsym and KJCFsym did not respond in the same manner during the walking conditions. While step lengths (SL) were asymmetric during early adaptation but become more symmetric by late adaptation (p < 0.01), KJCF was symmetric throughout adaptation. Conversely, SL and KJCF exhibited similar responses during the baseline and post-adaptation conditions, with symmetry at baseline and asymmetry during post-adaptation (p < 0.01). In the post-adaptation condition, higher peak forces were demonstrated on the limb taking a shorter step. Results suggest a SBTM program may alter KJCF and KJCFsym between limbs. Furthermore, a comparison between baseline and post-adaptation may be more appropriate for evaluating the relationship between SL and KJCF.

The effect of intermittent theta burst stimulation on corticomotor excitability of the biceps brachii in nonimpaired individuals.

Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (TMS) that can increase corticomotor excitability in distal upper limb muscles, but the effect on the more proximal biceps is unknown. The study objective was to determine the effect of iTBS on corticomotor excitability of the biceps brachii in non-impaired individuals. Ten individuals completed three sessions, and an additional ten individuals completed one session in a secondary study; each session included sham and active iTBS. Resting and active motor thresholds (RMT, AMT) were determined prior to sham and active iTBS. Motor evoked potentials (MEPs) in response to single pulse TMS served as our measure of corticomotor excitability. In our primary cohort, MEPs were recorded with biphasic stimulation to accurately capture the same neurons affected by biphasic iTBS. MEPs were recorded at an intensity of 120% of RMT, or for instances of high RMTs, 100% of the maximum stimulator output (MSO), at baseline, and 10, 20, and 30 minutes after iTBS. MEPs were normalized by the maximum voluntary isometric muscle activity. In the secondary, MEPs were recorded with monophasic stimulation, which increased our ability to record MEPs at 120% of RMT. Linear mixed effects models were used to determine the effect of iTBS on normalized MEPs (nMEPs), with analyses to evaluate the interaction of the biceps AMT:RMT ratio as a measure of corticomotor conductance. Change in nMEPs from baseline did not differ for the active and sham conditions (p = 0.915 ) when MEPs were assessed with biphasic stimulation. With MEPs assessed by monophasic stimulation, there was an increase in biceps nMEPs after active iTBS, and no change in nMEPs after sham. Our results suggest that when RMTs are expected to be high when measured with biphasic stimulation, monophasic stimulation can better capture changes in MEPs induced by iTBS, and biphasic stimulation appears limited in its ability to capture changes in biceps MEPs in nonimpaired individuals. In both cohorts, increased corticomotor excitability after iTBS occurred when the biceps AMT:RMT ratio was high. Thus, the AMT:RMT ratio may be a predictive measure to evaluate the potential for iTBS to increase biceps corticomotor excitability.

Effect of biceps-to-triceps transfer on rotator cuff stress during upper limb weight-bearing lift in tetraplegia: A modeling and simulation analysis.

Rotator cuff stress during upper limb weight-bearing lifts presumably contribute to rotator cuff disease, which is the most common cause of shoulder pain in individuals with tetraplegia. Elbow extension strength appears to be a key determinant of rotator cuff stress during upper limb weight-bearing lifts since individuals with paraplegia who generate greater elbow extensor moments experience lower rotator cuff stress relative to individuals with tetraplegia. Biceps-to-triceps transfer surgery can increase elbow extension strength in individuals with tetraplegia. The purpose of this study was to determine whether active elbow extension via biceps transfer decreases rotator cuff stress during weight-bearing lifts in individuals with tetraplegia. A forward dynamics computational framework was used to estimate muscle stress during the lift; stress was computed as muscle force divided by the peak isometric muscle force. We hypothesized that rotator cuff stresses would be lower in simulated lifting with biceps transfer relative to simulated lifting without biceps transfer. We found that limited elbow extension strength in individuals with tetraplegia, regardless of whether elbow strength is enabled via biceps transfer or is residual after spinal cord injury, results in muscle stresses exceeding 85% of the peak isometric muscle stress in the supraspinatus, infraspinatus, and teres minor. The rotator cuff stresses we estimated suggest that performance of weight-bearing activities should be minimized or assisted in order to reduce the risk for shoulder pain. Our results also indicate that biceps transfer is unlikely to decrease rotator cuff stress during weight-bearing lifts in individuals with tetraplegia.

Voluntary activation of biceps-to-triceps and deltoid-to-triceps transfers in quadriplegia.

The biceps or the posterior deltoid can be transferred to improve elbow extension function for many individuals with C5 or C6 quadriplegia. Maximum strength after elbow reconstruction is variable; the patient's ability to voluntarily activate the transferred muscle to extend the elbow may contribute to the variability. We compared voluntary activation during maximum isometric elbow extension following biceps transfer (n = 5) and deltoid transfer (n = 6) in three functional postures. Voluntary activation was computed as the elbow extension moment generated during maximum voluntary effort divided by the moment generated with full activation, which was estimated via electrical stimulation. Voluntary activation was on average 96% after biceps transfer and not affected by posture. Individuals with deltoid transfer demonstrated deficits in voluntary activation, which differed by posture (80% in horizontal plane, 69% in overhead reach, and 70% in weight-relief), suggesting inadequate motor re-education after deltoid transfer. Overall, individuals with a biceps transfer better activated their transferred muscle than those with a deltoid transfer. This difference in neural control augmented the greater force-generating capacity of the biceps leading to increased elbow extension strength after biceps transfer (average 9.37 N-m across postures) relative to deltoid transfer (average 2.76 N-m across postures) in our study cohort.

Posture-Dependent Corticomotor Excitability Differs Between the Transferred Biceps in Individuals With Tetraplegia and the Biceps of Nonimpaired Individuals.

BACKGROUND: Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. OBJECTIVE: Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. METHODS: Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. RESULTS: Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. CONCLUSIONS: Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.

Posture-dependent changes in corticomotor excitability of the biceps after spinal cord injury and tendon transfer.

Following tendon transfer of the biceps to triceps after cervical spinal cord injuries (SCI), individuals must learn to activate the transferred biceps muscle to extend the elbow. Corticomotor excitability of the transferred biceps may play a role in post-operative elbow extension strength. In this study, we evaluated whether corticomotor excitability of the transferred biceps is related to an individuals' ability to extend the elbow, and whether posture and muscle length affects corticomotor excitability after SCI and tendon transfer similarly to the nonimpaired biceps. Corticomotor excitability was assessed in twelve nonimpaired arms and six arms of individuals with SCI and biceps-to-triceps transfer using transcranial magnetic stimulation (TMS) delivered at rest. Maximum isometric elbow extensor moments were recorded in transferred arms and the fiber length of the transferred biceps was estimated using a musculoskeletal model. Across the SCI subjects, corticomotor excitability of the transferred biceps increased with elbow extension strength. Thus, rehabilitation to increase excitability may enhance strength. Excitability of the transferred biceps was not related to fiber length suggesting that similar to nonimpaired subjects, posture-dependent changes in biceps excitability are primarily centrally modulated after SCI. All nonimpaired biceps were most excitable in a posture in the horizontal plane with the forearm fully supinated. The proportion of transferred biceps in which excitability was highest in this posture differed from the nonimpaired group. Therefore, rehabilitation after tendon transfer may be most beneficial if training postures are tailored to account for changes in biceps excitability.

Braking and propulsive impulses increase with speed during accelerated and decelerated walking.

The ability to accelerate and decelerate is important for daily activities and likely more demanding than maintaining a steady-state walking speed. Walking speed is modulated by anterior-posterior (AP) ground reaction force (GRF) impulses. The purpose of this study was to investigate AP impulses across a wide range of speeds during accelerated and decelerated walking. Kinematic and GRF data were collected from 10 healthy subjects walking on an instrumented treadmill. Subjects completed trials at steady-state speeds and at four rates of acceleration and deceleration across a speed range of 0-1.8 m/s. Mixed regression models were generated to predict AP impulses, step length and frequency from speed, and joint moment impulses from AP impulses during non-steady-state walking. Braking and propulsive impulses were positively related to speed. The braking impulse had a greater relationship with speed than the propulsive impulse, suggesting that subjects modulate the braking impulse more than the propulsive impulse to change speed. Hip and knee extensor, and ankle plantarflexor moment impulses were positively related to the braking impulse, and knee flexor and ankle plantarflexor moment impulses were positively related to the propulsive impulse. Step length and frequency increased with speed and were near the subjects' preferred combination at steady-state speeds, at which metabolic cost is minimized in nondisabled walking. Thus, these variables may be modulated to minimize metabolic cost while accelerating and decelerating. The outcomes of this work provide the foundation to investigate motor coordination in pathological subjects in response to the increased task demands of non-steady-state walking.

Muscle work is increased in pre-swing during hemiparetic walking.

BACKGROUND: Muscle mechanical work is likely affected by gait abnormalities in hemiparetic walking during the paretic pre-swing phase (i.e., double support phase preceding paretic toe-off). Previous experimental studies suggest that muscle work may be decreased in the paretic leg, but paretic work may have been underestimated since experimental approaches based on net joint moments do not account for co-contraction of antagonist muscles. Also, whether the non-paretic leg does more work compared to control subjects at matched speeds and how work generation may differ between hemiparetic subjects walking with different self-selected speeds remains unknown. METHODS: Three-dimensional forward dynamics simulations of two representative hemiparetic subjects walking with different self-selected speeds (i.e., limited community=0.45 m/s and community walkers=0.9 m/s) and a speed and age-matched control subject were generated to quantify musculotendon (fiber and in-series tendon) work during paretic pre-swing. FINDINGS: Total paretic and non-paretic fiber work were increased in both the limited community and community hemiparetic walkers compared to the control. Increased fiber work in the limited community walker was primarily related to decreased fiber and tendon work by the paretic plantar flexors requiring compensatory work by other muscles. Increased fiber work in the community walker was primarily related to increased work by the hip abductors and adductors. INTERPRETATION: The hemiparetic walkers would expend more metabolic energy during pre-swing if the hemiparetic and control subjects were to perform work with the same mechanical efficiency. These results may partly explain the increased metabolic cost of hemiparetic walkers compared to nondisabled walkers at matched speeds.

Pre-swing deficits in forward propulsion, swing initiation and power generation by individual muscles during hemiparetic walking.

Clinical studies of hemiparetic walking have shown pre-swing abnormalities in the paretic leg suggesting that paretic muscle contributions to important biomechanical walking subtasks are different than those of non-disabled individuals. Three-dimensional forward dynamics simulations of two representative hemiparetic subjects with different levels of walking function classified by self-selected walking speed (i.e., limited community=0.4-0.8 m/s and community walkers = or > 0.8m/s) and a speed-matched control were generated to quantify individual muscle contributions to forward propulsion, swing initiation and power generation during the pre-swing phase (i.e., double support phase proceeding toe-off). Simulation analyses identified decreased paretic soleus and gastrocnemius contributions to forward propulsion and power generation as the primary impairment in the limited community walker compared to the control subject. The non-paretic leg did not compensate for decreased forward propulsion by paretic muscles during pre-swing in the limited community walker. Paretic muscles had the net effect to absorb energy from the paretic leg during pre-swing in the community walker suggesting that deficits in swing initiation are a primary impairment. Specifically, the paretic gastrocnemius and hip flexors (i.e., iliacus, psoas and sartorius) contributed less to swing initiation and the paretic soleus and gluteus medius absorbed more power from the paretic leg in the community walker compared to the control subject. Rehabilitation strategies aimed at diminishing these deficits have much potential to improve walking function in these hemiparetic subjects and those with similar deficits.

Leg extension is an important predictor of paretic leg propulsion in hemiparetic walking.

Forward propulsion is a central task of walking that depends on the generation of appropriate anterior-posterior ground reaction forces (AP GRFs). The AP impulse (i.e., time integral of the AP GRF) generated by the paretic leg relative to the non-paretic leg is a quantitative measure of the paretic leg's contribution to forward propulsion and is variable across hemiparetic subjects. The purpose of this study was to investigate the underlying mechanisms of propulsion generation in hemiparetic walking by identifying the biomechanical predictors of AP impulses. Three-dimensional kinematics and GRFs were recorded from 51 hemiparetic and 21 age-matched control subjects walking at similar speeds on an instrumented treadmill. Hierarchical regression models were generated for each leg to predict the AP impulse from independent biomechanical variables. Leg extension was a significant predictor and positively related to the propulsive impulse in the paretic, non-paretic and control legs. Secondarily, the hip flexor moment impulse was negatively related to the propulsive impulse. Also, the relationship of paretic and non-paretic ankle moments with the propulsive impulse depended on the paretic step ratio, suggesting the plantar flexor contribution to the propulsive impulse depends on leg angle. These results suggest that increasing paretic leg extension will increase propulsion. Increasing paretic plantar flexor output and decreasing paretic hip flexor output could also increase paretic leg propulsion. While increased pre-swing hip flexor output has been suggested to compensate for decreased plantar flexor output, such output may further impair propulsion by the paretic leg if it occurs too soon in the gait cycle.