Ergogenic effects of spinal cord stimulation on exercise performance following spinal cord injury

doi:10.21203/rs.3.rs-4110336/v1

Importance:

Cervical or upper-thoracic spinal cord injury (SCI, ≥T6) often leads to low resting blood pressure and impaired cardiovascular responses to acute exercise due to disrupted supraspinal sympathetic drive. Epidural (invasive, ESCS) and transcutaneous spinal cord stimulation (non-invasive, TSCS) have been used to target sympathetic circuits and modulate cardiovascular responses, yet their impact on submaximal upper-body exercise performance in individuals with SCI is unknown.

Objective

To compare the effects of cardiovascular-optimised ESCS and TSCS versus sham ESCS and TSCS on modulating cardiovascular responses and improving submaximal upper-body exercise performance in individuals with SCI.

Design:

Double-blinded, randomised comparison trial.

Setting:

Research center.

Participants:

Seven males with a chronic, motor-complete SCI between C6-T4, underwent a mapping session to identify cardiovascular responses to spinal cord stimulation. Subsequently, four participants (two ESCS and two TSCS) completed submaximal exercise testing.

Exposures:

Stimulation parameters (waveform, frequency, intensity, epidural electrode array configuration, specific transcutaneous electrode locations in the lumbosacral region) were optimized to elevate cardiovascular responses (CV-SCS). A sham condition (SHAM-SCS) served as a comparison. Participants performed arm-crank exercise to fatigue at a fixed workload corresponding to above ventilatory threshold, on separate days, with CV-SCS or SHAM-SCS.

Main Outcomes and Measures:

The primary outcome was time to fatigue during submaximal exercise. Heart rate and gas exchange variables were recorded throughout exercise and used to calculate oxygen pulse (a surrogate for stroke volume, SV). Blood pressure (BP) was monitored before exercise (pre-post applying stimulation). Rating of perceived exertion (RPE) was recorded every 5-min.

Results

CV-SCS increased resting BP, left ventricular cardiac contractility and total peripheral resistance. CV-SCS increased time to fatigue with ESCS and TSCS, relative to SHAM-SCS. Relative to baseline, change in systolic BP at rest was greater with CV-SCS versus SHAM-SCS. Peak oxygen pulse during exercise was greater with CV-SCS relative to SHAM-SCS. Furthermore, RPE tended to be lower with CV-SCS than SHAM-SCS during exercise.

Conclusions and Relevance:

Comparable improvements in time to fatigue with ESCS and TSCS suggest that both approaches could be promising ergogenic aids to support exercise performance or rehabilitation, along with reducing fatigue during activities of daily living in individuals with SCI.

Neurology

Physiology

Cardiac & Cardiovascular Systems

Biomedical Engineering

Sports Medicine and Kinesiology

Physical Medicine & Rehab

Spinal cord injuries

spinal cord stimulation

autonomic nervous system

exercise performance

cardiovascular control

Question: Can the modulation of sympathetic spinal circuits with epidural (invasive) or transcutaneous (non-invasive) spinal cord stimulation (SCS) improve submaximal upper-body exercise performance in individuals with motor-complete spinal cord injury (SCI) above T6?

Findings: SCS resulted in improved time to fatigue compared to a sham condition, likely due to an increased resting blood pressure and oxygen pulse (a surrogate for stroke volume).

Meaning: The comparative responses with epidural and transcutaneous SCS suggest their potential as effective ergogenic aids. Transcutaneous SCS is a relatively non-invasive and less expensive alternative to epidural SCS. These findings have important ramifications for normalising physiological responses to exercise in a compromised clinical population, along with potentially optimising therapeutic adaptations during exercise training and offsetting risks associated with the progression and development of chronic diseases in individuals with SCI.

Spinal cord injury (SCI) is a multifaceted neurological condition affecting over 20 million people worldwide¹, resulting in a loss of sensory, motor and autonomic functions below the level of the lesion. Specifically, individuals with a cervical or upper-thoracic (i.e., above the sixth thoracic segment; >T6) SCI typically exhibit cardiovascular dysfunction resulting from disrupted pathways between the medulla oblongata and the sympathetic pre-ganglionic neurons at and below the level of injury.^2–4 During exercise, diminished supraspinal sympathetic output to the heart and blood vessels leads to reduced peak heart rates (HR), low brachial blood pressure (BP), reduced venous return and thus stroke volume (SV), which ultimately limits exercise performance.^5–8 Overtime, a reduction in habitual physical activity^9,10 results in an accelerated physical deconditioning that is associated with low levels of cardiorespiratory fitness (CRF).^11,12 Akin to non-injured individuals, the risk of developing chronic conditions such as cardiovascular disease, cerebrovascular dysfunction (e.g., stroke and cognitive impairments) and type-2 diabetes mellitus is significantly elevated with a low CRF^13,14, thereby increasing the risk of mortality.¹⁴ Moreover, individuals with a higher neurological level of injury are at a greater risk for developing such health complications.¹⁵

Spinal cord stimulation (SCS) has received overwhelming attention in recent years for targeting the recovery of various neurological dysfunctions. Epidural SCS (ESCS) involves the activation of dorsal root afferents using a surgically implanted electrode array on top of the dura that is connected to a pulse generator. Studies have shown that ESCS can effectively modulate cardiovascular control^16–19 and can increase peak oxygen uptake (V̇O_2peak) by up to 26% in an individual with motor-complete tetraplegia.²⁰ This acute improvement drastically outweighs the average 9% increase in V̇O_2peak achieved following 10–37 weeks of upper-body aerobic exercise training in individuals with tetraplegia.²¹ Despite its promising potential, the accessibility of ESCS within the SCI community is limited by its invasive surgical procedure²² and expensive cost.²³ Alternatively, non-invasive transcutaneous SCS (TSCS) can be used to target the same dorsal afferents as ESCS without surgical intervention.^24–26 While it has been demonstrated that TSCS can target cardio-autonomic dysfunction, such as the mitigation of orthostatic hypotension²⁷, its effectiveness for improving cardiovascular responses during acute, submaximal exercise is currently unknown. In comparison to ESCS, this approach may be safer and could offer greater flexibility in positioning electrodes to target cardiovascular function, and thus be used as a combined exercise strategy in the future.

This study aimed to compare the acute effects of ESCS and TSCS (relative to sham conditions) on modulating resting cardiovascular responses (e.g., BP, SV, cardiac contractility) and exercise performance, assessed as time to fatigue during submaximal upper-body exercise, in individuals with SCI. We hypothesized that there would be comparable improvements in time to fatigue with both ESCS and TSCS when optimized to improve cardiovascular control, relative to sham conditions.

This study received ethical approval from the University of British Columbia Clinical Research Ethics Board (H19-00932) and was conducted in accordance with the Declaration of Helsinki. Testing was performed at the International Collaboration on Repair Discoveries in the Blusson Spinal Cord Centre, University of British Columbia, Vancouver, Canada.

Participants were required to meet the following inclusion criteria: (1) aged 18–65 years; (2) non-progressive SCI ≥ T6; (3) ≥ 1-year post-injury; (4) motor-complete SCI [American Spinal Injury Association Impairment Scale (AIS) A-B, determined via the 2019 version of International Standards for Neurological Classification of Spinal Cord Injury exam²⁸]; (5) no musculoskeletal dysfunction, unhealed fractures, pressure sores, or active infections; (6) no cardiovascular, respiratory, bladder or renal disease unrelated to the SCI; and (7) no implanted medical devices (e.g., baclofen pumps, pacemakers etc.). Seven males provided written informed consent to participate in this study. Three participants had previously been implanted with a 16-electrode array [Restore-ADVANCED neurostimulator, Specify 5-6-5, Medtronic, Minneapolis, MN, USA] between the T10 and T12 spinal segments at least seven months prior to the study. Four participants were not implanted with an epidural stimulator and therefore received TSCS. Three participants completed the mapping session but withdrew from the study prior to the exercise trials for reasons unrelated to the study protocol (demographics are provided in supplementary material eFile 1). Therefore, two ESCS and two TSCS participants completed the study (Fig. 1).

Study Design and Assessments

During the first visit, participants underwent an ESCS or TSCS mapping session to identify the specific stimulation parameters (i.e., waveform, frequency, intensity, specific configurations and electrode locations over specific spinal processes) to be used during the exercise trials (Fig. 2). Parameters were chosen for two conditions: (1) those that achieved a gradual, optimal and controlled elevation in BP without discomfort or symptoms of autonomic dysreflexia (AD) [i.e., cardiovascular-optimized SCS (CV-SCS)], and (2) those that did not alter cardiovascular responses (SHAM-SCS). For the ESCS sham condition, specific electrode configurations were chosen that did not modulate BP. For the TSCS sham condition, the stimulation intensity was increased to sensory threshold and slowly decreased to 0 mA prior to the start of the exercise trial.²⁹ Representative traces for an ESCS and a TSCS participant, along with pooled data across all seven participants, are presented in Fig. 2.

Following the mapping session, participants performed a graded cardiopulmonary exercise test (CPET) to volitional exhaustion on an electronically braked arm-crank ergometer (Angio CPET, Lode B.V., Groningen, The Netherlands). Following a 3-min warm-up, workload was increased by 4–10 watts (W) per minute. These increments were chosen by a trained clinical exercise physiologist and were based on differing neurological levels of injury to facilitate volitional exhaustion within 8–12 minutes. Participants were advised to cycle at approximately 70 revolutions per minute (rpm) and were given consistent encouragement throughout. The test was terminated upon volitional exhaustion, defined as a drop in cadence below 30 rpm for a total of three times, or for more than 10 seconds on one occasion. Breath-by-breath gas exchange variables (K5, COSMED, Rome, Italy) and HR (Garmin Dual, Garmin, Olathe, KS, USA) were recorded continuously. Ratings of perceived exertion (RPE) were recorded at the end of each minute using the Borg 6–20 scale.³⁰ V̇O_2peak was determined as the highest 15-breath rolling average attained during the test. Attainment of V̇O_2peak required meeting two of the following three criteria: (1) plateau in V̇O₂, (2) respiratory exchange ratio (RER) ≥ 1.15, and (3) RPE ≥ 19.³¹ Ventilatory thresholds (V_T) were identified using a variety of strategies and via an online application tool.^32,33 All thresholds were agreed upon by two independent raters and enabled the identification of a workload corresponding to either V_T2 (prescribed for ESCS P1 and TSCS P1) or the midpoint between V_T1 and V_T2 (prescribed for ESCS P2 and TSCS P2).

Exercise Trials

A familiarization trial was conducted without SCS to cross-check the prescribed exercise intensity. Participants were then randomized to perform two exercise trials to fatigue, separated by at least 3-days of recovery, with CV-SCS and SHAM-SCS (Fig. 3). Participants and researchers were blinded to the trial allocation and therefore an unblinded clinician adjusted the stimulation parameters prior to exercise. Trials were performed at a constant workload corresponding to their V_T (see Fig. 1 for each participant’s workloads). On occasions where participants demonstrated no signs of fatiguing by the 40-min timepoint, the intensity was increased to a work rate corresponding to the next physiological threshold, or beyond (i.e., V_T2, + 10% V_T2, + 20% V_T2).³⁴ Trunk and lower extremity muscle activity was recorded via surface electromyography (EMG) sensors (Trigno, Delsys Inc., Boston, USA). However, we were unable to effectively filter TSCS artifacts from the EMG signals recorded at the trunk for subsequent analysis, so only EMG results from the legs are reported herein. Further information is provided as supplementary material (eMethods). Superficial femoral artery blood flow and vessel diameter (5.2-13MHz, Vivid 7, GE Healthcare, Mississauga, ON) were assessed in one matched SCS pair (ESCS P2 and TSCS P2) (eFigure 1).

Data Analysis

Data are presented as means with individual data points. Effect sizes are reported as Cohen’s d, with d > 0.2, d > 0.5 and d > 0.8 representing small, moderate and large effects, respectively.³⁵

Data from the mapping sessions indicate that with optimised stimulation parameters, ESCS and TSCS increased resting BP, left ventricular cardiac contractility and total peripheral resistance (TPR) (Fig. 2). Time to fatigue was greater with CV-SCS in all participants, relative to SHAM-SCS (Fig. 4A), and was similar between ESCS and TSCS. The change in systolic BP at rest was larger with CV-SCS relative to SHAM-SCS (Fig. 4B). Peak oxygen pulse was greater with CV-SCS in comparison to SHAM-SCS (Fig. 4C). Relative to SHAM-SCS, RPE tended to be lower with CV-SCS at each time point despite a matched workload prescribed across trials (Fig. 4D-E). Overall, leg muscle activity was similar between rest and exercise in both SHAM-SCS and CV-SCS (Fig. 4F). Average leg muscle activity increased no more than 1µV between condition for any participant, and the average increase in activity was only 0.16µV. Peak systolic velocity and shear rate were greater with CV-SCS, relative to SHAM-SCS (eFigure 1). Values for these comparisons are reported in Table 1. There were no adverse events related to the exercise protocol, ESCS or TSCS, but one ESCS participant developed a skin lesion on their back due to friction with their chair unrelated to the study.

This case-series demonstrated that ESCS and TSCS improved resting cardiovascular outcomes and subsequently enhanced acute submaximal upper-body exercise performance in individuals with an upper-thoracic or cervical, chronic, motor-complete SCI. Notably, not only is this study the first to show that non-invasive TSCS can improve upper-body exercise performance, but also the first to observe comparable improvements relative to ESCS.

Delivering SCS in the lower thoracic/lumbosacral region is the most commonly reported location for increasing BP at rest in individuals with SCI.³⁶ Others have identified this area as the ‘haemodynamic hotspot’ for modulating cardiovascular control.³⁷ Our mapping sessions with TSCS demonstrated robust haemodynamic responses upon receiving dual stimulation over the T11 and L1 spinal segments. Whilst there were similar increases in left ventricular contractility with both SCS strategies, there were greater changes in TPR with ESCS. This is perhaps due to how ESCS can target and thus activate specific sympathetic circuitry to improve vasomotor tone below the level of injury.³⁸ A plausible mechanism, known as the somato-autonomic reflex, has been discussed in a recent review.³⁹ In short, activation of primary afferent fibres results in the excitation of spinal interneurons, which relay these input signals to sympathetic pre-, and subsequently, post-ganglionic neurons that ultimately stimulate functional changes in the target organ, which in this case is vasoconstriction.

During exercise, the CV-SCS parameters seemingly modulated supraspinal sympathetic drive to increase resting BP and subsequently peak oxygen pulse, implying a greater peak SV²⁰ and thus cardiac output; which may be supported by no noticeable change in HR across trials. A greater peak systolic velocity and shear rate in the superficial femoral artery with CV-SCS, albeit in only two participants, complements the increases in BP and peak oxygen pulse. This potentially larger SV likely enabled a greater delivery of substrates to meet the metabolic demands of the upper-body musculature, supported the removal of waste metabolites, and ultimately prolonged the onset of fatigue.⁴⁰ Furthermore, the lack of change in leg muscle activity during the exercise trials suggests that the modulation of BP could be due to the reactivation of vasomotor tone alone rather than via a skeletal muscle pump mechanism to increase venous return. Limitations in filtering TSCS artifacts from the trunk EMG signals restricted our understanding of trunk muscle activation in response to CV-SCS, and whether this may have improved trunk stability and therefore exercise performance. Arm-cycling and other exercises are known to activate trunk musculature in individuals with SCI > T6^41–43, but it is possible that SCS may further increase this activation through recruitment of spinal pathways that innervate these muscles, or through direct stimulation of muscle tissue adjacent to the stimulation site (e.g., erector spinae).

A recent finding suggests that TSCS may increase BP by simply lowering the threshold for AD.⁴⁴ However, other TSCS studies have demonstrated its preventative and therapeutic effects on episodes of AD.^45,46 The rigorous mapping used in this study to identify optimal transcutaneous electrode placement together with cautious monitoring of cardiovascular responses, enabled a safe and controlled elevation in BP with TSCS without inducing cardiovascular-related adverse events. Importantly, this case-series included individuals with varying levels of fitness, one of which exhibited a V̇O_2peak on par with elite athletes with SCI.⁴⁷ The robust improvements in exercise performance across all participants suggests that the ergogenic benefits of SCS are not limited to either sedentary or trained populations.

Previously, strategies to augment cardiovascular responses in individuals with SCI have been explored (e.g., abdominal binding^48,49, lower-body positive pressure⁵⁰, compression garments⁵¹ and α-1 agonist midodrine⁵²), yet the evidence on their effectiveness to enhance acute upper-body exercise performance is inconclusive. Consequently, individuals, and particularly athletes, are known to intentionally induce AD to increase BP, a practice referred to as ‘boosting’^53,54, which can provide individuals with an ergogenic advantage.^55–57 Despite the potential benefits, there are life-threatening consequences associated with using this practice in the field.⁵⁸ A recent survey regarding the opinions of individuals with SCI on SCS strategies revealed that over 80% of respondents report that if they were to receive SCS, maintaining physical health would be a key benefit, and thus 91% would be willing to follow a specific training/rehabilitation protocol.⁵⁹ More individuals would be interested in trying TSCS (80%) versus ESCS (61%), perhaps owing its relatively non-invasive nature. With the eventual commercialization of TSCS devices, there is likely to be greater community uptake by individuals with SCI, with its utilisation improving acute exercise performance, minimising fatigue in everyday life and possibly eliciting greater therapeutic adaptations as part of a longitudinal intervention.

There are several considerations to this study. Firstly, our small sample size warrants adequately powered studies to corroborate our findings that ESCS and TSCS can improve exercise performance in individuals with SCI. Secondly, a recent study called for research to prescribe exercise intensity via traditional physiological anchors (e.g., ventilatory threshold) as the use of fixed percentages (i.e., %V̇O_2peak, %HR_peak) in individuals with SCI results in large inter-individual variation.⁶⁰ However, it is notoriously difficult to identify ventilatory thresholds in individuals with higher neurological levels of injury.^61,62 As such, it was difficult to identify these thresholds and subsequently prescribe a uniform exercise intensity across participants. Furthermore, during the familiarisation sessions we observed different responses to exercise performed at V_T1 versus V_T2, likely due to differences in age, aerobic capacity and upper-extremity function. Therefore, to overcome this we prescribed a workload corresponding to at or above the midpoint of V_T1 and V_T2, allowing individualised workloads while still implementing an element of consistency across both matched pairs of participants. Thirdly, while recent research has begun to report on novel filtering approaches to manage TSCS artifacts in EMG signals, these are only in EMG recordings from the limbs where TSCS contamination is considerably less, and often in recordings where substantial voluntary muscle activity is present.^63,64 Neither of these novel filters nor more common EMG filters were able to adequately filter TSCS artifacts from our trunk muscle recordings. As research continues to demonstrate the benefits of SCS therapies, there is a clear need for experts in the field of signal processing to develop techniques to effectively filter TSCS artifacts from nearby EMG recordings in the trunk so we may better understand the effect of SCS on trunk muscle activity. Finally, while our mapping data indicated a possible decrease in SV with ESCS, this is likely to be due to a limitation within the Modelflow prediction resulting from rapid alterations in haemodynamic control/stability with noisy SCS.⁶⁵

Evidently, further work is required to tease apart the distinct mechanisms by which ESCS and TSCS regulate cardiovascular control and thus contribute to improvements in upper-body exercise performance. Looking forward, researchers should consider using echocardiography to elucidate any changes in cardiac function during mapping sessions. Furthermore, given that we could only measure shear rate in two participants, adequately powered studies should explore whether increases in shear rate during exercise drive any beneficial endothelial physiological adaptations in non-active limbs in this population, and whether this is influenced by SCS. The long-term effects of both ESCS and TSCS on exercise capacity and other prominent health markers is also an important avenue for future research. Lastly, while there are promising data supporting the safety of both SCS strategies^66,67, infrequent adverse events have been reported⁶⁸ and therefore researchers should endeavour to be transparent with adverse event reporting going forward.

With optimized CV-SCS parameters, both ESCS and TSCS mitigated resting hypotension and improved acute upper-body exercise performance in individuals with a cervical or upper-thoracic, motor-complete SCI. These findings have important ramifications for normalising physiological responses to exercise in a compromised clinical population. However, further work is warranted to understand the mechanisms underpinning these improvements. As TSCS is a non-invasive and relatively less expensive alternative to ESCS, it could be used as a therapeutic tool to stimulate meaningful physiological adaptions during exercise training or rehabilitation, thereby reducing the risk of chronic disease and improving health-related quality of life in individuals with SCI.

Data Availability Statement

The raw data for this case-series will be made available by the authors, without undue reservation. Request to access this raw data should be directed to Tom E. Nightingale, [email protected].

Ethics Statement

Approval of this study was provided by the institutional review board of the University of British Columbia (Clinical Research Ethics Board: H19-00932). Participants provided their written informed consent to participate in this study.

Author Contributions

The study was conceived and designed by T.E.N and A.V.K, with conceptual guidance provided by D.D.H, A.M.M.W and T.L. Data was collected by D.D.H, A.M.M.W, C.S, S.S, S.J.T.B and T.E.N. Data was analysed by D.D.H, A.M.M.W, S.J.T.B and T.E.N. D.D.H wrote the manuscript with support from A.M.M.W, S.J.T.B and T.E.N. All authors provided critical revision of the manuscript and final approval of the version to be published.

Funding

D.D.H is supported by a Nathalie Rose Barr PhD studentship (#NRB123) from the International Spinal Research Trust, a registered charity in the UK. C.S is supported by a Paralyzed Veterans of America Fellowship and the Canadian Institute for Health Research. S.S is supported by a Paralyzed Veterans of America Fellowship and the Wings for Life Spinal Cord Research Foundation. S.J.T.B is supported by Heart Research United Kingdom. A.V.K holds an Endowed Chair in rehabilitation medicine, ICORD/UBC and his laboratory are supported by funds from the Canadian Institute for Health Research, Rick Hansen Foundation, Canadian Foundation for Innovation and BC Knowledge Development Fund. T.E.N was a recipient of a 2018/2020 Michael Smith Foundation for Health Research/ICORD Research Trainee Award (#17767). T.E.N was also supported by a Wellcome Trust ISSF award (#1458993) and a generous donation from Mr Nico Torresgrosa.

Conflict of Interest

The authors declare that this study received funding from St. Jude/Abbott in the form of in-kind implantable devices. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this manuscript, or the decision to submit it for publication. A.V.K reports having several patents related to neuromodulation. All remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We thank the participants for their dedicated involvement in this study and continued motivation for exercise testing at ICORD that facilitated these research findings. We would also like to acknowledge St. Jude/Abbott for the generous device donation in one epidural participant and we are grateful to Dr David Darrow and the ESTAND study group for carrying out the following procedures: surgical implantation, medical oversight and management, project management and engineering oversight (i.e., setting ESCS program configurations). We would also like to thank Dr Raza Malik and Miss Sharrise Lin for their assistance with data collection. Figures were created using R (Version 3.5.1, R Foundation for Statistical Computing, Vienna, Austria), GraphPad (Prism Version 10.0.0 for Mac, GraphPad Software, Boston, MA, USA) and Biorender.com.

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Table 1. Individual time to fatigue, cardiorespiratory and psychophysiological data for each epidural and transcutaneous participant during the exercise trials performed with cardiovascular-optimised (CV-SCS) and sham spinal cord stimulation (SHAM-SCS).

	ESCS P1		ESCS P2		ESCS d	TSCS P1		TSCS P2		TSCS d
	CV-SCS	SHAM-SCS	CV-SCS	SHAM-SCS	ESCS d	CV-SCS	SHAM-SCS	CV-SCS	SHAM-SCS	TSCS d
Time to fatigue (mm:ss)	68:35	49:24	40:11	28:24	0.88	40:04	22:15	67:30	51:02	0.86
SBP without SCS (mmHg)	104	100	134	129	0.22	118	130	107	105	0.37
DBP without SCS (mmHg)	53	55	68	62	0.24	70	72	65	57	0.38
ΔSBP with SCS (mmHg)	12	-1	11	2	6.96	24	13	17	4	2.17
O₂ pulse (mL/beat)	13.7	12.1	7.7	6.7	0.32	13.0	12.0	8.5	7.9	0.27
Peak O₂ pulse (mL/beat)	17.8	15.4	10.9	9.2	0.45	16.5	14.0	9.6	8.8	0.39
HR (bpm)	95	96	139	148	0.16	163	165	133	137	0.15
Peak HR (bpm)	108	105	158	156	0.07	182	172	144	146	0.17
V̇O₂ (L/min)	1.30	1.17	1.13	1.00	1.08	2.13	1.98	1.17	1.14	0.14
V̇O₂ (mL/kg/min)	15.8	14.4	16.7	14.8	3.22	29.3	27.2	14.0	13.8	0.11
V̇_E (L/min)	40.3	37.4	31.8	29.5	0.43	85.0	81.6	38.1	39.1	0.04
RER	0.99	0.95	0.91	0.96	0.14	1.09	1.11	1.06	1.10	1.26
RPE (6-20)	13	17	17	17	0.94	17	17	15	17	1.01
Enjoyment (1-7)	7	6	1	1	0.11	3	2	3	2	5.0
Data are presented as the mean throughout each trial, unless stated otherwise. Effect sizes are calculated using Cohen’s d, whereby >0.2, >0.5 and >0.8 represent small (black fill, white text), moderate (grey fill, black text) and large (grey fill, white text) effects, respectively. DBP, diastolic blood pressure; ESCS, epidural spinal cord stimulation HR, heart rate; RER, respiratory exchange ratio; RPE, rating of perceived exertion; SBP, systolic blood pressure; SCS, spinal cord stimulation; TSCS, transcutaneous spinal cord stimulation; V̇_E,minute ventilation; V̇CO₂,carbondioxide production; V̇O₂,oxygen consumption.

The authors declare potential competing interests as follows: The authors declare that this study received funding from St. Jude/Abbott in the form of in-kind implantable devices. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this manuscript, or the decision to submit it for publication. A.V.K reports having several patents related to neuromodulation. All remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Ergogenic effects of spinal cord stimulation on exercise performance following spinal cord injury

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Abstract

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Objective

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Main Outcomes and Measures:

Results

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KEY POINTS

INTRODUCTION

METHODS

Study Design and Assessments

Exercise Trials

Data Analysis

RESULTS

DISCUSSION

CONCLUSION

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REFERENCES

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Additional Declarations

Supplementary Files

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