Increasing the frequency of peripheral component in paired associative stimulation strengthens its efficacy

Tolmacheva, Aleksandra; Mäkelä, Jyrki P.; Shulga, Anastasia

doi:10.1038/s41598-019-40474-0

Cited by 20 publications

(40 citation statements)

References 21 publications

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“…Long-term application of PAS with the development of novel stimulation protocols has shown promising results in rehabilitation after SCI (12)(13)(14)(15). This protocol reinforces corticospinal transmission at a wide range of interstimulus intervals (ISIs) between TMS and PNS, plausibly due to an increased number of interactions between pre-and post-synaptic volleys (12).…”

Section: Introductionmentioning

confidence: 99%

Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study

et al. 2020

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Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at clinicaltrials.gov (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (R 2 adj = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.

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Section: Introductionmentioning

confidence: 99%

Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study

et al. 2020

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“…When TMS alone is used, lasting inhibitory aftereffects can be achieved with 1-Hz repetitive TMS and facilitatory aftereffects with high-frequency (more than 1 Hz) repetitive TMS [18]. In healthy subjects, TMS and PNS components alone do not increase MEPs and thus do not induce plastic changes on their own [7,9]. Thus, it is highly improbable that TMS alone would have accounted for the obtained results.…”

Section: Discussionmentioning

confidence: 93%

“…The resting motor threshold (RMT) in all muscles was over 100% of the maximum stimulator output (MSO) of the TMS device and therefore all M1 mapping was performed with a weak motor preactivation. TMS was delivered at 100% of MSO during PAS, as described previously [9,12].…”

Section: Case Presentationmentioning

confidence: 99%

“…Since conventional PAS protocols strongly depend on the exact determination of the interval between TMS and PNS (interstimulus interval, ISI) and on numerous other conditions [4], we developed a modified version of PAS. This version utilizes high-frequency PNS trains and TMS pulses given at 100% of stimulator output and leads to a robust motor-evoked potential (MEP) potentiation, an indicator of LTP-like plasticity [8,9]. Unlike conventional protocols, this modified PAS does not require exact calculation of ISI between TMS and PNS and is not highly sensitive to small inaccuracies in TMS target determination [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…This version utilizes high-frequency PNS trains and TMS pulses given at 100% of stimulator output and leads to a robust motor-evoked potential (MEP) potentiation, an indicator of LTP-like plasticity [8,9]. Unlike conventional protocols, this modified PAS does not require exact calculation of ISI between TMS and PNS and is not highly sensitive to small inaccuracies in TMS target determination [8,9]. Thus, it is feasible in challenging clinical conditions where measurements with millisecond precision are not always possible.…”

Section: Introductionmentioning

confidence: 99%

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Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report

Shulga

Savolainen

Kirveskari

et al. 2020

Spinal Cord Ser Cases

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Introduction Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) and induces plastic changes in the human corticospinal tract. We have previously shown that PAS consisting of TMS pulses given at 100% of stimulator output and high-frequency PNS is beneficial for motor rehabilitation of patients with a chronic incomplete spinal cord injury (SCI). The therapeutic possibilities of this PAS variant for walking rehabilitation of paraplegic patients are unexplored. Case presentation A 47-year old man with traumatic incomplete paraplegia (AIS D, neurological level T7) received PAS to his left leg for 3 months at 12 months post injury (PAS1) and for an additional 3 months at 24 months post injury (PAS2). The right leg had normal AIS scores and was not stimulated. Before PAS, the patient was nonambulatory, could not stand without weight support, and was consequently not eligible for conventional walking rehabilitation. After PAS1, the patient could stand for 1.5 min and take 13 steps (24 steps in follow up) on parallel bars without weight support and was enrolled into conventional walking rehabilitation. He achieved independent walking ability with a rollator. During PAS2, walking distance increased 2.4 times faster than during the preceding year. The left leg AIS score and spinal cord independence measure mobility subscore increased. No adverse effects were detected. Discussion This is the first report of PAS with a high-frequency peripheral component that enabled and promoted walking rehabilitation. Together with previous reports on this technique, this result encourages further research into its therapeutic potential and mechanism.

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A Bayesian approach to analysing cortico-cortical associative stimulation induced increases in the excitability of corticospinal projections in humans

et al. 2020

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Repeated pairing of transcranial magnetic stimulation (TMS) over left and right primary motor cortex (M1), at intensities sufficient to generate descending volleys, produces sustained increases in corticospinal excitability. In other paired associative stimulation (PAS) protocols, in which peripheral afferent stimulation is the first element, changes in corticospinal excitability achieved when the second stimulus consists of brief bursts of transcranial alternating current stimulation (tACS), are comparable to those obtained if TMS is used instead (McNickle and Carson 2015). The present aim was to determine whether associative effects are induced when the first stimulus of a cortico-cortical pair is tACS, or alternatively subthreshold TMS. Bursts of tACS (500 ms; 140 Hz; 1 mA) were associated (180 stimulus pairs) with single magnetic stimuli (120% resting motor threshold rMT) delivered over the opposite (left) M1. The tACS ended 6 ms prior to the TMS. In a separate condition, TMS (55% rMT) was delivered to right M1 6 ms before (120% rMT) TMS was applied over left M1. In a sham condition, TMS (120% rMT) was delivered to left M1 only. The limitations of null hypothesis significance testing are well documented. We therefore employed Bayes factors to assess evidence in support of experimental hypotheses—defined precisely in terms of predicted effect sizes, that these two novel variants of PAS increase corticospinal excitability. Although both interventions induced sustained (~ 20–30 min) increases in corticospinal excitability, the evidence in support of the experimental hypotheses (over specified alternatives) was generally greater for the paired TMS-TMS than the tACS-TMS conditions.

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Increasing the frequency of peripheral component in paired associative stimulation strengthens its efficacy

Cited by 20 publications

References 21 publications

Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study

Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study

Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report

A Bayesian approach to analysing cortico-cortical associative stimulation induced increases in the excitability of corticospinal projections in humans

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