study-design-for-navigated-repetitive-transcranial-magnetic

Study Design for Navigated Repetitive Transcranial Magnetic Stimulation for Speech Cortical Mapping

The cortical areas involved in human speech should be characterized reliably prior to surgery for brain tumors or drug-resistant epilepsy. The functional ...

University of Helsinki and Helsinki University Hospital

In spinal paired associative stimulation (PAS), orthodromic volleys are induced by transcranial magnetic stimulation (TMS) in upper motor neurons, and antidromic volleys by peripheral nerve stimulation (PNS) in lower motor neurons of human corticospinal tract. The volleys arriving synchronously to the corticomotoneuronal synapses induce spike time-dependent plasticity in the spinal cord. For clinical use of spinal PAS, it is important to develop protocols that reliably induce facilitation of corticospinal transmission. Due to variability in conductivity of neuronal tracts in neurological patients, it is beneficial to estimate interstimulus interval (ISI) between TMS and PNS on individual basis. Spinal root magnetic stimulation has previously been used for this purpose in spinal PAS targeting upper limbs. However, at lumbar level this method does not take into account the conduction time of spinal nerves of the cauda equina in the spinal canal.

The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation.

Emerging therapeutic strategies for spinal cord injury aim at sparing or restoring at least part of the corticospinal tract at the acute stage. Hence, approaches that strengthen the weak connections that are spared or restored are crucial. Transient plastic changes in the human corticospinal tract can be induced through paired associative stimulation, a noninvasive technique in which transcranial magnetic brain stimulation is synchronized with electrical peripheral nerve stimulation. A single paired associative stimulation session can induce transient plasticity in spinal cord injury patients. It is not known whether paired associative stimulation can strengthen neuronal connections persistently and have therapeutic effects that are clinically relevant. We recruited two patients with motor-incomplete chronic (one para- and one tetraplegic) spinal cord injuries. The patients received paired associative stimulation for 20-24 weeks. The paraplegic patient, previously paralyzed below the knee level, regained plantarflexion and dorsiflexion of the ankles of both legs. The tetraplegic patient regained grasping ability. The newly acquired voluntary movements could be performed by the patients in the absence of stimulation and for at least 1 month after the last stimulation session. In this unblinded proof-of-principle demonstration in two subjects, long-term paired associative stimulation induced persistent and clinically relevant strengthening of neural connections and restored voluntary movement in previously paralyzed muscles. Further study is needed to confirm whether long-term paired associative stimulation can be used in rehabilitation after spinal cord injury by itself and, possibly, in combination with other therapeutic strategies.

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients.

A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 ± 0.17 points (p < 0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 ± 29%, p = 0.046, n = 5 patients). Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.

Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand.

The intracarotid amobarbital procedure (IAP) is the current "gold standard" in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG).

A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients.

Accurate re-positioning of the coil is challenging in magnetic stimulation at the cervical spinal level. The applicability of coil location control for this type of stimulation is unexplored.

The use of electronic coil location control for focal magnetic stimulation at the cervical level.

Long-term paired associative stimulation (PAS) is a non-invasive combination of transcranial magnetic stimulation and peripheral nerve stimulation and leads to improved hand motor function in individuals with incomplete traumatic tetraplegia. Spinal cord injuries (SCIs) can also be induced by neurological diseases. We tested a similar long-term PAS approach in patients with non-traumatic neurological SCI.

Paired associative stimulation improves hand function after non-traumatic spinal cord injury: A case series.

To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis.

Interictal magnetoencephalography in parietal lobe epilepsy - Comparison of equivalent current dipole and beamformer (SAMepi) analysis.

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 ( = 0.014 and  = 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 (  = 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.

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

Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.

A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial.

Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called "high-PAS", induces motor-evoked potential (MEP) potentiation in healthy subjects and improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as "minimal intensity required to produce F-responses". We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence ("baseline"). In addition, we applied this intensity at + 25%, - 25%, and - 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of "baseline" and "baseline - 25%" levels but not at + 25% or - 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.

Article	Year
The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation. Journal of neuroscience methods\| PubMed ID: 25597909	2015
Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. Spinal cord series and cases\| PubMed ID: 28053760	2016
Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand. Journal of neurotrauma\| PubMed ID: 28635523	2017
A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients. PloS one\| PubMed ID: 29966017	2018
The use of electronic coil location control for focal magnetic stimulation at the cervical level. Journal of neuroscience methods\| PubMed ID: 31574289	2019
Paired associative stimulation improves hand function after non-traumatic spinal cord injury: A case series. Clinical neurophysiology practice\| PubMed ID: 31886442	2019
Interictal magnetoencephalography in parietal lobe epilepsy - Comparison of equivalent current dipole and beamformer (SAMepi) analysis. Clinical neurophysiology practice\| PubMed ID: 32258834	2020
Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study. Frontiers in neurology\| PubMed ID: 32508738	2020
A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial. Neuromodulation : journal of the International Neuromodulation Society\| PubMed ID: 35670063	2022
Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects. Scientific reports\| PubMed ID: 35864177	2022

Erika Kirveskari

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