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

ABSTRACT: 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?

SUBMITTER: Tolmacheva A

PROVIDER: S-EPMC5610384 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Tolmacheva Aleksandra A Savolainen Sarianna S Kirveskari Erika E Lioumis Pantelis P Kuusela Linda L Brandstack Nina N Ylinen Aarne A Mäkelä Jyrki P JP Shulga Anastasia A

Journal of neurotrauma 20170721 18

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 h ...[more]

PMID: 28635523

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Project description:OBJECTIVE:To determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response. METHODS:Neurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging. RESULTS:PAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = -0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS. INTERPRETATION:Assessment of PAS-induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well-tolerated "electrophysiological biomarker" to monitor therapy response in the future. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov: Identifier: NCT01865578.

Project description:Advances in our understanding of neural plasticity have prompted the emergence of neuromodulatory interventions, which modulate corticomotor excitability (CME) and hold potential for accelerating stroke recovery. Endogenous paired associative stimulation (ePAS) involves the repeated pairing of a single pulse of peripheral electrical stimulation (PES) with endogenous movement-related cortical potentials (MRCPs), which are derived from electroencephalography. However, little is known about the optimal parameters for its delivery. A factorial design with repeated measures delivered four different versions of ePAS, in which PES intensities and movement type were manipulated. Linear mixed models were employed to assess interaction effects between PES intensity (suprathreshold (Hi) and motor threshold (Lo)) and movement type (Voluntary and Imagined) on CME. ePAS interventions significantly increased CME compared to control interventions, except in the case of Lo-Voluntary ePAS. There was an overall main effect for the Hi-Voluntary ePAS intervention immediately post-intervention (p = 0.002), with a sub-additive interaction effect at 30 min' post-intervention (p = 0.042). Hi-Imagined and Lo-Imagined ePAS significantly increased CME for 30 min post-intervention (p = 0.038 and p = 0.043 respectively). The effects of the two PES intensities were not significantly different. CME was significantly greater after performing imagined movements, compared to voluntary movements, with motor threshold PES (Lo) 15 min post-intervention (p = 0.012). This study supports previous research investigating Lo-Imagined ePAS and extends those findings by illustrating that ePAS interventions that deliver suprathreshold intensities during voluntary or imagined movements (Hi-Voluntary and Hi-Imagined) also increase CME. Importantly, our findings indicate that stimulation intensity and movement type interact in ePAS interventions. Factorial designs are an efficient way to explore the effects of manipulating the parameters of neuromodulatory interventions. Further research is required to ensure that these parameters are appropriately refined to maximise intervention efficacy for people with stroke and to support translation into clinical practice.

Project description:Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cognition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China (approval No. TJ-A20151102) on July 11, 2015.

Project description:IntroductionStroke survivors can have a high disability rate with low quality of daily life, resulting in a heavy burden on family and society. Transcranial magnetic stimulation has been widely applied to brain injury repair, neurological disease treatment, cognition and emotion regulation and so on. However, there is still much to be desired in the theories of using these neuromodulation techniques to treat stroke-caused hemiplegia. It is generally recognised that synaptic plasticity is an important basis for functional repair after brain injury. This study protocol aims to examine the corticocortical paired associative stimulation (ccPAS) for inducing synaptic plasticity to rescue the paralysed after stroke.Methods and analysisThe current study is designed as a 14-week double-blind randomised sham-controlled clinical trial, composed of 2-week intervention and 12-week follow-up. For the study, 42 patients who had a stroke aged 40-70 will be recruited, who are randomly assigned either to the ccPAS intervention group, or to the control group at a 1:1 ratio, hence an equal number each. In the intervention group, ccPAS is practised in conjunction with the conventional rehabilitation treatment, and in the control group, the conventional rehabilitation treatment is administered with sham stimulation. A total of 10 interventions will be made, 5 times a week for 2 weeks. The same assessors are supposed to evaluate the participants' motor function at four time points of the baseline (before 10 interventions), treatment ending (after 10 interventions), and two intervals of follow-up (1 and 3 months later, respectively). The Fugl-Meyer Assessment Upper Extremity is used for the primary outcomes. The secondary outcomes include changes in the assessment of Action Research Arm Test (ARAT), Modified Barthel Index (MBI), electroencephalogram (EEG) and functional MRI data. The adverse events are to be recorded throughout the study.Ethics and disseminationThis study was approved by the Medical Ethics Committee of Yueyang Hospital. All ethical work was performed in accordance with the Helsinki declaration. Written informed consent was obtained from all individual participants included in the study. Study findings will be disseminated in the printed media.Trial registration numberChinese Clinical Trial Registry: ChiCTR2000036685.

Dataset Information

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

Publications

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

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