Short Intracortical Inhibition Research Articles

Modulation Of Corticospinal Excitability and Short Intracortical Inhibition During Different Levels Of Voluntary Contraction In Untrained And Chronically Resistance Trained Individuals.

Modulation Of Corticospinal Excitability and Short Intracortical Inhibition During Different Levels Of Voluntary Contraction In Untrained And Chronically Resistance Trained Individuals.

P74-T Reduced hand dexterity in Parkinson’s disease correlates with the level of short-latency intracortical inhibition impairment

Background In Parkinson’s disease (PD), primary motor cortex (M1) shows number of impairments in excitability and plasticity. However, there has been scarce attempts to check whether there is a link between these impairments and impaired hand dexterity in PD. Methods In a group of 29 PD patients (Hoehn & Yahr stage range 1–4), measures of M1 excitability (short latency intracortical inhibition [SICI] and intracortical facilitation [ICF], and plasticity (paired associative stimulation [PAS] protocol) were collected. They were correlated with results on the Perdue pegboard task (PPT), as a measure of hand dexterity, as well as with scores on a standard clinical scale (motor section of the Unified Parkinson’s Disease Scale [UPDRS]). Patients were tested off medication, after an overnight withdrawal. All measurements were carried out on the worst affected hand. Results Increase in MEP size immediately after and 30 min after the PAS protocol did not correlate with either PPT score or UPDRS motor cores and two derived scores, lateralised UPDRS and bradykinesia score (for the worst affected side). Same was with ICF. However, there was a significant correlation between amount of SICI and PPT score (Spearman R = 0.42, p = 0.023) – the larger the inhibition the higher the PPT scores; SICI did not correlate with other clinical measures. Conclusion It seems that in untreated PD patients there is a direct link between intracortical inhibition and hand dexterity. Lack of adequate short-latency intracortical inhibition most likely interferes with fine selection of movements which is of crucial importance for hand dexterity.

Differential Neuroplastic Changes in Fibromyalgia and Depression Indexed by Up-Regulation of Motor Cortex Inhibition and Disinhibition of the Descending Pain System: An Exploratory Study.

Background: Major depressive disorder (MDD) and fibromyalgia (FM) present overlapped symptoms. Although the connection between these two disorders has not been elucidated yet, the disruption of neuroplastic processes that mediate the equilibrium in the inhibitory systems stands out as a possible mechanism. Thus, the purpose of this cross-sectional exploratory study was: (i) to compare the motor cortex inhibition indexed by transcranial magnetic stimulation (TMS) measures [short intracortical inhibition (SICI) and intracortical facilitation (ICF)], as well as the function of descending pain modulatory systems (DPMS) among FM, MDD, and healthy subjects (HS); (ii) to compare SICI, ICF, and the role of DPMS evaluated by the change on Numerical Pain Scale (NPS) during the conditioned pain modulation test (CPM-test) between FM and MDD considering the BDNF-adjusted index; (iii) to assess the relationship between the role of DPMS and the BDNF-adjusted index, despite clinical diagnosis.Patients and Methods: A cohort of 63 women, aged 18 to 75 years [FM (n = 18), MDD (n = 19), and HC (n = 29)].Results: The MANCOVA analysis revealed that the mean of SICI was 53.40% larger in FM compared to MDD [1.03 (0.50) vs. 0.55 (0.43)] and 66.99% larger compared to HC [1.03 (0.50) vs. 0.34 (0.19)], respectively. The inhibitory potency of the DPMS assessed by the change on the NPS during CPM-test was 112.29 % lower in the FM compared to MDD [0.22 (1.37) vs. −0.87 (1.49)]. The mean of BDNF from FM compared to MDD was 35.70% higher [49.82 (16.31) vs. 14.12 (8.86)]. In FM, the Spearman’s coefficient between the change in the NPS during CPM-test with the SICI was Rho = −0.49, [confidence interval (CI) 95%; −0.78 to −0.03]. The BDNF-adjusted index was positively correlated with the disinhibition of the DPMS.Conclusion: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM.

Effects of Acupuncture Treatment on Lower Limb Spasticity in Patients Following Hemorrhagic Stroke: A Pilot Study

Background and Purpose: Lower limb spasticity is often a significant problem in stoke rehabilitation. The purpose of this study was to investigate the effects of acupuncture treatment on lower limb spasticity in patients following hemorrhagic stroke. Methods: Fifty-nine patients following hemorrhagic stroke were randomized to receive acupuncture treatment combined with conventional treatment (treatment group [TG]) or conventional treatment only (control group [CG]). Acupuncture treatments were given in 24 sessions over 4 weeks. Blinded evaluation was based on Modified Ashworth Scale (MAS), short intracortical inhibition (SICI), and Hmax/Mmax ratio as the primary outcomes. In addition, Fugl-Meyer Assessment (FMA), Barthel Index (BI), motor evoked potential (MEP) and surface integrated electromyogram (IEMG) were employed as the secondary outcomes. All the evaluations were performed at 14 and 28 days after the start of the treatment. Results: Compared with the CG, the TG showed a significantly greater over-time decrease in MAS for knee (p = 0.022) and ankle (p = 0.017), SICI (p = 0.000) and Hmax/Mmax ratio (p = 0.000). In all patients of TG, we found a greater improvement in lower-limb FMA and MEP but not in BI. IEMG show that TG obtained a greater reduction in spastic agonist muscles and a greater enhancement in spastic antagonist muscles. A significant correlation between a greater decrease in ankle MAS and a greater increase in SICI for spastic muscles was found (r = 0.390, p = 0.002). Conclusions: Acupuncture could improve the lower limb spasticity and motor function, thus providing a safe and economical approach for treating stroke patients. The potential mechanism underpinning the greater improvement may be attributed to a reshape of corticospinal plasticity induced by acupuncture.

Short Intracortical Inhibition During Voluntary Movement Reveals Persistent Impairment Post-stroke.

Objective: Short intracortical inhibition (SICI) is a GABAA-mediated phenomenon, argued to mediate selective muscle activation during coordinated motor activity. Markedly reduced SICI has been observed in the acute period following stroke and, based on findings in animal models, it has been posited this disinhibitory phenomenon may facilitate neural plasticity and contribute to early motor recovery. However, it remains unresolved whether SICI normalizes over time, as part of the natural course of stroke recovery. Whether intracortical inhibition contributes to motor recovery in chronic stroke also remains unclear. Notably, SICI is typically measured at rest, which may not fully reveal its role in motor control. Here we investigated SICI at rest and during voluntary motor activity to determine: (1) whether GABAA-mediated inhibition recovers, and (2) how GABAA-mediated inhibition is related to motor function, in the chronic phase post-stroke.Methods: We studied 16 chronic stroke survivors (age: 64.6 ± 9.3 years; chronicity: 74.3 ± 52.9 months) and 12 age-matched healthy controls. We used paired-pulse transcranial magnetic stimulation (TMS) to induce SICI during three conditions: rest, submaximal grip, and performance of box-and-blocks. Upper-extremity Fugl-Meyer Assessment and Box-and-Blocks tests were used to evaluate motor impairment in stroke survivors and manual dexterity in all participants, respectively.Results: At rest, SICI revealed no differences between ipsilesional and contralesional hemispheres of either cortical or subcortical stroke survivors, or healthy controls (P's > 0.05). During box-and-blocks, however, ipsilesional hemisphere SICI was significantly reduced (P = 0.025), especially following cortical stroke (P < 0.001). SICI in the ipsilesional hemisphere during box-and-blocks task was significantly related to paretic hand dexterity (r = 0.56, P = 0.039) and motor impairment (r = 0.56, P = 0.037).Conclusions: SICI during motor activity, but not rest, reveals persistent impairment in chronic stroke survivors indicating that inhibitory brain circuits responsible for motor coordination do not fully normalize as part of the natural history of stroke recovery. Observation that reduced SICI (i.e., disinhibition) is associated with greater motor impairment and worse dexterity in chronic hemiparetic individuals suggests the response considered to promote neuroplasticity and recovery in the acute phase could be maladaptive in the chronic phase post-stroke.

Novel Insights of Effects of Pregabalin on Neural Mechanisms of Intracortical Disinhibition in Physiopathology of Fibromyalgia: An Explanatory, Randomized, Double-Blind Crossover Study.

Background: The fibromyalgia (FM) physiopathology involves an intracortical excitability/inhibition imbalance as measured by transcranial magnetic stimulation measures (TMS). TMS measures provide an index that can help to understand how the basal neuronal plasticity state (i.e., levels of the serum neurotrophins brain-derived neurotrophic factor (BDNF) and S100-B protein) could predict the effect of therapeutic approaches on the cortical circuitries. We used an experimental paradigm to evaluate if pregabalin could be more effective than a placebo, to improve the disinhibition in the cortical circuitries in FM patients, than in healthy subjects (HS). We compared the acute intragroup effect of pregabalin with the placebo in FM patients and healthy subjects (HS) on the current silent period (CSP) and short intracortical inhibition (SICI), which were the primary outcomes. Pain scores and the pain pressure threshold (PPT) were secondary outcomes.Methods: This study included 27 women (17 FM and 10 HS), with ages ranging from 19 to 65 years. In a blinded, placebo-controlled clinical trial, participants were randomized to receive, in a cross-over manner, oral pregabalin of 150 mg or a placebo. The cortical excitability pain measures were assessed before and 90 min after receiving the medication.Results: A generalized estimating equation (GEE) model revealed that in FM, pregabalin increased the CSP by 14.34% [confidence interval (CI) 95%; 4.02 to 21.63] and the placebo reduced the CSP by 1.58% (CI 95%; −57 to 25.9) (P = 0.00). Pregabalin reduced the SICI by 8.82% (CI 95%, −26 to 46.00) and the placebo increased it by 19.56% (CI 95%; 8.10 to 59.45; P = 0.02). Pregabalin also improved the pain measures. In the treatment group, the BDNF-adjusted index was positively correlated and the serum S100-B negatively correlated with the CSP, respectively. However, in the HS, pregabalin and the placebo did not induce a statistically significant effect in either intracortical excitability or pain measures.Conclusion: These results suggest that pregabalin’s effect on cortical neural networks occurs, particularly under basal neuronal hyperexcitability, because its impact on the cortical excitability and the pain measures was observed only in the FM group. This indicates that pregabalin increased the CSP to induce inhibition in specific neural networks, while it increased the SICI to improve the excitability in other neurobiological systems. Trial registration in clinicaltrials.gov Identifier: NCT02639533.

An optimal protocol for measurement of corticospinal excitability, short intracortical inhibition and intracortical facilitation in the rectus femoris

The study aimed to determine the optimal application of single- and paired-pulse transcranial magnetic stimulation (TMS) in the rectus femoris. Twenty-nine male adults participated in the study, which involved 5 separate experiments. Experiments 1 to 3 assessed the effect of conditioning stimulus (CS) intensity (60, 70, 80 and 90% active motor threshold, AMT), contraction strength (5, 10, 20 and 50% maximum voluntary contraction, MVC), and inter-stimulus interval (ISI, 2–5 ms for short-interval intracortical inhibition, SICI and 10–15 ms for intracortical facilitation, ICF) on SICI and ICF. In Experiment 4, 30 measurements of corticospinal excitability (CSE), SICI and ICF were recorded, with the minimum number of consecutive measurements required as a probability of falling within the 95% CI determined. In Experiment 5, within- and between-day reliability of CSE, SICI and ICF was assessed. The results suggest that for SICI, a CS of 70% AMT, ISI of 2 ms, and contraction strength of 5 or 10% MVC induces the greatest level of inhibition. Negligible differences in ICF were seen across stimulus variables. The minimum number of measurements required to obtain an accurate estimate of CSE, SICI and ICF was 21, 18 and 17, respectively. Using the optimal stimulus variables and number of measurements, CSE, SICI and ICF can be measured reliably both within- and between-days (intraclass correlation coefficient, ICC ≥ 0.87, ≥0.74, and ≥0.61, respectively). The current findings can be used to guide future investigations using single- and paired-pulse TMS to elicit responses in the rectus femoris.

Intracortical facilitation within the migraine motor cortex depends on the stimulation intensity. A paired-pulse TMS study

IntroductionConnectivity within the primary motor cortex can be measured using the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates the effect of a first conditioning stimulus on the motor evoked potential (MEP) elicited by a second test stimulus when different interstimulus intervals are used. Aim of the present study was to provide, in patients suffering from migraine without aura (MwoA), additional information on intracortical facilitation (ICF), short intracortical inhibition (SICI), and long intracortical inhibition (LICI), using different intensities of the test stimulus (TS).MethodsWe enrolled 24 patients with episodic MwoA and 24 age- and sex-matched healthy volunteers. Both patients and controls were randomly assigned to two different experimental groups: the first group underwent evaluation of ICF, while in the second group we assessed SICI and LICI. All these measures were assessed by using three different suprathreshold intensities of the TS (110%, 130% and 150% of the resting motor threshold, RMT). Interstimulus intervals (ISIs) of 10 ms were used for testing ICF, while SICI and LICI were carried out by using 2 ms and 100 ms ISIs respectively. All migraine patients underwent the experimental protocol while in the interictal pain-free state.ResultsA main finding of the study was that an increased ICF could be seen in migraineurs as compared to the healthy subjects only by using a 110% intensity of the TS. Instead, no significant differences were observed between patients and controls as regards both measures of intracortical inhibition.ConclusionWe show that hyperresponsivity of the glutamatergic intracortical circuits can be detected in the migraine motor cortex only by applying a low suprathreshold intensity of stimulation. Our results strengthen the notion that, to be reliable, the assessment of cortical excitability in migraine should always include evaluation of the cortical response to different stimulation intensities.

Neurophysiological Comparison Among Tonic, High Frequency, and Burst Spinal Cord Stimulation: Novel Insights Into Spinal and Brain Mechanisms of Action

Spinal cord stimulation (SCS) is an effective option for neuropathic pain treatment. New technological developments, as high-frequency (HF) and theta burst stimulation (TBS), have shown promising results, although putative mechanisms of action still remain debated. thirty patients with lower back pain were enrolled and underwent LF, HF, and TBS. Laser evoked potentials (LEPs) were recorded by using a Nd:YAG laser. Amplitudes and latencies of the main two components (N1, N2/P2) were compared among different experimental sessions. Changes in resting motor threshold (RMT), cortical silent period (cSP), short intracortical inhibition (SICI), and intracortical facilitation (ICF) were also evaluated. TBS dampened LEP amplitudes compared with LF (N1: p = 0.032; N2/P2: p < 0.0001) and HF stimulation (N1: p = 0.029; N2/P2: p < 0.0001, Holm-Sidak post-hoc test). Concurrently, TBS increased N1 latency, when compared with baseline and LF stimulation (p = 0.009 and 0.0033). Whereas RMT and SICI did not change among experimental conditions, TBS significantly prolonged cSP duration compared with baseline (p = 0.002), LF (p = 0.048), and HF-SCS (p = 0.016); finally, both HF (p = 0.004) and TBS (p = 0.0039) increased ICF. TBS modulates medial and lateral pain pathways through distinct mechanisms, possibly involving both GABA(a)ergic and Glutamatergic networks at an intracortical level. These results may have implications for therapy and for the choice of best stimulation protocol.

Metaplasticity: A Promising Tool to Disentangle Chronic Disorders of Consciousness Differential Diagnosis.

The extent of cortical reorganization after brain injury in patients with Vegetative State/Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) depends on the residual capability of modulating synaptic plasticity. Neuroplasticity is largely abnormal in patients with UWS, although the fragments of cortical activity may exist, while patients MCS show a better cortical organization. The aim of this study was to evaluate cortical excitability in patients with disorders of consciousness (DoC) using a transcranial direct current stimulation (TDCS) metaplasticity protocol. To this end, we tested motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). These measures were correlated with the level of consciousness (by the Coma Recovery Scale-Revised, CRS-R). MEP amplitude, SICI, and ICF strength were significantly modulated following different metaplasticity TDCS protocols only in the patients with MCS. SICI modulations showed a significant correlation with the CRS-R score. Our findings demonstrate, for the first time, a partial preservation of metaplasticity properties in some patients with DoC, which correlates with the level of awareness. Thus, metaplasticity assessment may help the clinician in differentiating the patients with DoC, besides the clinical evaluation. Moreover, the responsiveness to metaplasticity protocols may identify the subjects who could benefit from neuromodulation protocols.

F64. High frequency somatosensory stimulation in cervical dystonia: Evidence for defective homeostatic plasticity in sensorimotor inhibitory circuits

Apart from motor symptoms, multiple deficits of sensory processing have been demonstrated in dystonia. The most consistent behavioural measure of this is abnormal somatosensory temporal discrimination threshold (STDT), which has recently been associated with physiological measures of reduced inhibition within the primary somatosensory area, namely paired-pulse somatosensory evoked potentials (pp-SEP) and high-frequency oscillations (HFO). High-frequency repetitive sensory stimulation (HF-RSS) is a patterned electric stimulation that, when applied to the skin through surface electrodes, has been recently reported to shorten STDT in healthy subjects and to increase the resting level of excitability in several different types of inhibitory interactions in the primary somatosensory cortex (S1) and even the primary motor cortex (M1). We asked here whether HF-RSS was able to increase inhibition also in dystonia, where a lack of inhibitory interactions has been previously described. We tested whether HF-RSS could augment cortical inhibition and, in parallel, ameliorate STDT in 12 patients with cervical dystonia. To this aim, STDT and a number of electrophysiological measures of S1 (pp-SEP, HFO, lateral inhibition) and M1 (short intracortical inhibition (SICI)) were measured before and after 45 min of HF-RSS. The results were also compared with those of 12 age-matched healthy controls. Compared with healthy controls, in whom HF-RSS, as expected, shortened STDT and increased S1 and M1 inhibition assessed with the mentioned tests, patients with cervical dystonia showed a consistent, paradoxical response: they had reduced suppression in pp-SEP, a reduced area of HFO, a smaller amount of lateral inhibition and less SICI. STDT deteriorated after HF-RSS, and the change was correlated with those in pp-SEP and HFO. We suggest that patients with dystonia have abnormal homeostatic plasticity in the inhibitory circuitry within S1, and possibly M1, and that this is responsible for their paradoxical response to HF-RSS.

Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation

Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). Herein we investigated whether neurofeedback learning using SICI enabled us to control the GABAergic system within the M1 area. Forty-five healthy subjects were randomly divided into two groups: those receiving SICI neurofeedback learning or those receiving no neurofeedback (control) learning. During both learning periods, subjects made attempts to change the size of a circle, which was altered according to the degree of SICI in the SICI neurofeedback learning group, and which was altered independent of the degree of SICI in the control learning group. Results demonstrated that the SICI neurofeedback learning group showed a significant enhancement in SICI. Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders.

Neurophysiological and cognitive impairment following repeated sports concussion injuries in retired professional rugby league players

ABSTRACTBackground: Concussion is regarded as a common injury in rugby league, however no studies have explored the long-term neurophysiological and cognitive effects of repeated concussion injuries in this sport.Methods: Former professional rugby athletes (n = 25) were compared to 25 age-matched participants with no history of a concussion. All participants completed standardised motor dexterity, reaction time, and cognitive tasks for working memory, associative learning and rule acquisition and reversal. Single-pulse transcranial magnetic stimulation (TMS) acquired motor evoked potentials and cortical silent period (cSP), as well as paired-pulse TMS for short latency intracortical inhibition and long intracortical inhibition (LICI).Results: Compared to controls, dexterity and visuomotor reaction time was slower in the rugby group compared to controls (p = 0.02, p < 0.01, respectively). The rugby group also demonstrated poorer cognitive performance than controls (p range 0.02 to < 0.01). TMS revealed significantly reduced cSP at suprathreshold stimulation intensities (p range 0.02 to <0.01), and increased LICI (p = 0.03) in the rugby group.Discussion: These findings of motor and cognitive changes, along with neurophysiological alterations, particularly with intracortical inhibition, nearly two decades post-concussion provides evidence for long-term sequelae for athletes with a history of repeated head trauma in contact sports.

Short latency intracortical inhibition in the angular gyrus characterized by paired-pulse TMS and EEG co-registration

Short latency intracortical inhibition in the angular gyrus characterized by paired-pulse TMS and EEG co-registration

8. Neurophysiological comparison among tonic, high frequency and burst spinal cord simulation: Novel insights into spinal and brain mechanisms of action

Spinal cord Stimulation (SCS) is an effective option for neuropathic pain treatment. New technological developments, as high-frequency (HF) and Theta Burst Stimulation (TBS), have shown promising results, although putative mechanisms of action are still debated. Twenty-five patients with lower back pain were enrolled and underwent LF, HF and TBS. LEPs were recorded by using a Nd:YAG laser: amplitudes and latencies of the main two components (N1, N2/P2) were compared among different experimental conditions. Similarly, changes in Resting Motor Threshold (RMT), cortical Silent Period (cSP), Short Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) were evaluated. TBS dampened LEP amplitudes compared with LF (N1: p = 0.016; N2/P2: p = 0.02) and HF stimulation (p = 0.015; p = 0.031); while RMT and SICI did not change among experimental conditions, TBS significantly prolonged cSP duration compared with baseline (p = 0.002), LF (p = 0.048) and HF-SCS (p = 0.016); both HF (p = 0.004) and TBS (p = 0.0039) increased ICF. TBS modulates the sensory-discriminative and the affective-emotional dimension of pain through distinct mechanisms, thus involving intracortical GABAergic and Glutamatergic networks. These results have implications for therapy and for the choice of the stimulation protocol.

25. The LRRK2-R1441C mutation disrupts long-term potentiation-like plasticity in Parkinson’s disease patients

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) account for up to 13% of dominant familial Parkinson’s disease (PD) cases. The clinical and pathological features of LRRK2-PD are often indistinguishable from idiopathic PD (iPD). Recent evidence pointed out that LRRK2 acts directly at the secretory and endocytic molecular machinery. Importantly, in southern Italy the R1441C mutation is the most frequent mutation reported so far. Based on the LRRK2-role on synaptic transmission, we aimed to investigate in vivo excitability and plasticity of the motor cortex by means of transcranial magnetic stimulation (TMS). Paired pulse TMS was used to investigate cortical excitability by using short intracortical inhibition and facilitation and short afferent inhibition paradigm. Intermittent theta burst stimulation (iTBS) was used to test long-term potentiation-like cortical plasticity (LTP). Eight LRRK2-PD patients harboring the R1441C mutation and 11 iPD were tested on the more affected side in ON l-dopa therapy. We observed the lack of LTP-like motor cortex plasticity in R1441C-LRRK2 patients compared to healthy-subjects and with a similar profile observed for iPD patients. Motor cortex excitability profile did not exhibit any difference among the three groups. R1441C mutation disrupts motor cortex LTP-like plasticity in Parkinson’s disease patients.

Treadmill Walking Combined With Anodal Transcranial Direct Current Stimulation in Parkinson Disease: A Pilot Study of Kinematic and Neurophysiological Effects.

We tested the hypothesis that combining treadmill walking with transcranial direct current stimulation (tDCS) enhances the gait improvements associated with treadmill walking in Parkinson disease. We explored the effects of these combined methodologies on corticospinal parameters. Eighteen participants with Parkinson disease were evaluated under the following three conditions: treadmill walking alone (treadmill), treadmill walking combined with anodal tDCS (AtDCS+treadmill) delivered over the motor cortex, and treadmill walking combined with sham stimulation (StDCS+treadmill). Overground walking performance, soleus H-reflex, reciprocal Ia inhibition from the tibialis anterior to the soleus muscle, intracortical facilitation, and short intracortical inhibition of the tibialis anterior muscle, were measured before and after each treadmill condition. The soleus H-reflex and walking performance on the treadmill were also evaluated. All treadmill conditions improved walking performance and modulated spinal and corticospinal parameters in a similar way. However, AtDCS+treadmill lead to a different modulation of reciprocal Ia inhibition in comparison with the other treadmill conditions. A single session combining treadmill walking and anodal tDCS delivered over the motor cortex resulted in a specific modulation of the reciprocal Ia inhibition from the tibialis anterior to the soleus muscle. However, this acute effect did not result in improvements of gait parameters associated with treadmill walking in Parkinson disease.

Is two better than one? Muscle vibration plus robotic rehabilitation to improve upper limb spasticity and function: A pilot randomized controlled trial.

Even though robotic rehabilitation is very useful to improve motor function, there is no conclusive evidence on its role in reducing post-stroke spasticity. Focal muscle vibration (MV) is instead very useful to reduce segmental spasticity, with a consequent positive effect on motor function. Therefore, it could be possible to strengthen the effects of robotic rehabilitation by coupling MV. To this end, we designed a pilot randomized controlled trial (Clinical Trial NCT03110718) that included twenty patients suffering from unilateral post-stroke upper limb spasticity. Patients underwent 40 daily sessions of Armeo-Power training (1 hour/session, 5 sessions/week, for 8 weeks) with or without spastic antagonist MV. They were randomized into two groups of 10 individuals, which received (group-A) or not (group-B) MV. The intensity of MV, represented by the peak acceleration (a-peak), was calculated by the formula (2πf)2A, where f is the frequency of MV and A is the amplitude. Modified Ashworth Scale (MAS), short intracortical inhibition (SICI), and Hmax/Mmax ratio (HMR) were the primary outcomes measured before and after (immediately and 4 weeks later) the end of the treatment. In all patients of group-A, we observed a greater reduction of MAS (p = 0.007, d = 0.6) and HMR (p<0.001, d = 0.7), and a more evident increase of SICI (p<0.001, d = 0.7) up to 4 weeks after the end of the treatment, as compared to group-B. Likewise, group-A showed a greater function outcome of upper limb (Functional Independence Measure p = 0.1, d = 0.7; Fugl-Meyer Assessment of the Upper Extremity p = 0.007, d = 0.4) up to 4 weeks after the end of the treatment. A significant correlation was found between the degree of MAS reduction and SICI increase in the agonist spastic muscles (p = 0.004). Our data show that this combined rehabilitative approach could be a promising option in improving upper limb spasticity and motor function. We could hypothesize that the greater rehabilitative outcome improvement may depend on a reshape of corticospinal plasticity induced by a sort of associative plasticity between Armeo-Power and MV.

PB 18 The sensorimotor μ-rhythm as pulsed inhibition of the human motor cortex? – an EEG-triggered paired-pulse TMS study

According to the influential “pulsed inhibition hypothesis” (Jensen and Mazaheri, FHN 2010), the 8–14 Hz alpha oscillation, termed μ -rhythm in the sensorimotor cortex, is driven by bouts of inhibition (or deflections of the cortical excitation-inhibition balance towards inhibition), rhythmically suppressing neural processing during the inhibitory phase, while permitting it during the excitable phase (or “duty cycle”). Since alpha is supposed to be asymmetric (Mazaheri and Jensen, JN 2008; Schalk, FHN 2015), increasing amplitudes would result from stronger bouts of inhibition rather that excitation, thereby gradually shortening the duration of the duty cycle during which local neural processing can occur. Indeed, sensorimotor μ -rhythm power (Sauseng et al., Neuropsychologia 2009) and phase (Zrenner et al., submitted for publication) have been found to modulate corticospinal excitability, as indexed by the amplitude of motor evoked responses (MEPs) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). However, the asymmetry of the oscillation and its proposed inhibitory nature have not yet been explicitly tested. Here we set out to explicitly test the “pulsed inhibition hypothesis” by disentangling the contribution of μ -rhythm power and phase to the modulation of both cortical excitability and inhibition, measuring the GABA-A-receptor mediated short intra-cortical inhibition (SICI) via EEG-triggered paired-pulse TMS. SICI consists of a conditioning stimulus (CS) at subthreshold stimulation intensity followed by a test stimulus (TS) at suprathreshold intensity with an inter-stimulus interval (ISI) of 2.0 ms. Here, CS+TS and TS alone trials are randomly intermingled and EEG-triggered in real-time based on the online extracted μ -rhythm to target two power levels (high, low) and four different phase angles (rising flank, peak, falling flank, trough). The real-time EEG-triggered TMS setup consists of a NeurOne 64-channel EEG system feeding the signal of all channels into a real-time computer, which is running the analyses via a Simulink model and triggers four monophasic Magstim 200 2 systems connected to a single coil via the Magstim 4-into-1 module to allow shorter inter-trial intervals ( ∼ 2 s) and fully flexible external control. MEP amplitudes are analyzed in an amplitude- and phase-dependent manner to characterize the GABA-A-ergic profile of human sensorimotor μ -rhythm and thereby test a fundamental assumption of the “pulsed inhibition hypothesis”.

P271 The LRRK2-R1441C mutation disrupts long-term potentiation-like plasticity in Parkinson’s disease patients

Background Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) account for up to 13% of dominant familial Parkinson’s disease (PD) cases. The clinical and pathological features of LRRK2-PD are often indistinguishable from idiopathic PD (iPD). Recent evidence pointed out that LRRK2 acts directly at the secretory and endocytic molecular machinery. Importantly, in southern Italy the R1441C mutation is the most frequent mutation reported so far. Objective Based on the LRRK2-role on synaptic transmission, we aimed to investigate in vivo excitability and plasticity of the motor cortex by means of transcranial magnetic stimulation (TMS). Methods Paired pulse TMS was used to investigate cortical excitability by using short intracortical inhibition and facilitation and short afferent inhibition paradigm. Intermittent theta burst stimulation (iTBS) was used to test long-term potentiation-like cortical plasticity (LTP). Eight LRRK2-PD patients harboring the R1441C mutation and 11 iPD were tested on the more affected side in ON l-dopa therapy. Results We observed the lack of LTP-like motor cortex plasticity in R1441C-LRRK2 patients compared to healthy-subjects and with a similar profile observed for iPD patients. Motor cortex excitability profile did not exhibit any difference among the three groups. Conclusions R1441C mutation disrupts motor cortex LTP-like plasticity in Parkinson’s disease patients.