NMDA receptor-dependent metaplasticity by high-frequency magnetic stimulation

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-termpotentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-primingwas diminishedwhen applied in the presence of themetabotropic glutamate receptor antagonists (RS)- -methylserine-O-phosphate (MSOP) and (RS)--methyl-4-carboxyphenylglycine (MCPG).Moreover,whenHFMSwas delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 M), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity

NMDA receptor-dependent metaplasticity by high-frequency magnetic stimulation

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-termpotentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-primingwas diminishedwhen applied in the presence of themetabotropic glutamate receptor antagonists (RS)- -methylserine-O-phosphate (MSOP) and (RS)--methyl-4-carboxyphenylglycine (MCPG).Moreover,whenHFMSwas delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 M), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity

Dietary Nitrate Supplementation Improves Exercise Tolerance by Reducing Muscle Fatigue and Perceptual Responses

The present study was designed to provide further insight into the mechanistic basis for the improved exercise tolerance following dietary nitrate supplementation. In a randomized, double-blind, crossover design, twelve recreationally active males completed a dynamic time-to-exhaustion test of the knee extensors after 5 days of consuming both nitrate-rich (NITRATE) and nitrate-depleted beetroot juice (PLACEBO). Participants who improved their time-to-exhaustion following NITRATE performed a time-matched trial corresponding to the PLACEBO exercise duration with another 5 days of dietary nitrate supplementation. This procedure was performed to obtain time-matched exercise trials with (NITRATEtm) and without dietary nitrate supplementation (PLACEBO). Neuromuscular tests were performed before and after each time-matched condition. Muscle fatigue was quantified as percentage change in maximal voluntary torque from pre- to post-exercise (ΔMVT). Changes in voluntary activation (ΔVA) and quadriceps twitch torque (ΔPS100) were used to quantify central and peripheral factors of muscle fatigue, respectively. Muscle oxygen saturation, quadriceps muscle activity as well as perceptual data (i.e., perception of effort and leg muscle pain) were recorded during exercise. Time-to-exhaustion was improved with NITRATE (12:41 ± 07:18 min) compared to PLACEBO (09:03 ± 04:18 min; P = 0.010). NITRATEtm resulted in both lower ΔMVT and ΔPS100 compared to PLACEBO (P = 0.002; P = 0.001, respectively). ΔVA was not different between conditions (P = 0.308). NITRATEtm resulted in reduced perception of effort and leg muscle pain. Our findings extend the mechanistic basis for the improved exercise tolerance by showing that dietary nitrate supplementation (i) attenuated the development of muscle fatigue by reducing the exercise-induced impairments in contractile muscle function; and (ii) lowered the perception of both effort and leg muscle pain during exercise

Investigation of first ray mobility during gait by kinematic fluoroscopic imaging-a novel method

<p>Abstract</p> <p>Background</p> <p>It is often suggested that sagittal instability at the first tarso-metatarsal joint level is a primary factor for hallux valgus and that sagittal instability increases with the progression of the deformity. The assessment of the degree of vertical instability is usually made by clinical evaluation while any measurements mostly refer to a static assessment of medial ray mobility (i.e. the plantar/dorsal flexion in the sagittal plane). Testing methods currently available cannot attribute the degree of mobility to the corresponding anatomical joints making up the medial column of the foot. The aim of this study was to develop a technique which allows for a quantification of the in-vivo sagittal mobility of the joints of the medial foot column during the roll-over process under full weight bearing.</p> <p>Methods</p> <p>Mobility of first ray bones was investigated by dynamic distortion-free fluoroscopy (25 frames/s) of 14 healthy volunteers and 8 patients with manifested clinical instability of the first ray. A CAD-based evaluation method allowed the determination of mobility and relative displacements and rotations of the first ray bones within the sagittal plane during the stance phase of gait.</p> <p>Results</p> <p>Total flexion of the first ray was found to be 13.63 (SD 6.14) mm with the healthy volunteers and 13.06 (SD 8.01) mm with the patients (resolution: 0.245 mm/pixel). The dorsiflexion angle was 5.27 (SD 2.34) degrees in the healthy volunteers and increased to 5.56 (SD 3.37) degrees in the patients. Maximum rotations were found at the naviculo-cuneiform joints and least at the first tarso-metatarsal joint level in both groups.</p> <p>Conclusions</p> <p>Dynamic fluoroscopic assessment has been shown to be a valuable tool for characterisation of the kinematics of the joints of the medial foot column during gait.</p> <p>A significant difference in first ray flexion and angular rotation between the patients and healthy volunteers however could not be found.</p

Interaction Between Transcranial Random Noise Stimulation and Observation-Execution Matching Activity Promotes Motor Cortex Excitability

Pathways of the human mirror neuron system are activated during both, action observation and action execution, including lateralized activation of respective areas, as shown by observed right-or left-hand actions. Here, we investigated whether execution-dependent motor cortex excitability is affected by prior interaction between transcranial random noise stimulation (tRNS) and action observation. Sham or real tRNS (1 mA) was applied for 10-min over the left primary motor cortex during action observation. In the main experiments, participants received sham or real tRNS while they watched a video showing repeated tapping tasks, involving either the right-hand (Experiment 1, congruent action observation), or a mirror-reversed video showing the same performance (Experiment 2), followed by action execution of the right-hand. In control Experiments 1–3, participants received real tRNS while observing a perceptual sequence, watching a landscape picture, or observing the left-hand performing the action (the sequence was identical to Experiment 1), followed by action execution of the right-hand. In control Experiment 4, participants received real tRNS during congruent action observation, and then took 6-min rest. Motor-evoked potentials (MEP) were recorded before action observation, a perceptual sequence or a landscape picture, immediately after, and after action execution, or an interval of 6-min, dependent on the respective experimental condition. MEPs in the right first dorsal interosseous muscle increased significantly after real tRNS combined with congruent action observation, and after action execution compared to the sham session in Experiment 1 and control experiments. We conclude that prior interaction between real tRNS and action observation of mirror-matched movements modulates subsequent execution-dependent motor cortex excitability

How thoughts give rise to action - conscious motor intention increases the excitability of target-specific motor circuits.

The present study shows evidence for conscious motor intention in motor preparation prior to movement execution. We demonstrate that conscious motor intention of directed movement, combined with minimally supra-threshold transcranial magnetic stimulation (TMS) of the motor cortex, determines the direction and the force of resulting movements, whilst a lack of intention results in weak and omni-directed muscle activation. We investigated changes of consciously intended goal directed movements by analyzing amplitudes of motor-evoked potentials of the forearm muscle, flexor carpi radialis (FCR), and extensor carpi radialis (ECR), induced by transcranial magnetic stimulation over the right motor cortex and their motor outcome. Right-handed subjects were asked to develop a strong intention to move their left wrist (flexion or extension), without any overt motor output at the wrist, prior to brain stimulation. Our analyses of hand acceleration and electromyography showed that during the strong motor intention of wrist flexion movement, it evoked motor potential responses that were significantly larger in the FCR muscle than in the ECR, whilst the opposite was true for an extension movement. The acceleration data on flexion/extension corresponded to this finding. Under no-intention conditions again, which served as a reference for motor evoked potentials, brain stimulation resulted in undirected and minimally simultaneous extension/flexion innervation and virtually no movement. These results indicate that conscious intentions govern motor function, which in turn shows that a neuronal activation representing an "intention network" in the human brain pre-exists, and that it functionally represents target specific motor circuits. Until today, it was unclear whether conscious motor intention exists prior to movement, or whether the brain constructs such an intention after movement initiation. Our study gives evidence that motor intentions become aware before any motor execution

Modulating Observation-Execution-Related Motor Cortex Activity by Cathodal Transcranial Direct Current Stimulation

The aim of this randomized sham-controlled study was to examine the impact of cathodal transcranial direct current stimulation (ctDCS) of the primary motor cortex (M1) during movement observation on subsequent execution-related motor cortex activity. Thirty healthy participants received sham or real ctDCS (1 mA) over the left M1 for 10 minutes, respectively. The participants observed a video showing repeated button pressing tasks of the right hand during the sham or real ctDCS, followed by performance of these tasks by the right hand. Motor-evoked potentials (MEP) were recorded from the resting right first dorsal interosseous muscle before movement observation during the sham or real ctDCS, immediately after observation of actions, and after subsequent movement execution. The results of the ANOVA showed a significant main effect on the group (F1,28 = 4.60, p = 0.041) and a significant interaction between time and the group (F2,56 = 5.34, p = 0.008). As revealed by respective post hoc tests, ctDCS induced a significant reduction of MEP amplitudes in connection with movement observation (p = 0.026, Cohen’s d = 0.861) and after subsequent movement execution (p = 0.018, Cohen’s d = 0.914) in comparison with the sham stimulation. It is concluded that ctDCS during movement observation was effective in terms of modulating motor cortex excitability. Moreover, it subsequently influenced execution-related motor cortex activity. This indicates a possible application for rehabilitative treatment in syndromes with pathologically enhanced cortical activity. View Full-Tex

Rawdata and Effects of Intention on Motor Potentials and Kinetics.

<p>Representative trials of one subject (A) illustrates the MEP of the flexion directed movement (on the left side) with the flexor activities (top), the extensor activities (middle), and the time course of the wrist acceleration in the bottom graph. The columns represent the wrist flexion intention (left) and the wrist extension intention condition (middle) and the no-intention condition (BC right). All MEPs have the same scale-units. The acceleration of the left hand dorsum and electromyography (EMG) from the flexor carpi radialis (FCR) and extensor carpi radialis muscles (ECR) of the left hand were recorded for the kinetics of the wrist. (B) Mean values for the intention condition and the baseline condition with the ECR (intended extension) on the left and the FCR (intended flexion) on the right side are shown for each subject.</p

Motor Evoked Potentials of Intended Stimulation.

<p>The different experimental conditions of Flexion, Extension, and No-Intention (BC) resulted in different MEP-Amplitudes of the antagonistic muscle pair of the forearm (FCR and ECR). The Amplitudes of the EMG-data were not normalised. Mean (M) and standard deviations (SD) are presented.</p

Age-related differences in corticomotor facilitation indicate dedifferentiation in motor planning

Efficient motor control requires motor planning. Age-related changes in motor control are well described, e.g. increased movement variability and greater antagonistic muscle co-activation, as well as less functional and less regional specific brain activation. However, less is known about age-related changes in motor planning. By use of transcranial magnetic stimulation we investigated differences in corticomotor facilitation during motor planning in 17 young (25 ± 3 years) and 17 older healthy adults (70 ± 13 years) in a delayed movement paradigm for wrist movements. Motor evoked potentials (MEPs) were recorded for the flexor and extensor carpi radialis during movement preparation of wrist flexion and extension as well as during rest. We found that MEPs were less specifically facilitated during planning in older as compared to younger adults, as indicated by an Age × Condition × Muscle interaction. Young participants showed significantly facilitated MEPs in the respective muscle needed for wrist flexion or extension. By contrast MEPs in older participants were less specifically modulated. We conclude that age relates to dedifferentiated activation of the primary motor cortex already during preparation of distinct movements which might contribute to less efficient motor control in older adults