Shaping the excitability of human motor cortex with premotor rTMS

Recent studies have shown that low-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsal premotor cortex has a lasting influence on the excitability of specific neuronal subpopulations in the ipsilateral primary motor hand area (M1 _HAND ). Here we asked how these premotor to motor interactions are shaped by the intensity and frequency of rTMS and the orientation of the stimulating coil. We confirmed that premotor rTMS at 1 Hz and an intensity of 90% active motor threshold (AMT) produced a lasting decrease in corticospinal excitability probed with single-pulse TMS over the left M1 _HAND . Reducing the intensity to 80% AMT increased paired-pulse excitability at an interstimulus interval (ISI) of 7 ms. Opposite effects occurred if rTMS was given at 5 Hz: at 90% AMT, corticospinal excitability increased; at 80% AMT, paired-pulse excitability at ISI = 7 ms decreased. No effects were seen if rTMS was applied at the same intensities to prefrontal or primary motor cortices. These findings indicate that the intensity of premotor rTMS determines the net effect of conditioning on distinct populations of neurones in the ipsilateral M1 _HAND , but it is the frequency of rTMS that determines the direction of the induced change. By selecting the appropriate intensity and frequency, premotor rTMS allows to induce a predictable up- or down-regulation of the excitability in distinct neuronal circuits of human M1 _HAND .     

Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.     

Manipulation of phosphene thresholds by transcranial direct current stimulation in man

Transcranial direct current stimulation (tDCS) can modulate the excitability of the human motor cortex, as revealed by the amplitude of the motor-evoked potentials (MEP). The aim of our study has been to produce localized changes of cerebral excitability of the visual cortex in the intact human by weak anodal and cathodal stimulation. For quantification of current-induced excitability changes, we measured phosphene threshold (PT) using short trains of 5-Hz transcranial magnetic stimulation (TMS) pulses in nine healthy subjects before, immediately after, 10 min, and 20 min after the end of tDCS. PTs are suggested as representative values of visual cortex excitability changes. Reduced PT was detected immediately and 10 min after the end of anodal stimulation, while cathodal stimulation resulted in an opposite effect. Our results show that tDCS elicits a transient, reversible excitability alteration of the visual cortex, thus representing a promising tool for neuroplasticity research. Electronic Publication     

Increased corticospinal excitability after 5 Hz rTMS over the human supplementary motor area

Transcranial magnetic stimulation (TMS) can produce effects not only at the site of stimulation but also at distant sites to which it projects. Here we examined the connection between supplementary motor area (SMA) and the hand area of the primary motor cortex (M1_Hand) by testing whether prolonged repetitive TMS (rTMS) over the SMA can produce changes in excitability of the M1_Hand after the end of the stimulus train. We evaluated motor-evoked potentials (MEPs) and the cortical silent period (CSP) evoked by a single-pulse TMS, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) produced by a paired-pulse TMS, and forearm flexor H reflexes before and after 750 pulses of 5 Hz rTMS over SMA at an intensity of 110% active motor threshold (AMT) for the first dorsal interosseous (FDI) muscle. The amplitude of MEPs recorded from the right FDI muscle at rest as well as during voluntary contraction increased for at least 10 min after the end of rTMS, although the duration of the CSP, SICI and ICF did not change. There was no effect on H reflexes in the flexor carpi radialis muscle, even though the amplitude of the MEP obtained from the same muscle increased after rTMS. The effects on MEPs depended on the intensity of rTMS and were spatially specific to the SMA proper. We suggest that 5 Hz rTMS over SMA can induce a short-lasting facilitation in excitability of the M1_Hand compatible with the anatomical connections between SMA and the M1_Hand.     

Rapid-rate paired associative stimulation of the median nerve and motor cortex can produce long-lasting changes in motor cortical excitability in humans

Repetitive transcranial magnetic stimulation (rTMS) or repetitive electrical peripheral nerve stimulation (rENS) can induce changes in the excitability of the human motor cortex (M1) that is often short-lasting and variable, and occurs only after prolonged periods of stimulation. In 10 healthy volunteers, we used a new repetitive paired associative stimulation (rPAS) protocol to facilitate and prolong the effects of rENS and rTMS on cortical excitability. Sub-motor threshold 5 Hz rENS of the right median nerve was synchronized with submotor threshold 5 Hz rTMS of the left M1 at a constant interval for 2 min. The interstimulus interval (ISI) between the peripheral stimulus and the transcranial stimulation was set at 10 ms (5 Hz rPAS_10ms) or 25 ms (5 Hz rPAS_25ms). TMS was given over the hot spot of the right abductor pollicis brevis (APB) muscle. Before and after rPAS, we measured the amplitude of the unconditioned motor evoked potential (MEP), intracortical inhibition (ICI) and facilitation (ICF), short- and long-latency afferent inhibition (SAI and LAI) in the conditioned M1. The 5 Hz rPAS_25ms protocol but not the 5 Hz rPAS10_ms protocol caused a somatotopically specific increase in mean MEP amplitudes in the relaxed APB muscle. The 5 Hz rPAS_25ms protocol also led to a loss of SAI, but there was no correlation between individual changes in SAI and corticospinal excitability. These after-effects were still present 6 h after 5 Hz rPAS_25ms. There was no consistent effect on ICI, ICF and LAI. The 5 Hz rENS and 5 Hz rTMS protocols failed to induce any change in corticospinal excitability when given alone. These findings show that 2 min of 5 Hz rPAS_25ms produce a long-lasting and somatotopically specific increase in corticospinal excitability, presumably by sensorimotor disinhibition.     

Response linearity in primary auditory cortex of the ferret

The responses of neurons within the primary auditory cortex (A1) of the ferret elicited by broadband dynamic spectral ripple stimuli were examined over a range of ripple spectral densities and ripple velocities. The large majority of neurons showed modulated responses to these stimuli and responded most strongly at low ripple densities and velocities. The period histograms of their responses were subjected to Fourier analysis, and the ratio of the magnitudes of the f ₁ and f ₀ (DC) components of these responses were calculated to give a quantitative index of response linearity. For 82 out of 396 neurons tested (20.7%) this ratio remained above 1.0 over the entire range of ripple densities and velocities. These neurons were classified as 'consistently linear'. A further 134/396 (33.8%) of neurons maintained an f ₁/ f ₀ ratio above 1.0 for either a range of ripple densities at a fixed ripple velocity, or over a range of ripple velocities at a specific ripple density, and were classified as 'locally linear'. Interestingly, for the superficial layers of the primary auditory cortex, consistently linear and locally linear neurons outnumbered nonlinear neurons by a 2:1 ratio. The converse was true for the deep layers. Unlike in primary visual cortex, where f ₁/ f ₀ ratios have been reported to exhibit a bimodal distribution with a minimum at   f ₁/ f ₀≈ 1  , f ₁/ f ₀ ratios for A1 are unimodally distributed with a peak at   f ₁/ f ₀≈ 1  .     

Changes of blood lactate levels after repetitive transcranial magnetic stimulation

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50 μV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10 min after a single session of low frequencies (1 Hz for 15 min) rTMS (LF rTMS) or high frequency (20 Hz for 15 min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10 min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood–brain barrier.     

Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA_A receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA_A activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA_A activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI  ( F _3,9= 3.19, P = 0.039)  . In contrast to SICI, SAI was significantly reduced by lorazepam  ( F _3,9= 9.39, P = 0.0002)  . Our findings demonstrate that GABA_A activity enhancement determines a suppression of SAI and an increase of SICI.     

Modulation of visual cortex excitability in migraine with aura: Effects of valproate therapy

We explored the effects of valproate treatment on visual cortex excitability changes in migraine with aura patients. Abnormal cortical excitability has been suggested to play an important role in the etiopathogenesis of migraine; in particular, it has been suggested a failure of inhibitory circuits in migraine with aura. Valproate acts as a central GABA agonist and it is reasonable suppose that VPA could modify cortical excitability state. Phosphene threshold (PT) was assessed at baseline and after 1 Hz rTMS before and after one month therapy. We found that low-frequency rTMS in drug-free migraineurs decreased PT, while the treatment with the GABA agonist valproate is able to revert the effect of 1 Hz rTMS over the occipital cortex. If the paradoxical increasing of PT to 1 Hz rTMS is consequent upon the deficiency of intracortical inhibitory circuits in migraine, it seems reasonable to suppose that the effect of valproate is due to a recovery of activity of these circuits.     

IgE responses to Dermatophagoides pteronyssinus native major allergens Der p 1 and Der p 2 during long-term specific immunotherapy

We investigated by ELISA the IgE response to whole extract of the house-dust mite Dermatophagoides pteronyssinus (Dp) and to the native major allergens, Der p 1 and Der p 2, in sera from 18 adult patients (group A) with Dp-allergic asthma before ( t ₀) and 1, 2, 3, and 4 ( t ₁– t ₄) years after subcutaneous specific immunotherapy (SIT). A qualitative reduction ( P =0.05) of the IgE responses to Dp and Der p 2 was observed from t ₁ to t ₄, but a highly statistical significant decrease appeared at t ₃, ( P < 0.01). With regard to Der p 1 IgE values, the immunotherapy induced a significant decrease ( P < 0.01) at t ₃, but not before. In group A, the IgE responses to Der p 1 and Der p 2 were not correlated at t ₀ ( r _s=0.31; P = 0.2l) but were correlated at t₃ ( r _s= 0.78; P=0.001). We also examined sera from 14 adult patients (group B, same SIT schedule as group A) who were without respiratory symptoms at the end of the third year (t₃) of Dp SIT. At this time ( t ₃), there were no significant differences in Der p 1 and Der p 2 IgE levels between group A and group B.     

Neurokinin-1 receptor desensitization to consecutive microdialysis infusions of substance P in human skin

Unloaded shortening velocity ( V ₀) of human triceps surae muscle was measured in vivo by applying the 'slack test', originally developed for determining V ₀ of single muscle fibres, to voluntary contractions at varied activation levels (ALs). V ₀ was measured from 10 subjects at five different ALs defined as a fraction (5, 10, 20, 40 and 60%) of the maximum voluntary contraction (MVC) torque. Although individual variability was apparent, V ₀ tended to increase with AL  ( R ²= 0.089; P = 0.035)  up to 60%MVC (8.6 ± 2.6 rad s⁻¹). This value of V ₀ at 60%MVC was comparable to the maximum shortening velocity of plantar flexors reported in the previous studies. Electromyographic analysis showed that the activities of soleus, medial gastrocnemius and lateral gastrocnemius muscles increased with AL during isometric contraction and after the application of quick release in a similar manner. Also, it showed that the activity of an antagonist, tibialis anterior muscle, was negligible, even though a slight increase took place after the quick release of agonist. Correlation analysis showed that there were no significant correlations between V ₀ and MVC torque normalized with respect to body mass, although the correlation coefficient was relatively high at low ALs. The results suggest that in human muscle, V ₀ represents the unloaded velocity of the fastest muscle fibres recruited, and increases with AL possibly because of progressive recruitment of faster fibres. Individual variability may be explained, at least partially, by the difference in fibre-type composition.     

Phosphene threshold as a function of contrast of external visual stimuli

Transcranial magnetic stimulation (TMS) of the occipital lobe is frequently used to induce visual percepts by direct stimulation of visual cortex. The threshold magnetic field strength necessary to elicit a visual percept is often regarded as a measure of electrical excitability of visual cortex. Using single-pulse TMS during visual motion stimulus presentation, we investigated the relationship between different degrees of visual cortical preactivation and cortical phosphene threshold (PT). The two possible, mutually exclusive, predictions on the outcome of this experiment were that a) PT increases with stronger preactivation because of a decrease in the signal-to-noise ratio, or b) that PT decreases with increased preactivation because of the increase in neuronal response towards some threshold. PTs for single-pulse stimulation of the occipital lobe were determined for eight subjects while they passively viewed a horizontally drifting luminance-modulated sinewave grating. Gratings used were of four different luminance contrasts while the spatial and temporal frequencies remained constant. PTs were shown to increase significantly as the background grating increased in contrast. These results suggest that the neural activity underlying the perception of a phosphene can be considered a type of signal that can be partially masked by another signal, in this case the visual cortical activation produced by passive viewing of drifting gratings.

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This revised version was published online in May 2005. The preceding version was showing a false article.     

Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles

Maximum shortening velocity ( V ₀) was determined in single fibres dissected from hind limb skeletal muscles of rabbit and mouse and classified according to their myosin heavy chain (MHC) isoform composition. The values for rabbit and mouse V ₀ were compared with the values previously obtained in man and rat under identical experimental conditions. Significant differences in V ₀ were found between fibres containing corresponding myosin isoforms in different species: as a general rule for each isoform V ₀ decreased with body mass. Myosin isoform distributions of soleus and tibialis anterior were analysed in mouse, rat, rabbit and man: the proportion of slow myosin generally increased with increasing body size. The diversity between V ₀ of corresponding myosin isoforms and the different myosin isoform composition of corresponding muscles determine the scaling of shortening velocity of whole muscles with body size, which is essential for optimisation of locomotion. The speed of actin translocation ( V _f) in in vitro motility assay was determined with myosins extracted from single muscle fibres of all four species: significant differences were found between myosin isoforms in each species and between corresponding myosin isoforms in different species. The values of V ₀ and V _f determined for each myosin isoform were significantly correlated, strongly supporting the view that the myosin isoform expressed is the major determinant of maximum shortening velocity in muscle fibres.     

Tidal volume, cardiac output and functional residual capacity determine end-tidal CO2 transient during standing up in humans

In man assuming the upright position, end-tidal P _CO2 ( P _ETCO2 ) decreases. With the rising interest in cerebral autoregulation during posture change, which is known to be affected by P _ETCO2 , we sought to determine the factors leading to hypocapnia during standing up from the supine position. To study the contribution of an increase in tidal volume ( V _T ) and breathing frequency, a decrease in stroke volume (SV), a ventilation–perfusion ( V/Q ) gradient and an increase in functional residual capacity (FRC) to hypocapnia in the standing position, we developed a mathematical model of the lung to follow breath-to-breath variations in P _ETCO2 . A gravity-induced apical-to-basal V/Q gradient in the lung was modelled using nine lung segments. We tested the model using an eight-subject data set with measurements of V _T , pulmonary O₂ uptake and breath-to-breath lumped SV. On average, the P _ETCO2 decreased from 40 mmHg to 36 mmHg after 150 s standing. Results show that the model is able to track breath-to-breath P _ETCO2 variations ( r ²= 0.74, P < 0.05). Model parameter sensitivity analysis demonstrates that the decrease in P _ETCO2 during standing is due primarily to increased V _T , and transiently to decreased SV and increased FRC; a slight gravity-induced V/Q mismatch also contributes to the hypocapnia. The influence of cardiac output on hypocapnia in the standing position was verified in experiments on human subjects, where first breathing alone, and then breathing, FRC and V/Q were controlled.     

Expression of α5 (CD49e) and α6 (CD49f) Integrin Subunits on T Cells in the Circulation and the Lamina Propria of Normal and Inflammatory Bowel Disease Colonic Mucosa

Intestinal lamina propria T cells are believed to be derived, via the systemic circulation, from gut-associated lymphoid tissue. After migration into the lamina propria, T cells are capable of luminally directed migration following the loss of surface epithelial cells. For adhesion and migration within the extracellular matrix, T cells are likely to utilize the integrin family of adhesion molecules. The aim of this study was to quantitatively and qualitatively investigate the expression of α₅ and α₆ integrin subunits on the surface of human T cells that: (a) migrated out of the lamina propria, (b) remained resident within the matrix and (c) were present in the circulation. In both subpopulations of CD4 and CD8-positive T cells, from both normal and inflamed (inflammatory bowel disease) colonic mucosa, there were significantly fewer α₅ and α₆-positive cells than in the peripheral blood. In addition, there were significantly fewer α₆ integrin molecules on the surface of CD4 and CD8-positive lamina propria T-cell subpopulations, compared with those in the circulation. Our studies suggest that, following migration into the lamina propria, there is down-regulation of α₅ and α₆ integrin-subunit expression on the surface of T cells. Molecules other than members of very late activation antigen-5 (VLA-5) (α₅β₁) and VLA-6 (α₆β₁) families of adhesion molecules are likely to be important in interactions with extracellular components in the lamina propria of normal and inflamed human colonic mucosa.     

Increased facilitation of the primary motor cortex following 1 Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans

Connections between the cerebellum and the contralateral motor cortex are dense and important, but their physiological significance is difficult to measure in humans. We have studied a group of 10 healthy subjects to test whether a modulation of the excitability of the left cerebellum can affect the excitability of the contralateral motor cortex. We used repetitive transcranial magnetic stimulation (rTMS) at 1 Hz frequency to transiently depress the excitability of the left cerebellar cortex and paired-pulse TMS testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) to probe the excitability of cortico-cortical connections in the right motor cortex. The cortical silent period was also measured before and after cerebellar rTMS. Motor evoked potentials (MEPs) were significantly larger after than before conditioning rTMS trains (p < 0.01). Moreover, left cerebellar rTMS increased the ICF of the right motor cortex as measured with paired-pulses separated by an interstimulus interval (ISI) of 15 ms. The effect lasted for up to 30 min afterward and was specific for the contralateral (right) motor cortex. The cortical silent period was unaffected by cerebellar rTMS. The implication is that rTMS of the cerebellar cortex can shape the flowing of inhibition from Purkinje cells toward deep nuclei, thereby increasing the excitability of interconnected brain areas.     

Transforming growth factor-β production during the development of renal fibrosis in rats with subtotal renal ablation

The histologic changes observed in the remnant kidney model include progressive mesangial expansion with collapse of capillary lumina, interstitial fibrosis and mononuclear cellular infiltration. Transforming growth factor-beta (TGF-β₁) is an important regulator of extracellular matrix formation. The purpose of this study was to investigate the production and distribution of TGF-β₁ in the kidney during the development of glomerulosclerosis and renal fibrosis in rats with subtotal renal ablation. Eighty-two female Wistar rats weighing 180–220 g were divided into two groups: 49 rats were subjected to 5/6 renal ablation and 33 to sham operation. Urinary albumin excretion, blood pressure and glomerular filtration rate (GFR) were evaluated after the surgical procedure. We also performed histology and immunohistochemistry and determined mRNA for TGF-β₁ in the kidneys of these rats 8, 15, 30 and 90 days after operation. The results showed progressively higher immunohistochemical TGF-β₁ staining in rats with subtotal renal ablation. Cortical renal content of TGF-β₁ mRNA was also higher in these animals and peaked at day 15.
The existence of a temporal association between glomerulosclerosis, interstitial fibrosis and intense mononuclear cellular infiltration on the one hand and higher immunohistochemical TGF-β₁ staining in the renal cortex on the other show that this polypeptide may contribute to the development of renal fibrosis in this model.     

Effects of repetitive TMS on visually evoked potentials and EEG in the anaesthetized cat: dependence on stimulus frequency and train duration

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability that lasts beyond the duration of rTMS application itself. High-frequency rTMS leads primarily to facilitation, whereas low-frequency rTMS leads to inhibition of the treated cortex. However, the contribution of rTMS train duration is less clear. In this study, we investigated the effects of nine different rTMS protocols, including low and high frequencies, as well as short and long applications (1, 3 and 10 Hz applied for 1, 5 and 20 min), on visual cortex excitability in anaesthetized and paralysed cats by means of visual evoked potential (VEP) and electroencephalography (EEG) recordings. Our results show that 10 Hz rTMS applied for 1 and 5 min significantly enhanced early VEP amplitudes, while 1 and 3 Hz rTMS applied for 5 and 20 min significantly reduced them. No significant changes were found after 1 and 3 Hz rTMS applied for only 1 min, and 10 Hz rTMS applied for 20 min. EEG activity was only transiently (<20 s) affected, with increased delta activity after 1 and 3 Hz rTMS applied for 1 or 5 min. These findings indicate that the effects of rTMS on cortical excitability depend on the combination of stimulus frequency and duration (or total number of stimuli): short high-frequency trains seem to be more effective than longer trains, and low-frequency rTMS requires longer applications. Changes in the spectral composition of the EEG were not correlated to changes in VEP size.     

Perturbation of visuospatial attention by high-frequency offline rTMS

The contribution of different cortical regions to visuospatial attention can be probed with the help of perturbation techniques, such as transcranial magnetic stimulation (TMS). Repetitive TMS (rTMS) has also been suggested as a tool for the therapy of brain injuries, by adjusting the neural excitability of injured or intact brain regions. Low- and high-frequency rTMS have been shown to result in subsequent (offline) reductions or increases of local cortical excitability, respectively. Previous studies demonstrated that low-frequency (1 Hz) rTMS of posterior parietal cortex (PPC) produced significantly reduced detection of stimuli in the visual hemifield contralateral to the stimulation site, as well as increased ipsilateral detection. We here explored the functional impact of high-frequency (20 Hz) rTMS with an attention task similar to that of a previous low-frequency study (Hilgetag et al. in Nat Neurosci 4:953–957, 2001). Normal healthy subjects (N = 14) received high-frequency rTMS (20 Hz, 10 min, 50% stimulator output) over right or left PPC (coordinate points P4 or P3). After stimulation of the right PPC, detection of single visual stimuli in the contralateral hemifield was significantly impaired. Generally, rTMS of right and left PPC produced mirror-symmetric trends in reduced contralateral detection. These effects were still present after post-TMS sham stimulation (more than 20 min after the end of active rTMS). The results suggest that attentional function can be perturbed by high-frequency rTMS as well as by low-frequency rTMS, despite potential differences in the underlying neural mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Transcranial direct current stimulation modulates motor responses evoked by repetitive transcranial magnetic stimulation

Introduction

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques able to induce changes in corticospinal excitability. In this study, we combined rTMS and tDCS to understand possible interactions between the two techniques, and investigate whether they are polarity dependent.

Materials and methods

Eleven healthy subjects participated in the study. Each patient underwent both anodal and cathodal conditioning tDCS in two separate sessions; brief 5 Hz-rTMS trains were delivered over the primary motor cortex at an intensity of 120% the resting motor threshold (RMT) before tDCS (T0), immediately after (T1) and 10 min after current offset (T2). We then analysed changes induced by cathodal and anodal tDCS on TMS variables.

Results

Our results showed that in both anodal and cathodal sessions, the motor evoked potential (MEP) amplitude increased significantly in size before stimulation (T0). Conversely, after anodal tDCS, the MEP facilitation measured at T1 and T2 was absent, whereas after cathodal tDCS it was preserved.

Conclusions

Our findings provide new direct neurophysiological evidence that tDCS influences primary motor cortex excitability.